The expression of SOCS1 is regulated by promoter DNA methylation and is associated with mitochondria-mediated apoptosis of T-2 induced chondrocytes.

At present, the function of SOCS1 in Kashin-Beck disease (KBD) has not been reported. This study aims to explore the expression and mechanism of SOCS1 in KBD, and provide theoretical basis for the prevention and treatment of KBD. The expression of SOCS1 were measured by qRT-PCR and Western blot. ELISA was used to detect the content of SOCS1 in serum and synovial fluid. CCK-8 kits were selected to measure the cell viability. Methylation Specific PCR (MSP) assay is used to detect the methylation level of SOCS1 in chondrocytes. Flow cytometry was used to analyze the apoptosis rate of chondrocytes in different groups. The expression of apoptosis related proteins (caspase-3 and caspase-9) and Cytochrome c were detected using Western blot. The mitochondrial ROS, ATP and the activity of mitochondrial respiratory chain complexes were detected using commercial kits. The results showed that the expression of SOCS1 significantly increases in KBD patients and T-2 induced chondrocytes. Further research has found that the methylation levels of SOCS1 were significantly reduced in KBD patients and T-2 induced chondrocytes. Functional studies have found that SOCS1 silencing inhibited chondrocyte apoptosis and mitochondrial dysfunction. More importantly, SOCS1 regulated mitochondrial mediated chondrocyte apoptosis through the IGF-1/IGF-1R/FAK/Drp1 pathway. In conclusion, SOCS1 expression is increased and methylation levels are decreased in KBD, and is involved in regulating mitochondrial mediated apoptosis in T-2 induced chondrocytes through IGF-1/IGF-1R/FAK/Drp1 signaling. This study provides new theoretical basis for the treatment and prevention of KBD in clinical practice.

Comparison of different macroinvertebrates bioassessment indices in a large near-natural watershed under the context of metacommunity theory.

The metacommunity theory proposes that community structure and biodiversity are influenced by both local processes (such as environmental filtering) and regional processes (such as dispersal). Despite the extensive use of traditional bioassessments based on species-environment relationships, the impact of dispersal processes on these assessments has been largely overlooked. This study aims to compare correlations between various bioassessment indices, including Shannon Weiner (H'), Biological Monitoring Working Party (BMWP), average score per taxon (ASPT), biotic index (BI), and EPT taxa index (EPT), based on macroinvertebrates collected from 147 sampling sites in a subtropical Chinese near-natural catchment. Modified indices were calculated by removing species strongly influenced by dispersal processes to address the influence of dispersal processes. Their relationship with environmental factors was then compared to the original indices. The study employed random forest regression (RFR) to compare the explanatory power of environmental factors using the two sets of indices. The spearman rank correlation analysis was conducted to examine the correlation between indices and environmental factors. The river health assessment was performed based on both modified and original indices. The results reveal significant differences between original and modified indices (especially H' and BI) providing a more accurate reflection of environmental conditions. Furthermore, the sensitivity of the different indices to various environmental factors varied, leading to differences in the bioassessment results between the modified and the original indices. Notably, original H', BMWP, and ASPT overestimated the bioassessment results, whereas the original BI underestimated them. These findings offer valuable insights into bioassessment and river health assessment evaluation within the catchment and other interconnected freshwater ecosystems, such as lakes, reservoirs, and wetlands. Our study underscores the importance of assessing and mitigating the impact of dispersal processes on bioassessment to obtain a more precise representation of the status of freshwater ecosystems.

Construction and Validation of a Gastric Cancer Diagnostic Model based on Blood Groups and Tumor Markers.

Objective: The aim of this study is to explore the value of combined detection of ABO blood group and tumor markers in the diagnosis of gastric cancer. Methods: A total of 3650 gastric cancer patients treated in our center from January 2015 to December 2019, and 5822 controls were recruited, and divided into training set and validation set according to 7:3. The diagnostic and predictive model of gastric cancer was constructed by binary logistic regression method in the training set. The diagnostic value of the prediction model for gastric cancer was evaluated by calculating the prediction probability P value and drawing the Receiver operating characteristic (ROC) curve, and was verified in the validation set. Results: The Area under the curve (AUC) of the diagnosis and prediction model in the training set was 0.936 (95%CI: 0.926-0.941), the sensitivity was 81.66%, and the specificity was 98.61%. In the validation set, the AUC was 0.941 (95%CI: 0.932-0.950), the sensitivity was 82.33%, and the specificity was 99.02%. Furthermore, the diagnostic model obtained in this study had a high diagnostic value for early gastric cancer patients in the healthy population (AUC of training set, validation set and total population were 0.906, 0.920 and 0.908, respectively). Conclusions: We constructed a diagnostic model for gastric cancer including blood group and tumor markers, which has high reference value for the diagnosis of gastric cancer patients, and the model can better distinguish early gastric cancer from healthy people.

Celastrol Alleviates Mitochondrial Oxidative Stress and Brain Injury After Intracerebral Hemorrhage by Promoting OPA1-Dependent Mitochondrial Fusion.

Mitochondrial oxidative stress is one of the characteristics of secondary brain injury (SBI) after intracerebral hemorrhage (ICH), contributing largely to the apoptosis of neurons. Celastrol, a quinone methide triterpene that possesses antioxidant and mitochondrial protective properties, has emerged as a neuroprotective agent. However, the activity of celastrol has not been tested in ICH-induced SBI. In this study, we found that celastrol could effectively alleviate neurological function deficits and reduce brain oedema and neuronal apoptosis caused by ICH. Through electron microscopy, we found that celastrol could significantly attenuate mitochondrial morphology impairment. Therefore, we tested the regulatory proteins of mitochondrial dynamics and found that celastrol could reverse the downwards trend of OPA1 expression after ICH. In view of this, by culturing OPA1-deficient primary neurons and constructing neuron-specific OPA1 conditional knockout mice, we found that the protective effects of celastrol on mitochondrial morphology and function after ICH were counteracted in the absence of OPA1. Further experiments also showed that OPA1 is indispensable for the protective effects of celastrol on ICH-induced secondary brain injury. In summary, we have demonstrated that celastrol is a potential drug for the treatment of ICH and have revealed a novel mechanism by which celastrol exerts its antioxidant effects by promoting OPA1-mediated mitochondrial fusion.

[Health Assessment of the Stream Ecosystem in Beijing, China].

With economic development, the health of river ecosystems is becoming severely threatened because of the increasing effects of human activities on river ecosystems. Here, 101 sites along regional river systems in Beijing rivers were investigated from autumn 2020 to summer 2021. A total of 34 metrics, including aquatic organisms, hydrology, water quality, and habitat, were calculated to be the candidate indicators. Principal component and correlation analyses were used to select the core metrics from the candidate indicators, and the weight of each core metric was estimated using the entropy method. The integrated index of stream ecological health was constructed to assess the health condition of the Beijing rivers. The results of the PCA and correlation analyses revealed that eleven metrics were selected as the core metrics to construct the integrated index of stream ecological health, including water temperature, flow velocity, BOD5, NH4+-N, Cu, the density of phytoplankton and zooplankton, the Shannon-Wiener diversity index of macroinvertebrates and fish, the BMWP index, and the qualitative habitat evaluation index. According to the health assessment results, 4.95% of the sampling sites were healthy, 23.76% were subhealthy, and 71.29% were in a fair or below healthy state. The river health status showed strong spatial heterogeneity, and the river health statuses in the northern and western regions were relatively good, whereas the river health status in the central and southeastern regions were relatively poor. The results of four aspects stream ecosystem assessment showed that the overall water quality of the rivers was "subhealthy" and the aquatic organisms and habitat were "general poor," but the hydrology was "poor." The evaluation results of five water systems demonstrated that the Chaobai River had the best health status, followed by that of the Yongding River, Daqing River, and Jiyun River, and the Beiyun River had the worst health status. Maintaining river ecological baseflow, ensuring river system connectivity, and improving and restoring the river habitat environment are the key aspects of river ecological restoration and protection in Beijing in the future.

Understanding the relative roles of local environmental, geo-climatic and spatial factors for taxonomic, functional and phylogenetic ß-diversity of stream fishes in a large basin, Northeast China.

The primary objective of this study was to determine the relative roles of local environmental (Local), geo-climatic (Geo), and spatial (Spatial) factors to taxonomic, functional, and phylogenetic ß-diversity of stream fish in a large basin in Northeast China. We quantified the current biodiversity patterns of fish communities in the Hun-Tai River using ß-diversity. We assessed (i) corresponding contributions of turnover and nestedness within the taxonomic, functional, and phylogenetic ß-diversity of fishes; (ii) correlations among ß-diversity facets (i.e., taxonomic, functional, and phylogenetic facets); (iii) relative contributions of Local, Geo, and Spatial factors to ß-diversity. We collected fish communities from 171 sampling sites. Mantel tests were used to examine the correlation of three facets of ß-diversity and their components (i.e., total, nestedness, and turnover). Distance-based redundancy analysis and variation partitioning assess the relative contributions of Local, Geo, and Spatial factors to ß-diversity. We found that turnover is the main driving mechanism for ß-diversity in fish. Among the facets of ß-diversity, taxonomic and phylogenetic facets have strong ecological information association. Spatial factors have a general contribution to various facets of ß-diversity and its components. From aspects of fish ß-diversity conservation, connectivity and habitat heterogeneity need to be maintained in the entire aquatic environment. In addition, protecting taxonomic ß-diversity is helpful for maintaining phylogenetic ß-diversity.

Expression and significance of CDX2, FXR, and TGR5 in esophageal cancer.

This study explored the expression and significance of three critical morphogenesis genes in normal esophagus, reflux esophagitis (RE), Barrett's esophagus (BE), esophageal adenocarcinoma (EA), and esophageal squamous cell carcinoma (ESCC). Esophageal tissue samples and tissue microarrays were used. CDX2, FXR, and TGR5 protein expression were measured by immunohistochemistry in normal esophageal, RE, BE, EA, and ESCC tissues. All 3 proteins had markedly changed expression during the progression of EA. The expressions of CDX2 and FXR were positively correlated in EA. In addition, TGR5 expression was positively correlated with CDX2 in RE and BE. The expressions of CDX2 and FXR were also positively correlated in ESCC. Although CDX2, FXR, and TGR5 were upregulated in ESCC, these factors might not be markers for the prognosis of ESCC. These results suggested that CDX2, FXR, and TGR5 might play different roles in EA and ESCC. They may represent novel therapeutic targets for patients with these cancers.

m6A-Related Angiogenic Genes to Construct Prognostic Signature, Reveal Immune and Oxidative Stress Landscape, and Screen Drugs in Hepatocellular Carcinoma.

Background: m6A modification plays a key role in the development of hepatocellular carcinoma (HCC). Angiogenesis-related genes (ARGs) are increasingly being used to define signatures predicting patient prognosis. The correlations between m6A-related ARGs (mARGs), clinical outcomes, and the immune and oxidative stress landscape are unclear. Methods: Univariate Cox regression analysis of 24 mARGs yielded 13 prognostic genes, which were then analyzed for their enriched functions and pathways. After LASSO regression analysis, a prognostic signature was constructed and its reliability validated. Patients were grouped by risk using the signature score, and then the clinical prognosis, the immune landscape, and the oxidative stress landscape between the two groups were analyzed. Drug sensitivity analysis was performed to identify potentially efficient therapeutic agents. Results: Thirteen prognosis-related mARGs consistently clustered patients with HCC into four groups with significantly different prognosis. Four mARGs (EGF, ITGA5, ITGAV, and PLG) were used to construct a prognostic signature and define risk groups. Among them, EGF, ITGA5, and ITGAV, were defined as prognostic risk factors, while PLG was defined as a prognostic protective factor. Compared to low-risk patients, HCC patients in the high-risk group had a poorer prognosis and showed significant differences in clinical characteristics, enriched pathways, tumor stemness, and tumor microenvironment. The drug sensitivity of oxaliplatin and LDK-378 negatively correlated with ITGAV expression. Ten drugs had lower IC50s in the high-risk group, indicating better antitumor efficacy than in the low-risk group, with epothilone B having the lowest IC50 value. Conclusions: A prognostic model consisting of mARGs can be used to predict the prognosis of HCC patients. The risk grouping of our model can be used to reveal differences in the tumor immune microenvironment of patients with HCC. Further in-depth study may provide new targets for future treatment.

Spatial Factors Outperform Local Environmental and Geo-Climatic Variables in Structuring Multiple Facets of Stream Macroinvertebrates' ß-Diversity.

One of the key targets of community ecology and biogeography concerns revealing the variability and underlying drivers of biodiversity. Most current studies understand biodiversity based on taxonomic information alone, but few studies have shown the relative contributions of multiple abiotic factors in shaping biodiversity based on taxonomic, functional, and phylogenetic information. We collected 179 samples of macroinvertebrates in the Hun-Tai River Basin. We validated the complementarity between the three facets and components of ß-diversity using the Mantel test. Distance-based redundancy analysis and variance partitioning were applied to explore the comparative importance of local environmental, geo-climatic, and spatial factors on each facet and component of ß-diversity. Our study found that taxonomic and phylogenetic total ß-diversity was mainly forced by turnover, while functional total ß-diversity was largely contributed by nestedness. There is a strong correlation between taxonomic and phylogenetic ß-diversity. However, the correlations of functional with both taxonomic and phylogenetic ß-diversity were relatively weak. The findings of variation partitioning suggested that distinct facets and components of macroinvertebrates' ß-diversity were impacted by abiotic factors to varying degrees. The contribution of spatial factors was greater than that of the local environment and geo-climatic factors for taxonomic, functional, and phylogenetic ß-diversity. Thus, studying different facets and components of ß-diversity allows a clearer comprehension of the influence of abiotic factors on diversity patterns. Therefore, future research should investigate patterns and mechanisms of ß-diversity from taxonomic, functional, and phylogenetic perspectives.

M2-like tumor-associated macrophage-related biomarkers to construct a novel prognostic signature, reveal the immune landscape, and screen drugs in hepatocellular carcinoma.

Background: M2-like tumor-associated macrophages (M2-like TAMs) have important roles in the progression and therapeutics of cancers. We aimed to detect novel M2-like TAM-related biomarkers in hepatocellular carcinoma (HCC) via integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to construct a novel prognostic signature, reveal the "immune landscape", and screen drugs in HCC. Methods: M2-like TAM-related genes were obtained by overlapping the marker genes of TAM identified from scRNA-seq data and M2 macrophage modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were carried out to screen prognostic genes from M2-like TAM-related genes, followed by a construction of a prognostic signature, delineation of risk groups, and external validation of the prognostic signature. Analyses of immune cells, immune function, immune evasion scores, and immune-checkpoint genes between high- and low-risk groups were done to further reveal the immune landscape of HCC patients. To screen potential HCC therapeutic agents, analyses of gene-drug correlation and sensitivity to anti-cancer drugs were conducted. Results: A total of 127 M2-like TAM-related genes were identified by integrative analysis of scRNA-seq and bulk-seq data. PDLIM3, PAM, PDLIM7, FSCN1, DPYSL2, ARID5B, LGALS3, and KLF2 were screened as prognostic genes in HCC by univariate Cox regression and LASSO regression analyses. Then, a prognostic signature was constructed and validated based on those genes for predicting the survival of HCC patients. In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested. Conclusions: Our findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.

Bile reflux and bile acids in the progression of gastric intestinal metaplasia.

ABSTRACT: Gastric intestinal metaplasia (GIM) is a precancerous lesion of gastric cancer (GC) and is considered an irreversible point of progression for GC. Helicobacter pylori infection can cause GIM, but its eradication still does not reverse the process. Bile reflux is also a pathogenic factor in GIM and can continuously irritate the gastric mucosa, and bile acids in refluxed fluid have been widely reported to be associated with GIM. This paper reviews in detail the relationship between bile reflux and GIM and the mechanisms by which bile acids induce GIM.

The clinicopathological characteristics of early-onset gastric cancer and its evolutionary trends: a retrospective study.

Although gastric cancer (GC) is most common in the elderly population, the rate of early-onset gastric cancer (EOGC) is increasing each year. In this study, the clinicopathological information of 9,406 patients who underwent GC resection in our institution from 2000 to 2019 was collected. We compared the clinicopathological characteristics between the EOGC group, in which patients were younger than 40, and the control group, summarizing the evolutionary trends of the EOGC group's characteristics. Then, we focused on the characteristics of EOGC in different sex groups and the evolutionary trends of female EOGC patients' clinicopathological characteristics. The results showed that a greater proportion of the EOGC group was female (47.32% vs. 23.53%), had poorly differentiated adenocarcinoma (84.78% vs. 64.11%), gastric antrum cancer (59.38% vs. 50.72%) and signet ring cell carcinoma (21.13% vs. 8.51%). Over the past 20 years, the proportion of EOGC patients with T4 stage (10.71% to 41.74%), N3 stage (0 to 30.73%) and poorly differentiated adenocarcinoma (70.37% to 92.23%) has increased. In the female EOGC group, there were more patients with stage III-IV disease (57.23% vs. 43.22%), T4 stage (35.85% vs. 22.60%), and poorly differentiated adenocarcinoma (91.88% vs. 78.68%). Additionally, the proportions of T4 stage (16.13% to 50.50%), N3 stage (0% to 31.68%), and poorly differentiated adenocarcinoma (69.23% to 98.97%) gradually increased. In conclusion, our study not only identified unique clinicopathological characteristics of EOGC but also revealed the evolutionary trends of these indicators, which may provide some theoretical basis for the prevention and diagnosis of EOGC.

Serum Total Bile Acids in Relation to Gastrointestinal Cancer Risk: A Retrospective Study.

Background: Bile acids (BAs) have been proposed to promote gastrointestinal cells carcinogenesis. However, studies on serum total bile acid (TBA) levels and gastrointestinal cancers (GICs) risk are rare. Methods: We conducted a retrospective case-control study from 2015 to 2019 at the First Affiliated Hospital of Air Force Military Medical University, in which 4,256 GICs cases and 1,333 controls were recruited. Patients' demographic, clinical and laboratory data were collected. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using binary logistic regression models. Results: Positive associations were observed between serum TBA levels and risks of esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC). Overall, ORs of EC, GC and CRC risk rose with the TBA levels increasing. After adjustment for potential confounders, the OR of TBA-positive for EC risk was 4.89 (95% CI: 3.20-7.49), followed by GC (OR: 3.92, 95% CI: 2.53-6.08), and CRC (OR: 3.32, 95% CI: 2.04-5.11). Patients aged 60 years or older have a higher risk of GICs, especially for EC patients. Males are associated with a higher risk of GC, while females are associated with a higher risk of CRC. Preoperative serum TBA positive and negative was significantly different in the presence or absence of hematogenous metastasis among EC patients (P=0.014), and lymph node metastasis among GC patients (P=0.018). Conclusions: This retrospective study showed positive associations between serum TBA level and GICs risk, and a higher serum TBA level constitutes a risk factor for GICs.

[Temporal-spatial distribution and ecological evaluation of macroinvertebrate functional feeding groups in Yongding River Basin]. / æ°¸å®šæ²³æµåŸŸå¤§åž‹åº•æ –åŠ¨ç‰©åŠŸèƒ½æ‘„é£Ÿç±»ç¾¤æ—¶ç©ºåˆ†å¸ƒåŠç”Ÿæ€è¯„ä»·.

We investigated community structure of macroinvertebrate, water environment factors, hydrological factors at 23 sampling sites of the Yongding River basin from spring 2017 (April) to autumn 2017 (November). We analyzed the composition, spatial and temporal distribution of the macroinvertebrate functional feeding groups, as well as their responses to changes in riverine habitat. A total of 78 macroinvertebrate species were identified, with 52, 50 and 53 macroinvertebrate species in spring, summer and autumn respectively. The dominant functional feeding groups were gather-collectors, followed by predators, while the proportion of scrapers, filter-collectors and shredders were extremely low. Dominant species in the three seasons were all gather-collectors, including Orthocladius, Rheotanytarsus, Cricotopus in spring, Glyptotendipes in summer, and Polypedilum, Chironomus, Orthocladius in autumn. Results of redundancy analysis showed that the functional feeding groups of macroinvertebrate community structure were mainly influenced by water temperature, flow velocity, salinity, and total phosphorus in spring, by total phosphorus, dissolved oxygen, conductivity and flow capacity in summer, and by total phosphorus and dissolved oxygen in autumn. Total phosphorus had positive correlation with gather-collectors in all three seasons, indicating that the functional feeding groups of macroinvertebrates were affected by water pollution. The evaluation based on the metrics of functional feeding groups showed that: 1) in terms of material cycle, primary productivity of Guishui River were significantly higher than other regions, and that in autumn were significantly higher than other seasons. The secondary productivity and decomposition capacity of Yanghe River were significantly higher than other regions, and those in spring were significantly higher than other seasons. The autotrophy/heterotrophy of Yanghe River was significantly lower than other regions, and that in spring were significantly higher than other seasons. 2) The longitudinal transport capacity of Sanggan River was significantly higher than other regions, and that in autumn was significantly higher than other seasons. 3) The lateral input capacity of Guishui River was significantly higher than other regions, and that in summer was significantly higher than other seasons.

[Distribution pattern of macroinvertebrate community and its relationships with environmental factors in the Yongding River Basin]. / æ°¸å®šæ²³æµåŸŸå¤§åž‹åº•æ –åŠ¨ç‰©ç¾¤è½åˆ†å¸ƒæ ¼å±€åŠå ¶å½±å“å› å­.

Human disturbances have altered global stream ecosystems in multiple ways. Understan-ding spatio-temporal dynamics of aquatic organism composition and their relationships with environmental factors play an important role in revealing changes in the structure and function of river ecosystems. The macroinvertebrates and environmental parameters were sampled in the Yongding River Basin at spring (March), summer (July), and autumn (November) in 2017. The results showed that chironomids were the dominant group in the Yongding River Basin, including Orthocladius, Chironomus, Glyptotendipes, and Polypedilum. Results of the cluster analysis showed significant spatial variations of macroinvertebrate community. Sampling sites were clustered into two groups based on the similarities of macroinvertebrate composition in the Yongding River. Sampling sites belonging to group 1 mainly located in the Sanggan River and Dongyang River, with Orthocladius sp.being the dominant species. Sampling sites belonging to group 2 mainly located in the Yang River, Guishui River and main section of the Yongding River, with Glyptotendipes sp. being the dominant species. The biomass, Shannon index, Margalef index, Pielou evenness index and taxa richness of group 2 were significantly higher than those of group 1. Higher values of biological indices indicated better ecological condition of the stream ecosystem. The density, biomass and diversity indices of summer were significantly lower than those of both spring and autumn. Results of Canonical correspondence analysis (CCA) showed that the spatio-temporal distribution of macroinvertebrate in the Yongding River was mainly influenced by water temperature, ammonium, pH, dissolved oxygen, and total phosphorus. From the perspective of hydrological characteristics, flow velocity and flow capacity were significantly correlated. The significant positive correlations between hydrological parameters of velocity and capacity and biological indices of density and EPT% in group 2 indicated the preference of fast flow to sensitive taxa of EPT (Ephemeroptera, Plecoptera, and Trichoptera). The negative correlations between flow capacity and biodiversity indices implied the adverse effects of high flow on macroinvertebrate biodiversity. Our results confirmed that the composition and biodiversity of macroinvertebrate were affected by both water environment and hydrology, which reflected the multiple human activities in aquatic ecosystems of the Yongding River. It is important to control water contamination and sustain environmental flow at the specific reaches for the restoration of Yongding River.

Identifying Clinically and Functionally Distinct Groups Among Healthy Controls and First Episode Psychosis Patients by Clustering on EEG Patterns.

OBJECTIVE: The mismatch negativity (MMN) is considered as a promising biomarker that can inform future therapeutic studies. However, there is a large variability among patients with first episode psychosis (FEP). Also, most studies report a single electrode site and on comparing case-control group differences. Few have taken advantage of the full wealth of multi-channel EEG signals to examine observable patterns. None, to our knowledge, have used machine learning (ML) approaches to investigate neurophysiological derived subgroups with distinct cognitive and functional outcome characteristics. In this study, we applied ML to empirically stratify individuals into homogeneous subgroups based on multi-channel MMN data. We then characterized the functional, cognitive, and clinical profiles of these neurobiologically derived subgroups. We also explored the underlying low frequency range responses (delta, theta, alpha) during MMN. METHODS: Clinical, neurocognitive, functioning data of 33 healthy controls and 20 FEP patients were collected. 90% of the patients had 6-month follow-up data. Neurocognition, social cognition, and functioning measures were assessed using the NCCB Cognitive Battery, the Awareness of Social Inference Test, UCSD Performance-Based Skills Assessment, and Multnomah Community Ability Scale. Symptom severity was collected using the PANSS. MMN amplitude and single-trial derived low frequency activity across 24 frontocentral channels were used as main variables in the ML k-means clustering analyses. RESULTS: We found a consistent pattern of two distinctive subgroups. We labeled them as "better functioning" and "poorer functioning" clusters, respectively. Each subgroup can be mapped onto either better or poorer clinical, cognitive, and functioning profiles. Also, we identified two subgroups of patients: one showed improved MMN and one showed worsening of MMN over time. Patients with improved MMN had better follow-up clinical, cognitive, and functioning profile than those with worsening MMN. Among the low frequency bands, delta frequency appeared to be the most relevant to the observed MMN responses in all individuals. However, higher delta responses were not necessarily associated with a better functioning profile, suggesting that delta frequency alone may not be useful in clinical characterization. CONCLUSIONS: The ML approach could be a robust tool to explore heterogeneity and facilitate the identification of neurobiological homogeneous subgroups in FEP.

[Spatio-Temporal Distribution and Risk Assessment of Heavy Metals in Middle and Lower Reaches of Le'an River].

The Le'an River is a main tributary of the Poyang Lake, which is the largest freshwater lake in China. The aim of this study is to research the distribution and potential ecological risks of heavy metals in the middle and lower reaches of the Le'an River, which is contaminated by nearby copper mines. Sediment and water samples were collected from 12 stations during the dry, wet, and normal season in 2016, respectively. The geo-accumulation index and potential ecological risk index were used to determine general pollution characteristics of trace metals in sediments. Results suggested that sediments in the Le'an River were considerably polluted by Cd, Pb, Cu, and Zn. Sediment concentrations of heavy metals showed significant spatial variations. The concentrations of heavy metals such as Cu, Zn, and Cd in water are higher in the dry season than in the normal and wet seasons. The distribution of heavy metals along the river is influenced by hydraulic conditions. The flow velocities in wet and normal seasons are positively correlated with the concentrations of heavy metals such as Cd, Pb, Cu, and Cr. There are seasonal differences in the distribution characteristics of heavy metals in surface sediments. In the dry season, the concentration of heavy metals in sediments is the highest in the middle reaches of rivers near mining areas, while during the wet and normal season, it reaches the highest value in the lower reach near the estuary. Except for Cd, whose major form of heavy metal in the sediment is in an exchanging state, the other heavy metals occur mainly in stable states. The assessment of the geo-accumulation index showed significant Cu, Cd, and Cr pollution. Among the heavy metals investigated, Cd was likely to result in more harmful effects.

Microbial community structure and functional properties in permanently and seasonally flooded areas in Poyang Lake.

Water level fluctuations are an inherent feature regulating the ecological structures and functions of lakes. It is vital to understand the effects of water level fluctuations on bacterial communities and metabolic characteristics in freshwater lakes in a changing world. However, information on the microbial community structure and functional properties in permanently and seasonally flooded areas are lacking. Poyang Lake is a typical seasonal lake linked to the Yangtze River and is significantly affected by water level fluctuations. Bottom water was collected from 12 sampling sites: seven inundated for the whole year (inundated areas) and five drained during the dry season (emerged areas). High-throughput 16S rRNA gene sequencing was used to identify the bacterial communities. The results showed that the taxonomic structure and potential functions of the bacterial communities were significantly different between the inundated and emerged areas. Cyanobacteria was dominant in both areas, but the relative abundance of Cyanobacteria was much higher in the emerged areas than in the inundated areas. Bacterial communities were taxonomically sensitive in the inundated areas and functionally sensitive in the emerged areas. Nitrogen, phosphorus, and dissolved organic carbon concentrations and their ratios, as well as dissolved oxygen, played important roles in promoting the bacterial taxonomic and functional compositional patterns in both areas. According to the metabolic predictions based on 16S rRNA gene sequences, the relative abundance of functional genes related to assimilatory nitrate reduction in the emerged areas was higher than in the inundated areas, and the relative abundance of functional genes related to dissimilatory nitrate reduction in the inundated areas was higher. These differences might have been caused by the nitrogen differences between the permanently and seasonally flooded areas caused by intra-annual water level fluctuations. The relative abundance of functional genes associated with denitrification was not significantly different in the inundated and emerged areas. This study improved our knowledge of bacterial community structure and nitrogen metabolic processes in permanently and seasonally flooded areas caused by water level fluctuations in a seasonal lake.