Relevance between age of onset and hospitalization characteristics of Major Depressive Disorders: A 16 years retrospective cohort study.

BACKGROUND: Age of onset (AOO) influences the prognosis of many diseases and even serves as potential driver. But in Major Depressive Disorder, there is no consensus regarding the effect of AOO on the course. METHODS: In this study, a total of 38,671 inpatients were surveyed over 16 years, and 6113 inpatients were eventually included in the statistical analysis after applying rigorous data criteria. Inpatients were divided into four AOO subgroups: adolescent onset, early adult onset, middle adult onset, and late adult onset. RESULTS: In the subset of first hospitalization (n = 4884), the differences in the length of stay between several AOO subgroups were statistically significant (F = 56.852, df1 = 3, df2 = 4880, P < 0.001, ω2 = 0.033). Similarly, this difference was also significant in the subset of relapse hospitalization (n = 1229, F = 5.985, df1 = 3, df2 = 1225, P < 0.001, ω2 = 0.012). The Bonferroni post hoc test suggested a longer length of stay in the adolescent onset group (P < 0.001). Besides, in the adolescent onset subgroup, the proportion with 2 or more relapses hospitalization within one year was higher than those without relapses (6.7 % Vs 2.7 %, χ2 = 12.685, df = 6, P < 0.001). Logistic regression suggests that patients with adolescent onset are at higher risk for 2 or more relapses hospitalization within one year (B = 0.881, OR = 2.41, 95 % CI 1.37-4.23, P = 0.002). LIMITATIONS: Retrospective design may have recall bias. CONCLUSIONS: This is the first large sample size study to examine age at onset and risk of relapse at the individual level in a Chinese population. Our study found that adolescent onset is more susceptible to the chronicity of MDD. These findings will contribute to the accurate typing of MDD, as well as customized individualized prevention and treatment options.

The effect of broad bean diet on structure, flavor and taste of fresh grass carp: A comprehensive study using E-nose, E-tongue, TPA, HS-SPME-GC-MS and LC-MS.

Broad bean (Vicia faba L.) has received particular attention with regards to the improvement of flesh meat quality. However, the effect of broad bean diet on structure, flavor and taste of flesh meat is unclear. In present study, E-nose, E-tongue, TPA, HS-SPME-GC-MS, and LC-MS were used to characterize the structure, flavor and taste of grass carp (Ctenopharyngodon idellus) fed with broad bean. Overall, broad bean significantly improved the texture of grass carp muscle, but reduced the overall taste and flavor. The 50 volatile compounds were detected using HS-SPME-GC-MS. The 252 differential metabolites were identified by LC-MS, of which 107 were up-regulated and 145 were down-regulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated this reduction in taste and flavor was associated with the metabolism of amino acids, lipids and nucleotides. Our findings provide a theoretical basis for improving meat quality and the functional applications of broad bean.

Community assembly patterns and processes of bacteria in a field-scale aquaculture wastewater treatment system.

Microbial communities are responsible for the biological treatment of wastewater, however, our comprehension of their diversity, assembly patterns, and functions remains limited. In this study, we analyzed bacterial communities in both water and sediment samples. These samples were gathered from a novel field-scale aquaculture wastewater treatment system (FAWTS), which employs a multi-stage purification process to eliminate nutrients from pond culture wastewater. Significant variations were observed in bacterial diversity and composition across various ponds within the system and at different stages of the culture. Notably, the bacterial community in the FAWTS displayed a distinct species abundance distribution. The influence of dispersal-driven processes on shaping FAWTS communities was found to be relatively weak. The utilization of neutral and null models unveiled that the assembly of microbial communities was primarily governed by stochastic processes. Moreover, environmental factors variables such as total nitrogen (TN), dissolved oxygen (DO), and temperature were found to be associated with both the composition and assembly of bacterial communities, influencing the relative significance of stochastic processes. Furthermore, we discovered a close relationship between that bacterial community composition and system functionality. These findings hold significant implications for microbial ecologists and environmental engineers, as they can collaboratively refine operational strategies while preserving biodiversity. This, in turn, promotes the stability and efficiency of the FAWTS. In summary, our study contributes to an enhanced mechanistic understanding of microbial community diversity, assembly patterns, and functionality within the FAWTS, offering valuable insights into both microbial ecology and wastewater treatment processes.

Short-term effects of PM2.5 and its components exposure on endothelial function in Chinese elders.

Particulate matter (PM2.5) and its components have been studied widely around the world and are associated with many adverse health events (e.g. cardiovascular diseases and death). Flow-mediated dilation (FMD) is a non-invasive assessment that is able to detect endothelial damage at an early stage, therefore, improving the prognosis of atherosclerotic cardiovascular disease. The current study used data from Shanghai to explore the relationship between PM2.5 and its components and FMD using multiple statistical models. The results of the analysis of 812 patients' data (age ≥ 65) suggested that as PM2.5 level rises, endothelial function reduces. Among the five PM2.5 components included in this study, black carbon was shown by both models to be the dominating factor three days post-exposure (lag3). However, results from lag4 and lag5 were inconclusive in the two models with some evidence proposing the significance of sulphate, organic matter, and ammonium. Our results are in concordance with previous literature and further prove the significance of black carbon as an individual pollutant in the atmosphere. More research is needed to confirm the role of sulphate, organic matter, and ammonium as independent pollutants in relation to health.

Interpretable ensemble prediction for anaerobic digestion performance of hydrothermal carbonization wastewater.

Hydrothermal carbonization (HTC) is a method to improve fuel quality that can directly treat wet solid waste, but the treatment produces large amounts of wastewater. Hydrothermal carbonation wastewater treatment for methane production by anaerobic digestion can lead to waste utilization and energy saving. However, anaerobic digestion performance prediction of HTC wastewater is challenging due to the complexity of influencing factors. This study applies interpretable machine learning combined with ensemble learning to construct ensemble prediction models for the biogas yield and CH4 concentration. The machine learning ensemble model can integrate the advantages of single models and effectively improve the prediction accuracy of the anaerobic digestion performance of HTC wastewater, with the best R2 reaching 0.836 and 0.820, respectively, which is better than 0.780 and 0.802 of the best single models. The SHapley Additive exPlanations theory is combined with the ensemble models to show that anaerobic digestion reacted time with HTC temperature, pH, and COD has a coupling effect on daily biogas yield and CH4 concentration.

Modulating in vitro gastrointestinal digestion of nanocellulose-stabilized pickering emulsions by altering particle surface charge.

An in vitro model of human gastrointestinal digestion was introduced to investigate the effects of surface charge of cellulose nanoparticles on emulsion structure during gastric phase, lipase activity, bile salt diffusion, and free fatty acid (FFA) release. Four carboxymethylated cellulose nanofibrils (CNF; C0, C0.36, C0.72, and C1.24) were used, showing different surface charge (p < 0.05). First, four carboxymethylated CNFs had no inhibition effects on lipase activity and bile salt diffusion. Moreover, we found that the lipid emulsion containing CNF formed gel structure to induce oil droplets aggregation during simulated gastric phase. Additionally, the particle surface charge greatly influenced the gel structure of emulsion where a denser gel structure was observed in the C0 (lowest surface charged CNF) stabilized emulsion. Finally, the released FFA results showed that the formed gel structure lowered the lipid emulsion digestion attributed to the restricted adherent area of oil droplets for lipase and bile salt.

Wedelolactone alleviates cholestatic liver injury by regulating FXR-bile acid-NF-κB/NRF2 axis to reduce bile acid accumulation and its subsequent inflammation and oxidative stress.

BACKGROUND: Cholestatic liver diseases (CLD) comprise a variety of disorders of bile formation, which causes chronic exposure to bile acid (BA) in the liver generally and results in hepatotoxicity and progressive hepatobiliary injury. Wedelolactone (7-methoxy-5, 11, 12-trihydroxy-coumestan, WED), the natural active compound derived from Ecliptae Herba, has been reported with valuable bioactivity for liver protection. Nevertheless, the effect of WED on cholestatic liver injury (CLI) remains unexplored. PURPOSE: The present study aims to elucidate the protective effect of WED on Alpha-naphthylisothiocyanate (ANIT)-induced CLI mice, and to investigate its potential pharmacological mechanism. METHODS: The anit-cholestatic and hepatoprotective effects of WED were evaluated in ANIT-induced CLI mice. Non-targeted metabolomics study combined with ingenuity pathway analysis (IPA) was used to explore the key mechanism of WED. The BA metabolic profile in enterohepatic circulation was analyzed to evaluate the effect of WED in regulating BA metabolism. Furthermore, molecular dynamics (MD) simulation and cellular thermal shift assay (CETSA) were used to simulate and verify the targeting activation of WED on the Farnesoid X receptor (FXR). The core role of FXR in WED promoting BA transportation, and alleviating BA accumulation-induced hepatotoxicity was further evaluated in WT and FXR knockout mice or hepatocytes. RESULTS: WED dose-dependently alleviated ANIT-induced cholestasis and liver injury in mice, and simultaneously suppressed the signaling pathway of nuclear factor-kappa B/nuclear factor-erythroid 2-related factor 2 (NF-κB/NRF2) to relieve inflammation and oxidative stress. At the metabolite level, WED improved the metabolic disorder in CLI mice focusing on the metabolism of BA, arachidonic acid, and glycerophospholipid, that closely related to the process of BA regulation, inflammation, and oxidative damage. WED targeting activated FXR, which then transcribed its target genes, including the bile salt export pump (BSEP) and the BA transporter, and subsequently increased BA transportation to restore the damaged enterohepatic circulation of BA. Meanwhile, WED alleviated hepatic BA accumulation and protected the liver from BA-induced damage via NF-κB/NRF2 signaling pathway. Furthermore, FXR deficiency suppressed the protective effect of WED in vitro and in vivo. CONCLUSION: WED regulated BA metabolism and alleviated hepatic damage in cholestasis. It protected the liver according to adjusted BA transportation and relieved BA accumulation-related hepatotoxicity via FXR-bile acid-NF-κB/NRF2 axis. Our study provides novel insights that WED might be a promising strategy for cholestatic liver disease.

Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy.

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory, resistant to antiepileptic drugs, and has a high recurrence rate. The pathogenesis of temporal lobe epilepsy is complex and is not fully understood. Intracellular calcium dynamics have been implicated in temporal lobe epilepsy. However, the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown, and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice. In this study, we used a multi-channel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process. We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes. In particular, cortical spreading depression, which has recently been frequently used to represent the continuously and substantially increased calcium signals, was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from grade II to grade V. However, vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures. Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to grade I episodes. In addition, the latency of cortical spreading depression was prolonged, and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced. Intriguingly, it was possible to rescue the altered intracellular calcium dynamics. Via simultaneous analysis of calcium signals and epileptic behaviors, we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced, and that the end-point behaviors of temporal lobe epilepsy were improved. Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades. Furthermore, the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy, thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Unveiling the hypoxia-induced mitophagy process through two-channel real-time imaging of NTR and viscosity under the same excitation.

Mitophagy is an essential physiological process that eliminates damaged mitochondria via lysosomes. It is reported that hypoxia, inflammatory stimuli or other stress conditions could lead to mitochondrial damage and mitochondrial dysfunction, which induces the process of mitophagy. Herein, we report a novel fluorescent probe PC-NTR for imaging hypoxia-induced mitophagy by monitoring the change of nitroreductase and viscosity simultaneously. To our delight, PC-NTR could respond simultaneously to nitroreductase and viscosity at different fluorescence channels with no mutual interference under the same excitation wavelength. The fluorescence emission around 535 nm was enhanced dramatically after addition of nitroreductase while the fluorescence emission around 635 nm heightened as the viscosity increased. The probe would be able to selectively targeting of mitochondria in cells because of the positively charged pyridine salt structure of PC-NTR. The probe was successfully applied to assess the different levels of hypoxia and real-time imaging of mitochondrial autophagy in live cells. More importantly, using dual channel imaging, PC-NTR could be used to distinguish cancer cells from normal cells and was successfully applied to imaging experiments in HeLa-derived tumor-bearing nude mice. Therefore, PC-NTR would be an important molecular tool for hypoxia imaging and detecting solid tumors in vivo.

Identification of a novel endocytosis­associated gene signature for prognostic prediction in lung adenocarcinoma.

Lung cancer is one of the most common malignant solid tumors and the leading cause of cancer-associated mortality worldwide. Endocytosis is an essential physiological activity for cells to maintain membrane homeostasis, and has been reported to serve an important role in tumorigenesis and progression. In the present study, the aim was to construct a prognostic prediction model of endocytosis-associated genes for patients with lung adenocarcinoma (LUAD). The endocytosis-associated gene signature was established using Lasso Cox regression analysis using the training set of the LUAD cohort from The Cancer Genome Atlas (TCGA) database, and verified using two datasets from the Gene Expression Omnibus (GEO) database. Kaplan-Meier survival curves were used to evaluate the effectiveness of the prognostic evaluation of patients with LUAD. Differentially expressed genes were screened in the tumor tissue of patients compared with paired paracancerous tissues. A series of candidate genes associated to the prognosis of patients with LUAD was obtained using univariate Cox's regression analysis. Using the Lasso Cox regression analysis, an appropriate risk model with 18 endocytosis-associated genes was established. A high-risk score was positively correlated with a higher tumor stage and pathologic grade. Patients with LUAD and high-risk scores had shorter survival times, increased intratumor heterogeneities and immune cell infiltration into tumor tissues, compared with those patients with LUAD and low-risk scores. The endocytosis inhibitor chloroquine could repress proliferation and increase the apoptosis of lung cancer cells. In summary, a novel endocytosis-associated gene signature was constructed using TCGA and GEO datasets. Patients with LUAD and high-risk scores, as calculated by the signature, had a poor prognosis and short survival time.

Association between dietary total choline and abdominal aorta calcification among older US adults: A cross-sectional study of the National Health and Nutrition Examination Survey.

BACKGROUND: Numerous studies indicate a potential bidirectional association between dietary choline intake and its derivative, betaine, and subclinical atherosclerosis. However, little research has been conducted on the relationship between dietary choline and severe abdominal aortic calcification (SAAC). METHODS: This cross-sectional study analyzed population-based data from the National Health and Nutrition Examination Survey (NHANES; 2013-2014). Choline intake and food sources were measured using two 24-hour dietary recall interviews. The abdominal aortic calcification score was measured using a Dual-emission X-ray Absorptiometry (DXA) scan. To assess the relationship between choline intake and SAAC, the study utilized restricted cubic spline (RCS) and a multivariable logistic regression model. RESULTS: Among the 2,640 individuals included in the study, 10.9% had SAAC. After adjusting for all selected covariates, compared to the lowest quartile of dietary choline, the odds ratio of SAAC for the second, third, fourth quartile dietary choline intake were 0.63 (95% CI: 0.43~0.93), 0.63(95% CI: 0.42~0.94) and 0.77(95% CI: 0.5~1.16). The study found an L-shaped relationship between dietary choline and SAAC in the dose-response analysis. Subgroup analyses did not demonstrate any statistically significant interaction effects for any subgroup. CONCLUSION: The study found that a higher intake of dietary choline is associated with a lower prevalence of SAAC. The dose-response analysis revealed an L-shaped relationship between dietary choline and SAAC. However, further studies are warranted to investigate the direct role of choline in the development of SAAC. This article is protected by copyright. All rights reserved.

Neural network mapping of gelastic behavior in children with hypothalamus hamartoma.

BACKGROUND: Hypothalamus hamartomas (HHs) are rare, congenital, tumor-like, and nonprogressive malformations resulting in drug-resistant epilepsy, mainly affecting children. Gelastic seizures (GS) are an early hallmark of epilepsy with HH. The aim of this study was to explore the disease progression and the underlying physiopathological mechanisms of pathological laughter in HH. METHODS: We obtained clinical information and metabolic images of 56 HH patients and utilized ictal semiology evaluation to stratify the specimens into GS-only, GS-plus, and no-GS subgroups and then applied contrasted trajectories inference (cTI) to calculate the pseudotime value and evaluate GS progression. Ordinal logistic regression was performed to identify neuroimaging-clinical predictors of GS, and then voxelwise lesion network-symptom mapping (LNSM) was applied to explore GS-associated brain regions. RESULTS: cTI inferred the specific metabolism trajectories of GS progression and revealed increased complexity from GS to other seizure types. This was further validated via actual disease duration (Pearson R = 0.532, P = 0.028). Male sex [odds ratio (OR) = 2.611, P = 0.013], low age at seizure onset (OR = 0.361, P = 0.005), high normalized HH metabolism (OR = - 1.971, P = 0.037) and severe seizure burden (OR = - 0.006, P = 0.032) were significant neuroimaging clinical predictors. LNSM revealed that the dysfunctional cortico-subcortico-cerebellar network of GS and the somatosensory cortex (S1) represented a negative correlation. CONCLUSIONS: This study sheds light on the clinical characteristics and progression of GS in children with HH. We identified distinct subtypes of GS and demonstrated the involvement of specific brain regions at the cortical-subcortical-cerebellar level. These valuable results contribute to our understanding of the neural correlates of GS.

Chemical stress in a largely deformed electrode: Effects of trapping lithium.

Lithium trapping, which is associated with the immobilization of lithium and is one of key factors contributing to structural degradation of lithium-ion batteries during electrochemical cycling, can exacerbate mechanical stress and ultimately cause the capacity loss and battery failure. Currently, there are few studies focusing on how lithium trapping contributes to mechanical stress during electrochemical cycling. This study incorporates the contribution of lithium trapping in the analysis of mechanical stress and mass transport in the framework of finite deformation. Two de-lithiation scenarios are analyzed: one with a constant concentration of trapped lithium and the other with inhomogeneous distribution of trapped lithium. The results show that the constant concentration of trapped lithium increases chemical stress and the inhomogeneous distribution of trapped lithium causes the decrease of chemical stress. The findings can serve as a basis for developing effective strategies to mitigate the lithium trapping and improve the battery performance.

A Dual-Polythiophene Blending Strategy to Reduce the Efficiency-Stability-Cost Gap of Solar Cells.

Benefiting from the photovoltaic material innovation and delicate device optimization, high-efficiency solar cells employing polymeric materials are thriving. Reducing the gap of cost, efficiency, and stability is the critical challenge faced by the emerging solar cells such as organics, quantum dots and perovskites. Poly(3-alkylthiophene) demonstrates great potential in organic solar cells and quantum dot solar cells as the active layer or the hole transport layer due to its large scalability, excellent photoelectric performance, and favorable hydrophobicity. The present low efficiency and insufficient stability, restrict its commercial application. In this work, a facile strategy of blending two simple polythiophenes is put forward to manipulate the film microstructure and enhance the device efficiency and thermal stability of solar cells. The introduction of P3PT can improve the power conversion efficiency (PCE) of a benchmark cost-effective blend P3HT:O-IDTBR to 7.41%, and the developed ternary solar cells also exhibit increased thermal stability. More strikingly, the quantum dot solar cells with the dual-polythiophene hole transport layer achieve the highest PCE of 10.51%, which is among the topmost efficiencies for quantum dots/polythiophene solar cells. Together, this work provides an effective route to simultaneously optimize the device efficiency and thermal stability of solar cells.

Cyanobacterial extracellular antibacterial substances could promote the spread of antibiotic resistance: impacts and reasons.

Many studies have shown that antibiotic resistance genes (ARGs) can be facilitated by a variety of antibacterial substances. Cyanobacteria are photosynthetic bacteria that are widely distributed in the ocean. Some extracellular substances produced by marine cyanobacteria have been found to possess antibacterial activity. However, the impact of these extracellular substances on ARGs is unclear. Therefore, we established groups of seawater microcosms that contained different concentrations (1000, 100, 10, 1, 0.1, 0.01, and 0 µg mL-1) of cyanobacterial extracellular substances (CES), and tracked the changes of 17 types of ARGs, the integron gene (intI1), as well as the bacterial community at different time points. The results showed that CES could enrich most ARGs (15/17) in the initial stage, particularly at low concentrations (10 and 100 µg mL-1). The correlation analysis showed a positive correlation between several ARGs and intI1. It is suggested that the abundance of intI1 increased with CES may contribute to the changes of these ARGs, and co-resistance of CES may be the underlying reason for the similar variation pattern of some ARGs. Moreover, the results of qPCR and high-throughput sequencing of 16S rRNA showed that CES had an inhibitory impact on the growth of bacterial communities. High concentrations of CES were found to alter the structure of bacterial communities. Co-occurrence networks showed that bacteria elevated in the high concentration group of CES and might serve as the potential hosts for a variety of ARGs. In general, marine cyanobacteria could play an important role in the global dissemination of ARGs and antibiotic-resistant bacteria (ARBs).

Epigenetic Aging is Associated with Measures of Midlife Muscle Volume and Attenuation in CARDIA Study.

BACKGROUND: GrimAge acceleration (GAA), an epigenetic marker that represents physiologic aging, is associated with age-related diseases including cancer and cardiovascular diseases. However, the associations between GAA and muscle mass and function are unknown. METHODS: We estimated measures of GAA in 1118 Black and White participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Study at exam years (Y) 15 (2000-01) and 20 (2005-06). Abdominal muscle composition was measured using CT scans at the year 25 (2010-11) visit. We used multivariate regression models to examine associations of GAA estimates with muscle imaging measurements. RESULTS: In the CARDIA study, each one-year higher GAA was associated with an average 1.1% (95% CI 0.6%, 1.5%) higher intermuscular adipose tissue [IMAT] volume for abdominal muscles. Each one-year higher GAA was associated with an average -0.089 Hounsfield unit (HU) (95% CI -0.146, -0.032) lower lean muscle attenuation and an average -0.049 HU (95% CI -0.092, -0.007) lower IMAT attenuation for abdominal muscles. Stratified analyses showed that GAA was more strongly associated with higher abdominal muscle IMAT volume in females and significantly associated with lower lean muscle attenuation for White participants only. CONCLUSIONS: Higher GAA is associated with higher abdominal muscle IMAT volume and lower lean muscle attenuation in a midlife population.

In situ label-free X-ray imaging for visualizing the localization of nanomedicines and subcellular architecture in intact single cells.

Understanding the intracellular behaviors of nanomedicines and morphology variation of subcellular architecture impacted by nanomaterial-biology (nano-bio) interactions could help guide the safe-by-design, manufacturing and evaluation of nanomedicines for clinical translation. The in situ and label-free analysis of nano-bio interactions in intact single cells at nanoscale remains challenging. We developed an approach based on X-ray microscopy to directly visualize the 2D or 3D intracellular distribution without labeling at nanometer resolution and analyze the chemical transformation of nanomedicines in situ. Here, we describe an optimized workflow for cell sample preparation, beamline selection, data acquisition and analysis. With several model bionanomaterials as examples, we analyze the localization of nanomedicines in various primary blood cells, macrophages, dendritic cells, monocytes and cancer cells, as well as the morphology of some organelles with soft and hard X-rays. Our protocol has been successfully implemented at three beamline facilities: 4W1A of Beijing Synchrotron Radiation Facility, BL08U1A of Shanghai Synchrotron Radiation Facility and BL07W of the National Synchrotron Radiation Laboratory. This protocol can be completed in ~2-5 d, depending on the cell types, their incubation times with nanomaterials and the selected X-ray beamline. The protocol enables the in situ analysis of the varieties of metal-containing nanomaterials, visualization of intracellular endocytosis, distribution and excretion and corresponding subcellular morphological variation influenced by nanomedicines in cell lines or primary cells by using this universal and robust platform. The results facilitate the understanding of the true principle and mechanism underlying the nano-bio interaction.

An early prediction model for type 2 diabetes mellitus based on genetic variants and nongenetic risk factors in a Han Chinese cohort.

Aims: We aimed to construct a prediction model of type 2 diabetes mellitus (T2DM) in a Han Chinese cohort using a genetic risk score (GRS) and a nongenetic risk score (NGRS). Methods: A total of 297 Han Chinese subjects who were free from type 2 diabetes mellitus were selected from the Tianjin Medical University Chronic Disease Cohort for a prospective cohort study. Clinical characteristics were collected at baseline and subsequently tracked for a duration of 9 years. Genome-wide association studies (GWASs) were performed for T2DM-related phenotypes. The GRS was constructed using 13 T2DM-related quantitative trait single nucleotide polymorphisms (SNPs) loci derived from GWASs, and NGRS was calculated from 4 biochemical indicators of independent risk that screened by multifactorial Cox regressions. Results: We found that HOMA-IR, uric acid, and low HDL were independent risk factors for T2DM (HR >1; P<0.05), and the NGRS model was created using these three nongenetic risk factors, with an area under the ROC curve (AUC) of 0.678; high fasting glucose (FPG >5 mmol/L) was a key risk factor for T2DM (HR = 7.174, P< 0.001), and its addition to the NGRS model caused a significant improvement in AUC (from 0.678 to 0.764). By adding 13 SNPs associated with T2DM to the GRS prediction model, the AUC increased to 0.892. The final combined prediction model was created by taking the arithmetic sum of the two models, which had an AUC of 0.908, a sensitivity of 0.845, and a specificity of 0.839. Conclusions: We constructed a comprehensive prediction model for type 2 diabetes out of a Han Chinese cohort. Along with independent risk factors, GRS is a crucial element to predicting the risk of type 2 diabetes mellitus.

PRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex.

The HIV-1 Tat protein hijacks the Super Elongation Complex (SEC) to stimulate viral transcription and replication. However, the mechanisms underlying Tat activation and inactivation, which mediate HIV-1 productive and latent infection, respectively, remain incompletely understood. Here, through a targeted complementary DNA (cDNA) expression screening, we identify PRMT2 as a key suppressor of Tat activation, thus contributing to proviral latency in multiple cell line latency models and in HIV-1-infected patient CD4+ T cells. Our data reveal that the transcriptional activity of Tat is oppositely regulated by NPM1-mediated nucleolar retention and AFF4-induced phase separation in the nucleoplasm. PRMT2 preferentially methylates Tat arginine 52 (R52) to reinforce its nucleolar sequestration while simultaneously counteracting its incorporation into the SEC droplets, thereby leading to its functional inactivation to promote proviral latency. Thus, our studies unveil a central and unappreciated role for Tat methylation by PRMT2 in connecting its subnuclear distribution, liquid droplet formation, and transactivating function, which could be therapeutically targeted to eradicate latent viral reservoirs.

Investigation of the antimicrobial susceptibility patterns of marine cyanobacteria in Bohai Bay: Cyanobacteria may be important hosts of antibiotic resistance genes in marine environment.

Marine cyanobacteria, as widely distributed and photosynthetically autotrophic bacteria in the ocean, may contribute to the global dissemination of antibiotic resistance genes (ARGs) and develop a different antimicrobial susceptibility pattern from heterotrophic bacteria and cyanobacteria from freshwater environments. However, studies on antimicrobial susceptibility and the carriage of ARGs in marine cyanobacteria are still very limited. In this study, the antibiotic resistance characteristics of cyanobacteria in nearshore waters were examined through field monitoring and laboratory investigations, which included PCR detection and ARG transformation. The results showed a positive correlation between marine cyanobacteria and some ARGs in the nearshore waters of Bohai Bay. Moreover, most screened cyanobacteria showed high minimum inhibitory concentration (MIC) values for polymyxins, tetracyclines, kanamycin, and sulfonamides, moderate MIC values for streptomycin, chloramphenicol, rifampicin, and norfloxacin, and low MIC values for roxithromycin and cephalosporins. The blaTEM, blaKPC, sul1, sul2, strA, tetA, tetB, tetC, tetM, mdfA, and intI1 genes were detected in the screened marine cyanobacteria. The highest detection rates were observed for blaTEM (93.3 %), sul1 (56.6 %), sul2 (90 %), and strA (73.3 %). The detection rate of tetA (33.3 %) was the highest among the tetracycline resistance genes, and mdfA, a multidrug-resistant pump gene with resistance to tetracycline, also showed a high detection level (23.3 %). Overall, most of the screened marine cyanobacteria were found to tolerate multiple antibiotics in seawater, and the condition of the ARGs carriage was serious. Furthermore, the screened marine Synechocystis sp. C12-2 demonstrated the ability to accept ARGs on the RP4 plasmid through natural transformation and showed reduced sensitivity to ampicillin, suggesting the possibility that some marine cyanobacteria could acquire ARGs from the environment through horizontal gene transfer. Thus, marine cyanobacteria may play an important role in the propagation of marine ARGs.