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Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis

  • Shan-Shan Guo , Gang Fu , Yan-Wei Hu , Jing Liu and Yu-Zhu Wang EMAIL logo
Published/Copyright: April 26, 2024
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Open Life Sciences
From the journal Open Life Sciences Volume 19 Issue 1

Abstract

Pathogens detected by metagenomic next-generation sequencing (mNGS) and the laboratory blood culture flask method were compared to understand the advantages and clinical significance of mNGS assays in the etiological diagnosis of peritoneal dialysis-associated peritonitis (PDAP). The study involved a total of 37 patients from the hospital’s peritoneal dialysis centre, six of whom were patients with non-peritoneal dialysis-associated peritonitis. Peritoneal dialysis samples were collected from the 37 patients, who were divided into two groups. One group’s samples were cultured using conventional blood culture flasks, and the other samples underwent pathogen testing using mNGS. The results showed that the positive rate of mNGS was 96.77%, while that of the blood culture flask method was 70.97% (p < 0.05). A total of 29 pathogens were detected by mNGS, namely 24 bacteria, one fungus, and four viruses. A total of 10 pathogens were detected using the bacterial blood culture method, namely nine bacteria and one fungus. The final judgment of the PDAP’s causative pathogenic microorganism was made by combining the clinical condition, response to therapy, and the whole-genome sequencing findings. For mNGS, the sensitivity was 96.77%, the specificity was 83.33%, the positive predictive value was 96.77%, and the negative predictive value was 83.33%. For the blood culture flask method, the sensitivity was 70.97%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 0%. In conclusion, mNGS had a shorter detection time for diagnosing peritoneal dialysis-related peritonitis pathogens, with a higher positive rate than traditional bacterial cultures, providing significant advantages in diagnosing rare pathogens.

Keywords: metagenomic next-generation sequencing; blood culture flask method; peritoneal dialysis-associated peritonitis; infection; pathogen

1 Introduction

Peritoneal dialysis-associated peritonitis (PDAP) is a common and serious complication of peritoneal dialysis, affecting its therapeutic effect and threatening patients’ lives [1]. The occurrence of PDAP is related to various factors, such as non-standard fluid replacement according to aseptic principles, peritoneal dialysis catheter-related infections, decreased intestinal function leading to the displacement of intestinal bacteria, and reduced peritoneal barrier function caused by long-term dialysis. Moreover, high-risk operations that may cause peritonitis are becoming more common [2]. For the treatment of PDAP, the application of multiple antibiotics active against Gram-positive and Gram-negative bacteria often occurs before the pathogen is determined, even though the targeted application of an antibiotic once a pathogen is known is more likely to result in success [3]. The blood culture flask method is currently the main method of detecting pathogenic bacteria. Although it can be accurate, this approach has shortcomings, such as a long culture time and generally low culture-positive rates [4]. Failure to identify pathogenic bacteria in many patients with PDAP has led to the empiric application of multiple antibiotics, increasing the toxic side effects of antibiotics and affecting the cure rate of peritonitis.

With the development of technology, especially the advancement and commercialisation of genetic technology, the price of testing is decreasing, making clinical genetic sequencing possible. The term metagenome, also known as a microbial environmental genome, was proposed by Handelsman et al. in 1998 to refer to the sum of all the biological genetic material in the environment, including genes for culturable and nonculturable microorganisms [5]. Metagenomic next-generation sequencing (mNGS) is a culture-free, non-preferred pathogen detection technique based on next-generation sequencing technology. High-throughput sequencing of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) extracted directly from clinical samples, followed by database alignment and bioinformatics analysis, allows for the detection of bacteria, fungi, viruses, parasites and other pathogens simultaneously [6]. Recently, mNGS has made many advances in identifying novel, rare, and important pathogens [7]. The range of mNGS assays covers 6,350 bacteria, 1,798 DNA viruses, 1,064 fungi, and 234 parasites whose current genome sequences are known. mNGS identifies the genus and species of pathogenic bacteria, classifies types, and indicates drug resistance genes; this is of great significance to providing clinical anti-infection treatment and conducting epidemiological investigation [8]. Currently, mNGS plays an important role in the diagnosis of various clinical diseases, including sepsis [9], alveolar inflammation [10], postoperative infection [11], respiratory disease diagnosis [12], and infection caused by immunodeficiency viruses [13]. However, there are no relevant reports of mNGS in diagnosing PDAP pathogens.

This study compared the sensitivity, specificity, positive and negative predictive values of the blood culture and mNGS methods for detecting PDAP, hoping to identify a more accurate and rapid diagnostic tool to provide a more precise clinical treatment based on analysis results.

2 Materials and methods

2.1 Study participants

Clinical data and ascites samples were collected between 1 January 2021 and 31 August 2022 from 37 patients with long-term attendance at the hospital’s peritoneal dialysis centre. Six patients were diagnosed with non-PDAP; 31 patients met the diagnostic criteria for PDAP established by the International Society for Peritoneal Dialysis (ISPD) in 2016 [14]. The results of 37 samples analysed by conventional bacterial culture and mNGS were submitted. This study was approved by the Medical Ethics Committee of the Beijing Haidian Hospital; the ethical approval number is BHHMEC-XM-2021-15. All the patients signed an informed consent form before each mNGS test.

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

  2. Ethical approval: The research related to human use has complied with all the relevant national regulations, and institutional policies and by the tenets of the Helsinki Declaration, and has been approved by the author’s institutional review board.

2.2 Inclusion and exclusion criteria

The inclusion criteria were as follows: (a) patients with PDAP diagnosed according to the 2016 ISPD criteria [14]; namely patients with (1) abdominal pain and cloudy peritoneal dialysate, with or without fever and other symptoms; (2) a leukocyte count of >100 μL and polymorphonuclear cells >50% in the peritoneal dialysate; and (3) a positive dialysis pathogen smear or culture. Diagnosing PDAP required meeting at least two of the criteria; and (b) patients that were followed up with long-term peritoneal dialysis.

The exclusion criteria were as follows: (a) patients with incomplete clinical data and (b) patients with systemic infection.

2.3 Study methods

Peritoneal dialysate of 100 mL was extracted from the 37 patients with a sterile, nucleic acid-free syringe in strict accordance with the aseptic principle of the peritoneal dialysate abdomen dwell time being >2 h. Of this extract, 10 mL of peritoneal dialysate was used for the ascites routine and 40 mL for the two groups of ascites culture using blood culture flasks. The remaining 50 mL of peritoneal dialysate was placed into a nucleic acid-free sampling tube and submitted to the Gene Sequencing Corporation. Culture and identification were performed in a microbiology laboratory.

Blood culture flask method: Peritoneal dialysis solution was injected aseptically into blood culture flasks (standard aerobic and anaerobic flasks); the flasks were then placed into the instrument incubator of the supporting BacT/ALERT 3D Microbial Detection System (bioMérieux France, Craponne, France). When a positive culture flask alarm was indicated, a sterile syringe was used to draw a 40 µL culture medium for microbial smears. Two culture medium plates, with blood agar and MacConkey agar, were simultaneously inoculated and incubated at 35℃. Cultures incubated for 7 days were considered negative if there was no bacterial growth detected. For positive blood cultures, microbiological analysis of the growing pathogens was identified using the VITEK 2 Compact Microbial Analysis System (bioMérieux France, Craponne, France).

mNGS: 50 mL of the samples were taken, centrifuged at 7,800 rpm for 10 min for 1 mL of precipitate, and DNA and RNA were extracted. The DNA extraction was performed using a PathoXtract® Basic universal kit (WYXM03211S, Willingmed, Beijing, China), and the extraction was performed using a PathoXtract® Virus DNA/RNA coextraction kit (WYXM03009S, Willingmed, Beijing, China) according to the kit instructions. The DNA and RNA were then mixed, and the RNA was reverse transcribed using a SuperScript™ duplex copy DNA (cDNA) synthesis kit (11917020, Invitrogen, Waltham, MA, USA) to obtain the cDNA for subsequent library construction.

Subsequently, the merged DNA library was constructed using an Illumina® DNA Prep (M) Tagmentation (20018705, Illumina, Inc., San Diego, CA, USA) kit according to the kit’s instructions. Sequencing was performed with a single-end 75 bp sequence on a NextSeq™ 550Dx (Illumina, Inc., San Diego, CA, USA). No less than 20 million pieces of data were obtained for each sample. The negative control samples were synchronised in each batch for quality control.

Sequencing data were automatically analysed to obtain detection reports. Among them, the pathogenic microbial genome data of bacteria, fungi, viruses, parasites and archaea were obtained from the National Centre for Biotechnology Information GenBank® database, and a clinical application-level reference genome database was constructed following the steps of genome filtering, screening, and validation. High-quality sequencing data were aligned to the human reference genome GRCh37 (hg19) using alignment software to remove human host sequences and obtain clean data that could be used for subsequent identification of pathogenic microorganisms. The clean data were compared with the established pathogen microbial database to complete the information annotation of the pathogen microbial species information, to provide the sequence number, relative abundance, and genome coverage of the species and to complete the reference report.

The judgment methods used for the mNGS results were as follows:

Bacteria (excluding mycobacteria), viruses, and parasites: the threshold for a bacterial diagnosis was a number of sequences greater than 30. If the result was a single bacterium or a highly pathogenic pathogen, it could still be identified as the pathogenic organism, even if the number of sequences was small.

Fungi: the diagnostic threshold was an abundance of the genus greater than 15% and a number of sequences greater than 50.

Mycobacterium: When the number of measured sequences of mycobacteria was ≥1, the reading was considered positive.

Viruses: Given that the presence of viruses in the peritoneal dialysate of non-peritonitis patients is rare, the possibility of viral colonisation was high [15].

2.4 Identification of the pathogenic microorganism causing PDAP

The final identification of the pathogenic microorganism causing PDAP required a combination of the clinical presentation, microbial characteristics, and disease outcome results [14]. The following assumptions were made:

  1. If mNGS and the laboratory blood culture flask methods identified the same microorganism, it was assumed to be the final pathogenic microorganism.

  2. If mNGS identified a variety of microorganisms, then the microorganism with the most sequences (usually five times that of any other microorganism) was likely to be the pathogenic microorganism.

  3. If a single microorganism was identified by mNGS and the number of sequences was larger than the reference value of environmental contamination, it was regarded as the pathogenic microorganism.

  4. If the detected microorganism was highly pathogenic, even if it was not an organism that normally colonised the abdominal cavity, it was judged as a pathogenic microorganism based on the clinical presentation.

2.5 Statistical analysis

Data processing and analysis were performed with the SPSS® (Statistical Software™ Version 22.0, IBM SPSS Statistics, IL, USA). Enumeration data were output as a relative digital composition (%) or ratio (%) using Fisher’s exact test. The sensitivity (number of true positives/[number of true positives + number of false negatives]), specificity (number of true negatives/[number of true negatives + number of false positives]), positive predictive value (number of true positive cases/[number of true positive cases + number of false positive cases]) and negative predictive value (number of true negative cases/[number of true negative cases + number of false negative cases]) of the two pathogen determination methods were calculated. Kappa values were used to compare the consistency of the mNGS results with the clinical microbial evidence. Statistical significance was considered to be p < 0.05.

3 Results

3.1 Basic patient information

The 37 patients, 25 of whom were men and 12 women, were aged 36–82 (61.05 ± 13.04 years old). The primary cause of uraemia was as follows: there were 22 patients with diabetic nephropathy; six patients with chronic nephritis; three patients with hypertensive renal injury; two patients with urinary tract obstruction; one patient with polycystic kidney disease; and three patients with unknown causes (Table 1 and Table S1). All the mNGS analyses were completed within 24 h, and the traditional laboratory tests took 1–15 days (Figure 1). Cases 20 and 29 eventually died, eight patients were switched to haemodialysis, and the remaining 20 patients improved significantly.

Table 1

Basic characteristics of the patients

N/ X ¯ ± S
Gender
 Male 25
 Female 12
Age (year) 61.05 ± 13.04
Causes
 Diabetic nephropathy 22
 Chronic nephritis 6
 Hypertensive renal injury 3
 Urinary tract obstruction 2
 Polycystic kidney disease 1
 Unknown causes 3
Total 37
Figure 1 Flow chart.
Figure 1

Flow chart.

3.2 Pathogen distribution

In this study, 37 samples were cultured in duplicate blood culture flasks; the samples were simultaneously submitted for mNGS. A total of 29 pathogens were detected by mNGS and consisted of 24 bacteria, one fungus, and four viruses. The top three identified pathogenic organisms were Staphylococcus (17.86%), Escherichia coli (16.07%), and Klebsiella pneumoniae (8.92% [Table 2]). A total of 10 pathogens, of which nine were bacteria and one fungus, were detected by the blood culture flask method. The top three species identified as pathogenic were Staphylococcus (28.57%), E. coli (28.57%), and K. pneumoniae (14.28% [Table 2]).

Table 2

Pathogen distribution (n/Detection rate)

Pathogen classification mNGS Blood culture
Staphylococcus haemolyticus 4/0.071 3/0.143
Enterococcus pallidum 1/0.018 —
Klebsiella pneumoniae 5/0.089 3/0.143
Alcaligenes faecalis 1/0.018 —
Morganella morganii 2/0.036 —
Escherichia coli 9/0.160 6/0.286
Enterococcus hirae 1/0.018 —
Staphylococcus aureus 1/0.018 —
Streptococcus salivarius 1/0.018 —
Serratia marcescens 1/0.018 1/0.048
Enterococcus faecalis 1/0.018 —
Acinetobacter berezonii 1/0.018 —
Mycobacterium tuberculosis 2/0.036 —
Gardnerella vaginalis 1/0.018 —
Staphylococcus epidermidis 4/0.071 3/0.143
Leuconostoc 1/0.018 —
Candida parapsilosis 1/0.018 1/0.048
Enterobacter cholerae 1/0.018 —
Leuconostoc lactis 1/0.018 1/0.048
Motibacter putrefaciens 1/0.018 —
Streptococcus pneumoniae 1/0.018 —
Klebsiella aerogenes 1/0.018 —
HPgV Virus Type C 3/0.054 —
Human herpesvirus 5 5/0.089 —
Human herpesvirus 6A 2/0.036 —
Corynebacterium unicolor 1/0.018 —
Prevotella melaninogenica 1/0.018 —
Streptococcus panorale 1/0.018 —
Human metapneumovirus 1/0.018 —
Leuconostoc mesenteroides — 1/0.048
Streptococcus sanguinis — 1/0.048
Enterococcus spp. — 1/0.048

Note: mNGS:metagenomic next-generation sequencing.

3.3 Sensitivity, specificity, positive and negative predictive values of the mNGS

To make the final judgment concerning the identity of the pathogenic microorganism, a combination of clinical presentation, microbial characteristics, and disease outcome was used as the gold standard. The positive detection rate of mNGS was 96.77% compared with 70.97% for the blood culture flask method. The positive rate of mNGS was significantly higher than that of the blood culture method (p < 0.05). The sensitivity of mNGS was 96.77%, the specificity was 83.33%, the positive predictive value was 96.77% and the negative predictive value was 83.33%. The sensitivity of the blood culture flask method was 70.97%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 40% (Tables 3 and 4). Furthermore, the positive rate for mNGS was 93.3 and 73.3% for the bacteria culture (p < 0.05). The results demonstrated mNGS’s high positive detection rate and sensitivity.

Table 3

Sensitivity, specificity, positive predictive values, and negative predictive values of Blood culture flask method

Pathogenic bacteria determined by clinical diagnosis
Positive Negative
Blood culture flask method Positive 22 0
Negative 9 6

Note: sensitivity 70.97%; specialty 100%; Positive Predictive Value (PPV) = 100%; Negative Predictive Value (NPV) = 40%.

Table 4

Sensitivity, specificity, positive predictive values, and negative predictive values of mNGS

Pathogenic bacteria determined by clinical diagnosis
Positive Negative
mNGS Positive 30 1
Negative 1 5

Note: sensitivity, 96.77%; specialty, 83.33%; Positive Predictive Value (PPV) = 96.77%; Negative Predictive Value (NPV) = 83.33%; mNGS, metagenomic next-generation sequencing.

4 Discussion

In recent years, the incidence of peritonitis has declined, but PDAP remains an important cause of dialysis treatment failure and can endanger patients’ lives [1]. Identifying the type of pathogen and achieving targeted application of antibiotic therapy is vital to successful PDAP treatment. Currently, the double blood culture flask method is the primary method of detecting pathogenic bacteria. According to ISPD peritoneal dialysis-related peritonitis guidelines [14], the positive pathogen culture analysis rate is required to reach 80%, but only a few centres can achieve this. In recent years, several literature reports have shown that the positive rate of pathogen culture in PDAP has increased to 61–72.2%; however, this figure still does not meet the required standard. The present study’s blood culture flask method positive rate was 70.97%, which was consistent with previously reported results, but the figure continues to fall short of the desired goal. Although traditional bacterial culture methods are accurate, the culture time is protracted, with it usually taking between 1 and 15 days to obtain results. Moreover, the bacterial culture-positive rate is generally low. The reasons for the low positive rate of pathogen culture are as follows: (1) some patients have used antibiotics before going to the hospital; (2) clinically, unqualified operation for obtaining peritoneal dialysate sample, and the bacterial content in the abdominal dialysate may be too small; and (3) bacterial culture conditions are harsh and easily affected by a variety of factors, such as the culture temperature, culture media, PH value, humidity and the pathogen’s ease of culture. With the development of molecular technologies, new techniques, such as polymerase chain reaction (PCR) and quantitative bacterial DNA PCR, have been used to detect peritonitis pathogens. However, PCR is used for the validation of relevant bacteria by designing primer probes and numerous basic experiments, which is demanding for bioinformatics analyses. Therefore, there has been little clinical application [16]. However, with the advancement of science and technology, genetic testing has become more mature and commercialisable, making mNGS in clinical settings possible. Li et al. [10] reported that a patient developed symptoms of pneumonia, but no pathogen was found after three biopsies. With the help of mNGS, the pathogen causing the patient’s external skin dermatitis was finally diagnosed as Dermatitis bacteriophage. Qu et al. [11] reported that mNGS is more sensitive than routine pathogen testing in diagnosing paediatric haematopoietic stem cell transplantation infection and can contribute to a clinical diagnosis. The mNGS of cerebrospinal fluid samples reported by Gan et al. [17] was used as a complementary test for cryptococcal meningeal diagnosis and enabled clear differentiation between Cryptococcus gatti and Cryptococcus neoformans.

This present study showed that the sensitivity of mNGS was 96.77%, the specificity was 83.33%, the positive predictive value was 96.77%, and the negative predictive value was 83.33%. The sensitivity of the blood culture flask method was 70.97%, the specificity was 100%, the positive predictive value was 0% and the negative predictive value was 40%. These results demonstrated that mNGS is much more sensitive than the blood culture flask method and pathogens are easier to detect, which is similar to the results of previous studies [9,10,11]. The differences between mNGS and the blood culture flask methods may be related to the different emphasis of each detection method. Blood culture focuses on detecting the pathogen function, and only some bacteria and fungi can be detected. Furthermore, some pathogens are difficult to culture or cannot be cultured at all using this method. Another possible reason is that the medium encourages the growth of a dominant bacterium during blood culture, and a competitive relationship develops between the dominant bacterium and any other bacteria present.

In contrast, mNGS focuses on pathogenic microorganism species, with the detection results covering a wide range of organisms. Although mNGS is more sensitive than blood culture, the specificity is lower, possibly because mNGS can detect both intact pathogenic viable bacteria and non-pathogenic nucleic acid fragments. This suggests that pathogenic bacteria identification should use a combination of clinical presentation, microbial characteristics, and disease outcome data.

Despite its benefits, false negatives can occur with mNGS. First, false negatives may arise because pathogen loads are below the detection depth. This depth can vary and ranges from a short 75 bp sequence to a 10,000 bp long sequence; the more sequences collected, the higher the sensitivity. Second, there are excessive background gene sequences in the host and microecology. The literature indicates that over 99% of metagenomic sequences are human and microecological gene sequences, with pathogenic microorganisms accounting for less than 1% [18]. Third, microbes have thick cell walls. For example, obtaining Mycobacterium tuberculosis nucleic acid sequences via mNGS is difficult, and wall-breaking techniques are needed. Moreover, it is proposed in the literature that changes in host gene transcription [19], spreading [20] of sequence distribution of pathogenic nucleic acid, and microecological diversity change [21] help to distinguish between infection, colonisation, contamination, and background bacteria, and these issues are increasingly the focus of mNGS research.

Although mNGS has advantages over blood culture methods, it has some limitations in clinical use. First, it is expensive compared to traditional culture methods and unsuitable for universal detection in all patients with suspected infectious diseases [22]. Second, each test facility needs consistent quality control; otherwise, its results can be inaccurate. Most nucleic acids found in pathogenic samples have a human background. Over 90% of sequencing data typically comes from human sequences, reducing pathogen sensitivity detection. Therefore, it is necessary to efficiently remove nucleic acids from the human host background to improve the sensitivity of pathogen detection [23]. Currently, there are no uniform interpretation criteria for mNGS reports. Since mNGS detects nucleic acid fragments, it can be performed if the nucleic acid fragments present in the sample can achieve valid detection data. In addition, it is impossible to distinguish if the reported organisms have colonised or infected or if the infection is previous or current. Therefore, NT infection needs to be identified using a combination of clinical manifestations and physical and chemical results. Thresholds, relative abundance, sequence readout, genome coverage, and depth are commonly used reference indicators in clinical practice; however, there is no uniform standard [24,25]. Li et al. [24] determined the infectious pathogen threshold by using mNGS analysis for a lung tissue biopsy of a suspected contagious disease, and the results were compared with standard cultures as follows: r-polar abundance at the bacterial or fungal genus level was >30%; sequence reads of a single species of bacteria or fungi in positive samples by culture or histopathological examination was ≥50; and sequence reads for Mycobacterium were t ≥ 1. There is no uniform standard for threshold, relative abundance, or sequence reads of mNGS. Therefore, mNGS needs further research and development.

The present study had several limitations. First, this study was a single-centre study with a small number of peritoneal dialysis-related peritonitis cases, so the sample size requirements for diagnostic tests could not be fully met, and there was a possibility of result bias. To draw more reliable conclusions will require large-scale multi-centre studies. Second, increased follow-up time is required for patients since the short review period may have affected the results. Third, the PDAP infections with positive mNGS pathogen identification that were not supported by traditional culture method results need further verification by PCR testing. Combined with this study’s results, the authors believe that the threshold of mNGS test results should be adjusted according to the actual situation, with the number of bacterial pathogen sequences commonly used clinically being >20, as the bacterial diagnostic threshold and the number of common fungal pathogen sequences in clinical practice are >50 as the diagnostic threshold. For some difficult-to-culture pathogens, such as M. tuberculosis, the infections they cause could be considered when their sequence is ≥1. When conventional bacterial cultures are negative, even the low sequence number of detected pathogens should be considered as pathogens. For example, in the present study, patient 26 was negative for blood culture flask analysis; however, the mNGS was positive for Streptococcus pneumoniae, and the sequence number was 1. The importance of identifying the pathogen is reflected in the fact that the patient’s condition improved after treatment with antibiotics effective against S. pneumoniae.

5 Conclusion

In conclusion, mNGS is a rapid, efficient, and accurate technique for detecting pathogenic microorganisms. Despite its limitations, the technique has excellent value in the pathogen identification of peritoneal dialysis-associated systemic inflammation and can be used as a complementary method to conventional culture methods.

# These authors contributed equally to this study.

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  1. Funding information: Funding for this project comes from the Youth Project of Beijing Haidian Hospital, project number KYQ2021004.

  2. Author contributions: Conception and design of the research: Guo SS, Fu G, Wang YZ. Acquisition of data: Guo SS, Hu YW. Analysis and interpretation of the data: Fu G, Liu J. Statistical analysis: Guo SS, Fu G, Wang YZ. Obtaining financing: None. Writing of the manuscript: Guo SS, Fu G. Critical revision of the manuscript for intellectual content: Wang YZ.

  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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Received: 2022-10-14
Revised: 2024-01-25
Accepted: 2024-03-19
Published Online: 2024-04-26

© 2024 the author(s), published by De Gruyter

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

Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
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  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
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  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
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  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
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  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
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  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
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  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
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https://doi.org/10.1515/biol-2022-0865
Keywords for this article
metagenomic next-generation sequencing; blood culture flask method; peritoneal dialysis-associated peritonitis; infection; pathogen
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
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