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Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis

  • Min Ding , Hong-xu Wang , Si-jia Gao , Xiao-fei Lai , An-long Li , Jia-jia Bao , Felycia-Fernanda Hosyanto and Lei Xu EMAIL logo
Published/Copyright: May 18, 2023
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From the journal Open Life Sciences Volume 18 Issue 1

Abstract

To explore the serum levels of IL-39, CXCL14, and IL-19 in patients with tuberculosis (TB) along with their clinical significances and their concentration changes in macrophages after Bacille Calmette-Guérin vaccine (BCG) or Mycobacterium tuberculosis (M. tb) H37Rv stimulation in vitro. The serum levels of IL-39, CXCL14, and IL-19 of 38 TB patients, and 20 healthy staff members were measured by enzyme-linked immunosorbent assay. Moreover, the levels of IL-19, CXCL14, and IL-39 in cultured THP-1 macrophages were detected at 12, 24, and 48 h after stimulation with BCG or M. tb H37Rv strains. It was found the serum level of IL-39 was significantly reduced and CXCL14 was remarkably elevated in TB patients. In vitro, at 48 h after stimulation, IL-39 level of cultured THP-1 macrophages in the H37Rv group was significantly lower than that in the BCG and control groups, and the CXCL14 level of cultured THP-1 macrophages in the H37Rv stimulation group was remarkably higher than that in the control group. Therefore, IL-39 and CXCL14 may be involved the pathogenesis of TB, and serum IL-39 and CXCL14 could potentially serve as a new biomarker of TB.

Keywords: IL-39; CXCL14; tuberculosis; BCG ; cytokine; biomarker

1 Introduction

Tuberculosis (TB) represents the leading cause of global deaths from one infectious agent before COVID-19 pandemic and has been recognized as a global public health emergency for the past 25 years [1,2]. Despite the numerous headways in TB diagnosis, there is currently no simple, high-detection test to determine the diagnosis of TB.

IL-39 is a newly identified member of the interleukin-12 (IL-12) family and is a heterodimeric cytokine consisting of the p19 and EBi3 subunits [3,4]. The natural IL-39 (p19/Ebi3) complex is present in the supernatant of cultured RAW264.7 macrophage cells and could be secreted by B cells [3,5]. IL-39 may increase the proliferation of cancer cells [6] and contribute to the pathogenesis of systemic lupus erythematosus [3]. So far, the research on IL-39 is mainly in cancer cell lines, while reports of animal models or human experiments are rare.

The chemokine CXCL14 is a highly conserved homeostatic chemokine that is constitutively expressed in epithelial organs and homeostatically expressed in mucosal tissues [7,8]. It has been well acknowledged that CXCL14 plays a critical role in the metastasis of breast cancer [9].

IL-19 is a member of the IL-10 cytokine family [10] and is also a member of the cytokine IL-20 subfamily [11]. Several cytokines from IL-10 family were proved critical for the regulation of host defense against infections, including IL-10, IL-22, IL-24, and IL-26 [10].

Heretofore, there are only few studies on three cytokines in TB. Research suggests that human immunity to Mycobacterium tuberculosis (M. tb) is crucial for the occurrence and development of TB [12,13]. Therefore, this study aims to understand the levels of these cytokines in patients with TB and the changes of these three cytokines in cultured macrophages stimulated by Bacille Calmette-Guérin vaccine (BCG) or M. tb H37Rv strains, as well as the further analysis of their clinical relationship with TB.

2 Materials and methods

2.1 Subjects

All TB patients and healthy staff members were recruited at the respiratory department and physical examination center of The First Affiliated Hospital of Chongqing Medical University from 2020 to 2021, respectively. The protocol was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Chongqing Medical University. According to the guidelines of the World Health Organization, we divided the patients with TB into active and inactive groups according to the clinical symptoms and signs, bacteriology, pathology, and radiological detection [14]. Active TB is defined by one or more of the following diagnostic methods: (1) identification of cultured M. tb from any clinical specimens or bronchoalveolar lavage fluid, sputum, intratracheal aspirates, and pleural fluid; (2) caseous granuloma recorded in histological examination of tissue specimens; (3) PCR detection of M. tb DNA; and (4) chest X-ray examination was performed in combination with clinical symptoms. On the other hand, inactive TB is defined as patients with previous TB or abnormally stable imaging results, who has positive result of tuberculin skin test, negative bacteriologic test, and absence of clinical or imaging evidences of current disease. All TB patients received standardized medical history collections and physical examinations. The T-spot test was performed in strict accordance with the manufacturer’s protocol (Oxford Immunotec Ltd., UK). The serum samples of TB patients were collected before the initiation or reinforcement of treatment and during regular hospital visits, respectively. Control sera were obtained from healthy staff members (n = 20). All serum samples were preserved at −20°C.

  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 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 Clinical Research Ethics Committee of the First Affiliated Hospital of Chongqing Medical University.

2.2 Macrophage cell line

The THP-1 human macrophage strain was obtained from China Center for Type Culture Collection (CCTCC). The cell line was made into 80 mg/ml suspension, stored at 4°C, and diluted 10 times before use. All the operations were completed under the guidance of the third level Biosafety Laboratory of Chongqing Center for Disease Control and Prevention.

2.3 Cell culture and BCG/H37Rv stimulation

THP-1 macrophages were cultured in 1640 medium (Gibco, USA) with 10% fetal bovine serum (Gibco, USA) at 37°C and 5% CO2. The cell pellet was resuspended with cell growth solution, adjusted the density to 2.5 × 105 cells/ml. Phorbol-12-Myristate-13-Acetate (PMA, SIGMA, USA) stock solution (to a final concentration of 5 ng/ml) was added to the culture to stimulate the transformation of THP-1 cells into macrophages, which was then incubated for 24 h. Subsequently, the cell culture supernatant was discarded, the cells were washed twice with D-Hanks, being replaced with new cell growth medium and incubated for another 72 h. The supernatant was then discarded. The cells were washed twice with D-Hanks and being replaced with cell growth medium containing BCG and H37Rv strains, respectively (MOI = 10:1). After that, the cells were incubated for 2 h and the supernatant was discarded. The cells were washed twice with D-hanks and replaced with new cell growth medium and samples were taken at 12, 24, and 48 h for the detection of IL-19, CXCL14, and IL-39 [14,15].

2.4 Measurement of IL-19, IL-39, and CXCL14

The levels of IL-39 (Ruipan, Shanghai, China), CXCL14 (Novus USA), and IL-19 (R&D Systems, Minneapolis, MI, USA) were determined by using enzyme-linked immunosorbent assay (ELISA). The operation processes were performed in strict accordance with the manufacturer’s protocol.

2.5 Statistical analysis

The Kruskal–Wallis test was used to assess the clinical features of the TB patients. CXCL14 concentrations did not have a Gaussian distribution; therefore, the Mann–Whitney U test was used to analyze the relationship between serum level of CXCL14 and TB classification or T-spot or BCG vaccination. For in vitro tests, data were expressed as the means and standard deviations of at least three independent experiments. Statistical significance was determined by Student’s t test. All data were expressed as mean ± SD. Differences were assumed statistically significant at p < 0.05. All analyses were performed using the Statistical Package for the Social Sciences (SPSS) statistical software for Windows, version SPSS 22.0 (SPSS Inc., IL, USA).

3 Results

3.1 The demographic and clinical characteristics of study subjects

Totally, there were 38 patients with TB and 20 healthy controls in the current study (Table 1). Among the 38 TB patients, 20 of them had active TB and the rest 18 patients had inactive TB. There was no difference between health control (HC) and TB patients in the aspect of age distribution. The proportion of TB patients (65%) from rural areas was higher than that of the control group (50%). The duration of TB was 5.5 (1.5–6) years (median [interquartile range, IQR]) and 3.2 (2.6, 3.9) years (median (IQR)) for inactive and active TB, respectively.

Table 1

Clinical features of the different disease severity in TB patients

Clinical features HC TB patients p valve*
Inactive Active (Kruskal–Wallis test)
Age, years (median (IQR)) 41 (26–59) 36 (25–48) 40 (32–50) 0.166
Rural area, N (%) 10 (50%) 11 (61%) 14 (70%) 0.021
Duration, years (median (IQR)) 0 5.5 (1.5–6) 3.2 (2.6–3.9) 0.010
BCG vaccination rate, N (%) 13 (65%) 10 (55.6%) 7 (35%) 0.010
WBC (109/L) 6.5 5.8 5.2 0.062
Neutrophil (%) 68 42 35 0.012
Lymphocyte (%) 30 57 59 0.001
CXCL14 (pg/ml) 25.12 ± 8.8 63.3 ± 31.4 151.1 ± 106.4 0.000
IL-39 (pg/ml) 0.15 ± 0.05 0.038 ± 0.029 0.031 ± 0.034 0.000
T-spot (+), N (%) 0 9 (50%) 19 (95%) 0.002
PPD (+), N (%) 2 (10%） 12 (66.7%) 20 (100%) 0.020

HC: health control; IQR: interquartile range; WBC: white blood cells; BCG: Bacille Calmette-Guérin vaccine; T-spot: Tuberculosis γ Interferon release analysis; PPD: pure protein derivative of tuberculin. *Bold values indicate statistical significance, p value <0.05.

There was no significant difference in the count of WBC (vs 6.5, p = 0.062) between the TB group and the control group, while the percentage of neutrophils (vs 68%, p = 0.012) in the TB group was lower than that of the control group, and the percentage of lymphocytes (vs 30%, p = 0.001) was significantly higher. The positive rates of T-spot in groups of active TB, inactive TB, and HC were 95, 50, and 0%. Meanwhile, the positive rates of purified protein derivative (PPD) test in these three groups were 100, 66.7, and 10%, respectively.

3.2 The serum levels of CXCL14, IL-39, and IL-19 in patients with TB

Compared with the HC, the serum level of CXCL14 was significantly increased in the TB group and the highest level was in the group of active TB (Figure 1a). The level of IL-39 was significantly decreased in patients with TB (Figure 1b). According to the concentration of CXCL14, patients with active and inactive TB were divided into five groups. The distribution of CXCL14 concentration was statistically different between the active and inactive TB groups. Eighty-five percentage (17/20) of the patients with active TB had CXCL14 >100 pg/ml, while 11.1% (2/18) of the patients with inactive TB had CXCL14 >100 pg/ml, and the concentration of CXCL14 was lower than 150 pg/ml in all patients with inactive TB (Table 2). In addition, there was a statistical difference in the distribution of CXCL14 concentrations between the T-spot-positive and -negative groups in TB patients (Table 3). Moreover, the distribution of CXCL14 level was statistically different between BCG vaccination and non-vaccination groups in active TB (Table 4), while there was no statistical difference in IL-19 concentration among these three groups (data were not shown).

Figure 1 The serum level of IL-39 and CXCL14 in patients with TB. (a) The serum level of CXCL14. (b) The serum level of IL-39. Thirty-eight TB patients (20 active TB patients and 18 inactive TB patients) and 20 healthy controls were recruited in this test. *p < 0.05. **p < 0.01. ***p < 0.001.
Figure 1

The serum level of IL-39 and CXCL14 in patients with TB. (a) The serum level of CXCL14. (b) The serum level of IL-39. Thirty-eight TB patients (20 active TB patients and 18 inactive TB patients) and 20 healthy controls were recruited in this test. *p < 0.05. **p < 0.01. ***p < 0.001.

Table 2

Relationship between serum level of CXCL14 and TB classification

TB 20 ≤ CXCLl4 ≤ 100 pg/ml 100 < CXCLl4 ≤ 150 pg/ml 150 < CXCLl4 ≤ 300 pg/ml CXCLl4 >300 pg/ml Test Z p value
Active (n = 20) 3 (15%) 7 (35%) 9 (45%) 1 (5%) Mann–Whitney U test −4.537 0.000
Inactive (n = 18) 16 (88.9%) 2 (11.1%) 0 (0%) 0 (0%)
Table 3

Relationship between serum CXCL14 and T-spot in TB patients

T-SPOT 20 ≤ CXCLl4 ≤ 100 pg/ml 100 < CXCLl4 ≤ 150 pg/ml 150 < CXCLl4 ≤ 500 pg/ml Test Z p value
P (n = 28) 10 (26.3%) 8 (21.1%) 10 (26.3%) Mann–Whitney U test −2.923 0.003
N (n = 10) 9 (23.7%) 1 (2.6%) 0 (0%)

P: positive result; N: negative result.

Table 4

Relationship between serum CXCL14 and BCG vaccination in patients with active and inactive TB

TB activity BCG 20 ≤ CXCLl4 ≤ 100 pg/ml 100 < CXCLl4 ≤ 150 pg/ml 150 < CXCLl4 ≤ 500 pg/ml Test Z p value
Active Y (n = 7) 3 (15%) 3 (15%) 1 (5%) Mann–Whitney U test −1.712 0.002
N (n = 13) 0 (0%) 4 (20%) 9 (45%)
Inactive Y (n = 10) 10 (55.5%) 0 (0%) 0 (0%) 1.630 0.103/0.183*
N (n = 8) 6 (33.3%) 2 (11.1%) 0 (0%)

*The p value calculated by the chi-square test for ignoring the 150 < CXCLL4 ≤ 500 pg/ml group.

3.3 The concentration variation in CXCL14, IL-39, and IL-19 in macrophage culture stimulated by BCG or H37Rv

Regarding the in vitro experiments of macrophages, CXCL14 gradually increased within 24 h and then decreased significantly after 48 h in the group of BCG stimulation. However, it gradually increased over time in the group of H37Rv stimulation (Figure 2a). Variation in IL-39 showed different trends after BCG and H37Rv stimulation. IL-39 was significantly reduced in macrophages 12 h after BCG or H37Rv stimulation. After that, the concentration of IL-39 in the group of BCG stimulation gradually increased at 24 h and reached the level of the control group at 48 h. Although the IL-39 concentration in the H37Rv stimulation group rapidly recovered to the control level within 24 h, it decreased significantly again at 48 h (Figure 2b). There was no statistical difference in IL-19 level in vitro test (Figure 2c).

Figure 2 The concentration of IL-39, CXCL14, and IL-19 variation in macrophages stimulated by BCG and H37Rv. (a) The level of CXCL14 variation in macrophages stimulated by BCG and H37Rv. (b) The level of IL-39 variation in macrophages stimulated by BCG and H37Rv. (c) The level of IL-19 variation in macrophages stimulated by BCG and H37Rv. THP-1 macrophages (2.5 × 105 cells/well) were stimulated by 5 ng/ml PMA first and then were infected with BCG or Mycobacterium tuberculosis H37Rv (MOI = 10:1), the supernatant was collected at 12, 24, and 48 h, respectively, for cytokines detection by ELISA assay. Results are expressed as the arithmetic mean ± SD from three independent experiments. *p < 0.05. **p < 0.01. ***p < 0.001. And representative experiment as shown.
Figure 2

The concentration of IL-39, CXCL14, and IL-19 variation in macrophages stimulated by BCG and H37Rv. (a) The level of CXCL14 variation in macrophages stimulated by BCG and H37Rv. (b) The level of IL-39 variation in macrophages stimulated by BCG and H37Rv. (c) The level of IL-19 variation in macrophages stimulated by BCG and H37Rv. THP-1 macrophages (2.5 × 105 cells/well) were stimulated by 5 ng/ml PMA first and then were infected with BCG or Mycobacterium tuberculosis H37Rv (MOI = 10:1), the supernatant was collected at 12, 24, and 48 h, respectively, for cytokines detection by ELISA assay. Results are expressed as the arithmetic mean ± SD from three independent experiments. *p < 0.05. **p < 0.01. ***p < 0.001. And representative experiment as shown.

3.4 The utility of CXCL14 as biomarkers versus T-spot assay for M. tb infection

To determine whether CXCL14 could be the biomarkers or diagnostic tests in TB, we calculated the receiver operating characteristics (ROC) curves for CXCL14 and these data were compared with the T-spot assay, an ideal method for TB diagnosis at present. The AUC of CXCL14 as diagnosis biomarkers for TB and inactive TB was 0.9816 (p < 0.0001, sensitivity: 92.11%, specificity: 95%) and 0.9611 (p < 0.0001, sensitivity: 83.33%, specificity: 95%), compared with the results test of T-spot assay, which was 0.8684 (p < 0.0001, sensitivity: 73.68%, specificity: 100%) and 0.7500 (p = 0.0085, sensitivity: 50%, specificity: 100%), respectively (Figure 3). These results showed that CXCL14 could be a possible molecular marker to screen serum samples with M. tb infection.

Figure 3 ROC curves for CXCL14 and T-spot in TB patients and inactive TB patients. (a) ROC curves for CXCL14 in TB patients (including inactive TB and active TB patients). (b) ROC curves for T-spot in TB patients (including inactive TB and active TB patients). (c) ROC curves for CXCL14 in inactive TB patients. (d) ROC curves for T-spot in inactive TB patients.
Figure 3

ROC curves for CXCL14 and T-spot in TB patients and inactive TB patients. (a) ROC curves for CXCL14 in TB patients (including inactive TB and active TB patients). (b) ROC curves for T-spot in TB patients (including inactive TB and active TB patients). (c) ROC curves for CXCL14 in inactive TB patients. (d) ROC curves for T-spot in inactive TB patients.

4 Discussion

TB remains a major global health problem and represents the leading global cause of death from an infectious agent before COVID-19 pandemic [2,13]. Controlling the spread of TB requires a vaccine that can prevent TB. However, due to the population who received BCG vaccination, the PPD test results are positive, and they are also positive in individuals with M. tb infection. Thereby, doctors need to differentiate M. tb.-infected individuals from BCG-vaccinated populations [16]. Meanwhile, the body’s defense status against M. tb fluctuated with time and condition. Therefore, it is of great significance to continuously explore the ideal markers associated with TB infection.

In the current study, we have performed the first evaluation of serum levels of IL-39, CXCL14, and IL-19 in patients with TB. Also, we tried to explore the changes in the levels of these cytokines in cultured macrophages stimulated by BCG and M. tb H37Rv.

IL-39 is a new member of the IL-12 family, in addition to IL-12, IL-23, IL-27, and IL-35. All members of the IL-12 cytokine family consist of two kinds of subunits: an α-cytokine subunit and a β-cytokine subunit [17]. This family is considered to be closely related to the occurrence and development of inflammation, and chain pairing rearrangement (disorder) is an important feature of this family. For instance, IL-12 has an α-subunit (IL-12p35) and a β-subunit (IL-12p40) [18]. IL-23 is strongly mediated through its two subunits (IL-23p19 and IL-12p40). IL-27 is made of with IL-27p28 and Epstein–Barr virus-induced gene3 (EBi3) [18]. IL-35 shares the IL-12p35 subunit with IL-12 and EBi3 with IL-27. Although the members of the family are composed of some common subunits, their functions are different. For example, IL-12 recognizes its receptors IL-12Rβ1 and IL-12Rβ2. It leads to the binding of non-receptor tyrosine protein kinase (Tyk2) and Janus kinase 2 (JAK2), activation of STAT4, and stimulation of IFN- γ. It can inhibit the proliferation of HIV. IL-23 passes through IFN-α to inhibit HIV. IL-27 cooperates with JAK2 to phosphorylate stat1–stat3 dimer through Jak1 and IFN-λ1 to inhibit HIV and HBV. Moreover, IL-35 inhibits IFN-γ and TNF-α and promotes the proliferation of HBV [19]. Even though IL-39 shares IL-23p19 with IL-23 and shares EBi3 [3] with IL-27 and IL-35, their roles in human infectious diseases are unclear. It has not been determined whether IL-39 is an inflammatory cytokine or not. On the other hand, the natural IL-39 (p19/EBI3) complex is present in the supernatant of cultured RAW264.7 macrophages and can be secreted by B cells [3,5]. Recently, IL-39 was considered a pathogenic factor in acute Graft-vs.-Host Disease (GVHD) [17], as its serum level in the recipient was positively correlated with the occurrence of acute GVHD [20]. Interestingly, we discovered the reduction in serum level of IL-39 in TB patients, and patients with active TB had the lowest level of IL-39. Meanwhile, after 48 h of stimulation, IL-39 level of THP-1 macrophages in the H37Rv stimulation group was significantly lower than that in the BCG and control groups. It may suggest that IL-39 could serve as a factor in the pathogenesis of TB and would shed light on further researches of IL-39 in TB. On the other hand, previous study suggested that IL-39 could be a theoretical cytokine in human, and it is secreted below the lower quantity of detection or it has no functional role [21]. In this study, IL-39 was detected by a commercially available ELISA reagent. Thereby, it is necessary to further study the role of IL-39 in TB infection.

Secondly, we found that CXCL14 levels in the serum of TB patients were increased, especially in the active TB group. After 48 h of stimulation, the level of CXCL14 in THP-1 macrophages in the H37Rv-stimulated group was significantly higher than that in the control, while that in the BCG-stimulated group was significantly lower than that in the control group. Thus, an elevation of CXCL14 may indicate TB infection. In addition, there were statistical differences in the distribution of CXCL14 levels between the control and active TB groups that were BCG vaccinated and non-vaccinated, and between active and inactive TB groups, as well as TB patients with T-spot-positive results and those of negative results. Collectively, our study suggests, for the first time, that elevated CXCL14 may be associated with TB infection, which is consistent with T-spot results, and may be used to distinguish between active and inactive TB that is independent of BCG vaccination. Although the potential role of CXCL14 in cancer has been a focus of research in recent years [9,22], other aspects of CXCL14 are also being explored. CXCL14 also regulates platelet function and migration [23,24] and mediates the recruitment of CD14 monocytes in the skin [25]. Furthermore, there was a study showing that CXCL14 shows certain antibacterial activity, and the antibacterial efficacy of CXCL14 is more advantageous than known anti-microbial peptides like human β-defensin-2 or chemokine CCL20 [25,26]. The principle may be that CXCL14 effectively kills Pseudomonas aeruginosa, Streptococcus pyogenes, and Streptococcus pneumoniae in a dose-dependent manner by inducing membrane depolarization and membrane rupture [26]. Furthermore, CXCL14 has been shown to have broad antibacterial effects against skin Gram-positive bacteria and Candida albicans, and those antibacterial activities exhibited by human and mouse CXCL14 can be neutralized by anti-CXCL14 monoclonal antibodies [27]. Thus, we speculate that the increase of CXCL14 in the peripheral blood of TB patients may be an immune response of the host against M. tb. It remains uncertain whether CXCL14 plays a protective role in TB infection, but our study provides some interesting clues.

Third, IL-19 is a member of the IL-10 cytokine family [10] and is also a member of the cytokine IL-20 subfamily [11].

Circulating IL-19 levels in patients with tuberculous lymphadenitis were significantly lower than those in TB and healthy controls, and their circulating IL-19 levels increased significantly after completion of anti-tuberculous treatment [27]. However, we found no significant differences in IL-19 levels among the active and inactive TB groups, as well as the control. Furthermore, there was no statistical difference in IL-19 level of THP-1 macrophages cultured in vitro after BCG or H37Rv stimulation.

Currently, the main laboratory detection methods of M. tb infection include acid fast staining, TB antibody detection, and real-time quantitative PCR. Unfortunately, these methods have numerous disadvantages, such as unsatisfactory sensitivity and specificity, high sample requirements, and sensitivity to immune status. A new method of T-spot TB assay (interferon [IFN]-γ release analysis) based on the detection of IFN secreted in M. tb-specific T cells stimulated by M. tb-specific antigens has been successfully used in determine the presence of M. tb infection. In this study, the T-spot assay is used as a comparison method. These ROC curves showed better sensitivity and similar specificity for CXCL14 in the serum, which are used as auxiliary diagnostic tests for TB including inactive TB and active TB. Therefore, serum CXCL14 may be combined with T-spot as a biomarker for screening for TB infection.

To sum up, IL-39 could serve as a protective factor in the pathogenesis of TB and CXCL14 may play a role in TB infection, which provided some interesting clues on further researches of IL-39 and CXCL14 in TB. More importantly, the cytokines show a greater predicate value for the diagnosis of TB and the evaluation of disease activity. Altogether, the recent study suggests that chemokines, produced by immune cells and induced by other molecules, occupy a vital role in the pathogenesis of TB through multifarious pathways.

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  1. Funding information: This work was financially supported by Scientific and Technological Research Program of Chongqing Municipal Education Commission (no. KJQN201900417), Chongqing Municipal Science and Technology Commission (no. cstc2017jcyjAX0409 and no. cstc2021jcyj-msxmX0123), Chongqing Science and Health Joint Project (no. 2023MSXM049), and Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0091).

  2. Author contributions: M.D. collected the specimens, X.-F.L. carried out the experiment, H.-X.W., F.-F.H., L.X., S.-J.G., A.-L.L., and J.-J.B. prepared the draft of the article. X.L. and X.-F.L. conceived and designed the experiments. All authors read and approved the final article.

  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: 2022-12-20
Revised: 2023-02-18
Accepted: 2023-03-12
Published Online: 2023-05-18

© 2023 the author(s), published by De Gruyter

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

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  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0594
Keywords for this article
IL-39; CXCL14; tuberculosis; BCG; cytokine; biomarker
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers
  3. Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis
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  31. Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis
  32. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
  33. Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
  42. Performance comparison of three scaling algorithms in NMR-based metabolomics analysis
  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
  44. The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy
  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
  52. Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves’ disease in children
  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
  54. Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome
  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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