Soil keystone viruses are regulators of ecosystem multifunctionality.

Ecosystem multifunctionality reflects the capacity of ecosystems to simultaneously maintain multiple functions which are essential bases for human sustainable development. Whereas viruses are a major component of the soil microbiome that drive ecosystem functions across biomes, the relationships between soil viral diversity and ecosystem multifunctionality remain under-studied. To address this critical knowledge gap, we employed a combination of amplicon and metagenomic sequencing to assess prokaryotic, fungal and viral diversity, and to link viruses to putative hosts. We described the features of viruses and their potential hosts in 154 soil samples from 29 farmlands and 25 forests distributed across China. Although 4,460 and 5,207 viral populations (vOTUs) were found in the farmlands and forests respectively, the diversity of specific vOTUs rather than overall soil viral diversity was positively correlated with ecosystem multifunctionality in both ecosystem types. Furthermore, the diversity of these keystone vOTUs, despite being 10-100 times lower than prokaryotic or fungal diversity, was a better predictor of ecosystem multifunctionality and more strongly associated with the relative abundances of prokaryotic genes related to soil nutrient cycling. Gemmatimonadota and Actinobacteria dominated the host community of soil keystone viruses in the farmlands and forests respectively, but were either absent or showed a significantly lower relative abundance in that of soil non-keystone viruses. These findings provide novel insights into the regulators of ecosystem multifunctionality and have important implications for the management of ecosystem functioning.

TRIM24 Up-Regulates ORM2 to Alleviate Abnormal Lipid Metabolism, Inflammation, and Oxidative Stress in Mice with Obstructive Sleep Apnea Syndrome and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Obstructive sleep apnea syndrome (OSAS) is associated with the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Tripartite motif containing 24 (TRIM24) deficiency was reported to cause hepatic lipid accumulation and hepatitis. However, the expression, function, and mechanism of TRIM24 in OSAS and MASLD remain unclear. OSAS and MASLD mouse model was established by intermittent hypoxia (IH) and high-fat diet. IH- and 1% free fatty acid-induced mouse liver cells served as an in vitro model. TRIM24 and HIF-1α were up-regulated under the IH condition. HIF-1α enhanced the transcriptional activity of TRIM24. Overexpression of TRIM24 reduced hepatic lipid accumulation, decreased serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol, and increased serum levels of high-density lipoprotein cholesterol in OSAS and MASLD mice. Additionally, overexpression of TRIM24 alleviated inflammation and oxidative stress, and modulated aberrant lipid metabolism. Mechanically, TRIM24 up-regulated the expression of ORM2, a key regulator of hepatic lipogenesis, by binding to H3K27ac and recruiting retinoic acid receptor-α to ORM2 promoter. The cell rescue model verified that ORM2 mediated the hepatoprotective effects of TRIM24. Our evidence reveals the important role of TRIM24 as an epigenetic coregulator of transcription in OSAS and MASLD, providing additional insights into understanding the pathogenesis and preventing the development of OSAS and MASLD.

Discovery of FO-4-15, a novel 1,2,4-oxadiazole derivative, ameliorates cognitive impairments in 3×Tg mice by activating the mGluR1/CaMKIIα pathway.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive impairments. Despite the limited efficacy of current treatments for AD, the 1,2,4-oxadiazole structure has garnered significant attention in medicinal chemistry due to its potential impact on mGluR1 and its association with AD therapy. In this study, a series of novel 1,2,4-oxadiazole derivatives were designed, synthesized, and evaluated for the neuroprotective effects in human neuroblastoma (SH-SY5Y) cells. Among all the derivatives tested, FO-4-15 (5f) existed the lowest cytotoxicity and the highest protective effect against H2O2. Based on these in vitro results, FO-4-15 was administered to 3×Tg mice and significantly improved the cognitive impairments of the AD mice. Pathological analysis showed that FO-4-15 significantly reduced Aß accumulation, Tau hyper-phosphorylation, and synaptic impairments in the 3×Tg mice. Dysfunction of the CaMKIIα/Fos signaling pathway in 3×Tg mice was found to be restored by FO-4-15 and the necessity of the CaMKIIα/Fos for FO-4-15 was subsequently confirmed by the use of a CaMKIIα inhibitor in vitro. Beyond that, mGluR1 was identified to be a potential target of FO-4-15, and the interaction of FO-4-15 and mGluR1 was displayed by Ca2+ flow increase, molecular docking, and interaction energy analysis. The target of FO-4-15 was further confirmed in vitro by JNJ16259685, a nonselective inhibitor of mGluR1. These findings suggest that FO-4-15 may hold promise as a potential treatment for Alzheimer's disease.

Individuals with genetic high-risk for psychosis experience impaired coping styles compared with healthy controls.

BACKGROUND: Individuals with schizophrenia tend to have negative coping styles and low levels of self-esteem, but it is unclear whether coping styles and self-esteem levels are altered in people in the prodromal phase of psychosis. AIMS: The study was designed to assess the role of coping style and self-esteem in the context of different phases of schizophrenia. METHODS: Recurrent Schizophrenia (ReSch), first-episode schizophrenia patients (FEP), genetic-high risk for psychosis (GHR) patients, and healthy controls (HC) (40 per group) were subjected to in-person clinical interviews. The results of these interviews were then used to gauge coping style and self-esteem using the Coping Styles Questionnaire (CSQ) and the Rosenberg's Self-Esteem Scale (RSES). Data were analyzed through ANCOVAs and logistic regression analyses. RESULTS: The results found that positive coping style (CSQ problem-solving and CSQ seeking for help) generally decline with progression through the HC, GHR, and FEP groups, while negative coping style (CSQ fantasy, CSQ repression and CSQ self-blame) generally increase with progression through the HC, GHR, and FEP groups (except that GHR group was slightly lower than HC group in CSQ self-blame). Results for members of ReSch group were in line with those of members of the FEP group in coping style. At the level of self-esteem, the GHR group was similar to the HC group and significantly higher than the FEP group and the ReSch group. Logistic regression analyses indicated that GHR group patients exhibited increased negative coping styles (CSQ fantasy) relative to members of the HC group, but had greater Positive coping style (CSQ problem-solving) than did members of the FEP group. DISCUSSION: These findings suggest that both GHR individuals experience impaired negative coping styles which expands the understanding of the psychological characteristics of the prodromal group. Further explorations are warranted to develop optimal psychosocial interventions.

A synthetic bacterial consortium improved the phytoremediation efficiency of ryegrass on polymetallic contaminated soil.

Polymetallic contamination of soils caused by mining activities seriously threatens soil fertility, biodiversity and human health. Bioremediation is thought to be of low cost and has minimal environmental risk but its effectiveness needs to be improved. This study aimed to identify the combined effect of plant growth and microbial strains with different functions on the enhancement of bioremediation of polymetallic contaminated soil. The microbiological mechanism of bioremediation was explored by amplicon sequencing and gene prediction. Soil was collected from polymetallic mine wastelands and a non-contaminated site for use in a pot experiment. Remediation efficiency of this method was evaluated by planting ryegrass and applying a mixed bacterial consortium comprising P-solubilizing, N-fixing and SO4-reducing bacteria. The plant-microbe joint remediation method significantly enhanced the above-ground biomass of ryegrass and soil nutrient contents, and at the same time reduced the content of heavy metals in the plant shoots and soil. The application of the composite bacterial inoculum significantly affected the structure of soil bacterial communities and increased the bacterial diversity and complexity, and the stability of co-occurrence networks. The relative abundance of the multifunctional genera to which the strains belonged showed a significant positive correlation with the soil nutrient content. Genera related to carbon (C), nitrogen (N), phosphorus (P), and sulphur (S) cycling and heavy metal resistance showed an up-regulation trend in heavy metal-contaminated soils after the application of the mixed bacterial consortium. Also, bacterial strains with specific functions in the mixed consortium regulated the expression of genes involved in soil nutrient cycling, and thus assisted in making the soil self-sustainable after remediation. These results suggested that the remediation of heavy metal-contaminated soil needs to give priority to the use of multifunctional bacterial agents.

Systematic review and meta-analysis of percutaneous nephrolithotomy in flank versus prone position.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficiency and safety of percutaneous nephrolithotomy (PCNL) between flank position and prone position for the treatment of renal stones. METHODS: PubMed, Embase, OVID, and Cochrane Library were comprehensively searched from their inception to Jul 2024. Randomized and nonrandomized trials evaluating renal calculi patients who underwent PCNL via flank position or prone position were included. Data extraction and quality assessment were conducted by two independent reviewers. The outcomes and complications of both groups were compared in this meta-analysis. RESULTS: This review involved five articles (554 patients). Specifically, four articles were randomized controlled trials, and the remaining publication was prospective cohort study. No significant difference was found in stone-free rate between the flank group and prone group after the PCNL procedure. Similarly, the percutaneous access time, operative time, and hospital stay of flank position had no significant difference compared with the prone group. There was no significant difference in the comparison of complication rates between the flank group and the prone group. Although further analysis indicated that patients in the prone position suffered more hemoglobin drop than the flank group, no significant difference was found in the hemorrhage and blood transfusion rates. CONCLUSIONS: Both surgical positions were appropriate for most PCNL procedures and had shown similar efficacy and safety. In practice, the optimal choice should be made according to the patients' conditions and urologists' acquaintance.

Unraveling the habitat preferences, ecological drivers, potential hosts, and auxiliary metabolism of soil giant viruses across China.

BACKGROUND: Soil giant viruses are increasingly believed to have profound effects on ecological functioning by infecting diverse eukaryotes. However, their biogeography and ecology remain poorly understood. RESULTS: In this study, we analyzed 333 soil metagenomes from 5 habitat types (farmland, forest, grassland, Gobi desert, and mine wasteland) across China and identified 533 distinct giant virus phylotypes affiliated with nine families, thereby greatly expanding the diversity of soil giant viruses. Among the nine families, Pithoviridae were the most diverse. The majority of phylotypes exhibited a heterogeneous distribution among habitat types, with a remarkably high proportion of unique phylotypes in mine wasteland. The abundances of phylotypes were negatively correlated with their environmental ranges. A total of 76 phylotypes recovered in this study were detectable in a published global topsoil metagenome dataset. Among climatic, geographical, edaphic, and biotic characteristics, soil eukaryotes were identified as the most important driver of beta-diversity of giant viral communities across habitat types. Moreover, co-occurrence network analysis revealed some pairings between giant viral phylotypes and eukaryotes (protozoa, fungi, and algae). Analysis of 44 medium- to high-quality giant virus genomes recovered from our metagenomes uncovered not only their highly shared functions but also their novel auxiliary metabolic genes related to carbon, sulfur, and phosphorus cycling. CONCLUSIONS: These findings extend our knowledge of diversity, habitat preferences, ecological drivers, potential hosts, and auxiliary metabolism of soil giant viruses. Video Abstract.

Risk stratification and survival time of patients with gram-negative bacillary pneumonia in the intensive care unit.

Introduction: Pneumonia is a common infection in the intensive care unit (ICU), and gram-negative bacilli are the most common bacterial cause. The purpose of the study was to investigate the risk factors for 30-day mortality in patients with gram-negative bacillary pneumonia in the ICU, construct a predictive model, and stratify patients based on risk to assess their short-term survival. Methods: Patients admitted to the ICU with gram-negative bacillary pneumonia at Fujian Medical University Affiliated First Hospital between January 2018 and September 2020 were selected. Patients were divided into deceased and survivor groups based on whether death occurred within 30 days. Multifactorial logistic regression analysis was used to identify independent risk factors for 30-day mortality in these patients, and a predictive nomogram model was constructed based on these factors. Patients were categorized into low-, medium-, and high-risk groups according to the model's predicted probability, and Kaplan-Meier survival curves were plotted to assess short-term survival. Results: The study included 305 patients. Lactic acid (odds ratio [OR], 1.524, 95% CI: 1.057-2.197), tracheal intubation (OR: 4.202, 95% CI: 1.092-16.169), and acute kidney injury (OR:4.776, 95% CI: 1.632-13.978) were identified as independent risk factors for 30-day mortality. A nomogram prediction model was established based on these three factors. Internal validation of the model showed a Hosmer-Lemeshow test result of X2=5.770, P=0.834, and an area under the ROC curve of 0.791 (95% CI: 0.688-0.893). Bootstrap resampling of the original data 1000 times yielded a C-index of 0.791, and a decision curve analysis indicated a high net benefit when the threshold probability was between 15%-90%. The survival time for low-, medium-, and high-risk patients was 30 (30, 30), 30 (16.5, 30), and 17 (11, 27) days, respectively, which were significantly different. Conclusion: Lactic acid, tracheal intubation, and acute kidney injury were independent risk factors for 30-day mortality in patients in the ICU with gram-negative bacillary pneumonia. The predictive model constructed based on these factors showed good predictive performance and helped assess short-term survival, facilitating early intervention and treatment.

Genome-wide association exploratory studies in individuals with ultra-high risk for schizophrenia in Chinese Han nationality in two years follow-up: A subpopulation study.

BACKGROUND: Although ultra-high risk for schizophrenia (UHR) is related to both genetic and environment factors, the precise pathogenesis is still unknow. To date, few studies have explored the Genome-Wide Association Studies (GWAS) in UHR or HR individuals especially in Han population in China. METHODS: In this study, a GWAS analysis for 36 participants with UHR and 43 with HR were performed, and all deletion variations in 22q11 region were also compared. RESULTS: Sixteen individuals with UHR (44.4%) and none with HR converted into schizophrenia in follow-up after two years. Six loci including neurexin-1(NRXN1) (rs1045881), dopamine D1 receptor (DRD1) (rs686, rs4532), chitinase-3-like protein 1 (CHI3L1) (rs4950928), velocardiofacial syndrome (ARVCF) (rs165815), dopamine D2 receptor (DRD2) (rs1076560) were identified higher expression with significant difference in individuals converted into schizophrenia after two years. The Family with Sequence Similarity 230 Member H (FAM230H) gene in the 22q11 region were also found high expression in UHR group. CONCLUSIONS: Further expansion of sample size and validation studies are needed to explore the pathogenesis of these risk loci in UHR conversion into schizophrenia in the future.

Mechanism study of ubiquitination in T cell development and autoimmune disease.

T cells play critical role in multiple immune processes including antigen response, tumor immunity, inflammation, self-tolerance maintenance and autoimmune diseases et. Fetal liver or bone marrow-derived thymus-seeding progenitors (TSPs) settle in thymus and undergo T cell-lineage commitment, proliferation, T cell receptor (TCR) rearrangement, and thymic selections driven by microenvironment composed of thymic epithelial cells (TEC), dendritic cells (DC), macrophage and B cells, thus generating T cells with diverse TCR repertoire immunocompetent but not self-reactive. Additionally, some self-reactive thymocytes give rise to Treg with the help of TEC and DC, serving for immune tolerance. The sequential proliferation, cell fate decision, and selection during T cell development and self-tolerance establishment are tightly regulated to ensure the proper immune response without autoimmune reaction. There are remarkable progresses in understanding of the regulatory mechanisms regarding ubiquitination in T cell development and the establishment of self-tolerance in the past few years, which holds great potential for further therapeutic interventions in immune-related diseases.

Discovery of palmatine derivatives as potent neuroprotective agents.

Alzheimer's disease is a neurodegenerative disorder characterized by the presence of neurodegenerative lesions and cognitive impairment. In this study, a series of novel palmatine derivatives were designed and synthesized through the introduction of a heteroatom using carbodiimide-mediated condensation. The synthesized compounds were then screened for toxicity and potency, leading to the identification of compound 2q, which exhibited low toxicity and high potency. Our findings demonstrated that compound 2q displayed significant neuroprotective activity in vitro, emerging as a promising candidate for Alzheimer's disease treatment.

PRL-mediated STAT5B/ARRB2 pathway promotes the progression of prostate cancer through the activation of MAPK signaling.

Previous study showed that higher expression of prolactin (PRL) was found in CRPC samples compared with hormone-naive prostate cancer (HNPC) and benign prostatic hyperplasia (BPH) samples. We further investigate the function of PRL in prostate cancer (PCa) and explored its downstream effects. We found heterogeneous expression of the PRLR in clinical prostate samples. The VCaP and 22Rv1 cells exhibited PRLR expression. Among the downstream proteins, STAT5B was the dominant subtype in clinical samples and cell lines. Human recombinant PRL stimulation of PCa cells with PRLR expression resulted in increased phosphorylation of STAT5B(pSTAT5B) and progression of PCa in vitro and in vivo, and STAT5B knockdown can suppress the malignant behavior of PCa. To understand the mechanism further, we performed Bioinformatic analysis, ChIP qPCR, and luciferase reporter gene assay. The results revealed that ARRB2 was the transcription target gene of STAT5B, and higher expression of ARRB2 was related to higher aggression and poorer prognosis of PCa. Additionally, Gene set enrichment analysis indicated that higher expression of ARRB2 was significantly enriched in the MAPK signaling pathway. Immunohistochemistry (IHC) demonstrated elevated pSTAT5B, ARRB2, and pERK1/2 expression levels in CRPC tissues compared to HNPC and BPH. Mechanically, ARRB2 enhanced the activation of the MAPK pathway by binding to ERK1/2, thereby promoting the phosphorylation of ERK1/2 (pERK1/2). In conclusion, our study demonstrated that PRL stimulation can promote the progression of PCa through STAT5B/ARRB2 pathway and activation of MAPK signaling, which can be suppressed by intervention targeting STAT5B. Blockade of the STAT5B can be a potential therapeutic target for PCa.

Subjective quality of life and schizophrenia: results from a large cohort study based in Chinese primary care.

INTRODUCTION: Much confusion exists between health-related QoL (HRQoL) scales and subjective QoL (SQoL) scales. One method to avoid confusion is use of a single question that asks What is your quality of life? or similar. This study explored the relationship between biopsychosocial factors and high SQoL, SQoL stability, and factors associated with improving SQoL. METHOD: We conducted a large cohort study of community-dwelling Chinese adults with schizophrenia, with two data points (2015-2016 (N = 742), 2017-2018 (N = 491)). Demographic and clinically related items and a comprehensive suite of published measures were collected. Direct logistic regressions were used to explore links between biopsychosocial factors and high SQoL and Improvement in SQoL across time. RESULTS: Sample at Baseline: Male = 62.3%; Med age = 38.5 years; Med Age at illness onset = 24 years; SQoL Mode = neither poor nor good. Three independent variables predicted high SQoL at T1. Contemporary age and the presence of clinically relevant symptoms had a negative relationship with high SQoL; insight had a positive relationship with high SQoL. SQoL changed significantly across time with a modest effect size. Age at illness onset was the single independent variable linked to improving SQoL favoring being older at the time of illness onset. DISCUSSION/CONCLUSIONS: SQoL can be high and changeable. While symptomology and illness insight may affect SQoL self-appraisals at single points in time, only age of illness onset was connected with improving SQoL. Thus, public health measures to delay illness onset are important. In addition, care about the distinction between HRQoL and SQoL in study design and choice of measures is necessary and will depend on the purpose and context.

Prevalence and Risk Factors of Hyperuricemia Among Young and Middle-Aged Tibetan Men Living at Ultrahigh Altitudes: A Cross-Sectional Study.

He, Ben, Jiayue Feng, Yan Shu, Lichun Yang, Zepin He, Kanxiu Liao, Hui Zhuo, and Hui Li. Prevalence and risk factors of hyperuricemia among young and middle-aged Tibetan men living at ultrahigh altitudes: a cross-sectional study. High Alt Med Biol. 25:42-48, 2024. Background: Few studies have examined the prevalence or risk factors of hyperuricemia among populations living at ultrahigh altitudes. Here we examined the prevalence of hyperuricemia and factors associated with it among young and middle-aged Tibetan men living at ultrahigh altitudes. Methods: This cross-sectional study analyzed 672 Tibetan men 18-60 years old living on the Qinghai-Tibet Plateau (mean altitude 4,014 m) within the county of Litang in the Ganzi Tibetan autonomous prefecture of Sichuan Province, China. Demographic and clinical data were collected from self-administered questionnaires, physical examinations and laboratory tests. Participants whose blood uric acid (UA) contained >420 µmol/l were classified as having hyperuricemia. Results: Of the 672 men analyzed, 332 (49.4%) had hyperuricemia. Multivariate logistic regression showed risk of hyperuricemia to correlate positively with body mass index (per 1 U increase: odds ratio [OR] 1.172, 95% confidence interval [CI] 1.1066-1.243), triglycerides (OR 1.408, 95% CI 1.084-1.828), red blood cell count (OR 1.376, 95% CI 1.009-1.875), and creatinine level (per 1 U increase: OR 1.051, 95% CI 1.033-1.070). Conversely, risk of hyperuricemia correlated negatively with the presence of diabetes mellitus (OR 0.412, 95% CI 0.175-0.968). Subgroup analyses showed that prevalence of hyperuricemia was significantly higher among those with polycythemia than among those without it, and that UA levels correlated positively with hematocrit and hemoglobin levels. Conclusions: Hyperuricemia is an important public health problem among Tibetan men living at ultrahigh altitudes in Ganzi autonomous prefecture. The region urgently requires appropriate prevention and management efforts.

Gene Polymorphisms and Expression of NRG1, DAOA, and DISC1 Genes in a Chinese Han Population with an Ultra-High Risk for Psychosis.

Purpose: Although there is previous evidence supporting that ultra-high risk (UHR) for psychosis transformation is associated with NRG1, DAOA, and DISC1 genes, there have been no relevant studies in the Chinese population. The objective of the current study was to explore the gene polymorphism and expression of NRG1, DAOA, and DISC1 genes in a Han population with UHR for psychosis in China. Methods: Eighteen UHR individuals, 61 first-degree relatives of patients with schizophrenia (FDR), 55 first-episode psychosis individuals (FEP), and 61 healthy controls (HC) were enrolled in the study. The genotypes at four loci of the NRG1 gene, four loci of the DAOA gene, and two loci of the DISC1 gene were tested for all subjects, and mRNAs of NRG1 and DISC1 were examined and analyzed in a pairwise comparison among the four groups. Statistical analysis of genetics was performed using snpStats software. For the case-control association analysis, a single site association study, epistatic effect analysis, and haplotype analysis were used to explore the association of the above genes. Results: This study found that rs3918341 in the DAOA gene was associated with susceptibility to UHR by single site association analysis. Epistatic effect analysis results showed that the NRG1 gene interacted with the DAOA gene and DISC1 gene in the susceptibility to UHR. Haplotype association analysis showed that all haplotypes were not significantly associated with UHR. NRG1 mRNA was significantly downregulated in the UHR group compared with the HC group as well as the FEP group. Conclusion: Our preliminary results show that NRG1, DAOA, and DISC1 genes may play a role in psychosis onset, opening the way to the identification of prognostic biomarkers.

Quantitative calculation of gases generation during low-temperature oxidation of coal.

The gases evolution during the low-temperature oxidation of coal is an essential parameter used to assess the state of coal oxidation and to estimate the gaseous pollutants. However, the current semi-quantitative method, which employs gas concentration as the measurement standard, is flawed. This paper presents a quantitative calculation method for gas products during coal oxidation. N2 is used as the tracer gas in the experiment, because nitrogen is an inert gas that will not participate in the reaction, and the amount of matter will not change in the reaction. According to the formula [Formula: see text], the corresponding mass flow rates of each gases component were calculated, and the gas yields during the reaction period were determined by comprehensive calculation. To this end, experiments were conducted on the low-temperature oxidation of coal using a flow reactor. After undergoing quantitative calculations, the main gas products' mass flow rates, yields, and energies, including CO, CO2, CH4, C2H4, C2H6, C2H2, and C3H8 between 30 and 180 °C were obtained. The findings showed that CO2 > CO > CH was generated in all the coal samples. The amount of gases produced in the low-temperature oxidation of coal is proportional to the level of oxygen concentration. When the oxygen concentration ranges from 0 to 21%, the gaseous production of MTH coal ranges from 381.44 g/ton to 8562.80 g/ton. The results of gaseous energy calculations showed that the energy loss for low temperature oxidation of the four coal samples ranged from 4334.14~26,772.73 kJ/ton under air atmosphere. Energy loss is also significantly affected by the oxygen concentration, and the energy loss of MTH coal increases significantly from 520.52 kJ/ton at 0% oxygen concentration to 26,772.73 kJ/ton at 21% oxygen concentration, an increase of about 50 times. Significantly, this method not only reflects the real gas evolution during low-temperature oxidation of coal but also computes the gas emission and energy loss, which is crucial for studying the mechanism of coal spontaneous combustion and assessing gases pollutants.

In situ enrichment of sulphate-reducing microbial communities with different carbon sources stimulating the acid mine drainage sediments.

The applications of sulphate-reducing microorganisms (SRMs) in acid mine drainage (AMD) treatment systems have received extensive attention due to their ability to reduce sulphate and stabilize metal(loid)s. Despite great phylogenetic diversity of SRMs, only a few have been used in AMD treatment bioreactors. In situ enrichment could be an efficient approach to select new effective SRMs for AMD treatment. Here, we performed in situ enrichment of SRMs in highly stratified AMD sediment cores using different kinds of carbon source mixture. The dsrAB (dissimilatory sulfite reductase) genes affiliated with nine phyla (two archaeal and seven bacterial phyla) and 26 genera were enriched. Remarkably, those genes affiliated with Aciduliprofundum and Vulcanisaeta were enriched in situ in AMD-related environments for the first time, and their relative abundances were negatively correlated with pH. Furthermore, 107 dsrAB-containing metagenome-assembled genomes (MAGs) were recovered from metagenomic datasets, with 14 phyla (two archaeal and 12 bacterial phyla) and 15 genera. The relative abundances of MAGs were positively correlated with total carbon and sulphate contents. Our findings expanded the diversity of SRMs that can be enriched in AMD sediment, and revealed the physiochemical properties that might affect the growth of SRMs, which provided guidance for AMD treatment bioreators.

Identification of a cancer-associated fibroblast signature for predicting prognosis and immunotherapeutic responses in bladder urothelial carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are the most important cellular components in bladder urothelial carcinoma (BLCA) and are involved in the development and immunosuppression of BLCA. Therefore, we aimed to construct a CAF-associated signature for predicting the prognosis and immunotherapy response in patients with BLCA. METHODS: CAF infiltration and stromal score were quantified using two algorithms. Weighted gene co-expression network analysis (WGCNA) was performed to identify the CAF-associated modules and hub genes. Univariate Cox and Least Absolute Shrinkage and Selection Operator regression analyses were used for constructing CAF signatures and calculating CAF scores. The ability of the CAF signature to predict prognosis and response to immunotherapy was validated using the data from three cohorts. RESULTS: WGCNA identified two CAF-associated modules and constructed a CAF signature containing 27 genes. In all three cohorts, patients with high CAF scores had markedly worse prognoses than those with low CAF scores, and CAF scores were independent risk factors. In addition, patients with high CAF scores did not respond to immunotherapy, whereas those with lower CAF scores responded to immunotherapy. CONCLUSION: CAF signature can be used to predict prognosis and immunotherapy response to guide individualized treatment planning in patients with BLCA.

Meta-analysis of gender differences in transition prevalence among individuals at clinical high risk of psychosis.

Gender differences have been found in several areas of individuals at clinical-high risk for psychosis(CHR). Therefore the risk of transition to psychosis may differ between male and female CHR, but previous work has not systematically reviewed and analyzed gender differences in conversion rates.We performed a meta-analysis according to PRISMA guidelines including all studies that assessed CHR with reliable instruments and provided data on the transition from male CHR and female CHR to psychosis to understand the conversion rate conversion in male and female CHR. Seventy-nine article were identified.A total of 1250 out of 5770 in the male CHR individuals, and 832 out of 4468 in the female CHR individuals translated to psychotic disorders. Transition prevalence were 19.4%(95%CI:14.2-25.8%)at 1 year, 20.6% at 2 year (95%CI:17.1-24.8%),24.3% at 3 years (95%CI:21.5-27.4%),26.3% at 4 years or older (95%CI:20.9-32.5%) and 22.3% at all (95%CI:20.0-24.8%) in male CHR and 17.7% (95%CI:12.6-24.4%) at 1 years, 17.5% (95%CI:14.2-21.4%) at 2 year, 19.9%(95%CI:17.3-0.228%) at 3 years,and 0.267 (95%CI:22.1-31.9%) at 4 years or older follow-up,20.4% at all (95%CI:18.1-22.9%) in female CHR. There were differences between the two groups in the overall conversion, the 2-year, and the 3-year follow up transition prevalence, which were higher in men CHR than in female CHR. Future research characterizing male versus female CHR is needed with the expectation that interventions will be developed that are tailored to the respective gender, further reducing the rate of conversion to CHR.

Convergent molecular evolution of thermogenesis and circadian rhythm in Arctic ruminants.

The muskox and reindeer are the only ruminants that have evolved to survive in harsh Arctic environments. However, the genetic basis of this Arctic adaptation remains largely unclear. Here, we compared a de novo assembled muskox genome with reindeer and other ruminant genomes to identify convergent amino acid substitutions, rapidly evolving genes and positively selected genes among the two Arctic ruminants. We found these candidate genes were mainly involved in brown adipose tissue (BAT) thermogenesis and circadian rhythm. Furthermore, by integrating transcriptomic data from goat adipose tissues (white and brown), we demonstrated that muskox and reindeer may have evolved modulating mitochondrion, lipid metabolism and angiogenesis pathways to enhance BAT thermogenesis. In addition, results from co-immunoprecipitation experiments prove that convergent amino acid substitution of the angiogenesis-related gene hypoxia-inducible factor 2alpha (HIF2A), resulting in weakening of its interaction with prolyl hydroxylase domain-containing protein 2 (PHD2), may increase angiogenesis of BAT. Altogether, our work provides new insights into the molecular mechanisms involved in Arctic adaptation.