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Abstract Background Previous studies into the interactions between native and invasive species under nitrogen (N) deposition have often overlooked the presence of co-occurring native species, a factor that could influence the outcomes of interspecific competition. Furthermore, publication bias may lead researchers to focus on rare native species with limited adaptability. In this study, we examined how two levels of N deposition affected the physiological and ecological traits and the interspecies interactions between three invasive and three common native species. Results N deposition promoted the growth of both invasive and native species. The relative dominance index (RDI) of invasive species was consistently higher than that of native species. Invasive species had an advantage over common native species in using the increased N effectively. The biomass distribution of invasive species was biased toward the aboveground parts, indicating competition for light resources. Conclusions N deposition conferred a stronger competitive advantage to invasive species than to native species, suggesting that the distribution range of invasive species may expand further under increased N deposition.

Abstract Although the relationship between hypertension and hyperuricemia is widely recognized, there is still a relative lack of research on prehypertensive individuals and the individual associations of systolic and diastolic blood pressure with the risk of hyperuricemia. From 2011 to 2016, we conducted a study on 53,323 individuals at Wuhu City Hospital in China. Based on initial blood pressure readings, participants were categorized into normal, prehypertension, or hypertension groups. We used Cox regression to analyze the associations with baseline factors. In subgroup analyses, systolic and diastolic pressures were treated as continuous variables, and their relationship with the risk of hyperuricemia was examined using restricted cubic spline analysis. The risk increased in the prehypertension and hypertension groups compared to the normal blood pressure group, with hazard ratios of 1.192 and 1.350, respectively. For each unit increase in blood pressure, the risk of hyperuricemia rose by 0.8% (systolic) and 0.9% (diastolic), especially when blood pressure levels exceeded 115/78 mmHg. Additionally, we observed that factors such as gender, alcohol consumption habits, obesity, and dyslipidemia might further influence this association. These findings emphasize the importance of early risk assessment and intervention in these patient populations in clinical practice.

Abstract Objective To investigate the influence of aerobic exercise on depression among the young people. Data sources PubMed, Web of science, Embase, Cochrane, EBSCO were searched from inception to November 2023. Study selection RCT studies, assessing the use of aerobic exercise in young people aged 6–35 years and then determining the development of depression in young people (aged 6–35 years), were selected, and mean ± SD values adjusted for the presence of baseline depression were extracted. Data extraction and synthesis Study quality was assessed using the Review manager 5.4.1 and Cochrane 5.1 item on risk of bias and precision of observational studies. Two reviewers conducted all review stages independently. Selected data were pooled using random-effects meta-analysis. Main outcomes and measures The included studies evaluated the relationship between aerobic exercise and depression at various time points among young individuals, and provided corresponding mean ± SD values. Depression diagnosis in the selected studies was conducted using the Depression Correlation Scale. Results After screening 2296 articles, 163 articles were selected for full-text review, and 8 of those were further reviewed. Ultimately, 12 studies, involving 658 individuals, were included in the meta-analysis. The results of the meta-analysis indicated that aerobic exercise could effectively improve depression in young people (d = -1.33, 95%CI: -1.78 ~ -0.87, P

Abstract Wooden buildings represent a unique aspect of China’s architectural heritage. However, over time, these buildings have suffered varying degrees of structural damage, particularly those located in China’s mountainous regions. Frequent natural disasters and inconvenient transportation further exacerbate the vulnerability of these structures. This study focuses on the typical wooden stilt houses found in the Wuling Mountain area of southwest Hubei. The different forms of columns and beams, as well as the overall structural symmetry of the stilt houses, were classified into five common structural types. Precise digital models were established via real photos and collected dimensional data, and these five models were evaluated for static, buckling, utilization, and ultimate limit states. The results indicate that: (1) overall symmetrical structures perform better than asymmetrical ones; (2) structures where all columns are grounded and act as support columns exhibit the best overall mechanical performance; and (3) transverse-tie beams(chuanfang) primarily serve a connecting role rather than a load-bearing role, thus an excess of transverse-tie beams(chuanfang) can reduce the stability of the building structure. Based on the analysis results, targeted protective measures and recommendations were proposed and verified through structural evaluations. These initiatives provide new methods and insights for the protection of architectural heritage.

Abstract Background Education is an important part of the work of most doctors. Clinical preceptors act as role models and supervisors. Preceptors’ quality of supervision strongly influences the learning quality of clinical interns (Bartlett et al. BMC Med Educ 20:165, 2020). To ensure a consistent approach to every preceptorship experience, the competency of clinical preceptors should be assessed to ensure that the desired outcomes are achieved. This study aims to evaluate clinical preceptors’ competency in learner-centered teaching, to provide constructive feedback to develop the preceptors’ competency and improve supervisory skills and internship quality at Kunming Medical University (KMU) in Kunming of China. Methods This is a cross-sectional study with a quantitative self-administered online questionnaire. The convenience sampling technique was employed. In the undergraduate internship stage of KMU, clinical preceptors (N = 340) and interns (N = 487) were invited to use the augmented Stanford Faculty Development Program questionnaire (SFDPQ) (Stalmeijer et al. Med Teach 30:e272–e277, 2008), to (self-) assess the preceptor’s competency of learner-centered teaching on a five-point scale (1 = strongly disagree, 5 = strongly agree). Results Two hundred twenty-eight preceptors and two hundred thirty-six interns completed the questionnaire correctly. Overall, the assessment was positive, but the preceptors’ self-assessment significantly higher than the interns’ (p

Abstract Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins is commonly associated with a variety of stress responses and cellular processes in eukaryotes, but its potential roles in bacteria are unclear. Here, we show that protein HmwC acts as an O-GlcNAc transferase (OGT) responsible for O-GlcNAcylation of multiple proteins in Yersinia pestis, a flea-borne pathogen responsible for plague. We identify 64 O-GlcNAcylated proteins (comprising 65 sites) with differential abundance under conditions mimicking the mammalian host (Mh) and flea vector (Fv) environments. Deletion of hmwC, encoding a putative OGT, structurally distinct from any existing member of the GT41 family, results in reduced O-GlcNAcylation, reduced growth, and alterations in virulence properties and survival under stress. Purified HmwC can modify target proteins in vitro using UDP-GlcNAc as sugar donor. One of the target proteins, OsdY, promotes Y. pestis survival under oxidative stress conditions. Thus, our results support that regulation of antioxidative responses through O-GlcNAcylation may be a conserved process shared by prokaryotes and eukaryotes.

Abstract Biological invasions pose a significant threat to ecosystems, disrupting local biodiversity and ecosystem functions. The genomic underpinnings of invasiveness, however, are still largely unknown, making it difficult to predict and manage invasive species effectively. The common reed (Phragmites australis) is a dominant grass species in wetland ecosystems and has become particularly invasive when transferred from Europe to North America. Here, we present a high-quality gap-free, telomere-to-telomere genome assembly of Phragmites australis consisting of 24 pseudochromosomes and a B chromosome. Fully phased subgenomes demonstrated considerable subgenome dominance and revealed the divergence of diploid progenitors approximately 30.9 million years ago. Comparative genomics using chromosome-level scaffolds for three other lineages and a previously published draft genome assembly of an invasive lineage revealed that gene family expansions in the form of tandem duplications may have contributed to the invasiveness of the lineage. This study sheds light on the genome evolution of Arundinoideae grasses and suggests that genetic drivers, such as gene family expansions and tandem duplications, may underly the processes of biological invasion in plants. These findings provide a crucial step toward understanding and managing the genetic basis of invasiveness in plant species.

Background: In past studies, non-medical factors in the social-healthcare-patient triad associated with the prevalence of COVID-19 have led to delays in the presentation of patients with acute appendicitis and an increase in complications. However, as research progresses, there is increasing evidence of a clinical association between COVID-19 and the development of acute appendicitis. Methods: The effect of COVID-19 prevalence and associated factors on acute appendicitis in the control (2016–2019) and exposed (2020−2023) groups was derived from a retrospective study of 3070 patients with acute appendicitis from 2016 to 2023. Results: After the implementation of the restrictions, the rate of acute appendicitis visits in the exposed group compared to the control group dropped sharply in the initial period (P = 0.047) and recovered gradually with the relaxation of the restrictions. Similar changes occurred in the number of acute complicated appendicitis visits. In addition, after the lifting of restrictions and the COVID-19 outbreak, the proportion of acute complicated appendicitis in the exposed group increased significantly (P

Abstract Background PM2.5 can induce and aggravate the occurrence and development of cardiovascular diseases (CVDs). The objective of our study is to estimate the causal effect of PM2.5 on mortality rates associated with CVDs using the instrumental variables (IVs) method. Methods We extracted daily meteorological, PM2.5 and CVDs death data from 2016 to 2020 in Binzhou. Subsequently, we employed the general additive model (GAM), two-stage predictor substitution (2SPS), and control function (CFN) to analyze the association between PM2.5 and daily CVDs mortality. Results The 2SPS estimated the association between PM2.5 and daily CVDs mortality as 1.14% (95% CI: 1.04%, 1.14%) for every 10 µg/m3 increase in PM2.5. Meanwhile, the CFN estimated this association to be 1.05% (95% CI: 1.02%, 1.10%). The GAM estimated it as 0.85% (95% CI: 0.77%, 1.05%). PM2.5 also exhibited a statistically significant effect on the mortality rate of patients with ischaemic heart disease, myocardial infarction, or cerebrovascular accidents (P

Abstract Background During the prolonged period from Human Papillomavirus (HPV) infection to cervical cancer development, Low-Grade Squamous Intraepithelial Lesion (LSIL) stage provides a critical opportunity for cervical cancer prevention, giving the high potential for reversal in this stage. However, there is few research and a lack of clear guidelines on appropriate intervention strategies at this stage, underscoring the need for real-time prognostic predictions and personalized treatments to promote lesion reversal. Methods We have established a prospective cohort. Since 2018, we have been collecting clinical data and pathological images of HPV-infected patients, followed by tracking the progression of their cervical lesions. In constructing our predictive models, we applied logistic regression and six machine learning models, evaluating each model’s predictive performance using metrics such as the Area Under the Curve (AUC). We also employed the SHAP method for interpretative analysis of the prediction results. Additionally, the model identifies key factors influencing the progression of the lesions. Results Model comparisons highlighted the superior performance of Random Forests (RF) and Support Vector Machines (SVM), both in clinical parameter and pathological image-based predictions. Notably, the RF model, which integrates pathological images and clinical multi-parameters, achieved the highest AUC of 0.866. Another significant finding was the substantial impact of sleep quality on the spontaneous clearance of HPV and regression of LSIL. Conclusions In contrast to current cervical cancer prediction models, our model’s prognostic capabilities extend to the spontaneous regression stage of cervical cancer. This model aids clinicians in real-time monitoring of lesions and in developing personalized treatment or follow-up plans by assessing individual risk factors, thus fostering lesion spontaneous reversal and aiding in cervical cancer prevention and reduction. Graphical Abstract

Abstract Introduction Hepatocellular carcinoma (HCC) is characterized by the complex pathogenesis, limited therapeutic methods, and poor prognosis. Endoplasmic reticulum stress (ERS) plays an important role in the development of HCC, therefore, we still need further study of molecular mechanism of HCC and ERS for early diagnosis and promising treatment targets. Method The GEO datasets (GSE25097, GSE62232, and GSE65372) were integrated to identify differentially expressed genes related to HCC (ERSRGs). Random Forest (RF) and Support Vector Machine (SVM) machine learning techniques were applied to screen ERSRGs associated with endoplasmic reticulum stress, and an artificial neural network (ANN) diagnostic prediction model was constructed. The ESTIMATE algorithm was utilized to analyze the correlation between ERSRGs and the immune microenvironment. The potential therapeutic agents for ERSRGs were explored using the Drug Signature Database (DSigDB). The immunological landscape of the ERSRGs central gene PPP1R16A was assessed through single-cell sequencing and cell communication, and its biological function was validated using cytological experiments. Results An ANN related to the ERS model was constructed based on SRPX, THBS4, CTH, PPP1R16A, CLGN, and THBS1. The area under the curve (AUC) of the model in the training set was 0.979, and the AUC values in three validation sets were 0.958, 0.936, and 0.970, respectively, indicating high reliability and effectiveness. Spearman correlation analysis suggests that the expression levels of ERSRGs are significantly correlated with immune cell infiltration and immune-related pathways, indicating their potential as important targets for immunotherapy. Mometasone was predicted to be the most promising treatment drug based on its highest binding score. Among the six ERSRGs, PPP1R16A had the highest mutation rate, predominantly copy number mutations, which may be the core gene of the ERSRGs model. Single-cell analysis and cell communication indicated that PPP1R16A is predominantly distributed in liver malignant parenchymal cells and may reshape the tumor microenvironment by enhancing macrophage migration inhibitory factor (MIF)/CD74 + CXCR4 signaling pathways. Functional experiments revealed that after siRNA knockdown, the expression of PPP1R16A was downregulated, which inhibited the proliferation, migration, and invasion capabilities of HCCLM3 and Hep3B cells in vitro. Conclusion The consensus of various machine learning algorithms and artificial intelligence neural networks has established a novel predictive model for the diagnosis of liver cancer associated with ERS. This study offers a new direction for the diagnosis and treatment of HCC.

Abstract Background Myocardial infarction (MI) leads to enhanced activity of cardiac fibroblasts (CFs) and abnormal deposition of extracellular matrix proteins, resulting in cardiac fibrosis. Tartrate-resistant acid phosphatase 5 (ACP5) has been shown to promote cell proliferation and phenotypic transition. However, it remains unclear whether ACP5 is involved in the development of cardiac fibrosis after MI. The present study aimed to investigate the role of ACP5 in post-MI fibrosis and its potential underlying mechanisms. Methods Clinical blood samples were collected to detect ACP5 concentration. Myocardial fibrosis was induced by ligation of the left anterior descending coronary artery. The ACP5 inhibitor, AubipyOMe, was administered by intraperitoneal injection. Cardiac function and morphological changes were observed on Day 28 after injury. Cardiac CFs from neonatal mice were extracted to elucidate the underlying mechanism in vitro. The expression of ACP5 was silenced by small interfering RNA (siRNA) and overexpressed by adeno-associated viruses to evaluate its effect on CF activation. Results The expression of ACP5 was increased in patients with MI, mice with MI, and mice with Ang II-induced fibrosis in vitro. AubipyOMe inhibited cardiac fibrosis and improved cardiac function in mice after MI. ACP5 inhibition reduced cell proliferation, migration, and phenotypic changes in CFs in vitro, while adenovirus-mediated ACP5 overexpression had the opposite effect. Mechanistically, the classical profibrotic pathway of glycogen synthase kinase-3β (GSK3β)/β-catenin was changed with ACP5 modulation, which indicated that ACP5 had a positive regulatory effect. Furthermore, the inhibitory effect of ACP5 deficiency on the GSK3β/β-catenin pathway was counteracted by an ERK activator, which indicated that ACP5 regulated GSK3β activity through ERK-mediated phosphorylation, thereby affecting β-catenin degradation. Conclusion ACP5 may influence the proliferation, migration, and phenotypic transition of CFs, leading to the development of myocardial fibrosis after MI through modulating the ERK/GSK3β/β-catenin signaling pathway.

Abstract Effective representation of molecules is a crucial factor affecting the performance of artificial intelligence models. This study introduces a flexible, fragment-based, multiscale molecular representation framework called t-SMILES (tree-based SMILES) with three code algorithms: TSSA (t-SMILES with shared atom), TSDY (t-SMILES with dummy atom but without ID) and TSID (t-SMILES with ID and dummy atom). It describes molecules using SMILES-type strings obtained by performing a breadth-first search on a full binary tree formed from a fragmented molecular graph. Systematic evaluations using JTVAE, BRICS, MMPA, and Scaffold show the feasibility of constructing a multi-code molecular description system, where various descriptions complement each other, enhancing the overall performance. In addition, it can avoid overfitting and achieve higher novelty scores while maintaining reasonable similarity on labeled low-resource datasets, regardless of whether the model is original, data-augmented, or pre-trained then fine-tuned. Furthermore, it significantly outperforms classical SMILES, DeepSMILES, SELFIES and baseline models in goal-directed tasks. And it surpasses state-of-the-art fragment, graph and SMILES based approaches on ChEMBL, Zinc, and QM9.

Abstract Cities are main carbon emissions generators. Land use changes can not only affect terrestrial ecosystems carbon, but also anthropogenic carbon emissions. However, carbon monitoring at a spatial level is still coarse, and low-carbon land use encounters the challenge of being unable to adjust at the patch scale. This study addresses these limitations by using land-use data and various auxiliary data to explore new methods. The approach involves developing a high-resolution carbon monitoring model and investigating a patch-scale low-carbon land use model by integrating high carbon sink/source images with the Future Land Use Simulation model. Between 2000 and 2020, the results reveal an increasing trend in both carbon emissions and carbon sinks in the Shangyu district. Carbon sinks can only offset approximately 3% of the total carbon emissions. Spatially, the north exhibits net carbon emissions, while the southern region functions more as a carbon sink. A total of 14.5% of the total land area witnessed a change in land-use type, with the transfer-out of cropland constituting the largest area at 96.44 km2, accounting for 50% of the total transferred area. Land-use transfer resulted in an annual increase of 77.72 × 104 t in carbon emissions between 2000 and 2020. Through land-use structure optimisation, carbon emissions are projected to increase by only 7154 t C/year from 2000 to 2030, significantly lower than the amount between 2000 and 2020. Further low-carbon land optimisation at the patch scale can enhance the carbon sink by 129.59 t C/year. The conclusion drawn is that there is considerable potential to reduce carbon emissions through land use control. The new methods developed in our study can effectively contribute to high-resolution carbon monitoring in spatial contexts and support low-carbon land use, promoting the application of low-carbon land use from theory to practice. This will provide technological guidance for land use planning, city planning, and so forth.

AIM: To explore the effect of epidermal growth factor receptor (EGFR) inhibition by erlotinib and EGFR siRNA on epidermal growth factor (EGF)-induced activation of retinal pigment epithelium (RPE) cells. METHODS: Human RPE cell line (ARPE-19 cells) was activated by 100 ng/mL EGF. Erlotinib and EGFR siRNA were used to intervene EGF treatment. Cellular viability, proliferation, and migration were detected by methyl thiazolyl tetrazolium (MTT) assay, bromodeoxyuridine (BrdU) staining assay and wound healing assay, respectively. EGFR/protein kinase B (AKT) pathway proteins and N-cadherin, α-smooth muscle actin (α-SMA), and vimentin were tested by Western blot assay. EGFR was also determined by immunofluorescence staining. RESULTS: EGF treatment for 24h induced a significant increase of ARPE-19 cells' viability, proliferation and migration, phosphorylation of EGFR/AKT proteins, and decreased total EGFR expression. Erlotinib suppressed ARPE-19 cells' viability, proliferation and migration through down regulating total EGFR and AKT protein expressions. Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin, α-SMA, and vimentin proteins. Similarly, EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation, viability, and migration, phosphorylation of EGFR/AKT proteins, and up-regulation of N-cadherin, α-SMA, and vimentin proteins. CONCLUSION: Erlotinib and EGFR-knockdown suppress EGF-induced cell viability, proliferation, and migration via EGFR/AKT pathway in RPE cells. EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy (PVR).

Abstract Sunlight is closely intertwined with daily life. It remains unclear whether there are associations between sunlight exposure and brain structural markers. General linear regression analysis was used to compare the differences in brain structural markers among different sunlight exposure time groups. Stratification analyses were performed based on sex, age, and diseases (hypertension, stroke, diabetes). Restricted cubic spline was performed to examine the dose–response relationship between natural sunlight exposure and brain structural markers, with further stratification by season. A negative association of sunlight exposure time with brain structural markers was found in the upper tertile compared to the lower tertile. Prolonged natural sunlight exposure was associated with the volumes of total brain (β: − 0.051, P

AIM: To explore the effects of hepatocyte growth factor (HGF) on retinal pigment epithelium (RPE) cell behaviors. METHODS: The human adult retinal pigment epithelial cell line-19 (ARPE-19) were treated by HGF or mesenchymal-epithelial transition factor (MET) inhibitor SU11274 in vitro. Cell viability was detected by a Cell Counting Kit-8 assay. Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay, respectively. The expression levels of MET, phosphorylated MET, protein kinase B (AKT), and phosphorylated AKT proteins were determined by Western blot assay. The MET and phosphorylated MET proteins were also determined by immunofluorescence assay. RESULTS: HGF increased ARPE-19 cells' viability, proliferation and migration, and induced an increase of phosphorylated MET and phosphorylated AKT proteins. SU11274 significantly reduced cell viability, proliferation, and migration and decreased the expression of MET and AKT proteins. SU11274 suppressed HGF-induced increase of viability, proliferation, and migration in ARPE-19 cells. Additionally, SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins. CONCLUSION: HGF enhances cellular viability, proliferation, and migration in RPE cells through the MET/AKT signaling pathway, whereas this enhancement is suppressed by the MET inhibitor SU11274. HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

Real-world passive radiative cooling requires highly emissive, selective, and omnidirectional thermal emitters to maintain the radiative cooler at a certain temperature below the ambient temperature while maximizing the net cooling power. Despite various selective thermal emitters have been demonstrated, it is still challenging to achieve these conditions simultaneously because of the extreme difficulty in controlling thermal emission of photonic structures in multidimension. Here we demonstrated hybrid polar dielectric metasurface thermal emitters with machine learning inverse design, enabling a high emissivity of ~0.92 within the atmospheric transparency window 8–13 μm, a large spectral selectivity of ~1.8 and a wide emission angle up to 80 degrees, simultaneously. This selective and omnidirectional thermal emitter has led to a new record of temperature reduction as large as ~15.4 °C under strong solar irradiation of ~800 W/m2, significantly surpassing the state-of-the-art results. The designed structures also show great potential in tackling the urban heat island effect, with modelling results suggesting a large energy saving and deployment area reduction. This research will make significant impact on passive radiative cooling, thermal energy photonics and tackling global climate change.

Abstract Background We aimed to explore the application value of various machine learning (ML) algorithms based on multicenter CT radiomics in identifying peripheral nerve invasion (PNI) of colorectal cancer (CRC). Methods A total of 268 patients with colorectal cancer who underwent CT examination in two hospitals from January 2016 to December 2022 were considered. Imaging and clinicopathological data were collected through the Picture Archiving and Communication System (PACS). The Feature Explorer software (FAE) was used to identify the peripheral nerve invasion of colorectal patients in center 1, and the best feature selection and classification channels were selected. Finally, the best feature selection and classifier pipeline were verified in center 2. Results The six-feature models using RFE feature selection and GP classifier had the highest AUC values, which were 0.610, 0.699, and 0.640, respectively. FAE generated a more concise model based on one feature (wavelet-HLL-glszm-LargeAreaHighGrayLevelEmphasis) and achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively, using the “one standard error” rule. Using ANOVA feature selection, the GP classifier had the best AUC value in a one-feature model, with AUC values of 0.611, 0.663, and 0.643 on the validation, internal test, and external test sets, respectively. Similarly, when using the “one standard error” rule, the model based on one feature (wave-let-HLL-glszm-LargeAreaHighGrayLevelEmphasis) achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively. Conclusions Combining artificial intelligence and radiomics features is a promising approach for identifying peripheral nerve invasion in colorectal cancer. This innovative technique holds significant potential for clinical medicine, offering broader application prospects in the field. Critical relevance statement The multi-channel ML method based on CT radiomics has a simple operation process and can be used to assist in the clinical screening of patients with CRC accompanied by PNI. Key points • Multi-channel ML in the identification of peripheral nerve invasion in CRC. • Multi-channel ML method based on CT-radiomics can detect the PNI of CRC. • Early preoperative identification of PNI in CRC is helpful to improve the formulation of treatment strategies and the prognosis of patients. Graphical Abstract

Abstract Background Intestinal barrier is a dynamic interface between the body and the ingested food components, however, dietary components or xenobiotics could compromise intestinal integrity, causing health risks to the host. Gossypol, a toxic component in cottonseed meal (CSM), caused intestinal injury in fish or other monogastric animals. It has been demonstrated that probiotics administration benefits the intestinal barrier integrity, but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear. Here, a strain (YC) affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia (Oreochromis niloticus) and its potential to repair gossypol-induced intestinal damage was evaluated. Results A total of 270 Nile tilapia (2.20 ± 0.02 g) were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON (control diet), GOS (control diet containing 300 mg/kg gossypol) and GP (control diet containing 300 mg/kg gossypol and 108 colony-forming unit (CFU)/g P. pentosaceus YC), respectively. After 10 weeks, addition of P. pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia. Transcriptome analysis and siRNA interference experiments demonstrated that NOD-like receptors (NLR) family caspase recruitment domain (CARD) domain containing 3 (Nlrc3) inhibition might promote intestinal stem cell (ISC) proliferation, as well as maintaining gut barrier integrity. 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) revealed that addition of P. pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut. In vitro studies on propionate’s function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model. Conclusions The present study reveals that P. pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level. This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations. Graphical Abstract

Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.

ABSTRACT Yersinia pestis has recently evolved into a highly lethal flea-borne pathogen through the pseudogenization of extensive genes and the acquisition of exogenous plasmids. Particularly noteworthy are the newly acquired pPCP1 and pMT1 plasmids, which encode the virulence determinants Pla and Yersinia murine toxin (Ymt), crucial for subcutaneous infection and survival within flea vector of Y. pestis, respectively. This study reveals that Pla can cleave Ymt at K299 both in vivo and in vitro. Y. pestis expressing YmtK299A displays enhanced in vitro biofilm formation and increased blood survival, indicating significant roles of Pla-mediated Ymt cleavage in these phenotypes. Intriguingly, although both the ancestral form of Pla and the prevalent Pla-I259T variant in modern Y. pestis strains are capable of cleaving Ymt at K299, the cleavage efficiency of Pla-I259T is only half that of the ancestral variant. In subcutaneous infection, mice infected with Δymt::ymt-K299A show significantly prolonged survival compared to those infected with Δymt::ymt. Similarly, infection with Δpla::pla-I259T also results in extended survival compared to Δpla::pla infection. These data demonstrate that the I259T substitution of Pla mitigates the enhanced virulence of Y. pestis in mice caused by Pla-mediated Ymt cleavage, thereby prolonging the survival period of infected animals and potentially conferring advantages on the transmission of Y. pestis to the next host. These findings deepen our understanding of the intricate interplay between two newly acquired plasmids and shed light on the positive selection of the Pla-I259T mutation, providing new insights into the virulence dynamics and transmission mechanisms of Y. pestis.IMPORTANCEThe emergence of Y. pestis as a highly lethal pathogen is driven by extensive gene pseudogenization and acquisition of exogenous plasmids pPCP1 and pMT1. However, the interplay between these two plasmids during evolution remains largely unexplored. Our study reveals intricate interactions between Ymt and Pla, two crucial virulence determinants encoded on these plasmids. Pla-mediated cleavage of Ymt significantly decreases Y. pestis survival in mouse blood and enhances its virulence in mice. The prevalent Pla-I259T variant in modern strains displays reduced Ymt cleavage, thereby extending the survival of infected animals and potentially increasing strain transmissibility. Our findings shed light on the nuanced evolution of Y. pestis, wherein reduced cleavage efficiency is a positive selection force, shaping the pathogen's natural trajectory.

Objectives: This research aims to establish a copper homeostasis-related gene signature for predicting the prognosis of epithelial ovarian cancer and to investigate its underlying mechanisms. Methods: We mainly constructed the copper homeostasis-related gene signature by LASSO regression analysis. Then multiple methods were used to evaluate the independent predictive ability of the model and explored the mechanisms. Results: The 15-copper homeostasis-related gene (15-CHRG) signature was successfully established. Utilizing an optimal cut-off value of 0.35, we divided the training dataset into high-risk and low-risk subgroups. Kaplan-Meier analysis revealed that survival times for the high-risk subgroup were significantly shorter than those in the low-risk group (P

ObjectiveThe purpose of this review was to synthesize the current literature on the relationship between sleep and physical activity in children and adolescents with neurodevelopmental disorders.MethodsArticles were searched in PubMed, Web of Science, EBSCO, Cochrane, and Embase until April 2024. The meta-analysis was performed using Review Manager 5.3.ResultsOur results show that measuring sleep parameters by means of different measuring tools yields different results. Most studies have found no association between sleep and physical activity in children with neurodevelopmental disorders, especially when measured subjectively, such as parent reports and sleep logs. Physical activity interventions had a significant effect on sleep efficiency, wake after sleep onset, and sleep duration when measured objectively using instruments such as wrist actigraphy. Meta-analysis showed that children and adolescents with neurodevelopmental disorders who participated in mind–body activities (SMD = −3.01, 95%CI = −4.15~−1.87, p < 0.001, I2 = 99%) showed significant improvements in sleep, which were sessions lasting more than 12 weeks (SMD = −1.01, p < 0.01, I2 = 97%), performed at least 3 times per week (SMD = −0.81, 95%CI = −1.53~−0.10, p = 0.03, I2 = 95%), and lasted for more than 60 min per session (SMD = −1.55, 95%CI = −2.67~−0.43, p = 0.007, I2 = 97%). However, the results of these subgroup analyses must be interpreted with caution because of the small number of studies included.ConclusionOur results show that measuring sleep parameters by means of different measuring tools yields different results. There was difficulty in interpreting many of the studies included in this meta-analysis, in view of the non-standardization of protocol, especially the ability range of the cohort, duration of the study, recommended exercises, whether the caregivers or researchers supervised the exercise regime/activity, and the practicality of continuing the exercise long-term by caregivers.Systematic review registrationIdentifier, CRD42024541300.

IntroductionAmidst an emerging infectious disease outbreak, the rational allocation of vaccines and medical resources is crucial for controlling the epidemic’s progression.MethodAnalysing COVID-19 data in Taiyuan City from December 2022 to January 2023, this study constructed a SV1V2V3EIQHR dynamics model to assess the impact of COVID-19 vaccination and resource allocation on epidemic trends.ResultsVaccination significantly reduces infection rates, hospitalisations, and severe cases, while also curtailing strain on medical resources by reducing congestion periods. An early and sufficient reserve of medical resources can delay the onset of medical congestion, and with increased maximum capacity of medical resources, the congestion’s end can be accelerated. Stronger resource allocation capabilities lead to earlier congestion resolution within a fixed total resource pool.DiscussionIntegrating vaccination and medical resource allocation can effectively reduce medical congestion duration and alleviate the epidemic’s strain on medical resource capacity (CCMR).

ABSTRACT Morganella morganii, encompassing two subspecies, subsp. morganii and subsp. sibonii, is a common opportunistic pathogen, notable for intrinsic resistance to multiple antimicrobial agents. Despite its clinical significance, research into the potential evolutionary dynamics of M. morganii remains limited. This study involved the analysis of genome sequences from 431 M. morganii isolates, comprising 206 isolates that cause host infections, obtained from this study and 225 from the NCBI genome data sets. A diverse array of antimicrobial resistance genes (ARGs) was identified in M. morganii isolates, including mcr-1, tet(X4), tmexCD-toprJ, and various carbapenemase genes. In addition, a novel blaKPC-2-bearing plasmid with demonstrated conjugative capability was discovered in M. morganii. The majority of virulence-related genes (VRGs), except for the hlyCABD gene cluster, were found in almost all M. morganii. Three novel genospecies of M. morganii were identified, designated as M. chanii, M. variant1, and M. variant2. Compared to M. sibonii, M. chanii genospecies possessed a greater number of flagellar-related genes, typically located within mobile genetic elements (MGEs), suggesting potential for better environmental adaptability. Phylogenetic analysis further disclosed that M. morganii was divided into 12 sequence clusters (SCs). Particularly, SC9 harbored an elevated abundance of ARGs and VRGs, mainly toxin-related genes, and was associated with a higher presence of MGEs compared to non-SC9 strains. The collective findings suggest that M. morganii undergoes evolution driven by the influence of MGEs, thereby significantly enhancing its adaptability to selective pressures of environmental changes and clinical antimicrobial agents.IMPORTANCEThe growing clinical significance of Morganella morganii arises from its abundant virulence factors and antimicrobial resistance genes, resulting in elevated infection rates and increased clinical scrutiny. However, research on the molecular epidemiology and evolutionary trends of M. morganii has been scarce. Our study established a list of virulence-related genes (VRGs) for M. morganii and conducted a large-scale epidemiological investigation into these VRGs. Based on genomic classification, three novel genotypes of M. morganii were identified, representing evolutionary adaptations and responses to environmental challenges. Furthermore, we discovered the emergence of a sequence cluster enriched with antimicrobial resistance genes, VRGs, and mobile genetic elements, attributed to the selective pressure of antimicrobial agents. In addition, we identified a novel conjugative plasmid harboring the blaKPC-2 gene. These findings hold significance in monitoring and comprehending the epidemiology of M. morganii.

Soil copper (Cu) pollution is a serious environmental risk in the Panax notoginseng planting area. However, the effect of Cu on soil microbial metabolism and nutrient cycling in this area remains unknown. Therefore, Biolog ECO-plate and enzyme stoichiometry methods were utilized in this study to investigate the impact of exogenous Cu (control: 0 mg·kg−1; Cu100: 100 mg·kg−1; Cu400: 400 mg·kg−1; and Cu600: 600 mg·kg−1) on the metabolic function of soil microbial and nutrient limitation in the P. notoginseng soil. The results indicated that Cu100 significantly increased soil organic carbon (SOC), total phosphorus (TP), soil C:N, microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) 9.89%, 15.65%, 17.91%, 61.87%, and 90.56% higher than the control, respectively. Moreover, the carbon source utilization ratio of carbohydrates, amino acids, and amphiphilic compounds of Cu100 also increased by 7.16%, 25.47%, and 84.68%, respectively, compared with the control. The activities of β-1,4-glucosidase, cellobiohyrolase, leucine amino peptidase, β-1,4-N-acetylglucosaminidase, and phosphatase significantly decreased with increasing Cu concentration. Soil enzyme stoichiometry showed that all treatments were limited by nitrogen (vector angle < 45°; 19.045–22.081). Cu600 led to the lowest carbon limitation (1.798) and highest carbon use efficiency (CUE:0.267). The PLS-SEM model also showed that MBC, MBN, MBP, and microbial diversity positively affected carbon and nitrogen limitation (0.654 and 0.424). Soil carbon, nitrogen, phosphorus, stoichiometric ratio, MBC, MBN, and MBP positively affected CUE (0.527 and 0.589). The microbial diversity index significantly negatively affected CUE (−1.490). Multiple linear stepwise regression analyses showed that CUE was mainly influenced by MBC, AP, C:P, and LAP. Thus, P. notoginseng soil can benefit soil microbial carbon and nitrogen limitations at low Cu concentrations. Clarifying the metabolic activity and nutritional status of microorganisms under Cu stress can provide some theoretical basis for realizing China's comprehensive and effective management and control policies for environmental risks from metals by 2035.

Background: Hypertrophic scar (HS) is a common fibrotic skin disease that occurs secondary to burns or injuries. The activation of the TGF-β signaling pathway contributes immensely to HS formation. Isorhamnetin (ISO) is a type of flavonoid compound that exerts an antifibrotic effect via TGF-β signaling suppression. However, whether ISO can inhibit HS formation via TGF-β signaling is yet to be elucidated. This study aimed to examine the influence of ISO on HS pathogenesis and TGF-β signaling, especially the downstream molecules and networks of TGF-β signaling that facilitate HS formation. Methods: Hypertrophic scar fibroblasts (HSFBs) were isolated from human HS tissues. The in vitro proliferation, migration, contractile ability, cell cycle, and apoptosis of HSFBs after ISO treatment were determined using cell viability assay, EdU staining, wound healing assay, collagen gel contraction assay, and flow cytometry. The expressions of genes and proteins involved in TGF-β signaling and its downstream molecules in ISO-treated HSFBs were determined using quantitative PCR (qPCR), immunofluorescence, and western blotting. In vivo, a rabbit HS model was established, and the effects of ISO on rabbit HS formation were investigated using histological analysis, immunohistochemical staining, and qPCR. Results: In vitro studies indicated that ISO treatment suppressed the proliferation, migration, and contractile ability of HSFBs; attenuated the expressions of COL Ⅰ, COL Ⅲ, and α-SMA; and inhibited TGF-β1 signaling-induced activation of HSFBs by decreasing the levels of phosphorylated Smad2/3 and cleaved CREB3L1 in a dose-dependent manner. Furthermore, ISO augmented apoptosis and G2 phase cell cycle arrest of HSFBs by upregulating the expressions of the proapoptotic proteins Bax and cleaved caspase-3 and downregulating the expression of the antiapoptotic protein Bcl-2. In vivo studies revealed that ISO ameliorated HS formation in the rabbit ear by lowering the scar elevation index, attenuating the collagen density, facilitating the regular arrangement of collagen fibers, and downregulating the expressions of TGF-β1, CREB3L1, COL Ⅰ, COL Ⅲ, and α-SMA. Conclusions: ISO suppressed HS pathogenesis by dampening TGF-β1/Smad and TGF-β1/CREB3L1 signaling pathways, which suggests that it may serve as a candidate inhibitor of TGF-β1 signaling and a promising anti-HS drug with a high therapeutic potential.

To address the lack of theoretical guidance for sponge city construction (SCC) in China, this study introduces a method to evaluate the available water volume (AWV) in urban watersheds. This evaluation is based on the water balance relationship, water volume, and ecological water demand (EWD). The Xi'an urban area was selected as a case study due to its water shortage and flooding issues. Results show monthly surface and subsurface AWV ranging between 53.06 and 53.98 million m3 and between 8,701.89 and 8,898.14 million m3, respectively. By maximizing the potential for surface AWV, an annual water supply of 527.75 million m3 could be provided, surpassing the annual artificial water consumption of 394.20 million m3, effectively addressing water scarcity. During the rainy season, implementing measures such as employing permeable paving materials, establishing wetlands and rainwater gardens, and constructing lakes and reservoirs can mitigate flooding caused by rainfall exceeding 32.8 mm. While the subsurface space in Xi'an holds significant potential for subsurface AWV utilization, revitalizing the ecological environment of subsurface water is crucial. Overall, the AWV theoretical framework offers a comprehensive solution to water shortage and flooding issues in the Xi'an urban area, serving as a vital theory for SCC. HIGHLIGHTS Available water volume (AWV) is a novel index to guide sponge city construction.; Water volume refers to the maximum volume to store water resources.; EWD refers to the minimum water resources to meet the ecological environment.; AWV refers to the total dynamic water volume to store water and used by humans.; Water shortage problem in Xi'an urban area can be solved by using AWV.;

In this study, the extruded Mg-Zn-Mn-Ce-Ca alloy tube with a low compression anisotropy along the ED, 45ED and TD was prepared. The effect of the second phases, initial texture and deformation behavior on this low mechanical anisotropy was investigated. The results revealed that the alloy tube contains the high content (Mg1-xZnx)11Ce phase and the low content of Mg12Ce phase. These second phases are respectively incoherent and coherent with the Mg matrix, and their influence can be ignored. Additionally, the alloy tube exhibited a weak basal fiber texture, where the c-axis was aligned along the 0° ∼ 30° tilt from TD to ED. Such a texture made the initial deformation (at 1.0% ∼ 1.6% strain) of the three samples controlled by comparable basal slip. As deformation progressed (1.6∼9.0% strain), larger amounts of ETWs nucleated and gradually approached saturation in the three samples, re-orienting the c-axis to a 0°∼±30° deviation with respect to the loading directions. Meanwhile, the prismatic 〈a〉 and pyramidal slips replaced the dominant deformation progressively until fracture. Eventually, the similar deformation mechanisms determined by the weak initial texture in the three samples contribute to the comparable strain hardening rates, resulting in the low compressive anisotropy of the alloy tube.

Abstract In the realm of photovoltaics, organometallic hybridized perovskite solar cells (PSCs) stand out as promising contenders for achieving high‐efficiency photoelectric conversion, owing to their remarkable performance attributes. Nevertheless, defects within the perovskite layer, especially at the perovskite grain boundaries and surface, have a substantial impact on both the overall photoelectric performance and long‐term operational stability of PSCs. To mitigate this challenge, we propose a method for water‐induced condensation polymerization of small molecules involving the incorporation of 1,3‐phenylene diisocyanate (1,3‐PDI) into the perovskite film using an antisolvent technique. Subsequent to this step, the introduction of water triggers the polymerization of [P(1,3‐PDI)], thereby facilitating the in situ passivation of uncoordinated lead defects inherent in the perovskite film. This passivation process demonstrates a notable enhancement in both the efficiency and stability of PSCs. This approach has led to the attainment of a noteworthy power conversion efficiency (PCE) of 24.66% in inverted PSCs. Furthermore, based on the P(1,3‐PDI) modification, these devices maintain 90.15% of their initial efficiency after 5000 h of storage under ambient conditions of 25°C and 50 ± 5% relative humidity. Additionally, even after maximum power point tracking for 1000 h, the PSCs modified with P(1,3‐PDI) sustain 82.05% of the initial PCE. Small molecules can rationally manipulate water and turn harm into benefit, providing new directions and methods for improving the efficiency and stability of PSCs.

Abstract The radiator with heat transfer capability is able to guarantee the stable operation of hydro generator set, while the long-term and continuous scouring on radiator pipes by cooling medium will lead to thinning or even perforation of pipe wall, which triggers wall failure. This paper analyzes and predicts the failure mechanism of radiator’s pipe wall, and investigates the effects of water flow velocity, sand content and sand particle size on erosion damage of radiator pipe by establishing a test bench for pipe erosion. The results show that the increase of above parameters will lead to the increasing erosion rate, especially when the sand content is 1%, the velocity is 8 m/s and the sand particle size is 0.85 mm, the erosion damage will be particularly serious. Based on experimental data, BP and LSSVM models are employed to predict the pipe wall failure, and PSO algorithm is used to optimize the two models. The optimized PSO-BP has the highest accuracy with the mean absolute error (MAE) of 0.2070 and the mean absolute percentage error (MAPE) of 4.702%. The findings provide a reference for wall failure analysis of radiator, which is of great significance for unit's safe operation.

Abstract A compact Archimedean spiral antenna with high gain for electrostatic discharge (ESD) detection is investigated. A frustum‐shaped cavity proposed in this work is formed to optimise the maximum antenna gain. Additionally, a helix arm is loaded to enhance antenna gain in lower band. The measured results demonstrate that the proposed antenna, which employs a unidirectional radiation mode, exhibits a maximum antenna gain ranging from −0.74 dBi to 9.46 dBi and a voltage standing wave ratio less than 3 across a frequency range of 0.65–5 GHz. A test system consisted of proposed antenna and a commercial ESD detection antenna is established. The verified results indicate that the proposed antenna has a performance close to the commercial antenna, so that proposed antenna with compact size is preferred to be utilised for ESD detection.

Abstract Microbial interactions can lead to different colonization outcomes of exogenous species, be they pathogenic or beneficial in nature. Predicting the colonization of exogenous species in complex communities remains a fundamental challenge in microbial ecology, mainly due to our limited knowledge of the diverse mechanisms governing microbial dynamics. Here, we propose a data-driven approach independent of any dynamics model to predict colonization outcomes of exogenous species from the baseline compositions of microbial communities. We systematically validate this approach using synthetic data, finding that machine learning models can predict not only the binary colonization outcome but also the post-invasion steady-state abundance of the invading species. Then we conduct colonization experiments for commensal gut bacteria species Enterococcus faecium and Akkermansia muciniphila in hundreds of human stool-derived in vitro microbial communities, confirming that the data-driven approaches can predict the colonization outcomes in experiments. Furthermore, we find that while most resident species are predicted to have a weak negative impact on the colonization of exogenous species, strongly interacting species could significantly alter the colonization outcomes, e.g., Enterococcus faecalis inhibits the invasion of E. faecium invasion. The presented results suggest that the data-driven approaches are powerful tools to inform the ecology and management of microbial communities.

Abstract Artificial Intelligence (AI) is currently experiencing a bloom driven by deep learning (DL) techniques, which rely on networks of connected simple computing units operating in parallel. The low communication bandwidth between memory and processing units in conventional von Neumann machines does not support the requirements of emerging applications that rely extensively on large sets of data. More recent computing paradigms, such as high parallelization and near-memory computing, help alleviate the data communication bottleneck to some extent, but paradigm- shifting concepts are required. Memristors, a novel beyond-complementary metal-oxide-semiconductor (CMOS) technology, are a promising choice for memory devices due to their unique intrinsic device-level properties, enabling both storing and computing with a small, massively-parallel footprint at low power. Theoretically, this directly translates to a major boost in energy efficiency and computational throughput, but various practical challenges remain. In this work we review the latest efforts for achieving hardware-based memristive artificial neural networks (ANNs), describing with detail the working principia of each block and the different design alternatives with their own advantages and disadvantages, as well as the tools required for accurate estimation of performance metrics. Ultimately, we aim to provide a comprehensive protocol of the materials and methods involved in memristive neural networks to those aiming to start working in this field and the experts looking for a holistic approach.

Traditional hot-dip galvanized coatings, typically single-silver in color, present increasing aesthetic challenges in diverse applications, while prevailing organic coating methods involve complex processes with high energy consumption and pollution emissions. In this study, a novel hot-dip process for in-situ synthesis of color coating on steel was proposed, capable of producing various uniform color coating. The microstructure of color coatings on steel was systematically examined, and an assessment of their corrosion and weather resistance was conducted. The results demonstrate the sequence of typical color variation is gold, purple, blue, cyan, red, green, and grey. By controlling the immersion temperature range, and regulating the final stable color of the oxide film. The coloration mechanism mainly is attributed to the light interference on the Mn oxide film. The cyan and brown coatings mainly consist of the dense rod-like ζ-FeZn13 phases which provide a structural foundation for corrosion resistance. Furthermore, the brown coating exhibited excellent weather resistance.

Abstract Background Yaks (Bos grunniens), prized for their ability to thrive in high-altitude environments, are indispensable livestock in the plateau region. Modifying their feeding systems holds significant promise for improving their growth and meat quality. Tenderness, a key determinant of yak meat quality and consumer appeal, is demonstrably influenced by dietary regimen. Indoor feeding regimes have been shown to enhance tenderness by lowering shear stress and optimizing pH values. CircRNAs, well-known modulators of circulatory function, also play a crucial role in skeletal muscle development across various animal species. However, their functional significance in yak skeletal muscle remains largely unexplored. Results In this study, we identified a total of 5,534 circRNAs within the longissimus dorsi muscle, and we found 51 differentially expressed circRNAs (20 up-regulated and 31 down-regulated) between the two feeding groups. Constructing a comprehensive ceRNA network illuminated intricate regulatory mechanisms, with PGP and circRNA_0617 converging on bta-miR-2285q, mirrored by KLF15/circRNA_0345/bta-miR-20b and CTSF/circRNA_0348/bta-miR-146a. These findings shed light on the potential of circRNAs to influence yak muscle development and meat quality, offering valuable insights for future research. Conclusions This investigation unraveled a complex interaction network between circRNAs、mRNAs and miRNAs in yak skeletal muscle. We further elucidated the target genes regulated by these target genes within the network, offering valuable insights into the potential regulatory mechanisms governing muscle development and meat quality-related traits in yaks.

Background: The Klebsiella oxytoca complex is an opportunistic pathogen that has been recently identified as an actual complex. However, the characteristics of each species remain largely unknown. We aimed to study the clinical prevalence, antimicrobial profiles, genetic differences, and interaction with the host of each species of this complex. Methods: One hundred and three clinical isolates of the K. oxytoca complex were collected from 33 hospitals belonging to 19 areas in China from 2020 to 2021. Species were identified using whole genome sequencing based on average nucleotide identity. Clinical infection characteristics of the species were analyzed. Comparative genomics and pan-genome analyses were performed on these isolates and an augmented dataset, including 622 assemblies from the National Center for Biotechnology Information. In vitro assays evaluating the adhesion ability of human respiratory epithelial cells and survivability against macrophages were performed on randomly selected isolates. Results: Klebsiella michiganensis (46.6%, 48/103) and K. oxytoca (35.92%, 37/103) were the major species of the complex causing human infections. K. michiganensis had a higher genomic diversity and larger pan-genome size than did K. oxytoca. K. michiganensis isolates with blaoxy-5 had a higher resistance rate to various antibiotics, antimicrobial gene carriage rate, adhesion ability to human respiratory epithelial cells, and survival rate against macrophages than isolates of other species. Conclusion: Our study revealed the genetic diversity of K. michiganensis and firstly identified the highly antimicrobial-resistant profile of K. michiganensis carrying blaoxy-5.

Abstract Background Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown. Methods High-throughput RNA sequencing techniques were performed to analyze the expression profiles of circRNAs and mRNAs in highly and poorly invasive clear cell renal cell carcinoma (ccRCC) cell lines. Functional experiments were performed to unveil the regulatory role of circPPAP2B in the proliferation and metastatic capabilities of ccRCC cells. RNA pulldown, Mass spectrometry analysis, RNA methylation immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP), next-generation RNA-sequencing and double luciferase experiments were employed to clarify the molecular mechanisms by which circPPAP2B promotes ccRCC metastasis. Results In this study, we describe a newly identified circular RNA called circPPAP2B, which is overexpressed in highly invasive ccRCC cells, as determined through advanced high-throughput RNA sequencing techniques. Furthermore, we observed elevated circPPAP2B in ccRCC tissues, particularly in metastatic ccRCC tissues, and found it to be associated with poor prognosis. Functional experiments unveiled that circPPAP2B actively stimulates the proliferation and metastatic capabilities of ccRCC cells. Mechanistically, circPPAP2B interacts with HNRNPC in a m6A-dependent manner to facilitate HNRNPC nuclear translocation. Subcellular relocalization was dependent upon nondegradable ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. Moreover, we found that circPPAP2B modulates the interaction between HNRNPC and splicing factors, PTBP1 and HNPNPK, and regulates pre-mRNA alternative splicing. Finally, our studies demonstrate that circPPAP2B functions as a miRNA sponge to directly bind to miR-182-5p and increase CYP1B1 expression in ccRCC. Conclusions Collectively, our study provides comprehensive evidence that circPPAP2B promotes proliferation and metastasis of ccRCC via HNRNPC-dependent alternative splicing and miR-182-5p/CYP1B1 axis and highlights circPPAP2B as a potential therapeutic target for ccRCC intervention.

Abstract Geometric deep learning has been revolutionizing the molecular modeling field. Despite the state-of-the-art neural network models are approaching ab initio accuracy for molecular property prediction, their applications, such as drug discovery and molecular dynamics (MD) simulation, have been hindered by insufficient utilization of geometric information and high computational costs. Here we propose an equivariant geometry-enhanced graph neural network called ViSNet, which elegantly extracts geometric features and efficiently models molecular structures with low computational costs. Our proposed ViSNet outperforms state-of-the-art approaches on multiple MD benchmarks, including MD17, revised MD17 and MD22, and achieves excellent chemical property prediction on QM9 and Molecule3D datasets. Furthermore, through a series of simulations and case studies, ViSNet can efficiently explore the conformational space and provide reasonable interpretability to map geometric representations to molecular structures.

Random phase interference is the main factor leading to uneven optical power distribution, which will affect the positioning accuracy of the four-quadrant detector. This paper uses the power spectrum inversion method to simulate the light spot power distribution affected by random phase interference, and studies the subdivision capability characteristics of the four-quadrant detector under different random phase interference. The simulation experiment results show that when the radius of the light spot received by the detector is 1/2 the radius of the detector, both detection range and positioning accuracy can be taken into account. When the random phase interference is enhanced, the detector's subdivision capability decreases. When the random phase interference is small, the detector can achieve more than 100 subdivisions. When the random phase interference is large, the light spot can only achieve 3 subdivision at the edge of the detector target surface. An experimental system was built to test the subdivision capability of the four-quadrant detector, the experimental test results were basically consistent with the simulation results. The research results provide a technical reference for the application of four-quadrant detector. in free space environments.

Unmanned Aerial Vehicle (UAV)-assisted Mobile Edge Computing (MEC) systems have emerged as promising solutions for enhancing the computational capabilities and reducing latency in next-generation wireless networks. However, the finite energy capacity of UAVs presents a significant challenge. In this study, we formulate a joint user association, computing resource allocation, and task offloading problem, called User Association and Computation Offloading (UACO), to minimize the energy consumption of both mobile devices and UAVs by considering the computational resource limitations of UAVs and the minimum user offloading data rate requirements. The UACO problem is a mixed-integer linear programming (MILP) problem that makes it NP-hard. We transform UACO into an Offload Exact Constrained Potential Game (OFECPG) based on game theory, which facilitates distributed execution. We propose the Best Response dynamics based on Local Decomposition (BR-LD) and Better Response dynamics based on the Local Switch operator (BR-LS) to enhance computational efficiency. We prove the existence of a pure strategy Nash Equilibrium (NE) and the convergence of the proposed algorithms. Extensive simulations demonstrated the effectiveness of the OFECPG, BR-LD, and BR-LS, showing significant improvements in system energy consumption compared to the baseline schemes. Our approach offers valuable insights into the design of efficient association and offloading schemes for multi-UAV MEC networks.

The rapid deployment of large-scale UAV-assisted cellular networks has emerged as an effective solution for delivering high-speed data services to ground users in areas where terrestrial base station (BS) infrastructure is inadequate. In this paper, we address a crucial problem in these networks by aiming to maximize the uplink total rate through joint optimization of Unmanned Aerial Vehicle (UAV) association and Orthogonal Frequency Division Multiple Access (OFDMA) subcarrier assignment. However, due to the mobility of pedestrians, fixed association and subcarrier assignments lack adaptation, and centralized optimization does not scale well, especially in large-scale UAV settings. To overcome these challenges, we formulate the joint optimization problem as an exact Constrained Potential Game, called the Subcarrier Assignment and UAV Association Game (SAUAG), based on game theory. In SAUAG, each user selfishness selects the most appropriate strategy with the objective of maximizing their own utility while still fulfilling the system’s Quality of Service (QoS) constraints. We analyze the conditions under which a Nash Equilibrium (NE) exists and provide rigorous proof of its existence.To mitigate the computational complexity typically associated with Best Response Dynamics (BRD), we introduce the Two-Step Better Response (TS-BR) algorithm, which significantly reduces the computational load while ensuring convergence to an NE. Furthermore, we proposed a distributed algorithm based on sequential play and demonstrated its effectiveness in achieving NE convergence. Through comprehensive simulations, the superiority of the proposed SAUAG and TS-BR algorithms was demonstrated, showing their potential in enhancing network performance and adaptability in UAV-assisted OFDMA networks with mobile ground users.

Enhancing power system resilience against extreme events is becoming increasingly critical. This paper discusses a unified framework for preventive control of power systems to enhance system resilience, which includes three parts: resilience assessment, resilience grading, and resilience enhancement. First, the resilience assessment contains facility-level and system-level resilience assessment. The concept of fragility curve is used in the facility-level resilience assessment. Various resilience indices are developed in system-level resilience assessment to roundly depict the impacts of extreme events on power systems and determine the system resilience. On this basis, the resilience is divided into different levels by resilience grading strategy, which can efficiently quantify the severity of the impact of extreme events and provide decision-making for the resilience enhancement strategies. Then, control strategies for enhancing power system resilience are also divided according to different resilience levels. A controlled islanding based preventive control is proposed to enhance system resilience, which aims to strengthen the first defensive line of power systems to deal with extreme events. Finally, taking the typhoon disaster in extreme events as an example, two tests carried out with two typhoons demonstrate the efficiency of the proposed method.

Abstract We conducted a retrospective study to evaluate the efficacy of immune checkpoint inhibitor (ICI) rechallenge in patients with advanced non-small cell lung cancer (NSCLC). The study included 111 patients who had previously received ICI therapy and experienced disease progression. The primary endpoints assessed were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Our findings revealed that the ICI rechallenge showed promising results in improving patient outcomes. OS (r) is the time from rechallenging with immune checkpoint inhibitors to the last follow-up or death from any cause. The median OS (r) was 14.3 months (95% CI 11.3–17.3 months), with a median PFS (r) of 5.9 months (95% CI 4.1–7.7 months). The ORR was 17.1%; the DCR was 82.3%. Subgroup analysis demonstrated that patients without brain or liver metastases had a longer OS (r) compared to those with metastases (21.6 vs. 13.8 months, χ2 = 3.873, P = 0.046; 20.8 vs. 9.1 months, χ2 = 10.733, P = 0.001, respectively). Moreover, patients without driver gene mutations exhibited significantly longer OS than those with mutations or wild-type patients (22.9 vs. 16.1 vs. 7.5 months, χ2 = 10.710, P = 0.005). Notably, patients who switched to a different ICI during the rechallenge had shorter OS than those who did not change medications (10.4 vs. 21.1 months, χ2 = 9.014, P = 0.003). The incidence of immune-related adverse events did not significantly differ between the two treatment phases. These findings suggest that ICI rechallenge may be a viable therapeutic strategy for select NSCLC patients. Further prospective studies are needed to validate these results and guide treatment decisions for advanced NSCLC.

Abstract Emerging evidence reveals associations between metabolic syndrome (MetS) and psychiatric disorders (PDs), although causality remains uncertain. Consequently, we conducted Mendelian randomization (MR) to systematically evaluate the causality between MetS and PDs. Linkage disequilibrium score regression estimated the heritability of PDs and their genetic correlations with MetS. In primary analyses, the main model employed inverse variance weighting method, with sensitivity analyses using various MR models to ensure robustness. Replication MR analyses, involving cohorts distinct from those in the primary analyses, were performed to validate the generalizability of the findings. Multivariable MR analyses were carried out to account for genetically predicted body mass index (BMI). As a result, genetic correlations of MetS with attention-deficit/hyperactivity disorder(ADHD), anorexia nervosa(ANO), major depressive disorder(MDD), and schizophrenia were identified. Causal effects of MetS on ADHD (OR: 1.59 [95% CI:1.45–1.74]), ANO (OR: 1.42 [95% CI:1.25–1.61]), MDD(OR: 1.23 [95% CI: 1.13–1.33]), and the effects of ADHD (OR: 1.03 [95% CI: 1.02–1.04]) and ANO (OR: 1.01 [95% CI: 1.01–1.02]) on MetS were observed in primary analyses. Results from sensitivity analyses and replication analyses were generally consistent with the primary analyses, confirming the robustness and generalizability of the findings. Associations between MetS and ADHD, as well as ANO persisted after adjusting for BMI, whereas the statistical significance of the association between MetS and MDD was no longer observable. These results contribute to a deeper understanding of the mechanisms underlying PDs, suggesting potential modifiable targets for public prevention and clinical intervention in specific PDs related to metabolic pathways.

AIM: To investigate the effects of Sonic hedgehog (Shh) gene-modified bone marrow mesenchymal stem cells (MSCs) on graft-induced retinal gliosis and retinal ganglion cells (RGCs) survival in diabetic mice. METHODS: Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs (MSC-Shh). Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs (MSC-Gfp; control) were administered in diabetic mice. After 4wk, the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography, and markers of gliosis were examined by immunofluorescence and Western blotting. The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence. The mechanisms underlying the effects of MSC-Shh was investigated. RESULTS: A significant reduction of proliferative vitreoretinopathy (PVR) was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp. Significant downregulation of glial fibrillary acidic protein (GFAP) was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp. The extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (AKT) and phosphatidylin-ositol-3-kinase (PI3K) pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) levels were significantly increased in the host retina, and RGCs loss was significantly prevented after MSC-Shh administration. CONCLUSION: MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice. The ERK1/2, AKT and PI3K pathways are involved in this process. MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

The role of the intratumoral microbiome in gastric cancer (GC) has not been comprehensively assessed. Here, we explored the relationship between the microbial community and GC prognosis and therapy efficacy. Several cancer-associated microbial characteristics were identified, including increased α-diversity, differential β-diversity, and decreased Helicobacter pylori abundance. After adjusting for clinical features, prognostic analysis revealed 2 phyla, 14 genera, and 5 species associated with the overall survival of patients with GC. Additionally, 2 phyla, 14 genera, and 6 species were associated with adjuvant chemotherapy (ACT) efficacy in patients with stage II – III GC. Furthermore, we classified GC microbiome structures into three microbial subtypes (MS1, MS2 and MS3) with distinguishing features. The MS1 subtype exhibited high immune activity and enrichment of microbiota related to immunotherapy and butyric acid-producing, as well as potential benefits in immunotherapy. MS2 featured the highest α-diversity and activation of the TFF pathway, MS3 was characterized by epithelial-mesenchymal transition and was associated with poor prognosis and reduced ACT efficacy. Collectively, the results of this study provide valuable insights into the microbial characteristics associated with GC prognosis and therapy efficacy.

Globally, water scarcity threatens food security, especially in arid and semi-arid food-producing regions, such as the Hetao Irrigation District (HID), where the water consumption during the non-growth season (spring irrigation, autumn irrigation) accounts for more than 30 % of the total irrigation volume. Meanwhile, mapping the characteristics of spatial and temporal evolution of the area of cropland irrigated in the spring and autumn and the pattern of water consumption is crucial for strengthening the management of agricultural water use. Evaporation and infiltration of irrigation water are difficult to capture in time due to insufficient timeliness or accuracy of single remote sensing data. This study integrates seven remote sensing datasets (Landsat5, Landsat7, Landsat8, HJ-1A/B, GF-1, Sentinel-2 and MODIS) for the first time to build a high spatial-temporal resolution dataset, and combines the water index NDWI and MNDWI to extract the maximum water range formed after irrigation by manually adjusting the threshold method. In addition to the global land use/cover dataset (GLC FCS30–1985_2020), the cropland layer was superimposed to accurately identify the cropland spring irrigation and autumn irrigation range from 2000 to 2021 in the HID. In the past 20 years, spring-irrigated (SI) areas increased by 1012.60 km2 (+49.96 %), and the autumn-irrigated (AI) areas decreased by 512.63 km2 (-11.02 %). Combined with the quantity of water diversion and displacement, the characteristics of irrigation water consumption in the non-growth season were further analysed. The results showed that the water consumption of spring irrigation increased by 0.67×108 m3 (+22.26 %), and that of autumn irrigation increased by 4.34×108 m3 (+38.82 %). The decrease of autumn- irrigated area and the increase of water consumption were mainly related to the stability of autumn irrigation water, imperfect irrigation and drainage conditions and insufficient field water management. In 2020­2021, the area of non-growth “autumn irrigation - spring irrigation” repeated irrigation is about 1271.52 km2, which can be used as a key control area. This study provides a theoretical basis and direction for rational water use in non-growth seasons of irrigation districts.