Several genome-wide association studies have discovered novel loci at chromosome 12q24, which includes mevalonate kinase (MVK), methylmalonic aciduria (cobalamin deficiency) cbIB type (MMAB), and potassium channel tetramerization domain-containing 10 (KCTD10), all of which influence HDL-cholesterol concentrations. However, there are few reports on the associations between these polymorphisms and HDL-C concentrations in Chinese population. This study aimed to evaluate the associations between functional polymorphisms in three genes (MVK, MMAB and KCTD10) and HDL-C concentrations, as well as coronary heart disease (CHD) susceptibility in Chinese individuals.

We performed a two-stage molecular epidemiological study to explore DNA methylation profiles for potential biomarkers of esophageal squamous cell carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was used to identify genes with differentially methylated CpG sites. Sixteen candidate genes were validated by sequencing 1160 CpG sites in their promoter regions using the Illumina MiSeq platform. When excluding sites with negative changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1, PRDM16 and PTX3) showed significantly different methylation levels among cancer lesions, remote normal-appearing tissues, and healthy controls. PRDM16 had the highest diagnostic value with the AUC (95% CI) of 0.988 (0.965-1.000), followed by PIK3R1, with the AUC (95% CI) of 0.969 (0.928-1.000). In addition, the methylation status was higher in patients with advanced cancer stages. These results indicate that aberrant DNA methylation may be a potential biomarker for the diagnosis of ESCC.

Background. This study aims to evaluate GenoType MTBDRplus and GenoType MTBDRsl for their ability to detect drug-resistant tuberculosis in a Chinese population. Methods. We collected 112 Mycobacteria tuberculosis strains from Jiangsu province, China. The conventional DST and line probe assay were used to detect drug resistance to rifampicin (RFP), isoniazid (INH), ofloxacin (OFX), kanamycin (Km), and ethambutol (EMB). Results. The sensitivity and specificity were 100% and 50% for RFP and 86.11% and 47.06% for INH, respectively. The most common mutations observed in MTBDRplus were rpoBWT8 omission + MUT3 presence, katGWT omission + MUT1 presence, and inhAWT1 omission + MUT1 presence. For drug resistance to OFX, Km, and EMB, the sensitivity of MTBDRsl was 94.74%, 62.50%, and 58.82%, respectively, while the specificity was 92.59%, 98.81%, and 91.67%, respectively. The most common mutations were gyrAWT3 omission + MUT3C presence, rrsMUT1 presence, embBWT omission + MUT1B presence, and embBWT omission + MUT1A presence. Sequencing analysis found several uncommon mutations. Conclusion. In combination with DST, application of the GenoType MTBDRplus and GenoType MTBDRsl assays might be a useful additional tool to allow for the rapid and safe diagnosis of drug resistance to RFP and OFX.

Spirometry is required to confirm a chronic obstructive pulmonary disease (COPD) diagnosis, but it is difficult to perform in resource-limited settings. This study aimed to evaluate symptom-based questions for screening of individuals with COPD among Chinese populations. We recruited 3969 adult subjects from the First Affiliated Hospital of Nanjing Medical University. Spirometric measurements of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were collected to confirm the COPD diagnosis. A symptom-based questionnaire was administered to collect data related to COPD. The sensitivity and specificity together with the area under the curve (AUC) were calculated. The traditional IPAG eight-item questionnaire yielded an AUC of 0.80(95% CI: 0.78-0.82), with a sensitivity of 67.8% and specificity of 76.8%. After removing and adding questions, a revised eleven-item questionnaire exhibited a significantly increased diagnostic accuracy, with an AUC of 0.85(95% CI: 0.84-0.87). At the inflection point of the curve, it demonstrated a sensitivity of 82.5% and specificity of 72.9%. We showed that the revised symptom-based questionnaire could be used to screen individuals with a high likelihood of COPD among Chinese populations. Further validation is required before we claim it is a useful diagnostic for primary care populations.

Drylands account for more than 30% of China's terrestrial area, while the ecological drivers of taxonomic (TD), functional (FD) and phylogenetic (PD) diversity in dryland regions have not been explored simultaneously. Therefore, we selected 36 plots of desert and 32 plots of grassland (10 × 10 m) from a typical dryland region of northwest China. We calculated the alpha and beta components of TD, FD and PD for 68 dryland plant communities using Rao quadratic entropy index, which included 233 plant species. Redundancy analyses and variation partitioning analyses were used to explore the relative influence of environmental and spatial factors on the above three facets of diversity, at the alpha and beta scales. We found that soil, climate, topography and spatial structures (principal coordinates of neighbor matrices) were significantly correlated with TD, FD and PD at both alpha and beta scales, implying that these diversity patterns are shaped by contemporary environment and spatial processes together. However, we also found that alpha diversity was predominantly regulated by spatial structure, whereas beta diversity was largely determined by environmental variables. Among environmental factors, TD was most strongly correlated with climatic factors at the alpha scale, while with soil factors at the beta scale. FD was only significantly correlated with soil factors at the alpha scale, but with altitude, soil and climatic factors at the beta scale. In contrast, PD was more strongly correlated with altitude at the alpha scale, but with soil factors at the beta scale. Environment and space explained a smaller portion of variance in PD than in TD and FD. These results provide robust evidence that the ecological drivers of biodiversity differ among different scales and facets of diversity. Future research that focuses on the comparisons among TD, FD and PD would likely provide new insights into elucidating the underlying community assembly.

Mirabilis himalaica (Edgew.) Heimerl is one of the most important genuine medicinal plants in Tibet, in which the special plateau habitat has been associated with its excellent medicinal quality and efficacy. However, the mechanisms by which environmental factors affect biosynthesis of secondary metabolic components remain unclear in this species. In this study, RNA sequencing and iTRAQ (isobaric Tags for Relative and Absolute Quantification) techniques were used to investigate the critical molecular "events" of rotenoid biosynthesis responding to UV-B radiation, a typical plateau ecological factor presented in native environment-grown M. himalaica plants. A total of 3641 differentially expressed genes (DEGs) and 106 differentially expressed proteins (DEPs) were identified in M. himalaica between UV-B treatment and control check (CK). Comprehensive analysis of protein and transcript data sets resulted in 14 and 7 DEGs from the plant hormone signal transduction and phosphatidylinositol signaling system pathways, respectively, being significantly enriched. The result showed that the plant hormone signal transduction and phosphatidylinositol signaling system might be the key metabolic strategy of UV-B radiation to improve the biosynthesis of rotenoid in M. himalaica. At same time, most of the DEGs were associated with auxin and calcium signaling, inferring that they might drive the downstream transmission of these signal transduction pathways. Regarding those pathways, two chalcone synthase enzymes, which play key roles in the biosynthesis of rotenoid that were thought as the representative medicinal component of M. himalaica, were significantly upregulated in UV-B radiation. This study provides a theoretical basis for further exploration of the adaptation mechanism of M. himalaica to UV-B radiation, and references for cultivation standardization.

Team-based learning (TBL) has been adopted as a new medical pedagogical approach in China. However, there are no studies or reviews summarizing the effectiveness of TBL on medical education. This study aims to obtain an overall estimation of the effectiveness of TBL on outcomes of theoretical teaching of medical education in China.

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors characterized by their aggressive nature and poor associated survival. MicroRNAs (miRs) have been found to play an important role in the occurrence and development of human cancers, but their role in the prognosis of TNBC patients remains unclear. We performed a meta-analysis to explore the prognostic value of miRs in TNBC.

Dryland ecosystems cover more than 30% of the terrestrial area of China, while processes that shape the biogeographic patterns of bacterial and fungal β-diversity have rarely been evaluated synchronously. To compare the biogeographic patterns and its drivers of bacterial and fungal β-diversity, we collected 62 soil samples from a typical dryland region of northwest China. We assessed bacterial and fungal communities by sequencing bacterial 16S rRNA gene and fungal ITS data. Meanwhile, the β-diversity was decomposed into two components: species replacement (species turnover) and nestedness to further explore the bacterial and fungal β-diversity patterns and its causes. The results show that both bacterial and fungal β-diversity were derived almost entirely from species turnover rather than from species nestedness. Distance-decay relationships confirmed that the geographic patterns of bacterial and fungal β-diversity were significantly different. Environmental factors had the dominant influence on both the bacterial and fungal β-diversity and species turnover, however, the role of geographic distance varied across bacterial and fungal communities. Furthermore, both bacterial and fungal nestedness did not significantly respond to the environmental and geographic distance. Our findings suggest that the different response of bacterial and fungal species turnover to dispersal limitation and other, unknown processes may result in different biogeographic patterns of bacterial and fungal β-diversity in the drylands of northwest China. Together, we highlight that the drivers of β-diversity patterns vary between bacterial and fungal communities, and microbial β-diversity are driven by multiple factors in the drylands of northwest China.

A large human natural single‑chain fragment variable (scFv) phage library was constructed based on Cre‑LoxP recombination, and used to successfully identify antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9). The library was derived from 400 blood samples, 30 bone marrow samples, and 10 cord blood samples from healthy donors. Lymphocytes were isolated from each sample and cDNA was synthesized using reverse transcription‑quantitative PCR. Two‑step overlap PCR was then used for scFv synthesis using a LoxP peptide as the linker. The scFv gene was inserted into the phagemid vector pDF by enzymatic digestion and ligation, and then transformed into Escherichia coli (E. coli) SS320 to establish a primary antibody library in the form of scFvs. A primary antibody library consisting of 5x107 peripheral blood and umbilical cord blood sources, as well as a primary antibody library of 5x107 bone marrow samples were obtained. By optimizing the recombination conditions, the primary phage library was used to infect E. coli BS1365 strain (which expresses the Cre enzyme), and a human scFv recombinant library with a size of 1x1011 was obtained through Cre‑LoxP enzyme‑mediated heavy and light chain replacement and recombination. This constructed recombinant library was employed to screen for antibodies against recombinant PCSK9. After four rounds of selection, a fully human antibody (3D2) was identified with a binding affinity of 1.96±1.56ⅹ10‑10 M towards PCSK9. In vitro, the PCSK9/low‑density lipoprotein receptor (LDLR) pathway of Hep‑G2 cells was inhibited by 3D2 treatment, thereby increasing LDL uptake in these cells. In addition, combination treatment with 3D2 and statin was more effective at increasing LDLR levels than treatment with 3D2 or statin alone. Furthermore, 3D2 resulted in a 3‑fold increase in hepatic LDLR levels, and lowered total serum cholesterol by up to 61.5% in vivo. Taken together, these results suggest that the constructed human Cre‑LoxP scFv phage display library can be used to screen fully human scFv, and that 3D2 may serve as a candidate hypolipidemic therapy.

Dysregulation of alternative splicing (AS) is a critical signature of cancer. However, the regulatory mechanisms of cancer-specific AS events, especially the impact of DNA methylation, are poorly understood.

The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain.

The root-knot nematode Meloidogyne incognita has a wide host range and it is one of the most economically important crop parasites worldwide. Biological control has been a good approach for reducing M. incognita infection, for which many nematophagous fungi are reportedly applicable. However, the controlling effects of Phanerochaete chrysosporium strain B-22 are still unclear. In the present study we characterized the parasitism of this strain on M. incognita eggs, second-stage juveniles (J2), and adult females. The highest corrected mortality was 71.9% at 3 × 108 colony forming units (CFU) mL-1 and the estimated median lethal concentration of the fungus was 0.96 × 108 CFU mL-1. Two days after treatment with Phanerochaete chrysosporium strain B-22 eggshells were dissolved. A strong lethal effect was noted against J2, as the fungal spores developed in their body walls, germinated, and the resulting hyphae crossed the juvenile cuticle to dissolve it, thereby causing shrinkage and deformation of the juvenile body wall. The spores and hyphae also attacked adult females, causing the shrinkage and dissolution of their bodies and leakage of contents after five days. Greenhouse experiments revealed that different concentrations of the fungal spores effectively controlled M. incognita. In the roots, the highest inhibition rate for adult females, juveniles, egg mass, and gall index was 84.61%, 78.91%, 84.25%, and 79.48%, respectively. The highest juvenile inhibition rate was 89.18% in the soil. Phanerochaete chrysosporium strain B-22 also improved tomato plant growth, therefore being safe for tomato plants while effectively parasitizing M. incognita. This strain is thus a promising biocontrol agent against M. incognita.

A variety of abnormalities in vitamin D metabolism have been reported in patients with active tuberculosis. However, intervention trials have produced inconsistent results. We hypothesized that genetic and epigenetic changes in the key genes of the vitamin D metabolic pathway may partly explain the differences between studies.

Green food consumption is a core issue that contributes to solving environmental pollution and achieving sustainable development. This study aims to investigate the mediating role of green food consumption and social trust in the relationship between perceived consumer effectiveness and psychological wellbeing to provide new insights into green food consumption, based on social ideal theory and social trust theory. Using a sample data of 514 consumers in China, the results of structural equation modeling showed that perceived consumer effectiveness was positively related to psychological wellbeing. Furthermore, green food consumption mediated the relationship between perceived consumer effectiveness and psychological wellbeing. In addition, social trust moderated the relationship between perceived consumer effectiveness and green food consumption. Social trust also moderated the indirect effect of perceived consumer effectiveness on psychological wellbeing through green food consumption. The findings of this study enrich the extant literature relating to green food consumption and have practical implications for business managers and policymakers.

G2/M DNA synthesis (G-MiDS) can be observed in one in five G2/M cells in unperturbed conditions by immunofluorescence microscopy. However, little is known of the genomic sites undergoing G-MiDS. Here, we describe a protocol which allows enriching for G2/M cells and investigating the sites of G-MiDS using BrdU-seq. This method can also be used to study the role of DNA replication or transcription-associated factors in affecting G-MiDS levels in different cell lines. For complete details on the use and execution of this protocol, please refer to Wang et al. (2021).

Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated.

Increasing evidence indicates that PM2.5 exposure disrupts early embryonic development, but the mechanisms remain unclear. We hypothesized that PM2.5 cause abnormal embryonic development by interfering with DNA methylation and mRNA expression. In this study, we observed that human embryonic stem cells (hESCs) treated with extractable organic matters (EOM) from PM2.5 concentrations above 100 μg/mL exhibited reduced viability. While EOM within non-cytotoxicity concentrations did not affect the expression levels of pluripotency genes, it did enhance cellular proliferation, as indicated by increased Edu incorporation and the upregulation of cell cycle genes (Cdk2, Mdm2). Additionally, EOM significantly influenced the transcriptome patterns in hESCs. Notably, the differentially expressed genes were found to be significantly enriched in processes such as extracellular matrix organization, cell-cell junction organization, chromatin organization, and DNA methylation. Furthermore, we observed whole genomic-wide DNA methylation changes. Through a cross-analysis of changes in DNA methylation and mRNA expression, we identified an enrichment of terms related to the VEGFR signaling pathway and extracellular matrix. The gene signal transduction networks revealed that crucial hubs were implicated in cell growth and division. In conclusion, our findings demonstrate that PM2.5 induce significant alterations in transcriptome and DNA methylome in hESCs, leading to aberrant cell proliferation. This research provides novel insights into the molecular mechanisms underlying the developmental toxicity of PM2.5.

The peripheral immune response contributes to neurologic impairment after stroke and the extent of initial damage is greater in males than females. We have previously shown that spleen cells directly contribute to ischemic damage in males, as splenectomy prior to experimental stroke eliminates the sex differences in infarct volume. This study aims to determine which specific subset of immune cells exert pathogenic effects when injected 24 hours before MCAO induction into splenectomized male and female WT mice. The results demonstrate that CD4/CD8/CD11b treated mice had no significant effect on infarct volumes vs. vehicle-treated control mice after MCAO. However, there were significant alterations to the resident peripheral immune composition. These results suggest that there are regulatory factors resulting from splenectomy or other possible influences that inhibit peripheral immune cell contribution to neuroinflammation and thus contributing to differential effects of the spleen on stroke outcome in males and female mice.

Chronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis (PTB) share a number of common risk factors, including innate immunity-related genetic factors. In the present study, we compared the role of genetic variations of the TLR4 gene in susceptibility to COPD and PTB and illuminated the underlying molecular mechanism of functional single-nucleotide polymorphisms (SNPs).