Home Life Sciences Circadian rhythm-based prognostic features predict immune infiltration and tumor microenvironment in molecular subtypes of hepatocellular carcinoma
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Circadian rhythm-based prognostic features predict immune infiltration and tumor microenvironment in molecular subtypes of hepatocellular carcinoma

  • Jinhai Wang , Li Ma , Jinjuan Wang , Zhe Ma , Weiwei Wang and Songning Yu EMAIL logo
Published/Copyright: January 1, 2026
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Open Life Sciences
From the journal Open Life Sciences Volume 20 Issue 1

Abstract

Hepatocellular carcinoma (HCC) poses a significant threat to human health. Tumor microenvironment alterations, particularly immune-related changes, play a pivotal role in HCC progression, with high-throughput technologies facilitating the exploration of these dynamics. This study aimed to investigate the role of long non-coding RNA (lncRNA) AC019080.1 in HCC cells. A total of 24 circadian rhythm-related (CRR) messenger RNAs (mRNAs) and 433 CRR-lncRNAs were identified. Among them, 46 prognostically relevant circadian rhythm-related lncRNAs (PCRR-lncRNAs) were found to be upregulated in the HCC group. Molecular clustering analysis of 370 HCC samples revealed expression differences of PCRR-lncRNAs across three subtypes. Immune cell infiltration levels and tumor microenvironment analysis revealed significant subtype-specific differences. AC019080.1 and MCM3AP-AS1 were identified as core PCRR-lncRNAs in HCC, with elevated expression in both HCC tissues and cell lines. Through suppression of the Wnt/β-catenin signaling pathway, knockdown of lncRNA AC019080.1 significantly inhibited the proliferation, colony formation, migration, and invasion of HCC cells, while promoting apoptosis. This study suggests that circadian rhythm-related genes can predict immune infiltration and the molecular subtypes of HCC, providing valuable insights for diagnosis and treatment. lncRNA AC019080.1 holds potential as a therapeutic target for HCC.

Keywords: circadian rhythm; prognostic features; hepatocellular carcinoma molecular subtypes; immune infiltration; tumor microenvironment; lncRNA AC019080.1

1 Introduction

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, accounting for approximately 90 % of all liver cancers worldwide, with high incidence and mortality rates [1]. Risk factors such as hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver diseases, and the increasingly prevalent non-alcoholic steatohepatitis (NASH) often contribute to late-stage diagnosis, as early HCC typically presents few clinical signs and symptoms [2]. Many patients are diagnosed at an advanced stage, missing the optimal surgical window, resulting in limited treatment options and a high risk of metastatic recurrence despite conservative therapies [3]. The 5-year survival rate for early-stage HCC is around 70 %, while the median survival for advanced-stage patients is merely 1–1.5 years [4], underscoring the urgent need for early diagnosis to improve treatment outcomes and patient survival. Existing diagnostic methods have significant limitations. Alpha-fetoprotein (AFP), the primary serum marker for screening, has low sensitivity and unreliable results [5]. Histopathological analysis, considered the “gold standard” for tumor diagnosis, has limited applicability in liver cancer detection due to high costs and limited access to tumor tissues [6].

High-throughput sequencing technology and bioinformatics have opened new avenues for understanding tumors. With decreasing sequencing costs and increasing sequencing depth, large-scale high-quality data can now be obtained, enabling the exploration of potential diagnostic, therapeutic, and prognostic targets [7]. Databases like The Cancer Genome Atlas (TCGA), co-founded by the National Human Genome Research Institute (NHGRI) and the National Cancer Institute (NCI) in 2006, which includes molecular characterization of over 20,000 primary malignant tumors and normal samples from 33 cancers along with comprehensive clinical data, play a vital role in data storage and analysis [8], [9], [10], [11].

The circadian rhythm is a cellular system that aligns the body’s metabolism with environmental light-dark cycles [12]. Regulated by central and peripheral molecular clocks, it operates through a transcriptional-translational feedback loop (TTFL) at the molecular level [13], [14], [15], [16]. As a central metabolic organ, the liver exhibits circadian rhythms in over 50 % of its metabolites [17]. Disruptions to circadian genes, whether genetic or environmental, can lead to hepatic metabolic disorders and worsen liver pathology, influencing processes such as glucose, bile acid, and fatty acid metabolism [18]. Non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play pivotal roles in regulating circadian rhythms and are implicated in the pathogenesis of HCC [19], 20]. MiRNAs regulate genes post-transcriptionally, and studies in mutant mice suggest that circadian-regulated miRNAs may contribute to liver cancer by modulating genes involved in cell proliferation, invasion, and metabolism [21]. LncRNAs, such as LncRNA-HULC, are upregulated in HCC tissues and positively correlated with the Clock activator, promoting HCC cell growth both in vitro and in vivo [22]. Risk factors for HCC, including chronic viral hepatitis, long-term carcinogen exposure, and diabetes, are associated with circadian rhythm disruptions [23]. Aberrant expression of circadian genes in HCC, such as the suppression of Per and Cry, disrupts the cancer cell circadian rhythm, promoting cancer cell survival and carcinogenesis [24], 25].

This study analyzed transcriptomic data from TCGA and identified associations between HCC, 24 circadian rhythm-related (CRR) mRNAs, and 433 CRR-lncRNAs. Immune cell infiltration and tumor microenvironment (TME) analyses, alongside quantitative real-time polymerase chain reaction (qRT-PCR), revealed significant positive co-expression of AC019080.1 with other prognostic CRR-lncRNAs. Our study aims to comprehensively explore the role and mechanism of lncRNA AC019080.1 in HCC cells by comparing its expression in normal and cancer cells and conducting loss-of-function assays. These findings could enhance our understanding of HCC molecular mechanisms and offer a novel lncRNA-based target for diagnosis and treatment.

2 Methods

2.1 Data collection and organization

Transcriptome expression data and clinical information for HCC samples were obtained from the TCGA database (https://tcga-data.nci.nih.gov/tcga/), a comprehensive cancer gene expression resource that includes 374 HCC tissue samples and 50 normal control (NC) tissue samples. Custom Perl and R scripts were utilized to clean and organize the data for subsequent bioinformatics and statistical analysis.

2.2 Identification of circadian rhythm-related lncRNAs by co-expression analysis

First, RNA categorization was performed on the transcriptome expression matrices of all HCC and NC samples to differentiate between mRNAs and lncRNAs. Subsequently, 24 CCR genes (CRRGs) were identified from the literature (PMID: 37183243 and PMID: 37373286), and the R package limma was used to extract the relative expression of these CRR-mRNAs from the gene expression matrix. Co-expression analysis of CRR-mRNAs with lncRNAs was subsequently performed using the Pearson correlation test to identify CRR-lncRNAs. A Pearson correlation coefficient of > 0.5 and a P-value of < 0.05 were considered statistically significant.

2.3 Identification of prognostically relevant CRR-lncRNAs in HCC

The expression matrix of CRR-lncRNAs was merged with clinical data (survival time and survival status) for patients with HCC. The R package survival was then used to identify prognostically relevant CRR-lncRNAs (PCRR-lncRNAs) through one-way Cox regression analysis. Differential expression analysis of PCRR-lncRNAs between HCC and NC groups was performed using the R package limma, and the results were visualized using box-and-whisker plots and heatmaps. A P-value < 0.001 was considered statistically significant.

2.4 Molecular cluster analysis of HCC samples

Based on the expression values of PCRR-lncRNAs, the R package ConsensusClusterPlus was employed to perform molecular clustering analysis on all patients with HCC. The maximum number of clusters (k) was set to 9, the clustering algorithm was set to “km,” and the similarity of the samples was assessed using the “Euclidean” distance. The optimal number of clusters (k) was determined by analyzing the cumulative distribution function (CDF) curve, cluster consensus scores, and the consensus matrix. Survival differences between patients with different molecular subtypes were analyzed using the survival and survminer R packages, and visualized using survival curves. Finally, the expression differences of PCRR-lncRNAs between patients with different molecular subtypes were explored, and clinical trait differences across subtypes were examined, with the results visualized in a heatmap.

2.5 Immune cell infiltration and microenvironmental analysis between different HCC molecular phenotypes

Based on the R package limma, immune cell infiltration analysis was performed on all HCC samples using algorithms including TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL, and EPIC. The infiltration levels of immune cells in samples with different HCC molecular subtypes were analyzed. Subsequently, using the R package estimate, TME analysis was conducted on all HCC samples, calculating the StromalScore, ImmuneScore, and ESTIMATEScore for each sample. Differences in these scores across different molecular subtypes were compared, and the results were visualized using heatmaps and box-and-whisker plots. A P-value < 0.05 was considered statistically significant.

2.6 Differential expression analysis and correlation analysis of core PCRR-lncRNAs

The top two genes with the highest hazard ratio (HR) from the PCRR-lncRNAs were selected as core PCRR-lncRNAs. Differential expression analysis of these core PCRR-lncRNAs was performed between the HCC group and the NC group, as well as among different molecular subtypes, using the R package limma, and the results were visualized through box-and-whisker plots. Co-expression correlation analysis between the core PCRR-lncRNAs and other PCRR-lncRNAs was performed using the corrplot package in R, and the correlation matrix was visualized.

2.7 Clinical sample collection

A total of 25 paired HCC and adjacent non-tumor tissues (collected within 2 cm of the tumor margin) were obtained from patients who underwent surgical resection for HCC between May 2024 and May 2025 at the General Hospital of Ningxia Medical University. Patients were included if they had histologically confirmed primary HCC, no prior anti-tumor treatment (such as chemotherapy, radiotherapy, or targeted therapy), and complete clinical data with written informed consent. Exclusion criteria included the presence of other primary malignancies, severe comorbidities (e.g., decompensated cirrhosis or major organ dysfunction), or incomplete clinical records. Fresh tissue samples were snap-frozen in liquid nitrogen within 30 min after resection and stored at −80 °C until RNA extraction.

Informed consent: Informed consent has been obtained from all individuals included in this study.

Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of the General Hospital of Ningxia Medical University.

2.8 Cell culture and treatment

The cell lines L-02 (normal) and Huh7, Hep3B, and HepG2 (HCC) were selected for this study. These cell lines were obtained from specialized cell banks, and their identities were authenticated using short tandem repeat (STR) profiling. After acquisition, the cells were cultured in high-glucose Dulbecco’s Modified Eagle Medium (DMEM) (HyClone, No. SH30243.01) containing 10 % fetal bovine serum (FBS, Gibco, No. 10099-141) and 1 % double antibody (penicillin-streptomycin mixture, HyClone, No. SV30010) in a humidified incubator at 37 °C with 5 % CO2 (Thermo Fisher Scientific). To induce the Wnt/β-catenin pathway, Huh7 and Hep3B cells were treated with 40 μM SKL2001 (MedChemExpress LLC, Monmouth Junction, NJ, USA) for 1 h.

2.9 Cell transfection

Gemma Genetics, a professional company, was commissioned to construct small interfering RNA (siRNA) sequences targeting lncRNA AC019080.1 (si-#1 and si-#2), with a non-targeting control siRNA (si-NC) serving as the negative control. SiRNAs (si-#1, si-#2, or si-NC) were transfected into Huh7 and Hep3B cells during their logarithmic growth phase using Lipofectamine 3,000 transfection reagent (Invitrogen, No. L3000015). One day prior to transfection, the cells were seeded into 6-well plates at an appropriate density to achieve 30 %–50 % confluence at the time of transfection. The transfection protocol was as follows: 5 μL of Lipofectamine 3,000 was mixed with 250 μL of Opti-MEM medium (Invitrogen, item no. 31985062) and incubated for 5 min at 25 °C. Meanwhile, 10 pmol of siRNAs (si-#1, si-#2, or si-NC) was mixed with 250 μL of Opti-MEM medium. The two mixtures were gently combined and incubated at 25 °C for 20 min, after which they were added dropwise to the wells of the 6-well plates and incubated for an additional 6–8 h. The cells were then used for subsequent experiments.

2.10 Cell counting kit-8 (CCK-8) assay

Huh7 and Hep3B cells were seeded into 96-well plates at a density of 5 × 103 cells per well, with five replicate wells per group. At 0, 24, 48, and 72 h post-transfection, 10 μL of CCK-8 reagent (Dojindo, CK04) was added to each well, and the cells were incubated for 1–4 h at 37 °C. The optical density (OD) was measured at 450 nm using a Bio-Tek Epoch2 microplate reader (Bio-Rad Laboratories, USA). Cell viability curves were generated based on the OD values to assess cell proliferation over time.

2.11 Colony formation assay

The clonogenic potential of Huh7 and Hep3B cells was evaluated by the colony formation assay. Cells were seeded at low density (500 cells/well in 6-well plates) and cultured in complete DMEM (10 % FBS) for 14 days, with medium changes every 3 days. Colonies were fixed with 4 % paraformaldehyde, stained with 0.1 % crystal violet, and those containing > 50 cells were counted under a light microscope (Axio Observer A1; Carl Zeiss, 40 × magnification). Three independent experiments were performed.

2.12 Transwell assay

In the migration assay, 200 μL of transfected cells were added to the upper chamber of a Transwell (Corning, No. 3422, 8.0 μm pore size polycarbonate membrane), with the lower chamber filled with 600 μL of medium containing 20 % FBS. After incubation, non-migrated cells in the upper chamber were removed, while cells that migrated to the lower surface were fixed with 4 % paraformaldehyde for 15 min, stained with crystal violet for 15 min, washed with phosphate-buffered saline (PBS), and counted under a microscope (Axio Observer A1, Carl Zeiss Shanghai Co., Ltd., Shanghai, China) in five randomly selected fields of view. In the invasion assay, Matrigel matrix gel (BD, No. 354234, 1:8 dilution) was applied to the upper chamber and air-dried at 4 °C overnight. The remaining procedures followed the migration assay, with the incubation time extended to 36 h to assess cell invasion capacity.

2.13 Flow cytometry assay

Following transfection, Huh7 and Hep3B cells were collected and resuspended in 500 μL of Binding Buffer (Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) Apoptosis Detection Kit, BD, No. 556547) at a concentration of 1 × 106 cells/mL. Next, 5 μL of Annexin V-FITC and 5 μL of PI were added to the cell suspension. The cells were incubated for 15 min at 25 °C, protected from light, and analyzed using a BD FACSCalibur flow cytometer within 1 h. The apoptosis rate was calculated using FlowJo software (Version 10; FlowJo, LLC).

2.14 Quantitative real-time polymerase chain reaction (qRT-PCR)

Total RNA was extracted using TRIzol reagent (Invitrogen, No. 15596026) from tissues and cells, and RNA concentration and purity were assessed using NanoDrop 2000 (Thermo Fisher Scientific), ensuring an A260/A280 ratio between 1.8 and 2.0. Reverse transcription into cDNA was carried out according to the instructions of the reverse transcription kit (TaKaRa, No. RR047A). Specific primers for lncRNA AC019080.1, MCM3AP-AS1, and GAPDH (used as an internal reference) were synthesized by Sangyo Bioengineering (Shanghai) Co. A 20 μL qRT-PCR reaction system was used on a Bio-Rad CFX96 Touch real-time fluorescence quantitative PCR instrument. The relative gene expression was calculated using the 2−ΔΔCt method based on Ct values.

2.15 Western blot

HCC cells (Huh7 and Hep3B) were lysed using RIPA buffer (P0013, Beyotime, Shanghai, China) containing protease and phosphatase inhibitors, and total protein was quantified using a BCA assay (Thermo Fisher Scientific). Equal amounts of protein (20 μg) were separated by SDS-PAGE and transferred onto PVDF membranes. The membranes were blocked with 5 % non-fat milk for 1 h at room temperature, then incubated overnight at 4 °C with primary antibodies against p-PI3K (1:1,000, ab138364), PI3K (1:1,000, ab302958), p-AKT (1:1,000, ab38449), AKT (1:10,000, ab179463), β-catenin (1:5,000, ab32572), and GAPDH (used as a loading control) (1:2,500, ab9485). After washing, membranes were incubated with appropriate HRP-conjugated secondary antibodies (1:2,000, ab6721) for 1 h at room temperature. Protein bands were visualized using enhanced chemiluminescence (ECL) reagents (#WBULS0100, Millipore, USA) and detected by a chemiluminescence imaging system. Band intensities were quantified using ImageJ software (NIH, Bethesda, MD, USA), and target protein levels were normalized to GAPDH for semi-quantitative analysis.

2.16 Statistical analysis

In this study, various statistical methods and bioinformatics tools were employed to systematically analyze the experimental data. CRR-lncRNAs were identified using Pearson’s correlation test, and PCRR-lncRNAs were selected through one-way COX regression analysis and analyzed for differential expression. Molecular clustering, immune assay, and core PCRR-lncRNAs analysis were conducted with the help of relevant R packages. Cellular experiments, including qRT-PCR and CCK-8, were used to assess relevant parameters, with all analyses performed in R to ensure the accuracy and reliability of the results. All wet-lab experiments were performed in triplicate, and numerical data are presented as mean ± standard deviation (SD). Statistical comparisons between two groups were performed using two-tailed Student’s t-tests, while one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test was used for comparisons among multiple groups.

3 Results

3.1 Identification of CRR-lncRNAs

The flowchart of this study is shown in Figure 1. A transcriptome expression matrix, including 59,427 RNAs, was collected and organized from the TCGA database (Table S1), comprising 16,773 lncRNAs and 19,895 mRNAs (Tables S2 and S3). A matrix of 24 CRR-mRNAs was constructed based on the mRNA matrix data reported in the literature and in HCC (Table S4). Co-expression network analysis identified 433 CRR-lncRNAs, with their expression matrices and co-expression relationships detailed in Tables S5 and S6. The co-expression networks visualized the correlation between the 24 CRR-mRNAs and the 433 CRR-lncRNAs (Figure 2).

Figure 1: Study flowchart.
Figure 1:

Study flowchart.

Figure 2: MCo-expression network between CRR-mRNAs and CRR-lncRNAs. Note: CRR, circadian rhythm-related.
Figure 2:

MCo-expression network between CRR-mRNAs and CRR-lncRNAs. Note: CRR, circadian rhythm-related.

3.2 Identification of PCRR-lncRNAs

Using one-way COX regression analysis, 46 PCRR-lncRNAs were identified (HR > 1, P < 0.001) (Figure 3). All of these PCRR-lncRNAs were upregulated in HCC tissues compared to the NC group (P < 0.001) (Figure 4A and B).

Figure 3: Forest plot showing 46 PCRR-lncRNAs for HCC. Note: HCC, hepatocellular carcinoma.
Figure 3:

Forest plot showing 46 PCRR-lncRNAs for HCC. Note: HCC, hepatocellular carcinoma.

Figure 4: Differential expression of PCRR-lncRNAs. Heatmap (A) and boxplot (B) demonstrating the differential expression of 46 PCRR-lncRNAs between the HCC and NC groups. *** P < 0.001. Note: PCRR, prognostically relevant circadian rhythm-related gene; HCC, hepatocellular carcinoma; NC, normal control.
Figure 4:

Differential expression of PCRR-lncRNAs. Heatmap (A) and boxplot (B) demonstrating the differential expression of 46 PCRR-lncRNAs between the HCC and NC groups. *** P < 0.001. Note: PCRR, prognostically relevant circadian rhythm-related gene; HCC, hepatocellular carcinoma; NC, normal control.

3.3 Identification of HCC molecular typing

Based on the expression profiles of the 46 PCRR-lncRNAs, molecular clustering analysis was performed on 370 HCC samples (only those with complete clinical data were retained). The cluster stability was highest when k = 3, as indicated by the fluctuation of the CDF curve between 0.2 and 1.0 (Figure 5A and B). The area under the CDF curve for k = 2 to 9 is shown in Figure 5C. Notably, the lowest level of interference between subtypes was observed when k = 3 (Figure 5D). Furthermore, a significant difference in survival prognosis was observed between the three subtypes, with the Cluster2 subtype showing the best prognosis and the Cluster3 subtype the worst prognosis (Figure 6A). The heatmap illustrates differences in the expression of PCRR-lncRNAs and the distribution of clinicopathologic features among the three subtypes (Cluster1, Cluster2, and Cluster3) (Figure 6B).

Figure 5: Identification of HCC molecular subtypes. (A) Clustering consensus matrix for k = 3. (B) CDF curve at k = 2–9. (C) Area under the CDF curve at k = 2–9. (D) Tracking plot for k = 2–9. Note: CDF, cumulative distribution function.
Figure 5:

Identification of HCC molecular subtypes. (A) Clustering consensus matrix for k = 3. (B) CDF curve at k = 2–9. (C) Area under the CDF curve at k = 2–9. (D) Tracking plot for k = 2–9. Note: CDF, cumulative distribution function.

Figure 6: Survival analysis of HCC molecular subtypes. (A) Survival curves demonstrating the difference in survival prognosis among the three groups of HCC subtypes. (B) Heatmap demonstrating the expression differences of PCRR-lncRNAs as well as the distribution of clinicopathologic features among the three groups of HCC subtypes. Note: PCRR, prognostically relevant circadian rhythm-related gene; HCC, hepatocellular carcinoma.
Figure 6:

Survival analysis of HCC molecular subtypes. (A) Survival curves demonstrating the difference in survival prognosis among the three groups of HCC subtypes. (B) Heatmap demonstrating the expression differences of PCRR-lncRNAs as well as the distribution of clinicopathologic features among the three groups of HCC subtypes. Note: PCRR, prognostically relevant circadian rhythm-related gene; HCC, hepatocellular carcinoma.

3.4 Differences in immune cell infiltration and tumor microenvironment between the three groups of HCC molecular subtypes

Immune cell infiltration levels across the three HCC subtypes were calculated using seven immune cell infiltration analysis algorithms. The heatmap displayed differences in immune cell infiltration between Cluster1, Cluster2, and Cluster3 under the different algorithms. In the majority of algorithms, the C1 subgroup exhibited elevated infiltration levels of B cells (including naive and memory B cells) and macrophages (M0, M1, and M2), indicating a complex immune microenvironment in this subgroup. The C2 subgroup demonstrated higher infiltration of CD8+ T cells, especially in the TIMER and EPIC algorithms, suggesting its potential as an optimal candidate for immune checkpoint inhibitor therapy. Meanwhile, the C3 subgroup showed increased infiltration of Tregs, particularly in the TIMER and CIBERSORT algorithms, indicating a robust immunosuppressive environment within this subgroup (Figure 7A). TME analysis revealed that the Cluster2 subtype had significantly higher StromalScore, ImmuneScore, and ESTIMATEScore than the Cluster1 subtype, with statistical differences (P < 0.05) (Figure 7A–C).

Figure 7: Immune infiltration and microenvironment differences among the three cluster subtypes. (A) Heatmap demonstrating the differences in immune cell infiltration between the three subtypes under different algorithms. (B, C, D) Box line plots demonstrating the differences in StromalScore, ImmuneScore, and ESTIMATEScore between the three subtypes.
Figure 7:

Immune infiltration and microenvironment differences among the three cluster subtypes. (A) Heatmap demonstrating the differences in immune cell infiltration between the three subtypes under different algorithms. (B, C, D) Box line plots demonstrating the differences in StromalScore, ImmuneScore, and ESTIMATEScore between the three subtypes.

3.5 Identification of the 2 core PCRR-lncRNAs

Among the 46 PCRR-lncRNAs, the top two lncRNAs with the largest HRs were AC019080.1 (HR = 4.31) and MCM3AP-AS1 (HR = 2.88), representing the core PCRR-lncRNAs in HCC. Both AC019080.1 and MCM3AP-AS1 were significantly upregulated in the HCC group compared to the NC group (P < 0.001) (Figure 8A and C). Additionally, the relative expression of AC019080.1 and MCM3AP-AS1 was lowest in the Cluster2 subgroup and highest in the Cluster3 subgroup (P < 0.001) (Figure 8B and D). The correlation matrix indicated significant positive co-expression between AC019080.1, MCM3AP-AS1, and other PCRR-lncRNAs (Figure 8E and F).

Figure 8: Expression patterns and correlations of core PCRR-lncRNAs. (A) Differential expression of AC019080.1 and (C) MCM3AP-AS1 between HCC and NC groups. (B) Differential expression of AC019080.1 and (D) MCM3AP-AS1 between the three groups of cluster subtypes. (E) Co-expression correlation of AC019080.1 and (F) MCM3AP-AS1 with other PCRR-lncRNAs, respectively. *** P < 0.001. Note: PCRR, prognostically relevant circadian rhythm-related gene; HCC, hepatocellular carcinoma; NC, normal control.
Figure 8:

Expression patterns and correlations of core PCRR-lncRNAs. (A) Differential expression of AC019080.1 and (C) MCM3AP-AS1 between HCC and NC groups. (B) Differential expression of AC019080.1 and (D) MCM3AP-AS1 between the three groups of cluster subtypes. (E) Co-expression correlation of AC019080.1 and (F) MCM3AP-AS1 with other PCRR-lncRNAs, respectively. *** P < 0.001. Note: PCRR, prognostically relevant circadian rhythm-related gene; HCC, hepatocellular carcinoma; NC, normal control.

3.6 The level of AC019080.1 and MCM3AP-AS1 Are upregulated in HCC tissues

To further validate the expression levels of AC019080.1 and MCM3AP-AS1, RNA was extracted from 25 paired HCC tissues and adjacent non-cancerous tissues. qRT-PCR analysis confirmed significantly higher expression levels of both AC019080.1 and MCM3AP-AS1 in HCC tissues compared to paracancerous tissues (P < 0.05) (Figure 9A and B). However, since MCM3AP-AS1 has already been studied in HCC [26], and AC019080.1 has not been previously investigated, AC019080.1 was selected for further functional validation.

Figure 9: The level of AC019080.1 and MCM3AP-AS1 are upregulated in HCC tissues. qRT-PCR was used to detect the expression levels of AC019080.1 (A) and MCM3AP-AS1 (B) in HCC tissues and paracancerous tissues. Data are presented as mean ± standard deviation (SD) from three independent experiments. * P < 0.05 versus Paracancer tissues. Note: qRT-PCR, quantitative real-time polymerase chain reaction.
Figure 9:

The level of AC019080.1 and MCM3AP-AS1 are upregulated in HCC tissues. qRT-PCR was used to detect the expression levels of AC019080.1 (A) and MCM3AP-AS1 (B) in HCC tissues and paracancerous tissues. Data are presented as mean ± standard deviation (SD) from three independent experiments. * P < 0.05 versus Paracancer tissues. Note: qRT-PCR, quantitative real-time polymerase chain reaction.

3.7 Knockdown of AC019080.1 inhibits HCC cell progression

Next, the role of lncRNA AC019080.1 in HCC was explored through multiple experimental approaches. First, qRT-PCR analysis revealed that AC019080.1 was significantly upregulated in HCC cell lines (Huh7, Hep3B, and HepG2) compared to the normal hepatic cell line L-02 (P < 0.001) (Figure 10A). To investigate its functional role, specific siRNAs (si-#1 and si-#2) targeting AC019080.1 were designed. qRT-PCR results confirmed successful knockdown, with si-#2 showing higher efficiency, and it was selected for subsequent experiments (P < 0.01, P < 0.001) (Figure 10B). Loss-of-function assays were conducted to explore its functional impact. The CCK-8 assay demonstrated that knockdown of AC019080.1 significantly inhibited cell proliferation in Huh7 and Hep3B cells compared to the si-NC group (P < 0.01, P < 0.001) (Figure 10C). Colony formation assays revealed that AC019080.1 knockdown impaired the clonogenic ability of both Huh7 and Hep3B cells (P < 0.001) (Figure 10D). Transwell assays indicated that silencing AC019080.1 significantly reduced the migratory and invasive capabilities of Huh7 and Hep3B cells compared to the si-NC group (P < 0.01) (Figure 10E and F). Finally, flow cytometric analysis revealed a significant increase in apoptosis rates in both Huh7 and Hep3B cells following AC019080.1 knockdown (P < 0.001) (Figure 10G). In conclusion, lncRNA AC019080.1 plays a critical role in regulating several biological behaviors in HCC cells.

Figure 10: Knockdown of AC019080.1 inhibits HCC cell progression. (A) qRT-PCR was utilized to detect the expression of AC019080.1 in normal cell line L-02 and HCC cell lines (Huh7, Hep3B, and HepG2). (B) The transfection efficiency of AC019080.1 was evaluated by qRT-PCR. (C) CCK-8 assay was carried out to assess the effect of AC019080.1 knockdown on the proliferation potential of HCC cells. (D) The clonogenic capacity of the indicated groups was assessed by colony formation assay. (E, F) Transwell assays were employed to detect the impact of AC019080.1 knockdown on the migration and invasion abilities of HCC cells. (G) Flow cytometry was used to examine the effect of AC019080.1 knockdown on the apoptosis of HCC cells. Data are presented as mean ± standard deviation (SD) from three independent experiments. ** P < 0.01, *** P < 0.001 versus si-NC group. Note: HCC, hepatocellular carcinoma; qRT-PCR, quantitative real-time polymerase chain reaction.
Figure 10:

Knockdown of AC019080.1 inhibits HCC cell progression. (A) qRT-PCR was utilized to detect the expression of AC019080.1 in normal cell line L-02 and HCC cell lines (Huh7, Hep3B, and HepG2). (B) The transfection efficiency of AC019080.1 was evaluated by qRT-PCR. (C) CCK-8 assay was carried out to assess the effect of AC019080.1 knockdown on the proliferation potential of HCC cells. (D) The clonogenic capacity of the indicated groups was assessed by colony formation assay. (E, F) Transwell assays were employed to detect the impact of AC019080.1 knockdown on the migration and invasion abilities of HCC cells. (G) Flow cytometry was used to examine the effect of AC019080.1 knockdown on the apoptosis of HCC cells. Data are presented as mean ± standard deviation (SD) from three independent experiments. ** P < 0.01, *** P < 0.001 versus si-NC group. Note: HCC, hepatocellular carcinoma; qRT-PCR, quantitative real-time polymerase chain reaction.

3.8 Knockdown of AC019080.1 suppresses HCC cell progression by inhibiting the Wnt/β-catenin signaling pathway

Given that the Wnt/β-catenin and PI3K/AKT signaling pathways are well-established key regulators in HCC development and progression [27], we investigated whether AC019080.1 exerts its effects through these pathways. First, we examined the expression levels of key proteins in the Wnt/β-catenin and PI3K/AKT pathways in HCC cells (Huh7 and Hep3B) following AC019080.1 knockdown using Western blot analysis. The results revealed a significant suppression of the Wnt/β-catenin pathway upon AC019080.1 silencing, while the activity of the PI3K/AKT pathway remained largely unchanged (P < 0.01) (Figure 11A). To further validate the involvement of Wnt/β-catenin signaling, rescue experiments were conducted using SKL2001, a known activator of the Wnt/β-catenin pathway [28]. Western blot data demonstrated that AC019080.1 knockdown markedly reduced β-catenin expression in Huh7 and Hep3B cells, and this reduction was effectively reversed by SKL2001 treatment (P < 0.05, P < 0.01) (Figure 11B). Subsequently, a series of functional assays were carried out to determine whether the biological effects of AC019080.1 are mediated via Wnt/β-catenin signaling. CCK-8 and colony formation assays, which measure proliferative capacity, showed that silencing AC019080.1 significantly impaired HCC cell proliferation, and this inhibition was partially reversed by SKL2001 treatment (P < 0.05, P < 0.01, P < 0.001) (Figure 11C and D). Transwell assays indicated that the suppression of migratory and invasive abilities caused by AC019080.1 knockdown was partially rescued by SKL2001 treatment (P < 0.05, P < 0.01) (Figure 11E and F). Furthermore, flow cytometric analysis showed a significant increase in apoptosis upon AC019080.1 silencing, the effect that was attenuated in the presence of SKL2001 (P < 0.05, P < 0.01) (Figure 11G). Collectively, these findings indicate that knockdown of AC019080.1 suppresses HCC progression by inhibiting the Wnt/β-catenin signaling pathway.

Figure 11: Knockdown of AC019080.1 suppresses HCC cell progression by inhibiting the Wnt/β-catenin signaling pathway. (A) Western blot was used to detect the expression levels of p-PI3K, PI3K, p-AKT, AKT, and β-catenin in HCC cell lines (Huh7, Hep3B). (B) Activation of the Wnt/β-catenin pathway was assessed by Western blot detection of β-catenin expression in HCC cells treated with the agonist SKL2001. (C) The impact of AC019080.1 knockdown on HCC cell proliferation was assessed by CCK-8 assay, both in the absence and presence of SKL2001. (D) colony formation assays were conducted to evaluate the effects of AC019080.1 knockdown and SKL2001 on the clonogenic potential of HCC cells. (E, F) Migration and invasion of AC019080.1-knockdown HCC cells were assessed by Transwell assays following treatment with SKL2001. (G) Flow cytometry was used to evaluate the effect of AC019080.1 knockdown on apoptosis in HCC cells, with or without activation of the Wnt/β-catenin pathway by the agonist SKL2001. Data are presented as mean ± standard deviation (SD) from three independent experiments. ** P < 0.05, ** P < 0.01, *** P < 0.001 versus si-NC or si-#2 group. Note: HCC, hepatocellular carcinoma; qRT-PCR, quantitative real-time polymerase chain reaction.
Figure 11:

Knockdown of AC019080.1 suppresses HCC cell progression by inhibiting the Wnt/β-catenin signaling pathway. (A) Western blot was used to detect the expression levels of p-PI3K, PI3K, p-AKT, AKT, and β-catenin in HCC cell lines (Huh7, Hep3B). (B) Activation of the Wnt/β-catenin pathway was assessed by Western blot detection of β-catenin expression in HCC cells treated with the agonist SKL2001. (C) The impact of AC019080.1 knockdown on HCC cell proliferation was assessed by CCK-8 assay, both in the absence and presence of SKL2001. (D) colony formation assays were conducted to evaluate the effects of AC019080.1 knockdown and SKL2001 on the clonogenic potential of HCC cells. (E, F) Migration and invasion of AC019080.1-knockdown HCC cells were assessed by Transwell assays following treatment with SKL2001. (G) Flow cytometry was used to evaluate the effect of AC019080.1 knockdown on apoptosis in HCC cells, with or without activation of the Wnt/β-catenin pathway by the agonist SKL2001. Data are presented as mean ± standard deviation (SD) from three independent experiments. ** P < 0.05, ** P < 0.01, *** P < 0.001 versus si-NC or si-#2 group. Note: HCC, hepatocellular carcinoma; qRT-PCR, quantitative real-time polymerase chain reaction.

4 Discussion

HCC remains a significant challenge in oncology, marked by high heterogeneity and poor prognosis. Our research explored the role of CRR-lncRNAs in HCC, revealing notable associations and novel insights. From the TCGA database, 24 CRR-mRNAs and 433 CRR-lncRNAs linked to HCC were identified. Using one-way COX regression, 46 PCRR-lncRNAs were screened, all of which were upregulated in HCC compared to normal tissues. Among these, AC019080.1 (HR = 4.31) and MCM3AP-AS1 (HR = 2.88) emerged as core PCRR-lncRNAs, showing significant positive co-expression with other PCRR-lncRNAs and higher expression in HCC tissues and cell lines. Functional assays demonstrated that knockdown of lncRNA AC019080.1 inhibited HCC cell proliferation, migration, and invasion, and induced apoptosis by inhibiting the Wnt/β-catenin signaling pathway.

Prior studies have highlighted the impact of circadian rhythm disruption in HCC. Zhu et al. [29] reported that abnormal circadian gene expression is closely associated with tumor malignancy and poor prognosis. Our findings of aberrantly expressed CRR-mRNAs and CRR-lncRNAs in HCC align with these observations, suggesting that dysregulation of the CRRG network is a key factor in HCC development. In a study by Padilla et al. [30], chronic circadian rhythm disruption in a humanized mouse liver model could induce NASH-related carcinogenesis, and the gene expression characteristics of the HCC transcriptome in mice with circadian rhythm disorder closely resembled those of patients with the worst prognosis, highlighting the significant influence of circadian rhythm on HCC progression. Mteyrek et al. [31] demonstrated that suppression of Per and Cry genes disrupted cancer cell circadian rhythms, promoting carcinogenesis. Zhu et al. [32] highlighted the role of genetic abnormalities, such as copy number variations, in prognosis, further complementing research on CRR-lncRNAs. Our identification of a substantial number of CRR-lncRNAs expands on this concept, suggesting that lncRNAs may also contribute to this process. For instance, Cui et al. [33] reported that the lncRNA HULC could upregulate the circadian oscillator CLOCK in hepatoma cells, perturbing the circadian rhythm and promoting hepatocarcinogenesis, further supporting the involvement of lncRNAs in the circadian-related development of HCC.

Regarding the TME, Xiao et al. [34] emphasized that immune cells within the TME interact with tumor cells, influencing tumor progression and treatment response. In the present study, three distinct HCC molecular subtypes with unique immune cell infiltration patterns and survival prognoses were identified. Bao et al. [35]demonstrated the relationship between lncRNAs and the immune landscape in other cancers, which supports our findings in HCC. The Cluster2 subtype exhibited a better prognosis and higher immune-related scores, consistent with the understanding that a more active immune microenvironment contributes to improved patient outcomes [36]. Research in head and neck squamous cell carcinoma (HNSCC) has shown that CCRG risk models are associated with the immune landscape. Specifically, the high-risk group in HNSCC showed increased abundance of activated mast cells, dendritic cells, and neutrophils, which were positively correlated with poor overall survival. This suggests commonalities in the relationship between circadian rhythms, the immune microenvironment, and prognosis across different cancers, providing valuable insights into the TME’s role in HCC.

The role of lncRNAs in cancer has been extensively researched. Shetty et al. [37] and Alshahrani et al. [38] reported that lncRNAs are involved in key tumor-related processes such as metabolic reprogramming and epithelial-mesenchymal transition. Our finding that AC019080.1 promotes HCC cell proliferation, migration, and invasion aligns with these reports, suggesting that this lncRNA may function as an oncogene. Wang et al. [39] described the role of angiogenesis-related lncRNAs in HCC, which is similar to the function of AC019080.1. Previous studies have shown that lncRNAs regulate tumor cell metabolism by modulating metabolic enzymes [40], [41], [42], [43], [44], [45]. It is plausible that AC019080.1 may also influence HCC cell metabolism, although this requires further investigation. For example, a study on melatonin in HCC found that melatonin inhibited HCC progression by regulating the lncRNA-CPS1-IT-mediated HIF-1α inactivation pathway, affecting epithelial-mesenchymal transition and HCC metastasis. This further supports the diverse regulatory roles of lncRNAs in HCC. Notably, our mechanistic investigations revealed that knockdown of AC019080.1 suppressed HCC progression through inhibition of the Wnt/β-catenin signaling pathway, as evidenced by reduced levels of β-catenin upon AC019080.1 knockdown and the reversal of this effect by the Wnt/β-catenin pathway agonist SKL2001. Given the well-established role of Wnt/β-catenin signaling in driving cell proliferation, stemness, and metastasis in HCC [46], the inhibition of the Wnt/β-catenin pathway observed upon AC019080.1 knockdown provides a possible mechanism for the oncogenic function of AC019080.1 itself. Importantly, while AC019080.1 significantly modulated Wnt/β-catenin activity, our data indicated that it had no significant influence on the PI3K/AKT signaling pathway – another key pathway frequently dysregulated in HCC [47]. This selective regulation highlights the functional specificity of AC019080.1 in HCC pathogenesis and suggests potential for targeted therapies. Specifically, targeting AC019080.1 may allow for more precise treatment by affecting a specific cancer-related pathway, without broadly interfering with other important cellular signals.

Nevertheless, this study has several limitations. Relying solely on the TCGA database for samples and data may introduce selection bias, and external validation using independent cohorts or datasets is essential. Furthermore, although our in vitro functional assays have demonstrated that AC019080.1 promotes HCC progression, at least in part, through modulation of the Wnt/β-catenin signaling pathway, the absence of ex vivo evidence means that the broader molecular mechanisms – particularly its downstream targets, interacting partners, and regulatory networks – remain to be fully elucidated. Future studies should extend these findings by identifying the interactions of AC019080.1 with other molecules in HCC cells and validating the functional roles and mechanisms of additional candidate lncRNAs identified in this study. Additionally, examining the role of these lncRNAs in the TME through in vivo models could provide valuable insights for developing targeted therapies. A study by the Liu Chang team from China Pharmaceutical University demonstrated that POLB could drive HCC progression in a circadian rhythm-dependent manner by mediating the demethylation of Per1’s 5′ UTR [48]. This finding serves as an example of an in-depth exploration of the relationship between genes, circadian rhythms, and HCC progression, indicating the potential of exploring the role of lncRNAs in similar contexts to provide new avenues for HCC treatment.

In summary, this study identified novel CRR-lncRNAs associated with HCC and highlights the critical role of lncRNA AC019080.1 in HCC cell progression. These findings not only expand our understanding of the molecular mechanisms underlying HCC but also provide potential targets for the development of innovative diagnostic and therapeutic strategies. Despite the existing limitations, this study lays a foundation for future research in this field, paving the way for more in-depth investigations into the complex relationship between circadian rhythms, lncRNAs, and HCC.

5 Conclusions

In conclusion, leveraging the TCGA database, this study identified correlations between HCC, 24 CRR-mRNAs, and 433 CRR-lncRNAs. It revealed that lncRNA AC019080.1 plays a pivotal role in HCC cell progression, offering potential new diagnostic and therapeutic strategies.

Corresponding author: Songning Yu, Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Yinchuan City, China, E-mail:

  1. Funding information: Authors state no funding involved.

  2. Author contribution: Songning Yu and Jinhai Wang conceptualized the study and wrote the original draft; Jinhai Wang performed the experiments, acquired data, and supervised the investigation; Li Ma, Jinjuan Wang, Zhe Ma, and Weiwei Wang analyzed and interpreted the data; All authors reviewed and approved the final manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/biol-2025-1208).

Received: 2025-05-12
Accepted: 2025-10-07
Published Online: 2026-01-01

© 2025 the author(s), published by De Gruyter, Berlin/Boston

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  22. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  23. Changes in blood glucose and metabolism in hyperuricemia mice
  24. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  25. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  26. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  27. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  28. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  29. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  30. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  31. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  32. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  33. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  34. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  35. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  36. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  37. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  38. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  39. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  40. Low-pressure exposure influences the development of HAPE
  41. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  42. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
  43. Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis
  44. A case of bloodstream infection caused by Neisseria gonorrhoeae
  45. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
  46. p-Cymene inhibits pro-fibrotic and inflammatory mediators to prevent hepatic dysfunction
  47. GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway
  48. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  49. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
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  51. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
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  54. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  55. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  56. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  57. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  58. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
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  60. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  61. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  62. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  63. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  64. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  65. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  66. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  67. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  68. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  69. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  70. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  71. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
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  75. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  76. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  77. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  78. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  79. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
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  231. Corrigendum
  232. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
  233. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans”
  234. Retraction
  235. Retraction of “Down-regulation of miR-539 indicates poor prognosis in patients with pancreatic cancer”
https://doi.org/10.1515/biol-2025-1208
Keywords for this article
circadian rhythm; prognostic features; hepatocellular carcinoma molecular subtypes; immune infiltration; tumor microenvironment; lncRNA AC019080.1
Creative Commons
BY 4.0

Articles in the same Issue

  1. Safety assessment and modulation of hepatic CYP3A4 and UGT enzymes by Glycyrrhiza glabra aqueous extract in female Sprague–Dawley rats
  2. Adult-onset Still’s disease with hemophagocytic lymphohistiocytosis and minimal change disease
  3. Role of DZ2002 in reducing corneal graft rejection in rats by influencing Th17 activation via inhibition of the PI3K/AKT pathway and downregulation of TRAF1
  4. Biomedical Sciences
  5. Mechanism of triptolide regulating proliferation and apoptosis of hepatoma cells by inhibiting JAK/STAT pathway
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  8. Post-pandemic insights on COVID-19 and premature ovarian insufficiency
  9. Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics
  10. Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification
  11. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway
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  13. Battling COVID-19 leveraging nanobiotechnology: Gold and silver nanoparticle–B-escin conjugates as SARS-CoV-2 inhibitors
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  15. Impact of fracture fixation surgery on cognitive function and the gut microbiota in mice with a history of stroke
  16. COLEC10: A potential tumor suppressor and prognostic biomarker in hepatocellular carcinoma through modulation of EMT and PI3K-AKT pathways
  17. High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway
  18. SIK1 inhibits IL-1β-stimulated cartilage apoptosis and inflammation in vitro through the CRTC2/CREB1 signaling
  19. Rutin–chitooligosaccharide complex: Comprehensive evaluation of its anti-inflammatory and analgesic properties in vitro and in vivo
  20. Knockdown of Aurora kinase B alleviates high glucose-triggered trophoblast cells damage and inflammation during gestational diabetes
  21. Calcium-sensing receptors promoted Homer1 expression and osteogenic differentiation in bone marrow mesenchymal stem cells
  22. ABI3BP can inhibit the proliferation, invasion, and epithelial–mesenchymal transition of non-small-cell lung cancer cells
  23. Changes in blood glucose and metabolism in hyperuricemia mice
  24. Rapid detection of the GJB2 c.235delC mutation based on CRISPR-Cas13a combined with lateral flow dipstick
  25. IL-11 promotes Ang II-induced autophagy inhibition and mitochondrial dysfunction in atrial fibroblasts
  26. Short-chain fatty acid attenuates intestinal inflammation by regulation of gut microbial composition in antibiotic-associated diarrhea
  27. Application of metagenomic next-generation sequencing in the diagnosis of pathogens in patients with diabetes complicated by community-acquired pneumonia
  28. NAT10 promotes radiotherapy resistance in non-small cell lung cancer by regulating KPNB1-mediated PD-L1 nuclear translocation
  29. Phytol-mixed micelles alleviate dexamethasone-induced osteoporosis in zebrafish: Activation of the MMP3–OPN–MAPK pathway-mediating bone remodeling
  30. Association between TGF-β1 and β-catenin expression in the vaginal wall of patients with pelvic organ prolapse
  31. Primary pleomorphic liposarcoma involving bilateral ovaries: Case report and literature review
  32. Effects of de novo donor-specific Class I and II antibodies on graft outcomes after liver transplantation: A pilot cohort study
  33. Sleep architecture in Alzheimer’s disease continuum: The deep sleep question
  34. Ephedra fragilis plant extract: A groundbreaking corrosion inhibitor for mild steel in acidic environments – electrochemical, EDX, DFT, and Monte Carlo studies
  35. Langerhans cell histiocytosis in an adult patient with upper jaw and pulmonary involvement: A case report
  36. Inhibition of mast cell activation by Jaranol-targeted Pirin ameliorates allergic responses in mouse allergic rhinitis
  37. Aeromonas veronii-induced septic arthritis of the hip in a child with acute lymphoblastic leukemia
  38. Clusterin activates the heat shock response via the PI3K/Akt pathway to protect cardiomyocytes from high-temperature-induced apoptosis
  39. Research progress on fecal microbiota transplantation in tumor prevention and treatment
  40. Low-pressure exposure influences the development of HAPE
  41. Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis
  42. AKAP12, mediated by transcription factor 21, inhibits cell proliferation, metastasis, and glycolysis in lung squamous cell carcinoma
  43. Association between PAX9 or MSX1 gene polymorphism and tooth agenesis risk: A meta-analysis
  44. A case of bloodstream infection caused by Neisseria gonorrhoeae
  45. Case of nasopharyngeal tuberculosis complicated with cervical lymph node and pulmonary tuberculosis
  46. p-Cymene inhibits pro-fibrotic and inflammatory mediators to prevent hepatic dysfunction
  47. GFPT2 promotes paclitaxel resistance in epithelial ovarian cancer cells via activating NF-κB signaling pathway
  48. Transfer RNA-derived fragment tRF-36 modulates varicose vein progression via human vascular smooth muscle cell Notch signaling
  49. RTA-408 attenuates the hepatic ischemia reperfusion injury in mice possibly by activating the Nrf2/HO-1 signaling pathway
  50. Decreased serum TIMP4 levels in patients with rheumatoid arthritis
  51. Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells
  52. Sodium butyrate aids brain injury repair in neonatal rats
  53. Interaction of MTHFR polymorphism with PAX1 methylation in cervical cancer
  54. Convallatoxin inhibits proliferation and angiogenesis of glioma cells via regulating JAK/STAT3 pathway
  55. The effect of the PKR inhibitor, 2-aminopurine, on the replication of influenza A virus, and segment 8 mRNA splicing
  56. Effects of Ire1 gene on virulence and pathogenicity of Candida albicans
  57. Small cell lung cancer with small intestinal metastasis: Case report and literature review
  58. GRB14: A prognostic biomarker driving tumor progression in gastric cancer through the PI3K/AKT signaling pathway by interacting with COBLL1
  59. 15-Lipoxygenase-2 deficiency induces foam cell formation that can be restored by salidroside through the inhibition of arachidonic acid effects
  60. FTO alleviated the diabetic nephropathy progression by regulating the N6-methyladenosine levels of DACT1
  61. Clinical relevance of inflammatory markers in the evaluation of severity of ulcerative colitis: A retrospective study
  62. Zinc valproic acid complex promotes osteoblast differentiation and exhibits anti-osteoporotic potential
  63. Primary pulmonary synovial sarcoma in the bronchial cavity: A case report
  64. Metagenomic next-generation sequencing of alveolar lavage fluid improves the detection of pulmonary infection
  65. Uterine tumor resembling ovarian sex cord tumor with extensive rhabdoid differentiation: A case report
  66. Genomic analysis of a novel ST11(PR34365) Clostridioides difficile strain isolated from the human fecal of a CDI patient in Guizhou, China
  67. Effects of tiered cardiac rehabilitation on CRP, TNF-α, and physical endurance in older adults with coronary heart disease
  68. Changes in T-lymphocyte subpopulations in patients with colorectal cancer before and after acupoint catgut embedding acupuncture observation
  69. Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment
  70. Alterations of metabolites related to microbiota–gut–brain axis in plasma of colon cancer, esophageal cancer, stomach cancer, and lung cancer patients
  71. Research on individualized drug sensitivity detection technology based on bio-3D printing technology for precision treatment of gastrointestinal stromal tumors
  72. CEBPB promotes ulcerative colitis-associated colorectal cancer by stimulating tumor growth and activating the NF-κB/STAT3 signaling pathway
  73. Oncolytic bacteria: A revolutionary approach to cancer therapy
  74. A de novo meningioma with rapid growth: A possible malignancy imposter?
  75. Diagnosis of secondary tuberculosis infection in an asymptomatic elderly with cancer using next-generation sequencing: Case report
  76. Hesperidin and its zinc(ii) complex enhance osteoblast differentiation and bone formation: In vitro and in vivo evaluations
  77. Research progress on the regulation of autophagy in cardiovascular diseases by chemokines
  78. Anti-arthritic, immunomodulatory, and inflammatory regulation by the benzimidazole derivative BMZ-AD: Insights from an FCA-induced rat model
  79. Immunoassay for pyruvate kinase M1/2 as an Alzheimer’s biomarker in CSF
  80. The role of HDAC11 in age-related hearing loss: Mechanisms and therapeutic implications
  81. Evaluation and application analysis of animal models of PIPNP based on data mining
  82. Therapeutic approaches for liver fibrosis/cirrhosis by targeting pyroptosis
  83. Fabrication of zinc oxide nanoparticles using Ruellia tuberosa leaf extract induces apoptosis through P53 and STAT3 signalling pathways in prostate cancer cells
  84. Haplo-hematopoietic stem cell transplantation and immunoradiotherapy for severe aplastic anemia complicated with nasopharyngeal carcinoma: A case report
  85. Modulation of the KEAP1-NRF2 pathway by Erianin: A novel approach to reduce psoriasiform inflammation and inflammatory signaling
  86. The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients
  87. Innovations in MALDI-TOF Mass Spectrometry: Bridging modern diagnostics and historical insights
  88. BAP1 complexes with YY1 and RBBP7 and its downstream targets in ccRCC cells
  89. Hypereosinophilic syndrome with elevated IgG4 and T-cell clonality: A report of two cases
  90. Electroacupuncture alleviates sciatic nerve injury in sciatica rats by regulating BDNF and NGF levels, myelin sheath degradation, and autophagy
  91. Polydatin prevents cholesterol gallstone formation by regulating cholesterol metabolism via PPAR-γ signaling
  92. RNF144A and RNF144B: Important molecules for health
  93. Analysis of the detection rate and related factors of thyroid nodules in the healthy population
  94. Artesunate inhibits hepatocellular carcinoma cell migration and invasion through OGA-mediated O-GlcNAcylation of ZEB1
  95. Endovascular management of post-pancreatectomy hemorrhage caused by a hepatic artery pseudoaneurysm: Case report and review of the literature
  96. Efficacy and safety of anti-PD-1/PD-L1 antibodies in patients with relapsed refractory diffuse large B-cell lymphoma: A meta-analysis
  97. SATB2 promotes humeral fracture healing in rats by activating the PI3K/AKT pathway
  98. Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration
  99. Understanding risk factors and prognosis in diabetic foot ulcers
  100. Atractylenolide I alleviates the experimental allergic response in mice by suppressing TLR4/NF-kB/NLRP3 signalling
  101. FBXO31 inhibits the stemness characteristics of CD147 (+) melanoma stem cells
  102. Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11
  103. Inhibiting CXCR6 promotes senescence of activated hepatic stellate cells with limited proinflammatory SASP to attenuate hepatic fibrosis
  104. Cadmium toxicity, health risk and its remediation using low-cost biochar adsorbents
  105. Pulmonary cryptococcosis with headache as the first presentation: A case report
  106. Solitary pulmonary metastasis with cystic airspaces in colon cancer: A rare case report
  107. RUNX1 promotes denervation-induced muscle atrophy by activating the JUNB/NF-κB pathway and driving M1 macrophage polarization
  108. Morphometric analysis and immunobiological investigation of Indigofera oblongifolia on the infected lung with Plasmodium chabaudi
  109. The NuA4/TIP60 histone-modifying complex and Hr78 modulate the Lobe2 mutant eye phenotype
  110. Experimental study on salmon demineralized bone matrix loaded with recombinant human bone morphogenetic protein-2: In vitro and in vivo study
  111. A case of IgA nephropathy treated with a combination of telitacicept and half-dose glucocorticoids
  112. Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study
  113. Wound healing and signaling pathways
  114. Combination of immunotherapy and whole-brain radiotherapy on prognosis of patients with multiple brain metastases: A retrospective cohort study
  115. To explore the relationship between endometrial hyperemia and polycystic ovary syndrome
  116. Research progress on the impact of curcumin on immune responses in breast cancer
  117. Biogenic Cu/Ni nanotherapeutics from Descurainia sophia (L.) Webb ex Prantl seeds for the treatment of lung cancer
  118. Dapagliflozin attenuates atrial fibrosis via the HMGB1/RAGE pathway in atrial fibrillation rats
  119. Glycitein alleviates inflammation and apoptosis in keratinocytes via ROS-associated PI3K–Akt signalling pathway
  120. ADH5 inhibits proliferation but promotes EMT in non-small cell lung cancer cell through activating Smad2/Smad3
  121. Apoptotic efficacies of AgNPs formulated by Syzygium aromaticum leaf extract on 32D-FLT3-ITD human leukemia cell line with PI3K/AKT/mTOR signaling pathway
  122. Novel cuproptosis-related genes C1QBP and PFKP identified as prognostic and therapeutic targets in lung adenocarcinoma
  123. Bee venom promotes exosome secretion and alters miRNA cargo in T cells
  124. Treatment of pure red cell aplasia in a chronic kidney disease patient with roxadustat: A case report
  125. Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status
  126. Kynurenine facilitates renal cell carcinoma progression by suppressing M2 macrophage pyroptosis through inhibition of CASP1 cleavage
  127. RFX5 promotes the growth, motility, and inhibits apoptosis of gastric adenocarcinoma cells through the SIRT1/AMPK axis
  128. ALKBH5 exacerbates early cardiac damage after radiotherapy for breast cancer via m6A demethylation of TLR4
  129. Phytochemicals of Roman chamomile: Antioxidant, anti-aging, and whitening activities of distillation residues
  130. Circadian gene Cry1 inhibits the tumorigenicity of hepatocellular carcinoma by the BAX/BCL2-mediated apoptosis pathway
  131. The TNFR-RIPK1/RIPK3 signalling pathway mediates the effect of lanthanum on necroptosis of nerve cells
  132. Longitudinal monitoring of autoantibody dynamics in patients with early-stage non-small-cell lung cancer undergoing surgery
  133. The potential role of rutin, a flavonoid, in the management of cancer through modulation of cell signaling pathways
  134. Construction of pectinase gene engineering microbe and its application in tobacco sheets
  135. Construction of a microbial abundance prognostic scoring model based on intratumoral microbial data for predicting the prognosis of lung squamous cell carcinoma
  136. Sepsis complicated by haemophagocytic lymphohistiocytosis triggered by methicillin-resistant Staphylococcus aureus and human herpesvirus 8 in an immunocompromised elderly patient: A case report
  137. Sarcopenia in liver transplantation: A comprehensive bibliometric study of current research trends and future directions
  138. Advances in cancer immunotherapy and future directions in personalized medicine
  139. Can coronavirus disease 2019 affect male fertility or cause spontaneous abortion? A two-sample Mendelian randomization analysis
  140. Heat stroke associated with novel leukaemia inhibitory factor receptor gene variant in a Chinese infant
  141. PSME2 exacerbates ulcerative colitis by disrupting intestinal barrier function and promoting autophagy-dependent inflammation
  142. Hyperosmolar hyperglycemic state with severe hypernatremia coexisting with central diabetes insipidus: A case report and literature review
  143. Efficacy and mechanism of escin in improving the tissue microenvironment of blood vessel walls via anti-inflammatory and anticoagulant effects: Implications for clinical practice
  144. Merkel cell carcinoma: Clinicopathological analysis of three patients and literature review
  145. Genetic variants in VWF exon 26 and their implications for type 1 Von Willebrand disease in a Saudi Arabian population
  146. Lipoxin A4 improves myocardial ischemia/reperfusion injury through the Notch1-Nrf2 signaling pathway
  147. High levels of EPHB2 expression predict a poor prognosis and promote tumor progression in endometrial cancer
  148. Knockdown of SHP-2 delays renal tubular epithelial cell injury in diabetic nephropathy by inhibiting NLRP3 inflammasome-mediated pyroptosis
  149. Exploring the toxicity mechanisms and detoxification methods of Rhizoma Paridis
  150. Concomitant gastric carcinoma and primary hepatic angiosarcoma in a patient: A case report
  151. YAP1 inhibition protects retinal vascular endothelial cells under high glucose by inhibiting autophagy
  152. Identification of secretory protein related biomarkers for primary biliary cholangitis based on machine learning and experimental validation
  153. Integrated genomic and clinical modeling for prognostic assessment of radiotherapy response in rectal neoplasms
  154. Stem cell-based approaches for glaucoma treatment: a mini review
  155. Bacteriophage titering by optical density means: KOTE assays
  156. Neutrophil-related signature characterizes immune landscape and predicts prognosis of esophageal squamous cell carcinoma
  157. Integrated bioinformatic analysis and machine learning strategies to identify new potential immune biomarkers for Alzheimer’s disease and their targeting prediction with geniposide
  158. TRIM21 accelerates ferroptosis in intervertebral disc degeneration by promoting SLC7A11 ubiquitination and degradation
  159. TRIM21 accelerates ferroptosis in intervertebral disc degeneration by promoting SLC7A11 ubiquitination and degradation
  160. Histone modification and non-coding RNAs in skin aging: emerging therapeutic avenues
  161. A multiplicative behavioral model of DNA replication initiation in cells
  162. Biogenic gold nanoparticles synthesized from Pergularia daemia leaves: a novel approach for nasopharyngeal carcinoma therapy
  163. Creutzfeldt-Jakob disease mimicking Hashimoto’s encephalopathy: steroid response followed by decline
  164. Impact of semaphorin, Sema3F, on the gene transcription and protein expression of CREB and its binding protein CREBBP in primary hippocampal neurons of rats
  165. Iron overloaded M0 macrophages regulate hematopoietic stem cell proliferation and senescence via the Nrf2/Keap1/HO-1 pathway
  166. Revisiting the link between NADPH oxidase p22phox C242T polymorphism and ischemic stroke risk: an updated meta-analysis
  167. Exercise training preferentially modulates α1D-adrenergic receptor expression in peripheral arteries of hypertensive rats
  168. Overexpression of HE4/WFDC2 gene in mice leads to keratitis and corneal opacity
  169. Tumoral calcinosis complicating CKD-MBD in hemodialysis: a case report
  170. Mechanism of KLF4 Inhibition of epithelial-mesenchymal transition in gastric cancer cells
  171. Dissecting the molecular mechanisms of T cell infiltration in psoriatic lesions via cell-cell communication and regulatory network analysis
  172. Circadian rhythm-based prognostic features predict immune infiltration and tumor microenvironment in molecular subtypes of hepatocellular carcinoma
  173. Ecology and Environmental Science
  174. Optimization and comparative study of Bacillus consortia for cellulolytic potential and cellulase enzyme activity
  175. The complete mitochondrial genome analysis of Haemaphysalis hystricis Supino, 1897 (Ixodida: Ixodidae) and its phylogenetic implications
  176. Epidemiological characteristics and risk factors analysis of multidrug-resistant tuberculosis among tuberculosis population in Huzhou City, Eastern China
  177. Indices of human impacts on landscapes: How do they reflect the proportions of natural habitats?
  178. Genetic analysis of the Siberian flying squirrel population in the northern Changbai Mountains, Northeast China: Insights into population status and conservation
  179. Diversity and environmental drivers of Suillus communities in Pinus sylvestris var. mongolica forests of Inner Mongolia
  180. Global assessment of the fate of nitrogen deposition in forest ecosystems: Insights from 15N tracer studies
  181. Fungal and bacterial pathogenic co-infections mainly lead to the assembly of microbial community in tobacco stems
  182. Influencing of coal industry related airborne particulate matter on ocular surface tear film injury and inflammatory factor expression in Sprague-Dawley rats
  183. Temperature-dependent development, predation, and life table of Sphaerophoria macrogaster (Thomson) (Diptera: Syrphidae) feeding on Myzus persicae (Sulzer) (Homoptera: Aphididae)
  184. Eleonora’s falcon trophic interactions with insects within its breeding range: A systematic review
  185. Agriculture
  186. Integrated analysis of transcriptome, sRNAome, and degradome involved in the drought-response of maize Zhengdan958
  187. Variation in flower frost tolerance among seven apple cultivars and transcriptome response patterns in two contrastingly frost-tolerant selected cultivars
  188. Heritability of durable resistance to stripe rust in bread wheat (Triticum aestivum L.)
  189. Molecular mechanism of follicular development in laying hens based on the regulation of water metabolism
  190. Molecular identification and control studies on Coridius sp. (Hemiptera: Dinidoridae) in Al-Khamra, south of Jeddah, Saudi Arabia
  191. 10.1515/biol-2025-1218
  192. Animal Science
  193. Effect of sex ratio on the life history traits of an important invasive species, Spodoptera frugiperda
  194. Plant Sciences
  195. Hairpin in a haystack: In silico identification and characterization of plant-conserved microRNA in Rafflesiaceae
  196. Widely targeted metabolomics of different tissues in Rubus corchorifolius
  197. The complete chloroplast genome of Gerbera piloselloides (L.) Cass., 1820 (Carduoideae, Asteraceae) and its phylogenetic analysis
  198. Field trial to correlate mineral solubilization activity of Pseudomonas aeruginosa and biochemical content of groundnut plants
  199. Correlation analysis between semen routine parameters and sperm DNA fragmentation index in patients with semen non-liquefaction: A retrospective study
  200. Plasticity of the anatomical traits of Rhododendron L. (Ericaceae) leaves and its implications in adaptation to the plateau environment
  201. Effects of Piriformospora indica and arbuscular mycorrhizal fungus on growth and physiology of Moringa oleifera under low-temperature stress
  202. Effects of different sources of potassium fertiliser on yield, fruit quality and nutrient absorption in “Harward” kiwifruit (Actinidia deliciosa)
  203. Comparative efficiency and residue levels of spraying programs against powdery mildew in grape varieties
  204. The DREB7 transcription factor enhances salt tolerance in soybean plants under salt stress
  205. Using plant electrical signals of water hyacinth (Eichhornia crassipes) for water pollution monitoring
  206. Response of hybrid grapes (Vitis spp.) to two biotic stress factors and their seedlessness status
  207. Metabolomic profiling reveals systemic metabolic reprogramming in Alternaria alternata under salt stress
  208. Effects of mixed salinity and alkali stress on photosynthetic characteristics and PEPC gene expression of vegetable soybean seedlings
  209. Food Science
  210. Phytochemical analysis of Stachys iva: Discovering the optimal extract conditions and its bioactive compounds
  211. Review on role of honey in disease prevention and treatment through modulation of biological activities
  212. Computational analysis of polymorphic residues in maltose and maltotriose transporters of a wild Saccharomyces cerevisiae strain
  213. Optimization of phenolic compound extraction from Tunisian squash by-products: A sustainable approach for antioxidant and antibacterial applications
  214. Liupao tea aqueous extract alleviates dextran sulfate sodium-induced ulcerative colitis in rats by modulating the gut microbiota
  215. Toxicological qualities and detoxification trends of fruit by-products for valorization: A review
  216. Polyphenolic spectrum of cornelian cherry fruits and their health-promoting effect
  217. Optimizing the encapsulation of the refined extract of squash peels for functional food applications: A sustainable approach to reduce food waste
  218. Advancements in curcuminoid formulations: An update on bioavailability enhancement strategies curcuminoid bioavailability and formulations
  219. Impact of saline sprouting on antioxidant properties and bioactive compounds in chia seeds
  220. The dilemma of food genetics and improvement
  221. Causal effects of trace elements on congenital foot deformities and their subtypes: a Mendelian randomization study with gut microbiota mediation
  222. Honey meets acidity: a novel biopreservative approach against foodborne pathogens
  223. Bioengineering and Biotechnology
  224. Impact of hyaluronic acid-modified hafnium metalorganic frameworks containing rhynchophylline on Alzheimer’s disease
  225. Emerging patterns in nanoparticle-based therapeutic approaches for rheumatoid arthritis: A comprehensive bibliometric and visual analysis spanning two decades
  226. Application of CRISPR/Cas gene editing for infectious disease control in poultry
  227. Preparation of hafnium nitride-coated titanium implants by magnetron sputtering technology and evaluation of their antibacterial properties and biocompatibility
  228. Preparation and characterization of lemongrass oil nanoemulsion: Antimicrobial, antibiofilm, antioxidant, and anticancer activities
  229. Fluorescent detection of sialic acid–binding lectins using functionalized quantum dots in ELISA format
  230. Smart tectorigenin-loaded ZnO hydrogel nanocomposites for targeted wound healing: synthesis, characterization, and biological evaluation
  231. Corrigendum
  232. Corrigendum to “Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells”
  233. Corrigendum to “Effects of Ire1 gene on virulence and pathogenicity of Candida albicans”
  234. Retraction
  235. Retraction of “Down-regulation of miR-539 indicates poor prognosis in patients with pancreatic cancer”
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