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The rapid expansion of the number of viral genome sequences in public databases necessitates a scalable, universal, and automated preliminary taxonomic framework for comprehensive virus studies. Here, we introduce VISTA (Virus Sequence-based Taxonomy Assignment), a computational tool that employs a novel pairwise sequence comparison system and an automatic demarcation threshold identification framework for virus taxonomy. Leveraging physio-chemical property sequences, k-mer profiles, and machine learning techniques, VISTA constructs a robust distance-based framework for taxonomic assignment. Functionally similar to PASC (Pairwise Sequence Comparison), a widely used virus assignment tool based on pairwise sequence comparison, VISTA demonstrates superior performance by providing significantly improved separation for taxonomic groups, more objective taxonomic demarcation thresholds, greatly enhanced speed, and a wider application scope. We successfully applied VISTA to 38 virus families, as well as to the class Caudoviricetes. This demonstrates VISTA's scalability, robustness, and ability to automatically and accurately assign taxonomy to both prokaryotic and eukaryotic viruses. Furthermore, the application of VISTA to 679 unclassified prokaryotic virus genomes recovered from metagenomic data identified 46 novel virus families. VISTA is available as both a command line tool and a user-friendly web portal at https://ngdc.cncb.ac.cn/vista., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Oral lichen planus (OLP) is a chronic oral mucosal inflammatory disease with a risk of becoming malignant. Emerging evidence suggests that microbial imbalance plays an important role in the development of OLP. However, the association between the oral microbiota and the metabolic features in OLP is still unclear., Methods: We conducted 16S rRNA sequencing and metabolomics profiling on 95 OLP patients and 105 healthy controls (HC).To study oral microbes and metabolic changes in OLP, we applied differential analysis, Spearman correlation analysis and four machine learning algoeithms., Results: The alpha and beta diversity both differed between OLP and HC. After adjustment for gender and age, we found an increase in the relative abundance of Pseudomonas , Aggregatibacter , Campylobacter , and Lautropia in OLP, while 18 genera decreased in OLP. A total of 153 saliva metabolites distinguishing OLP from HC were identified. Notably, correlations were found between Oribacterium , specific lipid and amino acid metabolites, and OLP's clinical phenotype. Additionally, the combination of Pseudomonas , Rhodococcus and (±)10-HDoHE effectively distinguished OLP from HC., Conclusions: Based on multi-omics data, this study provides comprehensive evidence of a novel interplay between oral microbiome and metabolome in OLP pathogenesis using the oral microbiota and metabolites of OLP patients., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To understand the gender characteristics of oral lichen planus (OLP) by identifying the gender-specific salivary microbiome and its potential biomarkers., Methods: A gender-based study was undertaken, commencing with the collection of saliva samples, followed by 16S rRNA gene sequencing, to explore the differences in the composition of saliva microbiome in OLP patients (40 males and 56 females) and healthy controls (40 males and 56 females), respectively., Results: Both male and female OLP patients had significant differences in saliva microbiome composition from healthy controls, especially in female patients. Notably, Pseudomonas was only enriched in female patients. Rhodococcus (AUC: 0.91) and Pseudomonas (AUC: 0.97) had great potential as diagnostic biomarkers in male and female patients, respectively. The KEGG results showed metabolic dysfunction was more pronounced in female patients and a high level of microbial metabolism in diverse environments, ABC transporters, Quorum sensing and Two-component system. Capnocytophaga was negatively correlated with the erosion area in male patients. Neisseria was negatively correlated with the erosion area and Rothia was positively correlated with the pain level in female patients., Conclusions: Our study revealed gender-specific perturbation in salivary microbiome within OLP patients, suggesting that the male and female patients with OLP may have different pathogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Recurrent aphthous ulcer (RAU) is a prevalent oral mucosal disease, affecting around 20% of the global population. It can greatly impair the quality of life for affected individuals. However, the exact etiology of RAU remains unknown., Subjects and Methods: 16S rRNA sequencing (16S rRNA-seq) and non-targeted liquid chromatography-mass spectrometry (LC-MS) were employed to investigate the salivary microbiota and metabolic phenotype between RAU patients (N = 61) and healthy controls (HCs) (N = 105)., Results: Findings from 16S rRNA -seq indicated reduced oral microbial diversity in RAU patients compared to HCs, but increased interactions. Clinical variables did not show any significant association with the overall diversity of oral microbiota in RAU patients. However, significant correlations were observed between specific microorganisms and clinical variables. LC-MS results revealed dysregulation of amino acid, lipid, nucleotide, and caffeine metabolism in RAU patients. Furthermore, correlation analysis of 16S rRNA-seq and LC-MS data revealed a significant association between salivary microbiota and metabolites in RAU patients., Conclusions: Our study revealed notable differences in salivary microbiota and metabolic profiles between RAU patients and HCs, indicating a strong link between oral microbiota dysbiosis, metabolic disturbances, and the onset and progression of RAU., (© 2024 Wiley Periodicals LLC.)

Purpose: To report the prevalence data for total corneal astigmatism (TCA) in cataract patients., Methods: The authors retrospectively collected and analyzed the preoperative biometric data of the patients who underwent cataract surgery in the Department of Ophthalmology, Peking University Third Hospital, from January 2019 to May 2023., Results: The mean age of the 10817 patients was 71 ± 10 years; the male/female ratio was 4653/6164. The mean TCA obtained by the IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany), the Abulafia-Koch (AK) formula, and the Barrett toric calculator was 1.11 ± 0.81 diopter (D), 1.13 ± 0.75 D, and 1.12 ± 0.74 D respectively, which was significantly greater than the mean standard keratometric (K) astigmatism (0.99 ± 0.75 D) obtained by IOLMaster 700. Against-the-rule (ATR) astigmatism was dominant in all the TCA measurements, and its proportion increased with age. TCA measurements by different methods exhibit high variability, with a total of 1574 (8.9%) data sets from 1016 (9.4%) patients showing a difference larger than 0.5 D in at least one pair of TCA measurements., Conclusion: The use of TCA rather than K astigmatism significantly influenced the choice of intraocular lenses (IOLs) as more patients would be candidates for toric IOLs. It was essential to carefully compare and select TCA obtained with multiple methods for optimal postoperative visual quality., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Antidepressants remain the first-line treatment for depression. However, the factors influencing medication response are still unclear. Accumulating evidence implicates an association between alterations in gut microbiota and antidepressant response. Therefore, the aim of this study is to investigate the role of the gut microbiota-brain axis in the treatment response of venlafaxine. After chronic social defeat stress and venlafaxine treatment, mice were divided into responders and non-responders groups. We compared the composition of gut microbiota using 16 S ribosomal RNA sequencing. Meanwhile, we quantified metabolomic alterations in serum and hippocampus, as well as hippocampal neurotransmitter levels using liquid chromatography-mass spectrometry. We found that the abundances of 29 amplicon sequence variants (ASVs) were significantly altered between the responders and non-responders groups. These ASVs belonged to 8 different families, particularly Muribaculaceae. Additionally, we identified 38 and 39 differential metabolites in serum and hippocampus between the responders and non-responders groups, respectively. Lipid, amino acid, and purine metabolisms were enriched in both serum and hippocampus. In hippocampus, the concentrations of tryptophan, phenylalanine, gamma-aminobutyric acid, glutamic acid, and glutamine were increased, while the level of succinic acid was decreased in the responders group, compared with the non-responders group. Our findings suggest that the gut microbiota may play a role in the antidepressant effect of venlafaxine by modulating metabolic processes in the central and peripheral tissues. This provides a novel microbial and metabolic framework for understanding the impact of the gut microbiota-brain axis on antidepressant response., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Anaerobic digestion for flexible biogas production can lead to digestion inhibition under high shock loads. While steel slag addition has shown promise in enhancing system buffering, its limitations necessitate innovation. This study synthesized the nitrogen-doped activated carbon composite from steel slag to mitigate intermediate product accumulation during flexible biogas production. Material characterization preceded experiments introducing the composite into anaerobic digestion systems, evaluating its impact on methane production efficiency under hydraulic and concentration sudden shocks. Mechanistic insights were derived from microbial community and metagenomic analyses, facilitating the construction of the modified Anaerobic Digestion Model No. 1 (ADM1) to quantitatively assess the material's effects. Results indicate superior resistance to concentration shocks with substantial increment of methane production rate up to 33.45% compared with control group, which is mediated by direct interspecies electron transfer, though diminishing with increasing shock intensity. This study contributes theoretical foundations for stable flexible biogas production and offers an effective predictive tool for conductor material reinforcement processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Breast cancer is the most prevalent cancer worldwide. With advancements in breast cancer diagnosis and treatment, the prognosis of patients with early-stage cancer has significantly improved. Enhancing the long-term quality of life of patients after antineoplastic therapy, including visual quality, has become a crucial research focus. This review aims to comprehensively summarize dry eye disease adverse reaction resulting from pharmacotherapy for early-stage breast cancer. Through a review of the relevant literature, this study explored the etiology, clinical features, and potential therapeutic strategies for drug-induced dry eye disease in breast cancer treatment. A thorough understanding of the medication-induced dry eye disease adverse reaction aid clinicians in monitoring and managing patients' ocular health more effectively, facilitating early diagnosis and intervention, preventing complications, and ensuring optimal visual protection for patients undergoing breast cancer treatment., (Copyright © 2024. Published by Elsevier Inc.)

Background: Biological rhythms denote the cyclical patterns of life activities anchored to a 24-hour cycle. Research shows that depression exhibits disturbances in biological rhythms. Yet, the relationship between these biological rhythms and concomitant anxiety symptoms is insufficiently investigated in structured clinical assessments., Methods: This multicenter study, carried out in four Chinese hospitals, comprehensively examined the relationship between anxiety and disruptions in biological rhythms among patients with depression. The study encompassed 218 patients diagnosed with depression and 205 matched healthy controls. The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry was utilized to evaluate the participants' biological rhythms, focusing on four dimensions: sleep, activity, social, and diet., Results: In patients with depression, there is a significant positive correlation between the severity of anxiety symptoms and the disturbances in biological rhythms. The severity of anxiety and depression, along with the quality of life, are independently associated with disruptions in biological rhythms. The mediation model reveals that anxiety symptoms mediate the relationship between depressive symptoms and biological rhythms., Conclusion: This research highlights the role of anxiety within the spectrum of depressive disorders and the associated disturbances in biological rhythms. Our findings shed light on potential pathways towards more targeted preventive strategies and therapeutic interventions for individuals battling depression and anxiety., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC). Organoid-formation assays and in vivo lineage tracing experiments demonstrate that Zeb1 + epithelioid cells are putative cells of origin for NEPC. Mechanistically, Zeb1 transcriptionally regulates the expression of several key glycolytic enzymes, thereby predisposing tumor cells to utilize glycolysis for energy metabolism. During this process, lactate accumulation-mediated histone lactylation enhances chromatin accessibility and cellular plasticity including induction of neuro-gene expression, which promotes NEPC development. Collectively, Zeb1-driven metabolic rewiring enables the epigenetic reprogramming of prostate cancer cells to license the adeno-to-neuroendocrine lineage transition., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Depression is a prevalent mental disorder with a complex biological mechanism. Following the rapid development of systems biology technology, a growing number of studies have applied proteomics and metabolomics to explore the molecular profiles of depression. However, a standardized resource facilitating the identification and annotation of the available knowledge from these scattered studies associated with depression is currently lacking. This study presents ProMENDA, an upgraded resource that provides a platform for manual annotation of candidate proteins and metabolites linked to depression. Following the establishment of the protein dataset and the update of the metabolite dataset, the ProMENDA database was developed as a major extension of its initial release. A multi-faceted annotation scheme was employed to provide comprehensive knowledge of the molecules and studies. A new web interface was also developed to improve the user experience. The ProMENDA database now contains 43,366 molecular entries, comprising 20,847 protein entries and 22,519 metabolite entries, which were manually curated from 1370 human, rat, mouse, and non-human primate studies. This represents a significant increase (more than 7-fold) in molecular entries compared to the initial release. To demonstrate the usage of ProMENDA, a case study identifying consistently reported proteins and metabolites in the brains of animal models of depression was presented. Overall, ProMENDA is a comprehensive resource that offers a panoramic view of proteomic and metabolomic knowledge in depression. ProMENDA is freely available at https://menda.cqmu.edu.cn ., (© 2024. The Author(s).)

Major depressive disorder (MDD) is a severe mental illness characterized by a lack of objective biomarkers. Mounting evidence suggests there are extensive transcriptional molecular changes in the prefrontal cortex (PFC) of individuals with MDD. However, it remains unclear whether there are specific genes that are consistently altered and possess diagnostic power. In this study, we conducted a systematic search of PFC datasets of MDD patients from the Gene Expression Omnibus database. We calculated the differential expression of genes (DEGs) and identified robust DEGs using the RRA and MetaDE methods. Furthermore, we validated the consistently altered genes and assessed their diagnostic power through enzyme-linked immunosorbent assay experiments in our clinical blood cohort. Additionally, we evaluated the diagnostic power of hub DEGs in independent public blood datasets. We obtained eight PFC datasets, comprising 158 MDD patients and 263 healthy controls, and identified a total of 1468 unique DEGs. Through integrated analysis, we identified 290 robustly altered DEGs. Among these, seven hub DEGs (SLC1A3, PON2, AQP1, EFEMP1, GJA1, CENPD, HSD11B1) were significantly down-regulated at the protein level in our clinical blood cohort. Moreover, these hub DEGs exhibited a negative correlation with the Hamilton Depression Scale score (P < 0.05). Furthermore, these hub DEGs formed a panel with promising diagnostic power in three independent public blood datasets (average AUCs of 0.85) and our clinical blood cohort (AUC of 0.92). The biomarker panel composed of these genes demonstrated promising diagnostic efficacy for MDD and serves as a useful tool for its diagnosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sphingolipids are an essential subset of bioactive lipids found in most eukaryotic cells that contribute to membrane biophysical properties and are involved in cellular differentiation, recognition, and mediating interactions. The described nanoHPLC-ESI-Q/ToF methodology utilizes known biosynthetic pathways, accurate mass detection, optimized collision-induced disassociation, and a robust nanoflow chromatographic separation for the analysis of intact sphingolipids found in human tissue, cells, and serum. The methodology was developed and validated with an emphasis on addressing the common issues experienced in profiling these amphipathic lipids, which are part of the glycocalyx and lipidome. The high sensitivity obtained using nanorange flow rates with robust chromatographic reproducibility over a wide range of concentrations and injection volumes results in confident identifications for profiling these low-abundant biomolecules.

Background: Major depressive disorder (MDD) was involved in widely transcriptional changes in central and peripheral tissues. While, previous studies focused on single tissues, making it difficult to represent systemic molecular changes throughout the body. Thus, there is an urgent need to explore the central and peripheral biomarkers with intrinsic correlation., Methods: We systematically retrieved gene expression profiles of blood and anterior cingulate cortex (ACC). 3 blood datatsets (84 MDD and 88 controls) and 6 ACC datasets (100 MDD and 100 controls) were obtained. Differential expression analysis, RobustRankAggreg (RRA) analysis, functional enrichment analysis, immune associated analysis and protein-protein interaction networks (PPI) were integrated. Furthermore, the key genes were validated in an independent ACC dataset (12 MDD and 15 controls) and a cohort with 120 MDD and 117 controls., Results: Differential expression analysis identified 2211 and 2021 differential expressed genes (DEGs) in blood and ACC, respectively. RRA identified 45 and 25 robust DEGs in blood and ACC based on DEGs, and all of them were closely associated with immune cells. Functional enrichment results showed both the robust DEGs in blood and ACC were enriched in humoral immune response. Furthermore, PPI identified 8 hub DEGs (CD79A, CD79B, CD19, MS4A1, PLP1, CLDN11, MOG, MAG) in blood and ACC. Independent ACC dataset showed the area under the curve (AUC) based on these hub DEGs was 0.77. Meanwhile, these hub DEGs were validated in the serum of MDD patients, and also showed a promising diagnostic power., Conclusions: The biomarker panel based on hub DEGs yield a promising diagnostic efficacy, and all of these hub DEGs were strongly correlated with immunity. Humoral immune response may be the key link between the brain and blood in MDD, and our results may provide further understanding for MDD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The Hospital Consultants' Job Stress Questionnaire (HCJSQ) has been widely used to assess sources and levels of job stress. However, its reliability and validity among Chinese dental workers have not been extensively studied. The objective of this study was to assess the reliability and validity of the HCJSQ specifically in Chinese dental workers., Methods: The HCJSQ was used to explore the sources and the global ratings of job stress among Chinese dental workers. To assess the reliability and validity of the HCJSQ, various statistical measures were employed, including Cronbach's alpha coefficient, Spearman-Brown coefficient, Spearman correlation coefficient, exploratory factor analysis, confirmatory factor analysis, convergent validity, and discriminant validity., Results: Of the participants, 526 (17.4%) reported high levels of stress, while 1,246 (41.3%) and 1,248 (41.3%) reported moderate and low levels of stress, respectively. The Cronbach's alpha coefficient for the modified HCJSQ was 0.903, and the Spearman-Brown coefficient was 0.904. Spearman correlation coefficient between individuals' items and the total score ranged from 0.438 to 0.785 (p < 0.05). Exploratory factor analysis revealed that three factors accounted for 60.243% of the total variance. Confirmatory factor analysis demonstrated factor loadings between 0.624 and 0.834 on the specified items. The fit indices of the confirmatory factor analysis indicated good model fit, with a Root Mean Square Error of Approximation of 0.064, Normative Fit Index of 0.937, Comparative Fit Index of 0.952, Incremental Fit Index of 0.952, Tucker-Lewis index of 0.941, and Goodness of Fit Index of 0.944. Additionally, the convergent validity and discriminant validity showed a good fit for the three-factor model., Conclusion: The results of this study confirm that Chinese dental workers experience high levels of stress, and the three-factor model of the HCJSQ proves to be a suitable instrument for evaluating the sources and levels of job stress among Chinese dental workers. Therefore, it is imperative that relevant entities such as hospitals, medical associations, and government take appropriate measures to address the existing situation., (© 2024. The Author(s).)

Hepatic fibrosis is an important pathological manifestation of chronic schistosome infection. Patients with advanced schistosomiasis show varying degrees of abnormalities in liver fibrosis indicators and bilirubin metabolism. However, the relationship between hepatic fibrosis in schistosomiasis and dysregulated bilirubin metabolism remains unclear. In this study, we observed a positive correlation between total bilirubin levels and the levels of ALT, AST, LN, and CIV in patients with advanced schistosomiasis. Additionally, we established mouse models at different time points following S. japonicum infection. As the infection time increased, liver fibrosis escalated, while liver UGT1A1 consistently exhibited a low expression, indicating impaired glucuronidation of bilirubin metabolism in mice. In vitro experiments suggested that SEA may be a key inhibitor of hepatic UGT1A1 expression after schistosome infection. Furthermore, a high concentration of bilirubin activated the NF-κB signaling pathway in L-O2 cells in vitro. These findings suggested that the dysregulated glucuronidation of bilirubin caused by S. japonicum infection may play a significant role in schistosomiasis liver fibrosis through the NF-κB signaling pathway.

Introduction: Schizophrenia is a complex psychiatric disorder, of which molecular pathogenesis remains largely unknown. Accumulating evidence suggest that gut microbiota may affect brain function via the complex gut-brain axis, which may be a potential contributor to schizophrenia. However, the alteration of gut microbiota showed high heterogeneity across different studies. Therefore, this study aims to identify the consistently altered gut microbial taxa associated with schizophrenia., Methods: We conducted a systematic search and synthesis of the up-to-date human gut microbiome studies on schizophrenia, and performed vote counting analyses to identify consistently changed microbiota. Further, we investigated the effects of potential confounders on the alteration of gut microbiota., Results: We obtained 30 available clinical studies, and found that there was no strong evidence to support significant differences in α-diversity and β-diversity between schizophrenic patients and healthy controls. Among 428 differential gut microbial taxa collected from original studies, we found that 8 gut microbial taxa were consistently up-regulated in schizophrenic patients, including Proteobacteria, Gammaproteobacteria, Lactobacillaceae , Enterobacteriaceae , Lactobacillus , Succinivibrio , Prevotella and Acidaminococcus . While 5 taxa were consistently down-regulated in schizophrenia, including Fusicatenibacter , Faecalibacterium , Roseburia , Coprococcus and Anaerostipes ., Discussion: These findings suggested that gut microbial changes in patients with schizophrenia were characterized by the depletion of anti-inflammatory butyrate-producing genera, and the enrichment of certain opportunistic bacteria genera and probiotics. This study contributes to further understanding the role of gut microbiota in schizophrenia, and developing microbiota-based diagnosis and therapy for schizophrenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Tao, Wang, Pu, Liu, Gui, Zhong, Yang, Zhou, Tao, Chen, Chen, Chen, Chen and Xie.)

The toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is generally believed to be mediated by aryl hydrocarbon receptor (AhR), but some evidence suggests that the effects of TCDD can also be produced through AhR-independent mechanisms. In previous experiments, we found that mainly AhR-dependent mechanism was involved in the migration inhibition of glioblastoma U87 cells by TCDD. Due to the heterogeneity of glioblastomas, not all tumor cells have significant AhR expression. The effects and mechanisms of TCDD on the migration of glioblastomas with low AhR expression are still unclear. We employed a glioblastoma cell line A172 with low AhR expression as a model, using wound healing and Transwell® assay to detect the effect of TCDD on cell migration. We found that TCDD can inhibit the migration of A172 cells without activating AhR signaling pathway. Further, after being pre-treated with AhR antagonist CH223191, the inhibition of TCDD on A172 cells migration was not changed, indicating that the effect of TCDD on A172 cells is not dependent on AhR activation. By transcriptome sequencing analysis, we propose dysregulation of the expression of certain migration-related genes, such as IL6, IL1B, CXCL8, FOS, SYK, and PTGS2 involved in cytokines, MAPK, NF-κB, and IL-17 signaling pathways, as potential AhR-independent mechanisms that mediate the inhibition of TCDD migration in A172 cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Di-2-ethylhexyl phthalic acid (DEHP) is one of the most widely used plasticizers in the industry, which can improve the flexibility and durability of plastics. It is prone to migrate from various daily plastic products through wear and leaching into the surrounding environment and decompose into the more toxic metabolite mono-2-ethylhexyl phthalic acid (MEHP) after entering the human body. However, the impacts and mechanisms of MEHP on neuroblastoma are unclear. We exposed MYCN-amplified neuroblastoma SK-N-BE(2)C cells to an environmentally related concentration of MEHP and found that MEHP increased the proliferation and migration ability of tumor cells. The peroxisome proliferator-activated receptor (PPAR) β/δ pathway was identified as a pivotal signaling pathway in neuroblastoma, mediating the effects of MEHP through transcriptional sequencing analysis. Because MEHP can bind to the PPARβ/δ protein and initiate the expression of the downstream gene angiopoietin-like 4 (ANGPTL4), the PPARβ/δ-specific agonist GW501516 and antagonist GSK3787, the recombinant human ANGPTL4 protein, and the knockdown of gene expression confirmed the regulation of the PPARβ/δ-ANGPTL4 axis on the malignant phenotype of neuroblastoma. Based on the critical role of PPARβ/δ and ANGPTL4 in the metabolic process, a non-targeted metabolomics analysis revealed that MEHP altered multiple metabolic pathways, particularly lipid metabolites involving fatty acyls, glycerophospholipids, and sterol lipids, which may also be potential factors promoting tumor progression. We have demonstrated for the first time that MEHP can target binding to PPARβ/δ and affect the progression of neuroblastoma by activating the PPARβ/δ-ANGPTL4 axis. This mechanism confirms the health risks of plasticizers as tumor promoters and provides new data support for targeted prevention and treatment of neuroblastoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: The study aims to explore the ocular biometry of a myopic population in Northern China, focusing specifically on anterior and posterior segment lengths. Methods: This is a cross-sectional study. The medical records of 3458 myopic patients who underwent refractive surgery were evaluated. Axial length (AL), anterior chamber depth (ACD), lens thickness (LT) and other biometric parameters were measured using the IOL Master 700. The study determined the anterior segment length (ASL = ACD + LT), the posterior segment length (PSL = AL - ASL) and the ratio of ASL to PSL (ASL/PSL). Results: This study included 3458 eyes from 3458 myopic patients (1171 men and 2287 women). The mean age was 27.38 ± 6.88, ranging from 16 to 48 years old. The mean ASL was 7.35 ± 0.27 mm, and the mean PSL was 18.39 ± 1.18 mm. The ASL and PSL trends demonstrate an age-related increase for both genders, with notable gender-specific variations. Across most age groups, males typically exhibited higher ASLs and PSLs than females, with the exception of the 35-40 and 40-45 age groups. The ASL and PSL consistently increased with a rising AL. The AL strongly correlates with the PSL and negatively correlates with the ASL/PSL ratio. The ACD and LT moderately correlate with the ASL, but an increased LT does not imply a longer posterior segment. The CCT and SE show little correlation with axial eye parameters. Conclusions: Among Chinese myopic patients, a longer ASL and PSL were correlated with older age and the male gender. The AL strongly correlates positively with the PSL and negatively correlates with the ASL/PSL ratio. An elongation of the posterior segment may primarily account for an eyeball's lengthening.

Background: Chronic restraint stress (CRS) has iteratively been reported to be possibly implicated in the development of numerous cancer types. However, its role in oral squamous cell carcinoma (OSCC) has not been well elucidated. Here we intended to evaluate the role and mechanism., Methods: The effects of CRS were investigated in xenograft models of OSCC by using transcriptome sequencing, LC-MS, ELISA and RT-PCR. Moreover, the role of CRS and ALDH3A1 on OSCC cells was researched by using Trans-well, flow cytometry, western blotting, immunofluorescence, ATP activity and OCR assay. Furthermore, immunohistochemical staining was employed to observe the cell proliferation and invasion of OSCC in xenotransplantation models., Results: CRS promoted the progression of OSCC in xenograft models, stimulated the secretion of norepinephrine and the expression of ADRB2, but decreased the expression of ALDH3A1. Moreover, CRS changed energy metabolism and increased mitochondrial metabolism markers. However, ALDH3A1 overexpression suppressed proliferation, EMT and mitochondrial metabolism of OSCC cells., Conclusion: Inhibition of ALDH3A1 expression plays a pivotal role in CRS promoting tumorigenic potential of OSCC cells, and the regulatory of ALDH3A1 on mitochondrial metabolism may be involved in this process., (© 2023. The Author(s).)

Diabetic retinopathy (DR), retinal vein occlusion (RVO), and age-related macular degeneration (AMD) pose significant global health challenges, often resulting in vision impairment and blindness. Automatic detection of these conditions is crucial, particularly in underserved rural areas with limited access to ophthalmic services. Despite remarkable advancements in artificial intelligence, especially convolutional neural networks (CNNs), their complexity can make interpretation difficult. In this study, we curated a dataset consisting of 15,089 color fundus photographs (CFPs) obtained from 8110 patients who underwent fundus fluorescein angiography (FFA) examination. The primary objective was to construct integrated models that merge CNNs with an attention mechanism. These models were designed for a hierarchical multilabel classification task, focusing on the detection of DR, RVO, AMD, and other fundus conditions. Furthermore, our approach extended to the detailed classification of DR, RVO, and AMD according to their respective subclasses. We employed a methodology that entails the translation of diagnostic information obtained from FFA results into CFPs. Our investigation focused on evaluating the models' ability to achieve precise diagnoses solely based on CFPs. Remarkably, our models showcased improvements across diverse fundus conditions, with the ConvNeXt-base + attention model standing out for its exceptional performance. The ConvNeXt-base + attention model achieved remarkable metrics, including an area under the receiver operating characteristic curve (AUC) of 0.943, a referable F1 score of 0.870, and a Cohen's kappa of 0.778 for DR detection. For RVO, it attained an AUC of 0.960, a referable F1 score of 0.854, and a Cohen's kappa of 0.819. Furthermore, in AMD detection, the model achieved an AUC of 0.959, an F1 score of 0.727, and a Cohen's kappa of 0.686. Impressively, the model demonstrated proficiency in subclassifying RVO and AMD, showcasing commendable sensitivity and specificity. Moreover, our models enhanced interpretability by visualizing attention weights on fundus images, aiding in the identification of disease findings. These outcomes underscore the substantial impact of our models in advancing the detection of DR, RVO, and AMD, offering the potential for improved patient outcomes and positively influencing the healthcare landscape.

Purpose: To compare the efficacy and relevant influencing factors of four ICL size selection methods established by four different parameters., Methods: This prospective study included 60 patients (120 eyes) who underwent bilateral ICL implantation. Patients were equally divided into four groups, and each group used the Parkhurst nomogram based on sulcus-to-sulcus (STS), the manufacturer's Online Calculation & Ordering System (OCOS) nomogram based on white-to-white (WTW), the KS formula based on angle-to-angle (ATA) and the NK formula based on anterior chamber width (ACW) to determine the ICL size. Recorded the vault one month after operation and compared the consistency between STS and WTW, ATA and ACW and their effects on the vault of different groups., Results: The Parkhurst nomogram, OCOS nomogram, KS formula and NK formula determined 86.7%, 70.0%, 83.3% and 66.7% of properly sized ICL, respectively. STS and ATA were correlated (P < 0.05). The mean difference between the STS and WTW, ATA and ACW was -0.37 ± 0.62 mm, -0.42 ± 0.53 mm and -0.44 ± 0.52 mm, respectively. The vault in the OCOS group was negatively correlated with △ STS-WTW, and the vault in the NK group was negatively correlated with △ STS-WTW, △ STS-ATA and △ STA-ACW. The vault in the Parkhurst group and KS group was not affected by anterior segment biometry variables., Conclusion: ATA can be served as an alternative parameter to STS, and STS-based Parkhurst nomogram and ATA-based KS formula determined the most appropriate ICL size. When using OCOS nomogram and NK formula to select ICL size, postoperative abnormal vault was associated with a larger difference between STS and other anterior segment parameters., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Herein, a cost-effective method for improving the anaerobic fermentation performance of sewage sludge (SS) is proposed. The highest volatile fatty acids (VFAs) reached up to 5550 mg COD/L with the supplementation of 0.2 g urea/g total suspended solids (TSS). Intensive exploration showed that SS decomposition was profoundly triggered by urea and the free ammonia generated due to the hydrolysis of urea, providing adequately bioaccessible substrates for acidogenic reactions and thus contributing to VFAs formation. Microbial composition analysis indicated that functional bacteria (i.e., Tissierella and Clostridium) associated with VFAs generation were enriched. Moreover, the metabolic activities of functional flora (i.e., membrane transport and fatty acid synthesis) were up-regulated due to the stimulation of urea. In general, the increase in bioavailable organic matter and functional microbes, and thus the increased microbial metabolic activities, improved the efficient production of VFAs. This study could provide a cost-effective approach for resource recovery from SS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

In this paper, a decision-making approach based on the triple bottom line concept is presented for evaluating the sustainability of demand-oriented biogas supply (DOBS) programs with regard to their environmental, economic, and social impacts. For the assessment, an indicator system was developed, whose main parameters were quantified by integrating emergy analysis, economic benefit assessment, and a proposed social risk accounting method. The Charnes-Cooper-Wei-Huang (CCWH) model with constrained cone was adopted to calculate the comprehensive sustainability via the synthesis of the economic, environmental, and social indicators, in which eight scenarios were set according to the flexibility hierarchy of biogas supplied for load demand, biogas production mode, and feeding substrates. The evaluation results show that the DOBS scenario of supplying for real-time varying power demand by using straw and livestock manure has the highest sustainability score in our case study. Based on the results, corresponding managerial implications are proposed., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mono-2-ethylhexyl phthalic acid (MEHP) is the most toxic metabolite of plasticizer di-2-ethylhexyl phthalic acid (DEHP), and there is limited information available on the effects of MEHP on neurotoxicity. This study aims to examine the neurotoxicity of MEHP and preliminarily explore its potential molecular mechanisms. We found that MEHP impeded the growth of zebrafish embryos and the neurodevelopmental-related gene expression at environmentally relevant concentrations. MEHP exposure also induces oxidative stress response and brain cell apoptosis accompanied by a decrease in acetylcholinesterase (AChE) activity in zebrafish larvae. RNA-Seq and bioinformatics analysis showed that MEHP treatment altered the nervous system, neurogenic diseases, and visual perception pathways. The locomotor activity in dark-to-light cycles and phototaxis test confirmed the abnormal neural behavior of zebrafish larvae. Besides, the immune system has produced a large number of differentially expressed genes related to neural regulation. Inflammatory factor IL1β and IL-17 signaling pathways highly respond to MEHP, indicating that inflammation caused by immune system imbalance is a potential mechanism of MEHP-induced neurotoxicity. This study expands the understanding of the toxicity and molecular mechanisms of MEHP, providing a new perspective for in-depth neurotoxicity exploration of similar compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Depression is a serious mental illness, but the molecular mechanisms of depression remain unclear. Previous research has reported metabolomic changes in the blood of patients with depression, while integrated analysis based on these altered metabolites was still lacking. The objective of this study was to integrate metabolomic changes to reveal the underlying molecular alternations of depression. We retrieved altered metabolites in the blood of patients with depression from the MENDA database. Pathway analysis was conducted to explore enriched pathways based on candidate metabolites. Pathway crosstalk analysis was performed to explore potential correlations of these enriched pathways, based on their shared candidate metabolites. Moreover, potential interactions of candidate metabolites with other biomolecules such as proteins were assessed by network analysis. A total of 854 differential metabolite entries were retrieved in peripheral blood of patients with depression, including 555 unique candidate metabolites. Pathway analysis identified 215 significantly enriched pathways, then pathway crosstalk analysis revealed that these pathways were clustered into four modules, including amino acid metabolism, nucleotide metabolism, energy metabolism and others. Additionally, eight molecular networks were identified in the molecular network analysis. The main functions of these networks involved amino acid metabolism, molecular transport, inflammatory responses and others. Based on integrated analysis, our study revealed pathway-based modules and molecular networks associated with depression. These results will contribute to the underlying knowledge of the molecular mechanisms in depression., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aging is a systemic physiological degenerative process, with alterations in gut microbiota and host metabolism. However, due to the interference of multiple confounding factors, aging-associated molecular characteristics have not been elucidated completely. Therefore, based on 16S ribosomal RNA (rRNA) gene sequencing and non-targeted metabolomic detection, our study systematically analyzed the composition and function of the gut microbiome, serum, and fecal metabolome of 36 male rhesus monkeys spanning from 3 to 26 years old, which completely covers juvenile, adult, and old stages. We observed significant correlations between 41 gut genera and age. Moreover, 86 fecal and 49 serum metabolites exhibited significant age-related correlations, primarily categorized into lipids and lipid-like molecules, organic oxygen compounds, organic acids and derivatives, and organoheterocyclic compounds. Further results suggested that aging is associated with significant downregulation of various amino acids constituting proteins, elevation of lipids, particularly saturated fatty acids, and steroids. Additionally, age-dependent changes were observed in multiple immune-regulatory molecules, antioxidant stress metabolites, and neurotransmitters. Notably, multiple age-dependent genera showed strong correlations in these changes. Together, our results provided new evidence for changing characteristics of gut microbes and host metabolism during aging. However, more research is needed in the future to verify our findings.

Polymyxins are last-line antibiotics employed against multidrug-resistant (MDR) Klebsiella pneumoniae. Worryingly, polymyxin resistance is rapidly on the rise globally. Polymyxins initially target lipid A of lipopolysaccharides (LPSs) in the cell outer membrane (OM), causing disorganization and cell lysis. While most studies focus on how genetic variations confer polymyxin resistance, the mechanisms of membrane remodeling and metabolic changes in polymyxin-resistant strains remain unclear, thus hampering the development of effective therapies to treat severe K. pneumoniae infections. In the present study, lipid A profiling, OM lipidomics, genomics, and metabolomics were integrated to elucidate the global mechanisms of polymyxin resistance and metabolic adaptation in a polymyxin-resistant strain (strain S01R; MIC of >128 mg/L) obtained from K. pneumoniae strain S01, a polymyxin-susceptible (MIC of 2 mg/L), New Delhi metallo-β-lactamase (NDM)-producing MDR clinical isolate. Genomic analysis revealed a novel in-frame deletion at position V258 of PhoQ in S01R, potentially leading to lipid A modification with 4-amino-4-deoxy-l-arabinose (L-Ara4N) despite the absence of polymyxin B. Comparative metabolomic analysis revealed slightly elevated levels of energy production and amino acid metabolism in S01R compared to their levels in S01. Exposure to polymyxin B (4 mg/L for S01 and 512 mg/L for S01R) substantially altered energy, nucleotide, and amino acid metabolism and resulted in greater accumulation of lipids in both strains. Furthermore, the change induced by polymyxin B treatment was dramatic at both 1 and 4 h in S01 but only significant at 4 h in S01R. Overall, profound metabolic adaptation was observed in S01R following polymyxin B treatment. These findings contribute to our understanding of polymyxin resistance mechanisms in problematic NDM-producing K. pneumoniae strains and may facilitate the discovery of novel therapeutic targets. IMPORTANCE Antimicrobial resistance (AMR) is a major threat to global health. The emergence of resistance to the polymyxins that are the last line of defense in so-called Gram-negative "superbugs" has further increased the urgency to develop novel therapies. There are frequent outbreaks of K. pneumoniae infections in hospitals being reported, and polymyxin usage is increasing remarkably. Importantly, the polymyxin-resistant K. pneumoniae strains are imposing more severe consequences to health systems. Using metabolomics, lipid A profiling, and outer membrane lipidomics, our findings reveal (i) changes in the pentose phosphate pathway and amino acid and nucleotide metabolism in a susceptible strain following polymyxin treatment and (ii) how cellular metabolism, lipid A modification, and outer membrane remodeling were altered in K. pneumoniae following the acquisition of polymyxin resistance. Our study provides, for the first time, mechanistic insights into metabolic responses to polymyxin treatment in a multidrug-resistant, NDM-producing K. pneumoniae clinical isolate with acquired polymyxin resistance. Overall, these results will assist in identifying new therapeutic targets to combat and prevent polymyxin resistance., Competing Interests: The authors declare no conflict of interest.

Major depressive disorder represents a serious public health challenge worldwide; however, the underlying cellular and molecular mechanisms are mostly unknown. Here, we profile the dorsolateral prefrontal cortex of female cynomolgus macaques with social stress-associated depressive-like behaviors using single-nucleus RNA-sequencing and spatial transcriptomics. We find gene expression changes associated with depressive-like behaviors mostly in microglia, and we report a pro-inflammatory microglia subpopulation enriched in the depressive-like condition. Single-nucleus RNA-sequencing data result in the identification of six enriched gene modules associated with depressive-like behaviors, and these modules are further resolved by spatial transcriptomics. Gene modules associated with huddle and sit alone behaviors are expressed in neurons and oligodendrocytes of the superficial cortical layer, while gene modules associated with locomotion and amicable behaviors are enriched in microglia and astrocytes in mid-to-deep cortical layers. The depressive-like behavior associated microglia subpopulation is enriched in deep cortical layers. In summary, our findings show cell-type and cortical layer-specific gene expression changes and identify one microglia subpopulation associated with depressive-like behaviors in female non-human primates., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The gut-brain axis has been shown to play an important role in depression. However, few studies have examined proteomic changes in the intestine of the nonhuman primate model of depression., Methods: We investigated the intestinal proteome of macaques (Macaca fascicularis) with depression-like (DL) behaviors by data-independent acquisition techniques. We also performed integration analyses of proteomic changes, previous metabolomic and microbiotic data. Moreover, we confirmed the gene expressions of key proteins., Results: Sixty-five differentially expressed proteins (DEPs) were identified, of which fifty-four DEPs were down-regulated and the others were altered conversely in DL macaques compared with the control group. Pathway analysis indicated that mitochondrial function and energy metabolism were representative functions of DEPs. The key DEPs were significantly associated with glycerophospholipid metabolism and imbalances of gut microbe. We confirmed that key molecules (NDUFB4, UQCR10, PISD) were significantly inhibited, which may disturb the energy transformation of the electron respiratory chain and the homeostasis of the mitochondrial membrane., Limitations: Further research is warranted to determine the effects of depression on other peripheral organs., Conclusions: These findings suggest the functional disorder of intestinal mitochondria in DL macaques. The disturbances of glycerophospholipid metabolism and gut microbiota may exacerbate disruptions of energy metabolism. Taking together, our study provides new clues to the relationship between depression and intestinal proteome., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Professional burnout refers to mental weariness caused by occupational stress. However, there is a lack of systematic studies on the prevalence of professional burnout among dentists. The purpose of this study was to investigate the prevalence of professional burnout among dentists. Databases including PubMed, PsycINFO, Embase, Cochrane, and Web of Science were systematically searched from inception to 28 October 2021. The random-effects model and forest plots were used to assess the pooled prevalence of professional burnout among dentists. A total of 15 studies with a total of 6038 study subjects were included in the meta-analysis, and the overall professional burnout among dentists was 13% (95%CI: 6-23). Subgroup analysis suggested a high prevalence of burnout in Europe, and the least in the Americas. The pooled burnout prevalence in cross-sectional surveys was significantly lower than that in longitudinal studies. In addition, the overall burnout prevalence in the last decade was significantly lower than that of a decade ago. This meta-analysis demonstrated that the prevalence of burnout was relatively low among dentists, and there was a downward trend. Therefore, it is important to continue to pay close attention to the mental health of dentists and effectively prevent and treat professional burnout to better maintain the provision of health care services.

Background: Numerous magnetic resonance spectroscopy (MRS) studies have reported metabolic abnormalities in the brains of patients with depression, although inconsistent results have been reported. The aim of this study was to explore changes in neurometabolite levels in patients with depression across large-scale MRS studies., Method: A total of 307 differential metabolite entries associated with depression were retrieved from 180 MRS studies retrieved from the Metabolite Network of Depression Database. The vote-counting method was used to identify consistently altered metabolites in the whole brain and specific brain regions of patients with depression., Results: Only few differential neurometabolites showed a stable change trend. The levels of total choline (tCho) and the tCho/N-acetyl aspartate (NAA) ratio were consistently higher in the brains of patients with depression, and that the levels of NAA, glutamate and glutamine (Glx), and gamma-aminobutyric acid (GABA) were lower. For specific brain regions, we found lower Glx levels in the prefrontal cortex and lower GABA concentrations in the occipital cortex. We also found lower concentrations of NAA in the anterior cingulate cortex and prefrontal cortex. The levels of tCho were higher in the prefrontal cortex and putamen., Conclusion: Our results revealed that most altered neurometabolites in previous studies lack of adequate reproducibility. Through vote-counting method with large-scale studies, downregulation of glutamatergic neurometabolites, impaired neuronal integrity, and disturbed membrane metabolism were found in the pathobiology of depression, which contribute to existing knowledge of neurometabolic changes in depression. Further studies based on a larger dataset are needed to confirm our findings., Competing Interests: Conflict of Interest No potential conflicts of interest were disclosed., (Copyright © 2022. Published by Elsevier B.V.)

Clinical and animal studies have shown that gut microbiome disturbances can affect neural function and behaviors via the microbiota-gut-brain axis, and may be implicated in the pathogenesis of several brain diseases. However, exactly how the gut microbiome modulates nervous system activity remains obscure. Here, using a single-cell nucleus sequencing approach, we sought to characterize the cell type-specific transcriptomic changes in the prefrontal cortex and hippocampus derived from germ-free (GF), specific pathogen free, and colonized-GF mice. We found that the absence of gut microbiota resulted in cell-specific transcriptomic changes. Furthermore, microglia transcriptomes were preferentially influenced, which could be effectively reversed by microbial colonization. Significantly, the gut microbiome modulated the mutual transformation of microglial subpopulations in the two regions. Cross-species analysis showed that the transcriptome changes of these microglial subpopulations were mainly associated with Alzheimer's disease (AD) and major depressive disorder (MDD), which were further supported by animal behavioral tests. Our findings demonstrate that gut microbiota mainly modulate the mutual transformation of microglial subtypes, which may lead to new insights into the pathogenesis of AD and MDD., (© 2023. The Author(s).)

Importance: No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers., Objective: To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD)., Design, Setting, and Participants: This was a multicohort case-control diagnostic analysis involving plasma samples from psychiatric patients and control individuals collected between July 17, 2009, and May 18, 2018. Study participants were recruited as consecutive and volunteer samples at multiple inpatient and outpatient mental health hospitals in Western Europe (Germany and Austria [DE-AT]), China (CN), and Russia (RU). Individuals with DSM-IV or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of SCZ, MDD, BPD, or a first psychotic episode, as well as age- and sex-matched healthy controls without a mental health-related diagnosis were included in the study. Samples and data were analyzed from January 2018 to September 2020., Main Outcomes and Measures: Plasma lipidome composition was assessed using liquid chromatography coupled with untargeted mass spectrometry., Results: Blood lipid levels were assessed in 980 individuals (mean [SD] age, 36 [13] years; 510 male individuals [52%]) diagnosed with SCZ, BPD, MDD, or those with a first psychotic episode and in 572 controls (mean [SD] age, 34 [13] years; 323 male individuals [56%]). A total of 77 lipids were found to be significantly altered between those with SCZ (n = 436) and controls (n = 478) in all 3 sample cohorts. Alterations were consistent between cohorts (CN and RU: [Pearson correlation] r = 0.75; DE-AT and CN: r = 0.78; DE-AT and RU: r = 0.82; P < 10-38). A lipid-based predictive model separated patients with SCZ from controls with high diagnostic ability (area under the receiver operating characteristic curve = 0.86-0.95). Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were found to be similar to those of SCZ (BPD: r = 0.89; MDD: r = 0.92; P < 10-79). Assessment of detected alterations in individuals with a first psychotic episode, as well as patients with SCZ not receiving medication, demonstrated only limited association with medication restricted to particular lipids., Conclusions and Relevance: In this study, SCZ was accompanied by a reproducible profile of plasma lipidome alterations, not associated with symptom severity, medication, and demographic and environmental variables, and largely shared with BPD and MDD. This lipid alteration signature may represent a trait marker of severe psychiatric disorders, indicating its potential to be transformed into a clinically applicable testing procedure.

Chlorinated hydrocarbons (CHCs) are often used in industrial processes, and they have been found in groundwater with increasing frequency in recent years. Several typical CHCs, including trichloroethylene (TCE), 1,1,1-trichloroethane (TCA), carbon tetrachloride (CT), etc., have strong cytotoxicity and carcinogenicity, posing a serious threat to human health and ecological environment. Advanced persulfate (PS) oxidation technology based on nano zero-valent iron (nZVI) has become a research hotspot for CHCs degradation in recent years. However, nZVI is easily oxidized to form the surface passivation layer and prone to aggregation in practical application, which significantly reduces the activation efficiency of PS. In order to solve this problem, various nZVI modification solutions have been proposed. This review systematically summarizes four commonly used modification methods of nZVI, and the theoretical mechanisms of PS activated by primitive and modified nZVI. Besides, the influencing factors in the engineering application process are discussed. In addition, the controversial views on which of the two (SO 4 · - and ·OH) is dominant in the nZVI/PS system are summarized. Generally, SO 4 · - predominates in acidic conditions while ·OH prefers neutral and alkaline environments. Finally, challenges and prospects for practical application of CHCs removal by nZVI-based materials activating PS are also analyzed.

Objective: To determine the optimal time to apply a fractional CO 2 laser for the treatment of postsecondary repair scars in patients with cleft lip., Methods: Forty-two patients with linear scarring after cleft lip repair were recruited from November 2021 to October 2022. A single-blind, randomized, controlled cohort study was conducted to examine the impact of fractional CO 2 laser treatment compared with conventional conservative treatment. Thirty patients started laser treatment at 1 month ( n = 10), 3 months ( n = 10), and 6 months ( n = 10) postoperatively, and 12 patients were in the control group. Each patient was treated with high-energy low-density fractional CO 2 laser treatment 3 times at an interval of 1 month. The Vancouver Scar Scale (VSS) was used for scar evaluation to determine vascularity, pigmentation, pliability, and height., Results: The VSS scores decreased significantly after laser treatment ( p < .05), with the most significant improvement in scars in the group that started treatment 1 month after the surgery., Conclusion: Early postoperative fractional CO 2 laser treatment of cleft lip scars is more effective than later treatment., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Schistosomiasis, an ancient and neglected tropical disease, which poses a huge threat to over 200 million people globally. It is necessary to have a general summary of schistosomiasis research after the new roadmap 2021-2030 issued by WHO. This study analyzes the current status of schistosomiasis research from the perspective of the One Health concept by analyzing important research literature published from 2011 to 2020, while further highlighting research priorities, difficulties, and research directions in order to propose suggestions for tropical disease studies research., Methods: Published literature related to schistosomiasis was searched from the Web of Science Core Collection (WoSCC) database. Focusing on a visual analysis of the main research literature in the field of schistosomiasis, CiteSpace software was used to conduct co-occurrence analysis with keywords, countries, institutions, and authors. Moreover, clustering and burst analyses of keywords and co-citation analysis of authors, publications, and journals were performed., Results: A total of 6638 schistosomiasis-related articles were published from 2011 to 2020, all of which can be sourced from the WoSCC database. The publication of schistosomiasis research has remained stable over the past 10 years, and contains studies in the area of human epidemiology, animal surveillance and the environment. The top five high-frequency keywords included Schistosoma mansoni, schistosomiasis, infection, praziquantel, and Schistosoma japonicum. The keywords formed nine clusters, including praziquantel, epidemiology, Schistosoma japonicum, helminths, protein, diagnosis, schistosomiasis, response, and haematobium. In recent years, most research studies focused on the mechanism of liver fibrosis, eliminating schistosomiasis, controlling risk factors, and the relationship between schistosomiasis infection and host immunity. The most productive countries include the United States, China, and Brazil, and the most productive institutions are the University of Basel, the Swiss Tropical and Public Health Institute, and the University of São Paulo. Highly productive authors include Jürg Utzinger and Donald P. McManus. At the time of writing, the author with the highest co-citation frequency (993 times) was Peter Hotez, and the journal with the highest co-citation frequency (3,720 times) was PLoS Neglected Tropical Diseases. Human schistosomiasis, published by Colley et al. (2014), was the most frequently co-cited publication (494 times)., Conclusions: This study provides a preliminary description of the current status of schistosomiasis research and an initial exploration of future research directions. The One Health concept was applied in the field of schistosomiasis control, as confirmed by this bibliometric analysis. Our study provides guidance for the development of research on schistosomiasis and other neglected tropical diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: To evaluate the retinal microvascular alteration after implantable collamer lens (ICL) implantation in moderate to high myopia patients using quantitative optical coherence tomography angiography (OCTA). Methods: This prospective cohort study included 50 eyes of 25 patients with preoperative spherical equivalent ≥ -3.00 D. Patients underwent bilateral ICL implantation at the Department of Ophthalmology, Peking University Third Hospital, from November 2018 to July 2019. OCTA was used to image the superficial and deep retinal capillary plexuses before ICL implantation surgery and at 3 months follow-up. Results: There was no significant difference in the microvascular density within each annular zone and all quadrantal zones of the superficial and deep layers found in myopia patients before and after ICL surgery. Conclusion: Levels of microvascular density in retinal capillary plexuses were stable, as detected by the OCTA, showing the high security of ICL implantation, which would not leave adverse effects on retinal microvasculature in myopia patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tang, Zhang, Sun, Xie, Liu, Liu, Sun and Qi.)

Chronic stress promotes tumor progression and may harm homeostasis of energy metabolism by disrupting key metabolic processes. Recently, emerging evidence that chemokines CXCL3 as a novel adipokine plays a new role in lipid metabolism and various human malignancies. However, the role and mechanism of the CXCL3 in oral squamous cell carcinoma (OSCC) progression and reprogramming lipid metabolism induced by chronic restraint stress is unclear. The analysis of transcriptome sequencing, LC-MS, GC-MS, CCK8, cell apoptosis assays, cell cycle analysis, qRT-PCR, ELISA, western blotting, immunofluorescence, immunohistochemistry, RNA interference and lentivirus transfection and a xenograft tumor growth and chronic restraint stress model were used to investigate the role of CXCL3 in the regulation of lipid metabolism and OSCC and explore the underlying molecular mechanisms. We showed that CXCL3 plays a critical role in in fatty acid de novo synthesis and tumor growth induced by chronic restraint stress. We demonstrated that chronic restraint stress promoted lipid accumulation, OSCC growth and metastasis in a mouse xenograft model. CXCL3 knockdown and FH535, an inhibitor of Wnt/β-catenin pathway, could attenuate fatty acid de novo synthesis, cell proliferation and epithelial-mesenchymal transition induced by chronic restraint stress in OSCC cells. Our findings demonstrate that chronic restraint stress promotes the proliferation and metastasis of OSCC by reprogramming fatty acid metabolism via CXCL3 mediated Wnt/β-catenin pathway. Our study provides novel insights to help understand the underlying mechanisms of CXCL3 in OSCC progression induced by chronic restraint stress., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Di-2-Ethylhexyl Phthalate (DEHP) is often used as an additive in polyvinyl chloride (PVC) to give plastics flexibility, which makes DEHP widely used in food packaging, daily necessities, medical equipment, and other products. However, due to the unstable combination of DEHP and polymer, it will migrate to the environment in the materials and eventually contact the human body. It has been recorded that low-dose DEHP will increase neurotoxicity in the nervous system, and the human health effects of DEHP have been paid attention to because of the extensive exposure to DEHP and its high absorption during brain development. In this study, we review the evidence that DEHP exposure is associated with neurodevelopmental abnormalities and neurological diseases based on human epidemiological and animal behavioral studies. Besides, we also summarized the oxidative damage, apoptosis, and signal transduction disorder related to neurobehavioral abnormalities and nerve injury, and described the potential mechanisms of neurotoxicity caused by DEHP. Overall, we found exposure to DEHP during the critical developmental period will increase the risk of neurobehavioral abnormalities, depression, and autism spectrum disorders. This effect is sex-specific and will continue to adulthood and even have an intergenerational effect. However, the research results on the sex-dependence of DEHP neurotoxicity are inconsistent, and there is a lack of systematic mechanisms research as theoretical support. Future investigations need to be carried out in a large-scale population and model organisms to produce more consistent and convincing results. And we emphasize the importance of mechanism research, which can enhance the understanding of the environmental and human health risks of DEHP exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To compare the postoperative binocular visual quality in six treatment protocols for bilateral age-related cataract surgery with presbyopia correction for clinical decisions., Materials and Methods: In this prospective two-center single-blinded cohort study, participants from North or South China who underwent bilateral phacoemulsification and intraocular lens implantation were divided into six protocols: monovision, diffractive bifocal, mixed, refractive bifocal, trifocal, and micro-monovision extended range of vision (EROV). Binocular visual quality was evaluated at 3 months postoperatively, including binocular uncorrected full-range visual acuity, binocular defocus curves (depth of focus [DoF] and area under the curve [AUC]), binocular visual function (fusion function and stereopsis), binocular subjective spectacle independence rates, visual analog scale (VAS) of overall satisfaction, 25-item visual function questionnaire (VFQ-25), and binocular dysphotopsia symptoms., Results: Of the 300 enrolled patients, 272 (90.7%; 544 eyes) were analyzed. The trifocal protocol showed excellent binocular full-range visual acuity and the best performance for most DoFs and AUCs. The monovision protocol presented the worst binocular visual quality in most perspectives, especially in convergence, distance, and near stereopsis ( p  < 0.001). The full-range subjective spectacle independence rates were sorted from highest to lowest as follows: trifocal (84.8%), refractive bifocal (80.9%), EROV (80.0%), mixed (73.3%), diffractive bifocal (65.2%), and monovision (32.6%) protocols, with no statistically significant differences between the former five protocols ( p  > 0.05). The EROV protocol achieved the highest VAS and VFQ-25 scores. The incidence of postoperative binocular dysphotopsia symptoms was comparable in all protocols., Conclusions: The trifocal protocol showed the best performance, and the monovision protocol presented the worst performance in most perspectives of binocular visual quality for presbyopia correction. The refractive bifocal, mixed, or EROV protocols can provide an approximate performance as a trifocal protocol. Ophthalmologists can customize therapies using different protocols.

Schistosomiasis elimination has been set as a target in the Neglected Tropical Disease Roadmap of 2021 to 2030. The present study assessed the level of understanding, awareness and behaviors of schistosomiasis among students in Zanzibar and explored the influencing factors as the basis for reliable suggestions for the follow-up policy on schistosomiasis prevention and control. A Knowledge, Attitude and Practices (KAP) survey on students’ perceptions of schistosomiasis was conducted on students from grades 4−9 at two selected schools on Pemba, Zanzibar, from May through September in 2021. A total of 217 valid participants responded to the questionnaires. T-test and chi-squared tests were used to examine the association between the dependent and explanatory variables. Multiple linear regressions were used to analyze the influencing factors of KAP. The findings indicated a lack of knowledge about schistosomiasis among the participants. Although respondents were aware of the risks of infection, they continued to engage in high-risk activities. Age, family size and presence of hematuria were found as contributing factors. Elder students performed better on knowledge (p = 0.02) and attitude (p < 0.01) scores, and students with a smaller family received higher attitude scores (p = 0.04). Practice was significantly correlated with gender (p < 0.01) and hematuria (p < 0.01). Several kinds of health education should be adopted to raise students’ basic knowledge of schistosomiasis. It is also critical to make the community aware regarding schistosomiasis. Future efforts for the prevention and control of schistosomiasis should employ an integrated strategy combining communities with schools to encourage behavioral change.

Surface oxidation chemistry involves the formation and breaking of metal-oxygen (M-O) bonds. Ideally, the M-O bonding strength determines the rate of oxygen absorption and dissociation. Here, we design reactive bridging O 2- species within the atomic Cu-O-Fe site to accelerate such oxidation chemistry. Using in situ X-ray absorption spectroscopy at the O K-edge and density functional theory calculations, it is found that such bridging O 2- has a lower antibonding orbital energy and thus weaker Cu-O/Fe-O strength. In selective NH 3 oxidation, the weak Cu-O/Fe-O bond enables fast Cu redox for NH 3 conversion and direct NO adsorption via Cu-O-NO to promote N-N coupling toward N 2 . As a result, 99% N 2 selectivity at 100% conversion is achieved at 573 K, exceeding most of the reported results. This result suggests the importance to design, determine, and utilize the unique features of bridging O 2- in catalysis., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Purpose: The objective of this study was to elucidate the characteristics and mechanism of formation of the fusion plasmid pHNSHP24 carrying mcr-1.1 ., Materials and Methods: mcr-1.1 -bearing Escherichia coli SHP24 and the corresponding transconjugant were subjected to whole-genome sequencing (WGS) combining the Illumina and MinION platforms to obtain the complete sequences of the fusion plasmid and its original plasmids., Results: Complete sequence analysis and S1 nuclease-pulsed field gel electrophoresis (S1-PFGE) results indicated that E. coli SHP24 carried four plasmids: mcr-1.1 -harboring phage-like plasmid pHNSHP24-3, F53:A-:B- plasmid pHNSHP24-4, pHNSHP24-1, and pHNSHP24-2. However, the plasmid pHNSHP24 carrying mcr-1.1 presents in the transconjugant differed from the four plasmids in the donor strain SHP24. Further analysis showed that pHNSHP24 may be the fusion product of pHNSHP24-3 and pHNSHP24-4 and is formed through a replicative transposition mechanism mediated by IS 26 in E. coli SHP24., Conclusion: This study is the first to report the fusion of an mcr-1.1 -harboring phage-like pO111 plasmid and an F53:A-:B- plasmid mediated by IS 26 . Our findings revealed the role of phage-like and fusion plasmids in the dissemination of mcr-1.1 ., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Wu et al.)

Introduction: The aim of this study was to explore a method to rank the cost-effectiveness of presbyopia correction in diverse strategies of bilateral cataract surgery to provide references for healthcare policymakers in rationalizing resource utilization and surgeons in customizing patient management., Methods: The cost-effectiveness analysis based on a prospective single-blind two-center clinical trial included seven strategies in bilateral cataract surgery: monofocal, monovision, diffractive bifocal, blended, refractive bifocal, trifocal, and extended depth of focus (EDOF) strategies. The effectiveness according to the objective spectacle independence rate (hereafter "rate", a novel indicator defined as the proportion of patients with binocular uncorrected distance, intermediate and near visual acuity all better than 0.1 logMAR, logarithm of the minimum angle of resolution), costs, average cost-effectiveness ratios (ACERs, $/1% rate), and incremental cost-effectiveness ratios (ICERs, $/1% incremental rate) were estimated., Results: In 194 participants (388 eyes), the trifocal strategy achieved the highest rate [93.10% (95% confidence interval (CI) 83.8-102.35%)]. The refractive bifocal strategy had the minimum ACER [$45.54/1% rate (95% CI 34.57-56.50)], followed by the blended [$59.10/1% rate (95% CI 31.72-86.48)], diffractive bifocal [$69.06/1% rate (95% CI 30.89-107.21)], EDOF [$72.85/1% rate (95% CI 52.02-93.70)], trifocal [$93.01/1% rate (95% CI 83.23-102.79)], monovision [$136.83/1% rate (95% CI - 55.40 to 329.14)], and monofocal [$264.45/1% rate (95% CI - 97.45 to 626.55)] strategies. Compared with the refractive bifocal strategy, the probabilities that the trifocal strategy (ICER $289.74/1% incremental rate) is very cost-effective and cost-effective were 81.7% and 93.2%, respectively, at the wiliness-to-pay threshold of one and three times China's annual disposable income per capita in 2021 per 10% incremental rates., Conclusions: Cost-effectiveness analysis with ACER and ICER according to objective spectacle independence rate is a helpful tool to identify highly cost-effective presbyopia-correcting strategies in cataract surgery for clinical and policy decisions., Trial Registration: Clinicaltrials.gov (NCT04265846)., (© 2022. The Author(s).)

Background: To assess and compare the efficacy, safety, accuracy, predictability and visual quality of a diffractive trifocal intraocular lens (IOL) and a refractive rotationally asymmetric bifocal IOL in eyes with axial myopia., Methods: This prospective cohort study enrolled patients with implantation of the diffractive trifocal IOL or the refractive bifocal IOL. Eyes were divided into four groups according to the IOL implanted and axial length. Manifest refraction, uncorrected and corrected visual acuity at far, intermediate and near distances, prediction error of spherical equivalent (SE), contrast sensitivity and aberrations were evaluated three months after surgery., Results: In total, 80 eyes of 80 patients were included: 20 eyes in each group. Three months postoperatively, the corrected distance visual acuity of two trifocal groups were significantly better than the axial myopia bifocal group (P = 0.007 and 0.043). There was no significant difference of postoperative SE (P = 0.478), but the SE predictability of the trifocal IOL was better, whether in axial myopia groups (P = 0.015) or in control groups (P = 0.027). The contrast sensitivity was similar among four groups. The total aberration, higher order aberration and trefoil aberration of bifocal groups were significantly higher (all P < 0.001)., Conclusions: The diffractive trifocal IOL and the refractive bifocal IOL both provided good efficacy, accuracy, predictability and safety for eyes with axial myopia. By contrast, the trifocal IOL had a better performance in corrected distance visual acuity and visual quality., Trial Registration: The study was retrospectively registered and posted on clinicaltrials.gov at 12/02/2020 (NCT04265846)., (© 2022. The Author(s).)