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Abstract Background Gliomas are aggressive brain tumors with poor prognosis. Understanding the tumor immune microenvironment (TIME) in gliomas is essential for developing effective immunotherapies. This study aimed to identify TIME-related biomarkers in glioma using bioinformatic analysis of RNA-seq data. Methods In this study, we employed weighted gene co-expression network analysis (WGCNA) on bulk RNA-seq data to identify TIME-related genes. To identify prognostic genes, we performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Based on these genes, we constructed a prognostic signature and delineated risk groups. To validate the prognostic signature, external validation was conducted. Results CD8 + T cell infiltration was strongly correlated with glioma patient prognosis. We identified 115 CD8 + T cell-related genes through integrative analysis of bulk-seq data. CDCA5, KIF11, and KIF4A were found to be significant immune-related genes (IRGs) associated with overall survival in glioma patients and served as independent prognostic factors. We developed a prognostic nomogram that incorporated these genes, age, gender, and grade, providing a reliable tool for clinicians to predict patient survival probabilities. The nomogram’s predictions were supported by calibration plots, further validating its accuracy. Conclusion In conclusion, our study identifies CD8 + T cell infiltration as a strong predictor of glioma patient outcomes and highlights the prognostic value of genes. The developed prognostic nomogram, incorporating these genes along with clinical factors, provides a reliable tool for predicting patient survival probabilities and has important implications for personalized treatment decisions in glioma.

Abstract Lung adenocarcinoma is the most common primary lung cancer seen in the world, and identifying genetic markers is essential for predicting the prognosis of lung adenocarcinoma and improving treatment outcomes. It is well known that alterations in circadian rhythms are associated with a higher risk of cancer. Moreover, circadian rhythms play a regulatory role in the human body. Therefore, studying the changes in circadian rhythms in cancer patients is crucial for optimizing treatment. The gene expression data and clinical data were sourced from TCGA database, and we identified the circadian clock-related genes. We used the obtained TCGA-LUAD data set to build the model, and the other 647 lung adenocarcinoma patients’ data were collected from two GEO data sets for external verification. A risk score model for circadian clock-related genes was constructed, based on the identification of 8 genetically significant genes. Based on ROC analyses, the risk model demonstrated a high level of accuracy in predicting the overall survival times of lung adenocarcinoma patients in training folds, as well as external data sets. This study has successfully constructed a risk model for lung adenocarcinoma prognosis, utilizing circadian rhythm as its foundation. This model demonstrates a dependable capacity to forecast the outcome of the disease, which can further guide the relevant mechanism of lung adenocarcinoma and combine behavioral therapy with treatment to optimize treatment decision-making.

Abstract Background Sulfate-reducing bacteria (SRB) is a potential pathogen usually detected in patients with gastrointestinal diseases. Hydrogen sulfide (H2S), a metabolic byproduct of SRB, was considered the main causative agent that disrupted the morphology and function of gut epithelial cells. Associated study also showed that flagellin from Desulfovibrio vulgaris (DVF), the representative bacterium of the Desulfovibrio genus, could exacerbate colitis due to the interaction of DVF and LRRC19, leading to the secretion of pro-inflammatory cytokines. However, we still have limited understanding about the change of gut microbiota (GM) composition caused by overgrowth of SRB and its exacerbating effects on colitis. Results In this study, we transplanted D. vulgaris into the mice treated with or without DSS, and set a one-week recovery period to investigate the impact of D. vulgaris on the mice model. The outcomes showed that transplanted D. vulgaris into the normal mice could cause the gut inflammation, disrupt gut barrier and reduce the level of short-chain fatty acids (SCFAs). Moreover, D. vulgaris also significantly augmented DSS-induced colitis by exacerbating the damage of gut barrier and the secretion of inflammatory cytokines, for instance, IL-1β, iNOS, and TNF-α. Furthermore, results also showed that D. vulgaris could markedly change GM composition, especially decrease the relative abundance of SCFAs-producing bacteria. Additionally, D. vulgaris significantly stimulated the growth of Akkermansia muciniphila probably via its metabolic byproduct, H2S, in vivo. Conclusions Collectively, this study indicated that transplantation of D. vulgaris could cause gut inflammation and aggravate the colitis induced by DSS.

Abstract The Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 is a multifunctional protein engaged in regulating mitochondrial ultrastructure and ciliogenesis, but its physiological role in the brain remains unclear. Here, we show that FAM92A1 is expressed in neurons starting from embryonic development. FAM92A1 knockout in mice results in altered brain morphology and age-associated cognitive deficits, potentially due to neuronal degeneration and disrupted synaptic plasticity. Specifically, FAM92A1 deficiency impairs diverse neuronal membrane morphology, including the mitochondrial inner membrane, myelin sheath, and synapses, indicating its roles in membrane remodeling and maintenance. By determining the crystal structure of the FAM92A1 BAR domain, combined with atomistic molecular dynamics simulations, we uncover that FAM92A1 interacts with phosphoinositide- and cardiolipin-containing membranes to induce lipid-clustering and membrane curvature. Altogether, these findings reveal the physiological role of FAM92A1 in the brain, highlighting its impact on synaptic plasticity and neural function through the regulation of membrane remodeling and endocytic processes.

Abstract Carbon chain elongation (CCE) is normally carried out using either chemical catalysts or bioenzymes. Herein we demonstrate a catalyst-free approach to promote demethylation C–C coupling reactions for advanced CCE constructed with functional groups under ambient conditions. Accelerated by the electric field, two organic cations containing a methyl group (e.g., ketones, acids, and aldehydes) approach each other with such proximity that the energy of the repulsive Coulomb interaction between these two cations exceeds the bond energy of the methyl group. This results in the elimination of a methyl cation and the coupling of the residual carbonyl carbon groups. As confirmed by high-resolution mass spectrometry and isotope-labeling experiments, the C–C coupling reactions (yields up to 76.5%) were commonly observed in the gas phase or liquid phase, for which the mechanism was further studied using molecular dynamics simulations and stationary-point calculations, revealing deep insights and perspectives of chemistry.

Abstract Background APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). Methods Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. Results Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). Conclusions This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

Abstract Background Depression is a complex mood disorder whose pathogenesis involves multiple cell types and molecular pathways. The prefrontal cortex, as a key brain region for emotional regulation, plays a crucial role in depression. Microglia, as immune cells of the central nervous system, have been closely linked to the development and progression of depression through their dysfunctional states. This study aims to utilize single-cell RNA-seq technology to reveal the pathogenic mechanism of YAP1 in prefrontal cortex microglia in depression. Methods Firstly, we performed cell type identification and differential analysis on normal and depressed prefrontal cortex tissues by mining single-cell RNA-seq datasets from public databases. Focusing on microglia, we conducted sub-clustering, differential gene KEGG enrichment analysis, intercellular interaction analysis, and pseudotime analysis. Additionally, a cross-species analysis was performed to explore the similarities and differences between human and rhesus monkey prefrontal cortex microglia. To validate our findings, we combined bulk RNA-Seq and WGCNA analysis to reveal key genes associated with depression and verified the relationship between YAP1 and depression using clinical samples. Results Our study found significant changes in the proportion and transcriptional profiles of microglia in depressed prefrontal cortex tissues. Further analysis revealed multiple subpopulations of microglia and their associated differential genes and signaling pathways related to depression. YAP1 was identified as a key molecule contributing to the development of depression and was significantly elevated in depression patients. Moreover, the expression level of YAP1 was positively correlated with HAMD scores, suggesting its potential as a biomarker for predicting the onset of depression. Conclusion This study utilized single-cell RNA-seq technology to reveal the pathogenic mechanism of YAP1 in prefrontal cortex microglia in depression, providing a new perspective for a deeper understanding of the pathophysiology of depression and identifying potential targets for developing novel treatment strategies.

Four new erythroneurine leafhopper species, Empoascanara aparaoides Wang & Song, sp. nov., Motaga mengyangensis Wang & Song, sp. nov., Motaga acicularis Wang & Song, sp. nov., and Tautoneura qingxiuensis Wang & Song, sp. nov. from karst areas in Southwestern China, are described and illustrated.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are characterized by excessive triglyceride accumulation in the liver. However, due to an incomplete understanding of its pathogenesis, more efforts are needed to identify specific and effective treatments. N4-acetylcytidine (ac4C) is a newly discovered RNA modification to regulate mRNA. N-acetyltransferase 10 (NAT10) has not been fully explored in MASLD and MASH. Methods: The clinical relevance of NAT10 was evaluated based on its expression in various mouse and human models of MASLD and MASH. Acetylated RNA immunoprecipitation sequencing and mRNA stability assays were used to explore the role of NAT10 in regulating ac4C modification and expression of target genes. Genetically engineered mice were employed to investigate the role of NAT10 in MASLD and MASH progression. Results: Hepatic NAT10 expression was significantly increased in multiple mice and humans of MASLD and MASH. Genetic knockout of NAT10 protected mice from diet-induced hepatic steatosis and steatohepatitis, whereas overexpression of NAT10 exacerbated high-fat-diet-induced liver steatosis. Mechanistically, NAT10 binds to Srebp-1c mRNA, promoting its stability and expression, thereby upregulating lipogenic enzymes. Treatment with Remodelin, a NAT10-specific inhibitor, effectively ameliorates liver steatosis and dyslipidemia in a preclinical mouse model. Conclusions: Our findings indicate that NAT10 could regulate lipid metabolism in MASLD and MASH by stabilizing Srebp-1c mRNA and upregulating lipogenic enzymes. This study highlights the role of NAT10 and RNA acetylation in the pathogenesis of MASLD and MASH. Thus, our findings suggest a promising new therapeutic approach, such as the use of NAT10 inhibitor, for treating metabolic liver disease.

Abstract Photothermal therapy (PTT) holds considerable clinical promise. However, insufficient PTT‐induced tumor recurrence and metastasis is an urgent practical problem that needs to be solved. Herein, a biomimetic mesoporous organosilicon nano‐system called PSAB is designed to precisely deplete cancer stem cells (CSCs) and prevent tumor recurrence and metastasis after PTT. The PSAB system is made up of Aggregation‐induced emission (AIE)‐active photothermal agent, 2TT‐oC26B, and SO2 prodrug, benzothiazole sulfinate (BTS), within mesoporous organosilicon nanoparticles (MON) enclosed by an exterior platelet membrane. PSAB effectively targets CSCs both in vitro and in vivo by P‐selectin/CD44 interaction. The degradation of MON and subsequent release of BTS and AIE molecules are facilitated by intracellular glutathione (GSH). Subsequently, the acidic tumor environment triggers the SO2 gas therapy from BTS. This process leads to the depletion of GSH and CSCs elimination. After combining PSAB with photothermal therapy, there is no significant tumor recurrence or metastasis. These results indicate that SO2 gas therapy and AIE‐mediated PTT act synergistically to offer a unique approach for preventing tumor recurrence and metastasis after PTT, thus holding significant promise for clinical applications in cancer PTT.

Tumor associated macrophages (TAMs) are the predominant innate immune cells in the tumor microenvironment (TME). Cytokines induce the differentiation of macrophages into distinct types of TAMs, primarily characterized by two phenotypes: M1-polarized and M2-polarized. Cancer growth is suppressed by M1-polarized macrophages and promoted by M2-polarized macrophages. The regulation of macrophage M1 polarization has emerged as a promising strategy for cancer immunotherapy. Polysaccharides are important bioactive substances found in numerous plants, manifesting a wide range of noteworthy biological actions, such as immunomodulation, anti-tumor effects, antioxidant capabilities, and antiviral functions. In recent years, there has been a significant increase in interest regarding the immunomodulatory and anti-tumor properties of polysaccharides derived from plants. The regulatory impact of polysaccharides on the immune system is mainly associated with the natural immune response, especially with the regulation of macrophages. This review provides a thorough analysis of the regulatory effects and mechanisms of plant polysaccharides on TAMs. Additionally, an analysis of potential opportunities for clinical translation of plant polysaccharides as immune adjuvants is presented. These insights have greatly advanced the research of plant polysaccharides for immunotherapy in tumor-related applications.

Abstract To explore the impacts of continuous Ganoderma lucidum cultivation on soil physicochemical factors, soil enzyme activity, and the metabolome of Ganoderma lucidum fruiting bodies, this study conducted two consecutive years of cultivation on the same plot of land. Soil physicochemical factors and enzyme activity were assessed, alongside non-targeted metabolomic analysis of the Ganoderma lucidum fruiting bodies under continuous cultivation. The findings unveiled that in the surface soil layer (0–15 cm), there was a declining trend in organic matter, ammonium nitrogen, available phosphorus, available potassium, pH, polyphenol oxidase, peroxidase, alkaline phosphatase, and sucrase, whereas nitrate nitrogen, electrical conductivity (EC), and salt content exhibited an upward trend. Conversely, in the deeper soil layer (15–30 cm), organic matter, ammonium nitrogen, available potassium, alkaline phosphatase, and sucrase demonstrated a decreasing trend, while nitrate nitrogen, available phosphorus, pH, EC, salt content, polyphenol oxidase, and soil peroxidase showed an increasing trend. Metabolomic analysis of Ganoderma lucidum fruiting bodies distinguished 64 significantly different metabolites between the GCK and GT groups, with 39 components having markedly higher relative contents in GCK and 25 components having significantly lower relative contents in GCK compared to GT. Moreover, among these metabolites, there were more types with higher contents in the fruiting bodies harvested in the first year (GCK) compared to those harvested in the second year (GT), with pronounced differences. KEGG pathway analysis revealed that GCK exhibited more complex metabolic pathways compared to GT. The metabolites of Ganoderma lucidum fruiting bodies were predominantly influenced by soil physicochemical factors and soil enzyme activity. In the surface soil layer (0–15 cm), the metabolome was significantly affected by soil pH, soil organic matter, available phosphorus, and soil alkaline phosphatase, while in the deeper soil layer (15–30 cm), differences in the Ganoderma lucidum metabolome were more influenced by soil alkaline phosphatase, soil catalase, pH, nitrate nitrogen, and soil sucrase.

Abstract Background Geographical factors affect the nutritional, therapeutic and commercial values of fruits. Dragon fruit (Hylocereus spp) is a popular fruit in Asia and a potential functional food with diverse pharmacological attributes. Although it is produced in various localities, the information related to the altitudinal variation of dragon fruit nutrients and active compounds is scarce. Hence, this study aimed to investigate the variations in metabolite profiles of H. polyrhizus (variety Jindu1) fruit pulps from three different altitudes of China, including Wangmo (WM, 650 m), Luodian (LD, 420 m), and Zhenning (ZN, 356 m). Jindu1 is the main cultivated pitaya variety in Guizhou province, China. Results The LC-MS (liquid chromatography-mass spectroscopy)-based widely targeted metabolic profiling identified 645 metabolites, of which flavonoids (22.64%), lipids (13.80%), phenolic acids (12.40%), amino acids and derivatives (10.39%), alkaloids (8.84%), and organic acids (8.37%) were dominant. Multivariate analyses unveiled that the metabolite profiles of the fruit differed regarding the altitude. Fruits from WM (highest altitude) were prime in quality, with higher levels of flavonoids, alkaloids, nucleotides and derivatives, amino acids and derivatives, and vitamins. Fruits from LD and ZN had the highest relative content of phenolic acids and terpenoids, respectively. We identified 69 significantly differentially accumulated metabolites across the pulps of the fruits from the three locations. KEGG analysis revealed that flavone and flavonol biosynthesis and isoflavonoid biosynthesis were the most differentially regulated. It was noteworthy that most active flavonoid compounds exhibited an increasing accumulation pattern along with the increase in altitude. Vitexin and isovitexin were the major differentially accumulated flavonoids. Furthermore, we identified two potential metabolic biomarkers (vitexin and kaempferol 3-O-[2-O-β-D-galactose-6-O-a-L-rhamnose]-β-D-glucoside) to discriminate between dragon fruits from different geographical origins. Conclusion Our findings provide insights into metabolic changes in dragon fruits grown at different altitudes. Furthermore, they show that growing pitaya at high altitudes can produce fruit with higher levels of bioactive compounds, particularly flavonoids.

Abstract Background Hamartoma is a common benign tumor that usually occurs in the kidney, liver, lung, and pancreas. Large renal hamartomas may spontaneously rupture and hemorrhage, which is potentially life-threatening. Case presentation This report describes a 46-year-old Han Chinese female patient with multiple renal and hepatic hamartomas with rupture and hemorrhage of giant hamartoma in the left kidney. She underwent arterial embolization three times successively, and her condition was stable during the 2-year follow-up. This report includes a review of the relevant literature Conclusions the findings in this report and previous literature suggest that arterial embolization can not only rapidly treat hamartoma hemorrhage in the acute phase but can also effectively control multiple lesions in the long term after repeated multisite arterial embolization.

Abstract Background Changes in precipitation patterns crucially impact soil microbial communities, and the ecosystem in Qinghai-Tibet Plateau (QTP) is highly vulnerable to climate change. However, we do not fully understand how soil microbial communities in the source wetlands of QTP respond to changes in precipitation. In this study, we employed advanced techniques such as high-throughput sequencing and metabolomics to investigate how soil microbial communities in a source wetland of Qinghai Lake respond to changes in precipitation after quadrennial precipitation treatment. Results Our findings showed that the predominant microbiota in the source wetland was Proteobacteria. Interestingly, alterations in precipitation levels, whether increased or reduced, did not significantly impact the diversity or functional groups of the microbial community. However, the structure of the microbial community did respond notably to changes in precipitation, leading to shifts in the relative abundance of Spirochaetes and Treponema. A notable finding was that reduced precipitation levels (– 25% and − 50%) and mild increases in precipitation (25%) within the region contributed to increased soil carbon content. However, this effect ceased to manifest when precipitation increased by 50%. Additionally, the reduction in precipitation prompted the release of soil metabolites like syringic acid and aldosterone, while enhanced precipitation resulted in a decrease in aldosterone content. Conclusions Precipitation changes altered the relative abundance of soil microbial communities and metabolites, which was conducive to increasing carbon storage in this alpine wetland.

Abstract Arsenic (As) detoxification in polluted soils by iron-based materials can be mediated by the endogenous soil organic matter (SOM), nevertheless the mechanisms remain unclear. Herein, endogenous SOM in a paddy soil was substantially removed to understand its roles on As immobilization by biochar-supported zero-valent iron (ZVI/BC). The results demonstrated that ZVI/BC application significantly decreased As bioavailability by 64.2% compared with the control soil under the anaerobic condition. XPS and HR-TEM suggested As immobilization by ZVI/BC mainly invoked the formation of ternary complexes (i.e., As-Fe-SOM). However, SOM depletion compromised the efficacy of ZVI/BC for As immobilization by 289.8%. This is likely because SOM depletion increased the fulvic acid and OH− contents in soils. Besides, ZVI/BC increased the proportion of As(III) in available As fraction, but SOM depletion altered the mechanisms associated with As(V) reduction. That is, As(V) reduction resulted from the reductive capacity of ZVI in the pristine soil, but the As(V)-reducing bacteria contributed greater to As(V) reduction in the SOM-depleted soil. Additionally, SOM depletion boosted the abundances of Fe(III)- and As(V)-reducing bacteria such as Bacillus and Ammoniphilus in soils, which enhanced the dissimilatory arsenate reduction. Thus, this work highlighted the importance of SOM in the remediation of As-contaminated soils by ZVI/BC. Graphical Abstract

Background Fibrotic metabolic dysfunction-associated steatohepatitis (MASH) is a condition at risk of progressing to advanced liver disease. We examined whether an innovative exhaled nitric oxide (eNO) breath test (BT) can accurately diagnose fibrotic MASH without requiring blood tests.Methods One hundred and forty-seven patients with MASH were recruited, and all tests were undertaken within 1 week of recruitment. With fibrotic MASH (NAS ≥ 4 and fibrosis stage ≥ 2) as the main outcome indicator, the diagnostic efficacy of eNO in identifying fibrotic MASH was compared to other validated models for advanced fibrosis requiring venesection, namely FAST, Agile 3+, and FIB-4 scores.Results The mean age was 40.36 ± 12.28 years, 73.5% were men. Mean body mass index was 28.83 ± 4.31 kg/m2. The proportion of fibrotic MASH was 29.25%. The area under the receiver operating curve for eNO in diagnosing fibrotic MASH was 0.737 [95% CI 0.650–0.823], which was comparable to FAST (0.751 [0.656–0.846]), Agile 3+ (0.764 [0.670–0.858]), and FIB-4 (0.721 [0.620-0.821]) (all DeLong test p > 0.05). A cut-off of eNO 13.5 ppb provided a specificity of 91.3% and a positive predictive value of 65.4% for ruling-in fibrotic MASH. Sensitivity analyses demonstrated that the diagnostic efficacy of eNO was similar across characteristics such as age. Moreover, adding vibration-controlled transient elastography-LSM (liver stiffness measurement) reduced the uncertainty interval from 46.9% to 39.5%.Conclusions The eNO-BT is a promising simple test for non-invasively identifying fibrotic MASH, and its performance is further improved by adding LSM measurement.

Background: Surveillance systems revealed that the prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased. We aim to investigate the epidemiological and genomic characteristics of VREfm in China. Methods: We collected 20,747 non-redundant E. faecium isolates from inpatients across 19 hospitals in six provinces between January 2018 and June 2023. VREfm was confirmed by antimicrobial susceptibility testing. The prevalence was analyzed using changepoint package in R. Genomic characteristics were explored by whole-genome sequencing. Results: 5.59% (1159/20,747) of E. faecium isolates were resistant to vancomycin. The prevalence of VREfm increased in Guangdong province from 5% before 2021 to 20−50% in 2023 (p

ObjectiveEpilepsy-related stigma is a global problem, yet there has been an inadequate focus on children and adolescents. The purpose of this study was to determine the status quo of stigma and its determinants among children and adolescents with epilepsy in China.MethodsA multicenter cross-sectional study was conducted across nine hospitals in eight cities within six provinces in China from 10 October 2023 to 15 June 2024. Participants included patients aged 8 to 18 years with epilepsy and their caregivers. Felt stigma was assessed with the Kilifi Stigma Scale for Epilepsy (KSSE). Social support and self-efficacy were collected through the Social Support Rating Scale (SSRS) and the Generalized Self-Efficacy Scale (GSES). The data were analyzed using t-tests, analysis of variance (ANOVA), Spearman correlation analysis, and multiple linear regression analysis.ResultsThe study enrolled 281 children and adolescents, with a mean age of 12.25 years (SD = 2.56), including 46.6% females. A total of 35.6% participants had self-reported felt stigma. The mean KSSE score is 9.58 (SD = 7.11). Meanwhile, stigma scores correlated strongly with reduced social support (r = −0.55, p 5 years), drug-resistant epilepsy (yes vs. no), comorbidities (yes vs. no), social support and self-efficacy are major influencing factors among the complex factors influencing the felt stigma among children and adolescents.ConclusionMedical staff should be more aware of stigma among children and adolescents with epilepsy, especially those who live in rural and western areas, have poor academic performance, have epilepsy duration of more than 5 years, have drug-resistant epilepsy, and have comorbidities, who are at higher risk of stigma. It is recommended that effective measures be taken to alleviate stigma by improving children and adolescents’ self-efficacy and providing more social support for them and their families.

Abstract Knowing the impacts of global climate change on the habitat suitability distribution of Limassolla leafhoppers contributes to understanding the feedback of organisms on climate change from a macroecological perspective, and provides important scientific basis for protecting the ecological environment and biodiversity. However, there is limited knowledge on this aspect. Thus, our study aimed to address this gap by analyzing Asian habitat suitability and centroid shifts of Limassolla based on 19 bioclimatic variables and occurrence records. Selecting five ecological niche models with the outstanding predictive performance (Maxlike, generalized linear model, generalized additive model, random forest, and maximum entropy) along with their ensemble model from 12 models, the current habitat suitability of Limassolla and its future habitat suitability under two Shared Socio‐economic Pathways (SSP1‐2.6 and SSP5‐8.5) in the 2050s and 2090s were predicted. The results showed that the prediction results of the five models are generally consistent. Based on ensemble model, 11 potential biodiversity hotspots with high suitability were identified. With climate change, the suitable range of Limassolla will experience both expansion and contraction. In SSP5‐8.52050s, the expansion area is 118.56 × 104 km2, while the contraction area is 25.40 × 104 km2; in SSP1‐2.62090s, the expansion area is 91.71 × 104 km2, and the contraction area is 26.54 × 104 km2. Furthermore, the distribution core of Limassolla will shift toward higher latitudes in the northeast direction, and the precipitation of warmest quarter was found to have the greatest impact on the distribution of Limassolla. Our research results supported our four hypotheses. Finally, this research suggests establishing ecological reserves in identified contraction to prevent habitat loss, enhancing the protection of biodiversity hotspots, and pursuing a sustainable development path with reduced emissions.

Parathyroid carcinoma (PC) is a rare and aggressive endocrine malignancy with limited treatment options. Current treatments such as chemotherapy and radiotherapy have demonstrated limited efficacy. Here, we report the case of a male patient who presented with symptoms including polydipsia, polyuria, and joint pain. Further examination revealed a neck lump, hypercalcemia, and hyperparathyroidism, leading to a diagnosis of PC after en bloc surgery. Seven months later, the patient developed local recurrence and lung metastases, which were resected via left lateral neck dissection and thoracoscopic wedge resection. A 422-gene panel test revealed the presence of epidermal growth factor receptor ( EGFR ) p.L858R (c. T2573G) mutation, which may sensitize the EGFR-tyrosine kinase inhibitor response, and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha ( PIK3CA ) p.E545KV (c. G1633A) mutation. After multidisciplinary treatment discussions, the patient was treated with the multi-target tyrosine kinase inhibitor, anlotinib, resulting in survival benefits for 19 months. This case highlights the potential of targeted therapy in terms of long-term survival in patients with distant metastatic PC, as well as the importance of precision therapy guided by genome sequencing to identify potential therapeutic targets.

A three-dimensional (3D) thermal lattice Boltzmann model of crystal growth is presented to study the magneto-hydrodynamics (MHD) mixed convection in the melt of Czochralski silicon single crystal growth in this paper. In order to solve the problem of lattice Boltzmann method’s difficulty in solving the flow of 3D cylindrical cavity, the 3D physical model of crystal growth is transformed from the Cartesian coordinate system to the Curvilinear coordinate system. And the irregular grids in the Cartesian coordinate system are transformed into regular grids in the Curvilinear coordinate system to facilitate the establishment of the Lattice Boltzmann model. Under the above operations, two coupled distribution functions are established to solve the governing equations. Two D3Q19 models are adopted to solve the melt velocity and temperature. And the 3D lattice Boltzmann modeling of crystal growth with cylinder boundary is realized by interpolation in Curvilinear coordinate system. The comparison with the experiment and other references proves that the proposed model and boundary treatment scheme is correct and it proposes a new way for studying the 3D crystal growth or other similar 3D cylindrical cavity simulations. Furthermore, the unstable melt flow for two cases are also simulated in this paper and the critical Reynolds number are also obtained. Results show that the introduction of the transverse magnetic field enhances the stability of the crystal growth system and increases the adjustable range of crystal rotation parameter. The obtained conclusion has an important reference for adjusting the process parameters during the CZ crystal growth.

Fluoride treatment of ZSM-5 zeolite can effectively adjust surface acidity and generate a secondary pore structure. In this study, a series of modified nano-HZSM-5 zeolites were prepared by NH4F-HF mixed solution treatment and applied to the selective conversion of bioethanol to propylene at 500 °C, atmospheric pressure, and a WHSV of 10 h−1. The results showed that NH4F-HF modification weakened the surface acidity of nano-HZSM-5 zeolites, thus inhibiting coke formation. Additionally, the mesopores in the nano-HZSM-5 zeolites increased after NH4F-HF treatment, thereby enhancing the mass transfer rate and improving the coke-resistance ability. The NH4F-HF mixed solution modification significantly improved the stability of nano-HZSM-5 zeolites in catalyzing bioethanol to propylene and greatly extended the working life of nano-HZSM-5 zeolites. It can be seen from the characterization of the deactivated catalysts that coke deposition and weakening of acidity may be the key factors for catalyst deactivation.

Background Reduced cardiorespiratory fitness levels are associated with increased short-term complications after surgery, and potentially exert long-lasting effects on the postoperative lives, work and educational pursuits of patients. Currently, research suggests that lifestyle interventions, such as preoperative physical exercise undertaken by patients themselves, may improve patients’ cardiopulmonary fitness and reduce post-operative complications. This study aims to investigate the effectiveness and feasibility of a remote medical supervision model for prehabilitation exercise in patients undergoing thoracoscopic lung tumour resection surgery. Methods/Design All enrolled patients will participate in a 4-week pre-operative exercise intervention to improve their cardiorespiratory fitness. During this period, patients will wear wearable devices and exercise at home based on exercise prescriptions. The exercise prescription comprises aerobic exercise (three times a week or more), muscle strengthening exercise (twice a week or more), and respiratory muscle exercise (once a day). The primary aim is to investigate whether baseline VO 2 max could be improved following a 4-week preoperative exercise program. Secondary objectives include changes in forced expiratory volume in 1 s and forced vital capacity, degree of acceptance of the technology, quality of life, handgrip strength, postoperative complication rate and length of hospital stay. Discussion This study aims to evaluate the influence of preoperative prehabilitation exercises in a telemedicine active supervision mode in patients undergoing thoracoscopic lung tumour resection. As such, results of this trial might have some impact on future implementations of group- and home-based prehabilitation exercises in lung cancers. Trial registration This study was approved by the Medical Ethics Committee of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (approval number: TJ-IRB20220564) with registration at ClinicalTrials.gov (identifier: NCT05608759).

Soil microbiomes play a crucial role in enhancing plant growth, health, and overall agricultural productivity. Nevertheless, the influence of distinct agricultural management practices on the microbial diversity and community structure within tea (Camellia sinensis) plantations has remained enigmatic. This study postulates that organic agricultural management models can enhance microbial diversity and optimise the microbial community structure within tea plantations, indirectly augmenting soil fertility and tea quality. We employed metagenome technology and conducted molecular ecological network analysis to explore the impact of organic management, pollution-free management, and conventional management on the microbial network structure of tea plantation soil in Weng'an County in the southwestern karst region. Soils subjected to organic management exhibited a higher relative abundance of soil microbial and carbohydrate-active enzyme functional genes than those subjected to other management regimes. Additionally, the relative abundance and diversity of dominant bacteria and keystone species were notably higher under organic management than under the other management regimes. Correlation analysis showed that soil microorganisms were closely related to soil fertility and tea quality, respectively. One-way analysis of variance and the structural equation modelling results showed significant variability in soil fertility under the three agricultural management modes and that soil fertility and soil microbial diversity had a direct impact on tea quality (P > 0.05). In conclusion, this study underscores the profound impact of management modes on microbial diversity and community structure within tea plantations. These management practices alter the soil microbial network structure and potential function, ultimately regulating the microecological dynamics of the soil community in tea plantations.

IntroductionMajor depressive disorder (MDD) is partially inheritable while its mechanism is still uncertain.MethodsThis cross-sectional study focused on gene pathways as a whole rather than polymorphisms of single genes. Deep sequencing and gene enrichment analysis based on pathways in Reactome database were obtained to reveal gene mutations.ResultsA total of 117 patients with MDD and 78 healthy controls were enrolled. The Digestion and Dietary Carbohydrate pathway (Carbohydrate pathway) was determined to contain 100% mutations in patients with MDD and 0 mutation in matched healthy controls.DiscussionFindings revealed in the current study enable a better understanding of gene pathways mutations status in MDD patients, indicating a possible genetic mechanism of MDD development and a potential diagnostic or therapeutic target.

Global climate change has altered the frequency of soil freeze–thaw cycles, but the response of soil microorganisms to different elevation gradients during the early freeze–thaw period remains unclear. So far, the influence of the altitudinal gradient on the microbial community and metabolic characteristics in the early freeze–thaw period of the Qinghai Lake Basin remains unclear. To this end, we collected soil at different elevations in the early freeze–thaw period of the Qinghai Lake Basin and investigated the influence of the elevation gradient on soil microbial community characteristics and soil metabolic processes as well as the corresponding environmental driving mechanism by high-throughput sequencing and LC–MS (Liquid Chromatograph-Mass Spectrometer) nontargeted metabolite determination. The results showed that Proteobacteria were the dominant microflora in the Qinghai Lake Basin. The dominant phyla associated with carbon and nitrogen are Proteobacteria and Firmicutes, both of which are significantly affected by elevation. The soil physicochemical factors jointly affected the soil microbial communities and metabolism. Total phosphorus nitrate nitrogen and pH were the main driving factors of the microbial community, and metabolites were sensitive to changes in chemical factors. In short, the microbial community structure and function, soil physicochemical factors and soil metabolic processes were significantly affected by the altitudinal gradient in the early freeze–thaw period, while the microbial community diversity showed no significant response to the altitudinal gradient. Additionally, a high potassium content in the soil may promote the growth and reproduction of bacteria associated with carbon and nitrogen cycling, as well as the production of metabolites.

The wide utilization of perovskite material as an absorber layer in solar cells necessitates favorable alignment with the perovskite's conduction band, governed by FTO/TiO2 (SnO2). Instead of an ideal electric-selective contact, further improvement of the hole-selective contact is crucial to enhance hole extraction and minimize carrier recombination at the interface between perovskite and spiro-OMeTAD. In this study, we employed series of polar organic molecules [2,4-dimethyl-6,8-bis(4-(methylthio)phenyl)pyrrolo [1,2-a]pyrimidine-7-carbonitrile (PCNS), 2,4-dimethyl-6,8-diphenylpyrrolo [1,2-a]pyrimidine-7-carbonitrile (PCN), and 2,4-dimethyl-6-8-(pyren-1-yl)pyrrolo [1,2-a]pyrimidine-7-carbonitrole (PCNP)] with cyano groups as the interfacial passivate layer to facilitate energy band matching between the perovskite and the hole transport layer as confirmed by the energy band bending at the perovskite surface. Consequently, we achieved effective charge carrier extraction and suitable bandgap alignment. A detailed comparative analysis of the photophysical and electrical properties among the three molecules elucidated the origin of higher open circuit voltage (1.18 ​V) and improved fill factor (83.15 %) in the solar cell device based on PCN molecule (24.22 %).

Abstract Depression is a prevalent mental illness that imposes a substantial public health burden. However, the diverse clinical phenotypes observed in patients make it difficult to realize precise diagnosis. Recently, accumulating preclinical and clinical evidence has suggested that inflammation is involved in the pathophysiology of depression. Herein, a molecular imaging–based strategy was proposed as a means to diagnose depression precisely by specifically visualizing the inflammation status associated with depression. Inflammation-targeting MRI nanoprobes were constructed by attaching an intercellular cell adhesion molecule-1 (ICAM-1)-targeting peptide to biocompatible Fe3O4 nanoparticles. Systematic studies demonstrated that the nanoprobes could specifically target inflamed vascular endothelial cells and visualize the spatial distribution of inflammation in the depressed brain in vivo through susceptibility-weighted imaging (SWI), which was further confirmed by histological analysis. Additionally, these inflammatory brain regions identified by nanoprobe-based imaging are consistent with the focal regions closely associated with the symptoms of depression as reported in previous behavioral studies. Overall, this is the first study to directly visualize the distribution of inflammation in the depressed brain in vivo through a molecular imaging strategy, which may not only facilitate insight into the biological mechanism underlying depression but also provide a potential target within the depressed brain for the further development of anti-inflammatory therapies.

Abstract Magnetic resonance (MR) angiography is one of the main diagnostic approaches for cardiac-cerebral vascular diseases. Nevertheless, the non-contrast-enhanced MR angiography suffers from its intrinsic problems derived from the blood flow-dependency, while the clinical Gd-chelating contrast agents are limited by their rapid vascular extravasation. Herein, we report a hypersensitive MR angiography strategy based on interlocking stratagem of zwitterionic Gd-chelate contrast agents (PAA-Gd). The longitudinal molar relaxivity of PAA-Gd was 4.6-times higher than that of individual Gd-chelates as well as appropriate blood half-life (73.8 min) and low immunogenicity, enabling sophisticated micro-vessels angiography with a resolution at the order of hundred micrometers. A series of animal models of cardiac-cerebrovascular diseases have been built for imaging studies on a 7.0 T MRI scanner, while the clinical translation potential of PAA-Gd has been evaluated on swine on a 3.0 T clinical MRI scanner. The current studies offer a promising strategy for precise diagnosis of vascular diseases.

The nitrogen cycling process in alpine wetlands is profoundly affected by precipitation changes, yet the dynamic response mechanism of denitrifiers to long-term precipitation shifts in the alpine wetland of the Qinghai-Tibet Plateau remains enigmatic. Utilizing high-throughput sequencing analysis of nirS-type functional genes, this study delved into the dynamic response mechanism of nirS-type denitrifiers to precipitation changes in the alpine wetland of Qinghai Lake. The findings revealed that nirS-type denitrifiers in the alpine wetland of Qinghai Lake were primarily Proteobacteria, and Alpha diversity exhibited a negative correlation with the precipitation gradient, with deterministic processes predominating in the community assembly of denitrifying microbes. A 50% increase in rainfall shifted the community assembly process of denitrifiers from deterministic to stochastic. Dominant microflora at the genus level responded significantly to precipitation changes, with aerobic bacteria comprising the majority of differentially abundant taxa (55.56%). As precipitation increased, the complexity of the microbial interaction network decreased, and a 25% reduction in precipitation notably elevated the relative abundance of three key functional groups: chemoheterotrophic, aerobic chemoheterotrophic, and nitrogen fixation. Precipitation notably emerged as the primary regulator of nirS-type denitrifiers in the alpine wetland of Qinghai Lake, accounting for 51% of the variation in community composition. In summary, this study offers a fresh perspective for investigating the ecological processes of nitrogen cycling in alpine ecosystems by examining the diversity and community composition of nirS-type denitrifiers in response to precipitation changes.

This paper analyses the condition necessary to guarantee no divergence for Caputo’s fractional order gradient descent (C-FOG) algorithm on multivariate functions. C-FOG is self-organizing, computationally efficient, simple, and understandable. It converges faster than the classical gradient-based optimization algorithms and converges to slightly different points when the order of the fractional derivative is different. The additional freedom of the order is very useful in situations where the diversity of convergence is required, and it also allows for more precise convergence. Comparative experiments on a typical poor conditioned function and adversarial sample generation frameworks demonstrate the convergence performance of C-FOG, showing that it outperforms currently popular algorithms in terms of convergence speed, and more excitingly, the diversity of convergence allows it to exhibit stronger and more stable attack capability in adversarial sample generation procedures (The code for experiments is available at: https://github.com/mulertan/self_optimizing/tree/main, accessed on 30 April 2024).

Abstract Background Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. Methods Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. Results T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. Conclusion This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis. Graphical Abstract

Abstract Central nervous system (CNS) diseases have been widely acknowledged as one of the major healthy concerns globally, which lead to serious impacts on human health. There will be about 135 million CNS diseases cases worldwide by mid-century, and CNS diseases will become the second leading cause of death after the cardiovascular disease by 2040. Most CNS diseases lack of effective diagnostic and therapeutic strategies with one of the reasons that the biological barrier extremely hampers the delivery of theranostic agents. In recent years, nanotechnology-based drug delivery is a quite promising way for CNS diseases due to excellent properties. Among them, cell membrane-based nanomaterials with natural bio-surface, high biocompatibility and biosafety, are of great significance in both the diagnosis and treatment of different CNS diseases. In this review, the state of art of the fabrication of cell membranes-based nanomaterials is introduced. The characteristics of different CNS diseases, and the application of cell membranes-based nanomaterials in the theranostics are summarized. In addition, the future prospects and limitations of cell membrane nanotechnology are anticipated. Through summarizing the state of art of the fabrication, giving examples of CNS diseases, and highlighting the applications in theranostics, the current review provides designing methods and ideas for subsequent cell membrane nanomaterials.

Abstract Background The primary objective of the research was to develop a method using radiomics-based computed tomography (CT) to predict muscle invasion in bladder cancer (BCa) before surgery. Methods A total of 269 patients with bladder cancer were divided into two groups; training group (n = 188 cases) and validation group (n = 81 cases). Radiomics characteristics were determined by analyzing the CT images of each patient. The least absolute shrinkage and selection operator (LASSO) technique was used for developing a radiomics signature. Furthermore, logistic regression (LR), the support vector machine (SVM), decision tree (DT), and Artificial Neural Network (ANN) models were applied to differentiate between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Their performance was determined using the area under the receiver operating characteristic curve (AUC-ROC). In addition, accuracy, specificity, and sensitivity evaluations were also conducted. Results The radiomics signature was found to be successful in its prediction. A total of 1036 radiomics features were found in the 269 patients, and out of those, 16 were selected as the best predictors of radiomics features. The results revealed that the ANN classifier had the best performance, with a validation set accuracy of 0.950. Conclusions The current work used machine learning and radiomics techniques to successfully construct a prediction model for muscle invasion in bladder cancer. The ANN model produced significant outcomes that may be used in clinical diagnosis or therapy.

The widespread contamination of the aquatic environment by cefalexin (CEX) has attracted extensive attention. Intimately coupled photocatalysis and biodegradation (ICPB) is considered as a promising green technology that provides a new approach for the degradation of this pollutant. Using TiO2 with high active {001} crystal facets exposed as photocatalyst and activated sludge as microbial inoculation source, we successfully constructed the ICPB system for the treatment of cefalexin wastewater. The results demonstrated that ICPB could accomplish rapid and stable contaminant degradation when using various concentrations of CEX to domesticate ICPB system and single biofilm system, which was superior to single biodegradation. The contributions of CEX removal in the ICPB system were photocatalytic (PC), bio-degradation (B), photolysis (P) and adsorption of the carrier (AD) in descending order. UPLC-MS analysis indicated that the ICPB system could convert contaminants into small molecules for microbial utilization or complete mineralization. Microbial community analysis revealed that the abundance of diverse bacteria in the ICPB system changed significantly after CEX addition. Proteobacteria, Firmicutes and Bacteroidetes gradually be-came the dominant genera and could deeply mineralize and utilize CEX as well as its intermediates. This study provides a new strategy for the effective treatment of antibiotic-contaminated domestic wastewater.

In order to ensure the accuracy and reliability of high resolution mass spectrometry for the determination of sildenafil derivatives in aphrodisiac oral liquid, it is necessary to evaluate the uncertainty of the determination results. In this study, the content of 6 sildenafil derivatives in oral liquid health food was determined by ultra-high performance liquid chromatography with quadrupole/electrostatic field Orbitrap high resolution mass spectrometry (UPLC-Q/Orbitrap HRMS). The mathematical model was established and the measurement uncertainty was evaluated according to JJF 1059.1-2012 “Evaluation and Expression of Measurement Uncertainty”. When the contents of N-demethyl sildenafil, dimethyl thiosildenafil, dimethyl sildenafil, hydroxythiocarmo sildenafil, thiocarmo sildenafil and thiosildenafil in oral solution were 0.90, 1.04, 1.22, 2.01, 1.51 and 1.14 mg/kg, the extended uncertainties were 0.07, 0.09, 0.10, 0.16, 0.13 and 0.09 mg/kg (k=2), respectively. The results show that the uncertainty mainly comes from UPLC-Q/Orbitrap HRMS, standard solution preparation, recovery and random effect.

Erythroneurine leafhoppers (Hemiptera, Cicadellidae, Typhlocybinae, Erythroneurini) are utilized to resolve the relationship between the four erythroneurine leafhopper (Hemiptera, Cicadellidae, Typhlocybinae, Erythroneurini): Arboridia (Arboridia) rongchangensis sp. nov., Thaia (Thaia) jiulongensis sp. nov., Mitjaevia bifurcata Luo, Song & Song, 2021 and Mitjaevia diana Luo, Song & Song, 2021, the two new species are described and illustrated. The mitochondrial gene sequences of these four species were determined to update the mitochondrial genome database of Erythroneurini. The mitochondrial genomes of four species shared high parallelism in nucleotide composition, base composition and gene order, comprising 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs) and an AT control region, which was consistent with majority of species in Cicadellidae; all genes revealed common trait of a positive AT skew and negative GC skew. The mitogenomes of four species were ultra-conservative in structure, and which isanalogous to that of others in size and A + T content. Phylogenetic trees based on the mitogenome data of these species and another 24 species were built employing the maximum likelihood and Bayesian inference methods. The results indicated that the four species belong to the tribe Erythroneurini, M. diana is the sister-group relationship of M. protuberanta + M. bifurcata. The two species Arboridia (Arboridia) rongchangensis sp. nov. and Thaia (Thaia) jiulongensis sp. nov. also have a relatively close genetic relationship with the genus Mitjaevia.

Objective: Cholinesterase inhibitor (ChEIs) is the first-line drug for Alzheimer’s disease (AD). Understanding torsade de pointes (TdP)/QT prolongation with different ChEIs is essential for its safe and rational administration. This study aimed to evaluate the correlation between different ChEIs and TdP/QT prolongation.Methods: All ChEIs related TdP/QT prolongation cases were retrieved from the FAERS database using standard MedDRA query (SMQ) from the first quarter of 2004 to the third quarter of 2022. Disproportionality and sensitivity analysis were used to determine the signal of TdP/QT prolongation related to ChEIs.Results: 557 cases of TdP/QT prolongation related to 3 ChEIs were searched by SMQ. The patients were mostly elderly people, with markedly more female than male. The signals of TdP/QT prolongation for ChEIs were detected by disproportionality analysis, and the signal of Donepezil was the strongest. The sensitivity analysis results indicate a robust and stable correlation between these signals with ChEIs. TdP/QT prolongation usually occurs within 1 month after taking ChEIs. The drug with the highest frequency of combination with donepezil and galantamine is citalopram, and the drug with the highest frequency of combination with rivastigmine is atorvastatin.Conclusion: The signals of TdP/QT prolongation related to ChEIs were strong and stable. It is necessary to be vigilant about the TdP/QT prolongation of various ChEIs, especially in elderly women, the initial stage after taking ChEIs, and when ChEIs combining with drugs that could prolong the QT interval.

Background: Drug-induced interstitial lung disease (DILD) is an increasingly common cause of morbidity and mortality. However, due to the lack of specificity, DILD detection remains an unsolved public health challenge. Objectives: For the first time, we aimed to examine DILD reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to identify demographic characteristics and top drugs associated with DILD at a group level (including age, sex, drug class, and country stratification) and individual drug level. Design: A retrospective analysis of the FAERS database was examined by disproportionality analysis. Methods: We reviewed the FAERS database from 2004 to 2021, using search terms ‘interstitial lung disease’ and sorting cases by generic drug name. The reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network were calculated as the measure of strength of association. Results: There were 32,821 DILD reports in the FAERS. After excluding reports without age, sex, or country data according to the specific measurement, the median age of patients was 68 (interquartile range: 59), 54.77% were male, and 46.00% of reports came from Japan. The top drug classes related to DILD in the FAERS were antineoplastic, followed by cardiovascular and antirheumatic agents, in varying order in different sexes. Fam-trastuzumab deruxtecan-nxki, ramucirumab, and eribulin were the top three drugs with the highest strength of association. We also found some drugs without DILD in the labels, such as amiodarone, temsirolimus, and ursodiol. There are significant differences in DILD reports in various countries. For example, the United States and France reported more cardiovascular agents, whereas Canada reported more antirheumatic agents. Conclusion: We found the top drugs and drug classes that were associated with DILD in the FAERS, which provides a real-world window for different ages, sexes, and countries to formulate precise pharmacovigilance policies.

Microbes are critical for flavor formation in fermented foods; however, their mechanisms of action are not fully understood. The microbial composition of 51 dairy and 47 vegetable products was functionally annotated and the carbohydrate-active enzyme (CAZyme) profiles of Lactiplantibacillus plantarum 84-3 (Lp84-3), isolated from dairy samples, can promote resistant starch (RS) degradation, were analyzed. Lactobacillus, Streptococcus, and Lactococcus were the predominant genera in dairy products, whereas the major genera in vegetables were Lactobacillus, Weissella, and Carnimonas. Phages from Siphoviridae, Myoviridae, and Herelleviridae were also present in dairy products. Additionally, the glycosyl hydrolase (GHs) family members GH1 and GH13 and the glycosyltransferase (GTs) family members GT2 and GT4 were abundant in Lp84-3. Moreover, Lp84-3 was enriched in butanoate metabolism enzymes and butanoate metabolite compounds. Therefore, fermented food microbes, especially Lp84-3, have an abundant repertoire of enzymes that promote flavor production, as starter improving the flavor of fermented dairy and vegetable products.

Abstract Effective treatment for metastasis, a leading cause of cancer‐associated death, is still lacking. To seed on a distal organ, disseminated cancer cells (DCCs) must adapt to the local tissue microenvironment. However, it remains elusive how DCCs respond the pro‐metastatic niche signals. Here, systemic motif‐enrichment identified myocyte enhancer factor 2D (MEF2D) as a critical sensor of niche signals to regulate DCCs adhesion and colonization, leading to intrahepatic metastasis and recurrence of liver cancer. In this context, MEF2D transactivates Itgb1 (coding β1‐integrin) and Itgb4 (coding β4‐integrin) to execute temporally unique functions, where ITGB1 recognizes extracellular matrix for early seeding, and ITGB4 acts as a novel sensor of neutrophil extracellular traps‐DNA (NETs‐DNA) for subsequent chemotaxis and colonization. In turn, an integrin‐FAK circuit promotes a phosphorylation‐dependent USP14‐orchastrated deubiquitination switch to stabilize MEF2D via circumventing degradation by the E3‐ubiquitin‐ligase MDM2. Clinically, the USP14(pS432)‐MEF2D‐ITGB1/4 feedback loop is often hyper‐active and indicative of inferior outcomes in human malignancies, while its blockade abrogated intrahepatic metastasis of DCCs. Together, DCCs exploit a deubiquitination‐dependent switch on MEF2D to integrate niche signals in the liver mesenchyme, thereby amplifying the pro‐metastatic integrin‐FAK signaling. Disruption of this feedback loop is clinically applicable with fast‐track potential to block microenvironmental cues driving metastasis.

In this study, we sequenced and reported the complete mitochondrial genomes of Kusala populi for the first time. The complete mitochondrial genome was registered in GenBank with accession number NC_064377 as the first complete mitogenome of the genus Kusala. The circular mitochondrial genome length is 15,402 bp, with nucleotide composition A (41.8%), C (11.4%), G (9.2%), T (37.6%), A + T (79.4%), and C + G (20.6%), comprising 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a D-loop region. All protein-coding genes were encoded by the H-strand, except for 4 genes (nad5, nad4, nad4L, nad1). 8 tRNA genes (tRNA-Gln, tRNA-Cys, tRNA-Tyr, tRNA-Phe, tRNA-His, tRNA-Pro, tRNA-Leu, tRNA-Val) and 2 rRNA genes (16S, 12S) were encoded in the L-strand. Phylogenetic analysis indicated that the newly sequenced species had a close relationship with Mitjaevia, another widespread Old-World genus of Erythroneurini.

Different modified atmosphere packaging bags combined with low temperature treatment were used to store and preserve freshness of Chimonabambusa quadrangularis shoots to investigate the optimal preservation process of freshness of Chimonabambusa quadrangularis shoots. The freshness of Chimonabambusa quadrangularis shoots were stored in four different modified atmosphere packaging bags (WK, PE20, PE30, PE40) for 50 d in a cool storage facility at (1.0±0.3) ℃. The respiration intensity, hardness, browning index, polyphenols, soluble protein, PAL and POD of freshness of Chimonabambusa quadrangularis shoots were measured by sampling every 10 d during storage. And the effect of preservation of freshness of Chimonabambusa quadrangularis shoots by different modified atmosphere packaging bags was analyzed by combining with principal component analysis. The results showed that: PE20 could effectively reduce the respiration intensity of freshness of Chimonabambusa quadrangularis shoots, inhibit the rise of hardness, delay the change of total color difference value of fresh bamboo shoots, and inhibit the rise of decay rate, browning index, POD activity and PAL activity during storage of fresh bamboo shoots. The nutrients (VC, soluble protein) of freshness of Chimonabambusa quadrangularis shoots were maintained at a high level. Principal component analysis showed that respiration intensity, medium hardness, and decay rate were the key indicators affecting the freshness of Chimonabambusa quadrangularis shoots. The results of the analysis were subjected to a composite evaluation score, and the composite evaluation score of PE20 packaging at 50 d was higher than that of the other three modified atmosphere packages. The combined index determination and principal component analysis concluded that the treatment with modified atmosphere packaging bags of PE20 was the most effective in preserving freshness of Chimonabambusa quadrangularis shoots.

Taxus × media, belonging to the genus Taxus of the Taxaceae family, is a unique hybrid plant derived from a natural crossbreeding between Taxus cuspidata and Taxus baccata. This distinctive hybrid variety inherits the superior traits of its parental species, exhibiting significant biological and medicinal values. This paper comprehensively analyzes Taxus × media from multiple dimensions, including its cultivation overview, chemical composition, and multifaceted applications in the medical field. In terms of chemical constituents, this study delves into the bioactive components abundant in Taxus × media and their pharmacological activities, highlighting the importance and value of these components, including paclitaxel, as the lead compounds in traditional medicine and modern drug development. Regarding its medicinal value, the article primarily discusses the potential applications of Taxus × media in combating tumors, antibacterial, anti-inflammatory, and antioxidant activities, and treating diabetes. By synthesizing clinical research and experimental data, the paper elucidates the potential and mechanisms of its primary active components in preventing and treating these diseases. In conclusion, Taxus × media demonstrates its unique value in biological research and tremendous potential in drug development.

Carbon-sequestering microorganisms play an important role in the carbon cycle of wetland ecosystems. However, the response mechanism of carbon-sequestering microbial communities to wetland type changes and their relationship with soil carbon remain unclear. To explore these differences and identify the main influencing factors, this study selected marsh wetlands, river wetlands and lakeside wetlands around Qinghai Lake as research subjects. High-throughput sequencing was employed to analyze the functional gene cbbM of carbon-sequestering microorganisms. The results revealed that the alpha diversity of cbbM carbon-sequestering microorganisms mirrored the trend in total carbon content, with the highest diversity observed in marsh wetlands and the lowest in lakeside wetlands. The dominant bacterial phylum was Proteobacteria, with prevalent genera including Thiothrix, Acidithiobacillus, and Thiodictyon. Acidithiobacillus served as a biomarker in lakeside wetlands, while two other genera were indicative of marsh wetlands. The hierarchical partitioning analysis indicated that the diversity of cbbM carbon-fixing microorganisms was primarily influenced by the total nitrogen content, while the community structure was significantly affected by the soil total carbon content. Moreover, an increased soil temperature and humidity were found to favor the carbon fixation processes of Thiomicrospira, Thiomonas, Polaromonas, and Acidithiobacillus. In summary, changes in wetland types seriously affected the characteristics of cbbM carbon sequestration in microbial communities, and a warm and humid climate may be conducive to wetland carbon sequestration.

With the rise of social media and the internet, the rapid dissemination of information has increased the likelihood of reputation infringement. This study utilizes judicial big data and AI to analyze intrinsic connections in reputation infringement cases, aiding judges in delivering consistent rulings. The challenge lies in balancing freedom of speech with the right to reputation and addressing the ambiguity and subjectivity in infringement cases. This research constructs a structured reputation infringement case dataset from Chinese Judgments Online. It introduces a Fractional Fuzzy Neural System (FFNS) to tackle the vagueness in reputation infringement acts and judicial language, enhancing prediction accuracy for case outcomes. The FFNS, integrating fractional calculus, fuzzy logic, and neural networks, excels in adaptability and nonlinear modeling. It uses fractional order fuzzy membership functions to depict the extent and severity of reputation infringement accurately, combining these outputs with neural networks for predictive analysis. The result is a more precise adjudication tool, demonstrating significant potential for judicial application.

We present a simulation-based study on a 3D heterogeneous photonic integration scheme based on a vertical microring coupler (VμRC). Our research introduces a more compact and efficient layout of photonic devices in the vertical direction, surpassing the limitations of traditional planar integration methods. This investigation focuses on optimizing the performance of the VμRC by analyzing critical parameters such as the dimensions of the microring and the waveguide and the refractive indices of surrounding materials, which serve as the guideline for future manufacturing of the device. The simulation results demonstrate that the careful selection and optimization of these parameters significantly impact the transmittance and coupling characteristics of the VμRC. To demonstrate the validity of this simulation model, we applied it to a few practical cases and achieved comparable results with our previous experiments.

Taxus mairei (Lemée and H.Lév.) S.Y.Hu, indigenous to the southern regions of China, is an evergreen tree belonging to the genus Taxus of the Taxaceae family. Owing to its content of various bioactive compounds, it exhibits multiple pharmacological activities and has been widely applied in clinical medicine. This article comprehensively discusses the current state of cultivation, chemical constituents, applications in the pharmaceutical field, and the challenges faced by T. mairei. The paper begins by detailing the ecological distribution of T. mairei, aiming to provide an in-depth understanding of its origin and cultivation overview. In terms of chemical composition, the article thoroughly summarizes the extracts and monomeric components of T. mairei, unveiling their pharmacological activities and elucidating the mechanisms of action based on the latest scientific research, as well as their potential as lead compounds in new drug development. The article also addresses the challenges in the T. mairei research, such as the difficulties in extracting and synthesizing active components and the need for sustainable utilization strategies. In summary, T. mairei is a rare species important for biodiversity conservation and demonstrates significant research and application potential in drug development and disease treatment.

Abstract Biology and the environment are inextricably linked. Insects are intricately linked to their habitats as part of the ecosystem. In this study, scanning electron microscopy (SEM) observations showed two sensilla chaetica, several sensilla trichodea, and at least one sensilla basiconicum on the antennae of typhlocybine insects. There were no sensilla on the labrum; however, the surface morphology was different. There were more sensilla trichodea on the surface, mostly symmetrically distributed along the labial groove, and there was little difference in the structure of the stylet fascicle. The correlation between the sensilla number on the body surface of typhlocybine insects and environmental factors in the 3 study areas was as follows: Huajiang > Bijie > Shibing, which is consistent with the classification of rocky desertification grade; that is, the higher the rocky desertification grade, the greater the sensilla number on leafhoppers affected by the environment. The correlation between the number of leafhoppers and environmental factors in the 3 months was as follows: end of September > end of May > end of July, which was consistent with the changing temperature trends. The results of this study enrich our knowledge of the morphological characteristics of leafhoppers and explore the potential value of insect surface ultra‐morphology for use by humans.