CCCTC-binding factor: the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 that upregulates the sialylation of anti-citrullinated protein antibodies in rheumatoid arthritis.

OBJECTIVE: Sialylation of the crystallizable fragment (Fc) of ACPAs, which is catalysed by ß-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) could attenuate inflammation of RA. In this study, we screened the transcription factor of ST6GAL1 and elucidated the mechanism of transcriptionally upregulating sialylation of ACPAs in B cells to explore its role in the progression of RA. METHODS: Transcription factors interacting with the P2 promoter of ST6GAL1 were screened by DNA pull-down and liquid chromatography with tandem mass spectrometry (LC-MS/MS), and verified by chromatin immunoprecipitation (ChIP), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The function of the CCCTC-binding factor (CTCF) on the expression of ST6GAL1 and the inflammatory effect of ACPAs were verified by knocking down and overexpressing CTCF in B cells. The CIA model was constructed from B cell-specific CTCF knockout mice to explore the effect of CTCF on arthritis progression. RESULTS: We observed that the levels of ST6GAL1 and ACPAs sialylation decreased in the serum of RA patients and were negatively correlated with DAS28 scores. Subsequently, CTCF was screened and verified as the transcription factor interacting with the P2 promoter of ST6GAL1, which enhances the sialylation of ACPAs, thus weakening the inflammatory activity of ACPAs. Furthermore, the above results were also verified in the CIA model constructed from B cell-specific CTCF knockout mice. CONCLUSION: CCCTC-binding factor is the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 in B cells that upregulates the sialylation of ACPAs in RA and attenuates the disease progression.

Achieving Long-Term Stability of Partial Nitrification and Autotrophic Denitrification in an MABR via Sulfide Dosing.

While partial nitrification (PN) has the potential to reduce energy for aeration, it has proven to be unstable when treating low-strength wastewater. This study introduces an innovative combined strategy incorporating a low rate of oxygen supply, pH control, and sulfide addition to selectively inhibit nitrite-oxidizing bacteria (NOB). This strategy led to a stable PN in a laboratory-scale membrane aerated biofilm reactor (MABR). Over a period of 260 days, the nitrite accumulation ratio exceeded 60% when treating synthetic sewage containing 50 mg NH4+-N/L. Through in situ activity testing and high-throughput sequencing, the combined strategy led to low levels of nitrite-oxidation activity (<5.5 mg N/m2 h), Nitrospira species (relative abundance <1%), and transcription of nitrite-oxidation genes (undetectable). The addition of sulfide led to simultaneous PN and autotrophic denitrification in the single-stage MABR, resulting in over 60% total inorganic nitrogen removal. Sulfur-based autotrophic denitrification consumed nitrite and inhibited NOB conversion of nitrite to nitrate. The combined strategy has potential to be applied in large-scale sewage treatment and deserves further exploration.

Factors associated with immunological non-response after ART initiation: a retrospective observational cohort study.

BACKGROUND: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. METHODS: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/µl after 24 months' treatment), immunological incomplete responders (ICRs) (200-350 cells/µl) and INRs (< 200 cells/µl). Multivariable logistic regression was used to assess factors associated with immunological non-response. RESULTS: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39-3.09), older age [40-49 years (vs. 18-29 years): 2.05, 1.29-3.25; 50-59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84-10.67], HBV co-infection (1.63, 1.14-2.34), HCV co-infection (2.01, 1.01-4.02), lower CD4 + T cell count [50-200 cells/µl (vs. 200-350 cells/µl): 40.20, 16.83-96.01; < 50 cells/µl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98-4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26-0.82). CONCLUSIONS: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor.

Influence of microbial inoculation site on trichloroethylene degradation in electrokinetic-enhanced bioremediation of low-permeability soils.

The integration of electrokinetic and bioremediation (EK-BIO) represents an innovative approach for addressing trichloroethylene (TCE) contamination in low-permeability soil. However, there remains a knowledge gap in the impact of the inoculation approach on TCE dechlorination and the microbial response with the presence of co-existing substances. In this study, four 1-dimensional columns were constructed with different inoculation treatments. Monitoring the operation conditions revealed that a stabilization period (∼40 days) was required to reduce voltage fluctuation. The group with inoculation into the soil middle (Group B) exhibited the highest TCE dechlorination efficiency, achieving a TCE removal rate of 84%, which was 1.1-3.2 fold higher compared to the others. Among degraded products in Group B, 39% was ethylene. The physicochemical properties of the post-soil at different regions illustrated that dechlorination coincided with the Fe(III) and SO42- reduction, meaning that the EK-BIO system promoted the formation of a reducing environment. Microbial community analysis demonstrated that Dehalococcoides was only detected in the treatment of injection at soil middle or near the cathode, with abundance enriched by 2.1%-7.2%. The principal components analysis indicated that the inoculation approach significantly affected the evolution of functional bacteria. Quantitative polymerase chain reaction (qPCR) analysis demonstrated that Group B exhibited at least 2.8 and 4.2-fold higher copies of functional genes (tceA, vcrA) than those of other groups. In conclusion, this study contributes to the development of effective strategies for enhancing TCE biodechlorination in the EK-BIO system, which is particularly beneficial for the remediation of low-permeability soils.

Complete degradation of di-n-butyl phthalate by Glutamicibacter sp. strain 0426 with a novel pathway.

Di-n-butyl phthalate (DBP) is widely used as plasticizer that has potential carcinogenic, teratogenic, and endocrine effects. In the present study, an efficient DBP-degrading bacterial strain 0426 was isolated and identified as a Glutamicibacter sp. strain 0426. It can utilize DBP as the sole source of carbon and energy and completely degraded 300 mg/L of DBP within 12 h. The optimal conditions (pH 6.9 and 31.7 °C) for DBP degradation were determined by response surface methodology and DBP degradation well fitted with the first-order kinetics. Bioaugmentation of contaminated soil with strain 0426 enhanced DBP (1 mg/g soil) degradation, indicating the application potential of strain 0426 for environment DBP removal. Strain 0426 harbors a distinctive DBP hydrolysis mechanism with two parallel benzoate metabolic pathways, which may account for the remarkable performance of DBP degradation. Sequences alignment has shown that an alpha/beta fold hydrolase (WP_083586847.1) contained a conserved catalytic triad and pentapeptide motif (GX1SX2G), of which function is similar to phthalic acid ester (PAEs) hydrolases and lipases that can efficiently catalyze hydrolysis of water-insoluble substrates. Furthermore, phthalic acid was converted to benzoate by decarboxylation, which entered into two different pathways: one is the protocatechuic acid pathway under the role of pca cluster, and the other is the catechol pathway. This study demonstrates a novel DBP degradation pathway, which broadens our understanding of the mechanisms of PAE biodegradation.

Long Noncoding RNAs in Response to Hyperosmolarity Stress, but Not Salt Stress, Were Mainly Enriched in the Rice Roots.

Due to their immobility and possession of underground parts, plants have evolved various mechanisms to endure and adapt to abiotic stresses such as extreme temperatures, drought, and salinity. However, the contribution of long noncoding RNAs (lncRNAs) to different abiotic stresses and distinct rice seedling parts remains largely uncharacterized beyond the protein-coding gene (PCG) layer. Using transcriptomics and bioinformatics methods, we systematically identified lncRNAs and characterized their expression patterns in the roots and shoots of wild type (WT) and ososca1.1 (reduced hyperosmolality-induced [Ca2+]i increase in rice) seedlings under hyperosmolarity and salt stresses. Here, 2937 candidate lncRNAs were identified in rice seedlings, with intergenic lncRNAs representing the largest category. Although the detectable sequence conservation of lncRNAs was low, we observed that lncRNAs had more orthologs within the Oryza. By comparing WT and ososca1.1, the transcription level of OsOSCA1.1-related lncRNAs in roots was greatly enhanced in the face of hyperosmolality stress. Regarding regulation mode, the co-expression network revealed connections between trans-regulated lncRNAs and their target PCGs related to OsOSCA1.1 and its mediation of hyperosmolality stress sensing. Interestingly, compared to PCGs, the expression of lncRNAs in roots was more sensitive to hyperosmolarity stress than to salt stress. Furthermore, OsOSCA1.1-related hyperosmolarity stress-responsive lncRNAs were enriched in roots, and their potential cis-regulated genes were associated with transcriptional regulation and signaling transduction. Not to be ignored, we identified a motif-conserved and hyperosmolarity stress-activated lncRNA gene (OSlncRNA), speculating on its origin and evolutionary history in Oryza. In summary, we provide a global perspective and a lncRNA resource to understand hyperosmolality stress sensing in rice roots, which helps to decode the complex molecular networks involved in plant sensing and adaptation to stressful environments.

Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice.

BACKGROUND: Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. RESULTS: The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). CONCLUSIONS: BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

A fully human connective tissue growth factor blocking monoclonal antibody ameliorates experimental rheumatoid arthritis through inhibiting angiogenesis.

BACKGROUND: Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology. RESULTS: A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis. CONCLUSION: The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF.

Alterations of gut microbiota are associated with blood pressure: a cross-sectional clinical trial in Northwestern China.

BACKGROUND: The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. METHODS: This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. RESULTS: GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P < 0.05). Functionally, ROC analysis revealed that Cellular Processes (0.796, 95% CI 0.620 ~ 0.916), Human Diseases (0.773, 95% CI 0.595 ~ 0.900), Signal transduction (0.806, 95% CI 0.631 ~ 0.922) and Two-component system (0.806, 95% CI 0.631 ~ 0.922) could differentiate HTN females as effective functional classifiers, which were also positively correlated with systolic blood pressure levels. CONCLUSIONS: This work provides evidence of fecal GM characteristics in HTN females and males in a northwestern Chinese population, further supporting the notion that GM dysbiosis may participate in the pathogenesis of HTN, and the role of sex differences should be considered. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019191. Registered 30 October 2018 - Retrospectively registered, http://www.chictr.org.cn/ .

Altered gut microbiota is associated with different immunologic responses to antiretroviral therapy in HIV-infected men who have sex with men.

The association between gut microbiota and immunologic nonresponse among people living with HIV (PLHIV) on antiretroviral therapy (ART) is not well documented. This study aimed to characterize gut microbiota among HIV-infected men who have sex with men (MSM) with different immunologic responses. We recruited HIV-infected MSM and HIV-uninfected MSM (healthy controls, HC) in Guangzhou, June-October 2021. HIV-infected MSM were grouped into good immunological responders (GIR) (CD4 + T cell count ≥ 350 cells/µL) and poor immunological responders (PIR) (<350 cells/µL). Blood and stool samples were collected. Microbial translocation in serum was performed using enzyme-linked immunosorbent assay (ELISA). Bacterial 16S ribosomal DNA sequencing was performed on stool samples, and microbial metabolites were obtained through gas chromatography-mass spectrometry. 56 GIR, 41 PIR, and 51 HC were included. Microbial translocation marker soluble cluster of differentiation 14 (sCD14) in both GIR and PIR groups was significantly higher than that in HC. Compared with PIR or HC groups, the genera of Coprococcus, Blautia, Clostridium, and SMB53 were decreased, whereas Megamonas and Megasphaera were more abundant in GIR group. Compared with GIR or PIR groups, Bifidobacterium, Collinsella, Faecalibacterium, Oscillospira, and Roseburia were more abundant, whereas Escherichia was decreased in HC group. The levels of benzenoids, imidazoles, phenylpropanoic acids, phenylpropanoids, and pyridines showed strongly significant correlations between differential genera. This study presented a comprehensive landscape of gut microbiota in PLHIV with different treatment outcomes. Megamonas, Coprococcus and Blautia were the major genera correlated with different immunologic responses in PLHIV.

Synthetic Nuclease-Producing Microbiome Achieves Efficient Removal of Extracellular Antibiotic Resistance Genes from Wastewater Effluent.

Antibiotic resistance gene (ARG) transmission poses significant threats to human health. The effluent of wastewater treatment plants is demonstrated as a hotspot source of ARGs released into the environment. In this study, a synthetic microbiome containing nuclease-producing Deinococcus radiodurans was constructed to remove extracellular ARGs. Results of quantitative polymerase chain reaction (qPCR) showed significant reduction in plasmid RP4-associated ARGs (by more than 3 orders of magnitude) and reduction of indigenous ARG sul1 and mobile genetic element (MGE) intl1 (by more than 1 order of magnitude) in the synthetic microbiome compared to the control without D. radiodurans. Metagenomic analysis revealed a decrease in ARG and MGE diversity in extracellular DNA (eDNA) of the treated group. Notably, whereas eight antibiotic-resistant plasmids with mobility risk were detected in the control, only one was detected in the synthetic microbiome. The abundance of the nuclease encoding gene exeM, quantified by qPCR, indicated its enrichment in the synthetic microbiome, which ensures stable eDNA degradation even when D. radiodurans decreased. Moreover, intracellular ARGs and MGEs and pathogenic ARG hosts in the river receiving treated effluent were lower than those in the river receiving untreated effluent. Overall, this study presents a new approach for removing extracellular ARGs and further reducing the risk of ARG transmission in receiving rivers.

Novel Sulfate Reduction Coupled to Simultaneous Nitrification and Autotrophic Denitrification Process for Removing Nitrogen and Organics from Saline Wastewater.

Highly efficient sulfate reduction coupled to autotrophic denitrification plus nitrification is demonstrated by integrating an anaerobic membrane bioreactor (AnMBR) with a membrane aerated biofilm reactor (MABR). Concurrent chemical oxygen demand (COD) removal and sulfate reduction were accomplished in the AnMBR, while simultaneous nitrification and autotrophic denitrification were carried out in the MABR. Separate operation of the MABR achieved >90% total nitrogen (TN) removal when the N/S ratio was controlled at 0.4 gN/gS. The integrated AnMBR-MABR system efficiently resisted influent variability, realizing >95% COD removal in the AnMBR and >75% TN removal in the MABR when the influent COD/N ratio was above 4 gCOD/gN. Membrane fouling did not happen during ∼170 days of operation. Due to sulfide oxidation, a large amount of elemental sulfur (S0) accumulated in the MABR biofilm, where it served as an electron donor for denitrification. Microbial community analysis indicated that Nitrospira and Thiobacillus played key roles in nitrification and sulfide-driven denitrification, respectively, and that they occurred in different layers of the biofilm. This novel process offers advantages of a small land-area footprint, modular operation, and high efficiency electron-donor and oxygen utilizations, particularly for wastewater with a low COD/N ratio.

pH-Dependent Hydrogenotrophic Denitratation Based on Self-Alkalization.

Producing stable nitrite is a necessity for anaerobic ammonium oxidation (anammox) but remains a huge challenge. Here, we describe the design and operation of a hydrogenotrophic denitratation system that stably reduced >90% nitrate to nitrite under self-alkaline conditions of pH up to 10.80. Manually lowering the pH to a range of 9.00-10.00 dramatically decreased the nitrate-to-nitrite transformation ratio to <20%, showing a significant role of high pH in denitratation. Metagenomics combined with metatranscriptomics indicated that six microorganisms, including a Thauera member, dominated the community and encoded the various genes responsible for hydrogen oxidation and the complete denitrification process. During denitratation at high pH, transcription of periplasmic genes napA, nirS, and nirK, whose products perform nitrate and nitrite reduction, decreased sharply compared to that under neutral conditions, while narG, encoding a membrane-associated nitrate reductase, remained transcriptionally active, as were genes involved in intracellular proton homeostasis. Together with no reduction in only nitrite-amended samples, these results disproved the electron competition between reductions of nitrate and nitrite but highlighted a lack of protons outside cells constraining biological nitrite reduction. Overall, our study presents a stably efficient strategy for nitrite production and provides a major advance in the understanding of denitratation.

Electrokinetic-Enhanced Bioremediation of Trichloroethylene-Contaminated Low-Permeability Soils: Mechanistic Insight from Spatio-Temporal Variations of Indigenous Microbial Community and Biodehalogenation Activity.

Electrokinetic-enhanced bioremediation (EK-Bio), particularly bioaugmentation with injection of biodehalogenation functional microbes such as Dehalococcoides, has been documented to be effective in treating a low-permeability subsurface matrix contaminated with chlorinated ethenes. However, the spatio-temporal variations of indigenous microbial community and biodehalogenation activity of the background matrix, a fundamental aspect for understanding EK-Bio, remain unclear. To fill this gap, we investigated the variation of trichloroethylene (TCE) biodehalogenation activity in response to indigenous microbial community succession in EK-Bio by both column and batch experiments. For a 195 day EK-Bio column (∼1 V/cm, electrolyte circulation, lactate addition), biodehalogenation activity occurred first near the cathode (<60 days) and then spread to the anode (>90 days), which was controlled by electron acceptor (i.e., Fe(III)) competition and microbe succession. Amplicon sequencing and metagenome analysis revealed that iron-reducing bacteria (Geobacter, Anaeromyxobacter, Geothrix) were enriched within initial 60 d and were gradually replaced by organohalide-respiring bacteria (versatile Geobacter and obligate Dehalobacter) afterward. Iron-reducing bacteria required an initial long time to consume the competitive electron acceptors so that an appropriate reductive condition could be developed for the enrichment of organohalide-respiring bacteria and the enhancement of TCE biodehalogenation activity.

Bioelectrochemical system accelerates reductive dechlorination through extracellular electron transfer networks.

Bioelectrochemical system is considered as a promising approach for enhanced bio-dechlorination. However, the mechanism of extracellular electron transfer in the dechlorinating consortium is still a controversial issue. In this study, bioelectrochemical systems were established with cathode potential settings at -0.30 V (vs. SHE) for trichloroethylene reduction. The average dechlorination rate (102.0 µM Cl·d-1) of biocathode was 1.36 times higher than that of open circuit (74.7 µM Cl·d-1). Electrochemical characterization via cyclic voltammetry illustrated that electrostimulation promoted electrochemical activity for redox reactions. Moreover, bacterial community structure analyses indicated electrical stimulation facilitated the enrichment of electroactive and dechlorinating populations on cathode. Metagenomic and quantitative polymerase chain reaction (qPCR) analyses revealed that direct electron transfer (via electrically conductive pili, multi-heme c-type cytochromes) between Axonexus and Desulfovibrio/cathode and indirect electron transfer (via riboflavin) for Dehalococcoides enhanced dechlorination process in BES. Overall, this study verifies the effectiveness of electrostimulated bio-dechlorination and provides novel insights into the mechanisms of dechlorination process enhancement in bioelectrochemical systems through electron transfer networks.

Heterotrophic denitrification: An overlooked factor that contributes to nitrogen removal in n-DAMO mixed culture.

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) has been recognized as a sustainable process for simultaneous removal of nitrogen and methane. The metabolisms of denitrifying anaerobic methanotrophs, including Candidatus Methanoperedens and Candidatus Methylomirabilis, have been well studied. However, potential roles of heterotrophs co-existing with these anaerobic methanotrophs are generally overlooked. In this study, we pulse-fed methane and nitrate into an anaerobic laboratory sequencing batch bioreactor and enriched a mixed culture with stable nitrate removal rate (NRR) of ∼28 mg NO3--N L-1 d-1. Microbial community analysis indicates abundant heterotrophs, e.g., Arenimonas (5.3%-18.9%) and Fimbriimonadales ATM1 (6.4%), were enriched together with denitrifying anaerobic methanotrophs Ca. Methanoperedens (10.8%-13.2%) and Ca. Methylomirabilis (27.4%-34.3%). The results of metagenomics and batch tests suggested that the denitrifying anaerobic methanotrophs were capable of generating methane-derived intermediates (i.e., formate and acetate), which were employed by non-methanotrophic heterotrophs for denitrification and biomass growth. These findings offer new insights into the roles of heterotrophs in n-DAMO mixed culture, which may help to optimize n-DAMO process for nitrogen removal from wastewater.

Auxin apical dominance governed by the OsAsp1-OsTIF1 complex determines distinctive rice caryopses development on different branches.

In rice (Oryza sativa), caryopses located on proximal secondary branches (CSBs) have smaller grain size and poorer grain filling than those located on apical primary branches (CPBs), greatly limiting grain yield. However, the molecular mechanism responsible for developmental differences between CPBs and CSBs remains elusive. In this transcriptome-wide expression study, we identified the gene Aspartic Protease 1 (OsAsp1), which reaches an earlier and higher transcriptional peak in CPBs than in CSBs after pollination. Disruption of OsAsp1 expression in the heterozygous T-DNA line asp1-1+/-eliminated developmental differences between CPBs and CSBs. OsAsp1 negatively regulated the transcriptional inhibitor of auxin biosynthesis, OsTAA1 transcriptional inhibition factor 1 (OsTIF1), to preserve indole-3-acetic acid (IAA) apical dominance in CPBs and CSBs. IAA also facilitated OsTIF1 translocation from the endoplasmic reticulum (ER) to the nucleus by releasing the interaction of OsTIF1 with OsAsp1 to regulate caryopses IAA levels via a feedback loop. IAA promoted transcription of OsAsp1 through MADS29 to maintain an OsAsp1 differential between CPBs and CSBs during pollination. Together, these findings provide a mechanistic explanation for the distributed auxin differential between CPBs and CSBs to regulate distinct caryopses development in different rice branches and potential targets for engineering yield improvement in crops.

Sexual risk behaviours among factory workers in Shenzhen, China: a cross-sectional study.

BACKGROUND: Factory workers are a key population for HIV transmission in China, as they often engage in sexual risk behaviours. This study aims to evaluate sexual risk behaviours and associated factors among factory workers in Shenzhen, China. METHODS: A cross-sectional study was conducted by using multi-stage stratified cluster random sampling. Full-time workers aged ≥18years were eligible to participate in the study. A self-administered questionnaire was used to collect information. Univariate and multivariable logistic regression were applied to assess factors associated with sexual risk behaviours. RESULTS: A total of 2029 factory workers were included. Mean age was 37.2 (±4.4)years; 48.5% were men. Two-thirds (64.9%) had had vaginal intercourse. Their sexual risk behaviours included condomless sex with casual partners in the last sex episode (23.6%), multiple sex partners (11.5%) and engaging in commercial sex (8.4%), in the past year. Having HIV/AIDS knowledge (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.24-0.70) and using a condom at sexual debut (AOR 0.08, 95% CI 0.05-0.13) were factors associated with condomless sex with casual partners in the last sex episode. Males (AOR 3.03, 95% CI 1.96-4.69 and AOR 2.19, 95% CI 1.33-3.60), local workers (AOR 2.11, 95% CI 1.01-4.42 and AOR 3.42, 95% CI 1.63-7.21), being single (AOR 2.04, 95% CI 1.39-3.01 and AOR 2.49, 95% CI 1.61-3.87), having sexual debut aged Conclusions : Sexual risk behaviours were prevalent despite most participants having basic HIV/AIDS knowledge. Future workplace-based prevention programs should target factory workers and there should be a focus on enhanced sexual education to reduce HIV transmission in China.

Transcriptome Screening of Long Noncoding RNAs and Their Target Protein-Coding Genes Unmasks a Dynamic Portrait of Seed Coat Coloration Associated with Anthocyanins in Tibetan Hulless Barley.

Many plants have the capability to accumulate anthocyanins for coloration, and anthocyanins are advantageous to human health. In the case of hulless barley (Hordeum vulgare L. var. nudum), investigation into the mechanism of anthocyanin formation is limited to the level of protein-coding genes (PCGs). Here, we conducted a comprehensive bioinformatics analysis to identify a total of 9414 long noncoding RNAs (lncRNAs) in the seed coats of purple and white hulless barley along a developmental gradient. Transcriptome-wide profiles of lncRNAs documented several properties, including GC content fluctuation, uneven length, a diverse range of exon numbers, and a wide variety of transcript classifications. We found that certain lncRNAs in hulless barley possess detectable sequence conservation with Hordeum vulgare and other monocots. Furthermore, both differentially expressed lncRNAs (DElncRNAs) and PCGs (DEPCGs) were concentrated in the later seed development stages. On the one hand, DElncRNAs could potentially cis-regulate DEPCGs associated with multiple metabolic pathways, including flavonoid and anthocyanin biosynthesis in the late milk and soft dough stages. On the other hand, there was an opportunity for trans-regulated lncRNAs in the color-forming module to affect seed coat color by upregulating PCGs in the anthocyanin pathway. In addition, the interweaving of hulless barley lncRNAs and diverse TFs may function in seed coat coloration. Notably, we depicted a dynamic portrait of the anthocyanin synthesis pathway containing hulless barley lncRNAs. Therefore, this work provides valuable gene resources and more insights into the molecular mechanisms underlying anthocyanin accumulation in hulless barley from the perspective of lncRNAs, which facilitate the development of molecular design breeding in crops.

Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF-κB/C-myc.

There is evidence that coinfection of cervicovaginal high-risk human papillomavirus (HR-HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR-HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR-HPV infection in women aged 20-45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20-45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR-HPV genotyping and cervical cytology were performed at each follow-up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C-myc, TLR4, NF-κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR-HPV infection and high-grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF-κB, C-myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR-HPV infection-related cervical lesions through host NF-κB and C-myc signaling.