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Abstract Respiratory diseases constitute a major health problem for ruminants, resulting in considerable economic losses throughout the world. Parainfluenza type 3 virus (PIV3) is one of the most important respiratory pathogens of ruminants. The pathogenicity and phylogenetic analyses of PIV3 virus have been reported in sheep and goats. However, there are no recent studies of the vaccination of sheep or goats against PIV3. Here, we developed a purified inactivated ovine parainfluenza virus type 3 (OPIV3) vaccine candidate. In addition, we immunized sheep with the inactivated OPIV3 vaccine and evaluated the immune response and pathological outcomes associated with OPIV3 TX01 infection. The vaccinated sheep demonstrated no obvious symptoms of respiratory tract infection, and there were no gross lesions or pathological changes in the lungs. The average body weight gain significantly differed between the vaccinated group and the control group (P

Abstract How to effectively utilize renewable energy and improve the economic efficiency of microgrid system and its ability to consume renewable energy has become one of the main problems facing China at present. In response to this challenge, this paper establishes a multiobjective capacity optimization model with the minimum levelized cost of energy, the maximum proportion of renewable energy consumption, and the minimum comprehensive system cost. Based on this model, a new improved beluga whale optimization algorithm is proposed to solve the multiobjective optimization problem in the capacity allocation process of wind–solar–storage microgrid system with the goal of ensuring that the microgrid can meet the maximum load demand at different moments throughout the year. In this paper, opposition‐based learning, artificial bee colony, dynamic opposite, and beluga whale optimization are combined to improve the population diversity and convergence accuracy, thereby enhancing the optimization performance of the algorithm. Finally, after finding the optimal Pareto front solution, the Technique for Order Preference by Similarity to an Ideal Solution is used to help decision‐makers select the optimal solution. Using real load data and meteorological data, the results of this paper show that the multiobjective capacity allocation optimization method of grid‐connected scenic storage microgrid system based on the improved beluga whale optimization algorithm can improve the economics of the wind–solar–storage microgrid system and promote the photovoltaic consumption simultaneously, providing a solution for the realization of low‐carbon power and regional economic development. The best‐found levelized cost of energy for the wind–solar–storage microgrid system is 0.192 yuan/kWh.

Abstract The complete cp genomes of Pedicularis chinensis (GenBank accession number: OQ587614) and Pedicularis kansuensis (GenBank accession number: OQ587613) were sequenced, assembled, and annotated. Their chloroplast (cp) genome lengths were 146,452 bp, and 146,852 bp, respectively; 120 and 116 genes were identified, comprising 75 and 72 protein-coding genes (PCGs), 37 and 36 transfer RNA (tRNA) genes, and 8 and 8 ribosomal RNA (rRNA) genes, for P. chinensis and P. kansuensis, respectively. A simple sequence repeat (SSR) analysis revealed that the repetitive sequences were mainly composed of mononucleotide repeats (A/T motif) and dinucleotide repeats (AT/TA motif). Comparative genomics identified several variant genes (rpl22, rps19, rpl12, ycf1, trnH, psbA, and ndhH) and variant regions (trnS-GGA, trnV-UAC, ndhJ-trnV, ycf4-cemA, ndhE-nhdG, and rpl32-trnL) with a high Pi, indicating the potential to serve as deoxyribo nucleic acid (DNA) barcodes for Pedicularis species identification. The results show that the cp genomes of P. chinensis and P. kansuensis were the same as those of other plants in Pedicularis, with different degrees of AT preference for codons. Large differences in the number of SSRs and the expansion of the inverted repeat (IR) region showed strong variability and interspecific differentiation between these two species and other species represented in the genus Pedicularis. A phylogenetic analysis showed that P. kansuensis had the closest relationship with P. oliveriana, and P. chinensis had the closest relationship with P. aschistorhyncha. These results will facilitate the study of the phylogenetic classification and interspecific evolution of Pedicularis plants.

Abstract Chronic obstructive pulmonary disease (COPD) is characterised by persistent airway inflammation even after cigarette smoking cessation. Neutrophil extracellular traps (NETs) have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke (CS). However, whether and how NETs contribute to sustained airway inflammation in COPD remain unclear. This study aimed to elucidate the immunoregulatory mechanism of NETs in COPD, employing human neutrophils, airway epithelial cells (AECs), dendritic cells (DCs), and a long-term CS-induced COPD mouse model, alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice (cGAS -−/− , TLR9 −/− ); Additionally, bronchoalveolar lavage fluid (BALF) of COPD patients was examined. Neutrophils from COPD patients released greater cigarette smoke extract (CSE)-induced NETs (CSE-NETs) due to mitochondrial respiratory chain dysfunction. These CSE-NETs, containing oxidatively-damaged DNA (NETs-DNA), promoted AECs proliferation, nuclear factor kappa B (NF-κB) activation, NF-κB-dependent cytokines and type-I interferons production, and DC maturation, which were ameliorated/reversed by silencing/inhibition of cGAS/TLR9. In the COPD mouse model, blocking NETs-DNA-sensing via cGAS −/− and TLR9 −/− mice, inhibiting NETosis using mitoTEMPO, and degrading NETs-DNA with DNase-I, respectively, reduced NETs infiltrations, airway inflammation, NF-κB activation and NF-κB-dependent cytokines, but not type-I interferons due to IFN-α/β receptor degradation. Elevated NETs components (myeloperoxidase and neutrophil elastase activity) in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels, but not type-I interferon levels. In conclusion, NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced COPD. Therefore, targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.

Soil metabolomics is an emerging approach for profiling diverse small molecule metabolites, i.e., metabolomes, in the soil. Soil metabolites, including fatty acids, amino acids, lipids, organic acids, sugars, and volatile organic compounds, often contain essential nutrients such as nitrogen, phosphorus, and sulfur and are directly linked to soil biogeochemical cycles driven by soil microorganisms. This paper presents an overview of methods for analyzing soil metabolites and the state-of-the-art of soil metabolomics in relation to soil nutrient cycling. We describe important applications of metabolomics in studying soil carbon cycling and sequestration, and the response of soil organic pools to changing environmental conditions. This includes using metabolomics to provide new insights into the close relationships between soil microbiome and metabolome, as well as responses of soil metabolome to plant and environmental stresses such as soil contamination. We also highlight the advantage of using soil metabolomics to study the biogeochemical cycles of elements and suggest that future research needs to better understand factors driving soil function and health.

Abstract Background Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host–parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. Methods Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host–parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. Results This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. Conclusions Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals. Graphical Abstract

Abstract Background Epidermal patterning factor / -like (EPF/EPFL) gene family encodes a class of cysteine-rich secretory peptides, which are widelyfound in terrestrial plants.Multiple studies has indicated that EPF/EPFLs might play significant roles in coordinating plant development and growth, especially as the morphogenesis processes of stoma, awn, stamen, and fruit skin. However, few research on EPF/EPFL gene family was reported in Gossypium. Results We separately identified 20 G. raimondii, 24 G. arboreum, 44 G. hirsutum, and 44 G. barbadense EPF/EPFL genes in the 4 representative cotton species, which were divided into four clades together with 11 Arabidopsis thaliana, 13 Oryza sativa, and 17 Selaginella moellendorffii ones based on their evolutionary relationships. The similar gene structure and common motifs indicated the high conservation among the EPF/EPFL members, while the uneven distribution in chromosomes implied the variability during the long-term evolutionary process. Hundreds of collinearity relationships were identified from the pairwise comparisons of intraspecifc and interspecific genomes, which illustrated gene duplication might contribute to the expansion of cotton EPF/EPFL gene family. A total of 15 kinds of cis-regulatory elements were predicted in the promoter regions, and divided into three major categories relevant to the biological processes of development and growth, plant hormone response, and abiotic stress response. Having performing the expression pattern analyses with the basic of the published RNA-seq data, we found most of GhEPF/EPFL and GbEPF/EPFL genes presented the relatively low expression levels among the 9 tissues or organs, while showed more dramatically different responses to high/low temperature and salt or drought stresses. Combined with transcriptome data of developing ovules and fibers and quantitative Real-time PCR results (qRT-PCR) of 15 highly expressed GhEPF/EPFL genes, it could be deduced that the cotton EPF/EPFL genes were closely related with fiber development. Additionally, the networks of protein–protein interacting among EPF/EPFLs concentrated on the cores of GhEPF1 and GhEPF7, and thosefunctional enrichment analyses indicated that most of EPF/EPFLs participate in the GO (Gene Ontology) terms of stomatal development and plant epidermis development, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of DNA or base excision repair. Conclusion Totally, 132 EPF/EPFL genes were identified for the first time in cotton, whose bioinformatic analyses of cis-regulatory elements and expression patterns combined with qRT-PCR experiments to prove the potential functions in the biological processes of plant growth and responding to abiotic stresses, specifically in the fiber development. These results not only provide comprehensive and valuable information for cotton EPF/EPFL gene family, but also lay solid foundation for screening candidate EPF/EPFL genes in further cotton breeding.

Abstract Tuberculosis (TB) remains a significant global health threat, necessitating effective strategies for diagnosis, prognosis, and treatment. This study employs a multi-cohort analysis approach to unravel the immune microenvironment of TB and delineate distinct subtypes within pulmonary TB (PTB) patients. Leveraging functional gene expression signatures (Fges), we identified three PTB subtypes (C1, C2, and C3) characterized by differential immune-inflammatory activity. These subtypes exhibited unique molecular features, functional disparities, and cell infiltration patterns, suggesting varying disease trajectories and treatment responses. A neural network model was developed to predict PTB progression based on a set of biomarker genes, achieving promising accuracy. Notably, despite both genders being affected by PTB, females exhibited a relatively higher risk of deterioration. Additionally, single-cell analysis provided insights into enhanced major histocompatibility complex (MHC) signaling in the rapid clearance of early pathogens in the C3 subgroup. This comprehensive approach offers valuable insights into PTB pathogenesis, facilitating personalized treatment strategies and precision medicine interventions.

Abstract Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

To investigate the effects of different brine and fermentation methods on the quality characteristics of fermented chili peppers, this study employed four different fermentation methods: Natural fermentation with sterile water, co-inoculation fermentation (Lactiplantibacillus plantarum KUST-D1303:Pichia manshurica KUST-F1705=1:1) with sterile water, natural fermentation with aged brine and co-inoculation fermentation with aged brine. The quality characteristics of the fermented chili peppers were compared and analyzed. Results showed that compared to other fermentation methods, co-inoculation fermentation with aged brine significantly (P

Abstract The secretagogin (SCGN) was originally identified as a secreted calcium-binding protein present in the cytoplasm. Recent studies have found that SCGN has a close relationship with cancer. However, its role in the occurrence, progression, and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we utilized a mutual authentication method based on public databases and clinical samples to determine the role of SCGN in the progression and prognosis of ccRCC. Firstly, we comprehensively analyzed the expression characteristics of SCGN in ccRCC in several public databases. Subsequently, we systematically evaluated SCGN expression on 252 microarrays of ccRCC tissues from different grades. It was found that SCGN was absent in all the normal kidney tissues and significantly overexpressed in ccRCC tumor tissues. In addition, the expression level of SCGN gradually decreased with an increase in tumor grade, and the percentage of SCGN staining positivity over 50% was 86.7% (13/15) and 73.4% (58/79) in Grade1 and Grade2, respectively, while it was only 8.3% (12/144) in Grade3, and the expression of SCGN was completely absent in Grade4 (0/14) and distant metastasis group (0/4). Additionally, the expression of SCGN was strongly correlated with the patient's prognosis, with the higher the expression levels of SCGN being associated with longer overall survival and disease-free survival of patients. In conclusion, our results suggest that reduced expression of SCGN in cancer cells is correlated with the progression and prognosis of ccRCC.

Abstract Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.

Abstract Objective Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia. Methods This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used. Results During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis. Conclusions This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.

Abstract Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC–IRAK1–MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

IntroductionFollicle development is a critical process in the female reproductive system, with significant implications for fertility and reproductive health. Germinal vesicle (GV) oocytes are primary oocytes that are arrested in the dictyate stage, also known as the diplotene stage of meiotic prophase I. Metaphase II (MII) is the stage at which the oocyte is typically retrieved for assisted reproductive technologies such as in vitro fertilization (IVF). The granulosa cells play a pivotal role in follicle development processes. 3D chromatin organization is a fundamental aspect of cellular biology that has significant implications for gene regulation and cellular function.MethodsIn this study, we investigated 3D chromatin organization in granulosacells from GV and MII follicles, which is essential for understanding the regulatory mechanisms governing oocyte development.ResultsThe results revealed distinct compartmentalization patterns,including stable genomic regions and transitions during oocyte maturation. Notably, there was a significant shift in functional gene activation, particularly in processes related to hormone metabolic pathways. Furthermore, alterations in topologically associating domains (TADs) were observed, with differential expression observed in genes that are involved in crucial biological processes. The analysis also identified a subset of genes with altered promoter-enhancer interactions (PEIs), reflecting a regulatory shift in gene expression related to reproductive processes.DiscussionThese findings provide valuable insights into 3D genome organization in granulosa cells with implications for reproductive health and the development of assisted reproductive technologies. Understanding spatial genome organization at different stages of follicular development may help realize novel strategies for enhancing success rates in assisted reproductive technologies.

BackgroundBreast cancer, characterized by its heterogeneity, is a leading cause of mortality among women. The study aims to develop a Machine Learning-Derived Liquid-Liquid Phase Separation (MDLS) model to enhance the prognostic accuracy and personalized treatment strategies for breast cancer patients.MethodsThe study employed ten machine learning algorithms to construct 108 algorithm combinations for the MDLS model. The robustness of the model was evaluated using multi-omics and single-cell data across 14 breast cancer cohorts, involving 9,723 patients. Genetic mutation, copy number alterations, and single-cell RNA sequencing were analyzed to understand the molecular mechanisms and predictive capabilities of the MDLS model. Immunotherapy targets were predicted by evaluating immune cell infiltration and immune checkpoint expression. Chemotherapy targets were identified through correlation analysis and drug responsiveness prediction.ResultsThe MDLS model demonstrated superior prognostic power, with a mean C-index of 0.649, outperforming 69 published signatures across ten cohorts. High-MDLS patients exhibited higher tumor mutation burden and distinct genomic alterations, including significant gene amplifications and deletions. Single-cell analysis revealed higher MDLS activity in tumor-aneuploid cells and identified key regulatory factors involved in MDLS progression. Cell-cell communication analysis indicated stronger interactions in high-MDLS groups, and immunotherapy response evaluation showed better outcomes for low-MDLS patients.ConclusionThe MDLS model offers a robust and precise tool for predicting breast cancer prognosis and tailoring personalized treatment strategies. Its integration of multi-omics and machine learning highlights its potential clinical applications, particularly in improving the effectiveness of immunotherapy and identifying therapeutic targets for high-MDLS patients.

Abstract Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment‐naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25% vs. 4%, p

Aims: This study explores the correlation between site-specific methylation levels of the KCNJ11 promoter and type 2 diabetes mellitus (T2DM), analyzing potential molecular mechanisms. Methods: Thirty patients newly diagnosed with T2DM and 30 healthy controls were selected to determine the CpG methylation levels in the promoter region of the KCNJ11 gene using the bisulfite assay. The online software JASPAR was used to predict transcription factors binding to differentially methylated sites. Key transcription factors were further validated through quantitative PCR (q-PCR) and chromatin immunoprecipitation followed by PCR (ChIP-PCR). Results: Methylation at multiple CpG sites within the KCNJ11 gene promoter was generally reduced in newly diagnosed T2DM patients compared with healthy individuals. The methylation status of CpG-471, a site crucial for the binding of the transcription factor TCF12, emerged as potentially influential in T2DM pathogenesis. This reduction in methylation at CpG-471 may enhance TCF12 binding, thereby altering KCNJ11 expression. Conclusion: Hypomethylation of specific CpG sites in the promoter region of the KCNJ11 gene in patients with incipient T2DM potentially contributes to the disease's pathogenesis. This hypomethylation may influence TCF12 binding, with potential regulatory effects on KCNJ11 expression and pancreatic beta-cell function, though further studies are needed to confirm the exact mechanisms involved.

Abstract Mica is a promising substrate for flexible photonic applications because it can be fabricated using wafer‐scale multiple exfoliations. However, the large lattice mismatch between mica and III‐nitrides hinders their application in III‐nitride semiconductor devices. In this study, two types of light‐emitting diode (LED) epilayers, blue and green, are epitaxially fabricated on 2‐inch exfoliated mica substrates using sputtered AlN as a buffer layer to address the lattice mismatch. The LED epilayers on mica substrate exhibit excellent single‐crystalline quality with a low threading dislocation density of 2.07 × 109 cm−2 in the GaN region and smooth surface morphology with a root mean square (RMS) roughness of 0.58 nm in a 5 × 5 µm2 scanned area, demonstrating that mica is an excellent platform for III‐nitride semiconductors. Moreover, the structures are reproduced stably on multiple exfoliated mica at the wafer scale, which verified the reusability and reproducibility of III‐nitride/mica in terms of crystallinity, surface morphology, and transparency. Strong electroluminescence of the LED epilayers confirmed the potential of mica in electrically driven flexible opto‐electronics. Therefore, this results demonstrated the potential of mica substrates in III‐nitride semiconductors and provide a novel pathway for revolutionizing the fabrication of III‐nitride‐based flexible devices.

IntroductionThe accelerated motorization has brought a series of environmental concerns and damaged public environmental health by causing severe air and noise pollution. The advocate of urban rail transit system such as metro is effective to reduce the private car dependence and alleviate associated environmental outcomes. Meanwhile, the increased metro usage can also benefit public and individual health by facilitating physical activities such as walking or cycling to the metro station. Therefore, promoting metro usage by discovering the nonlinear associations between the built environment and metro ridership is critical for the government to benefit public health, while most studies ignored the non-linear and threshold effects of built environment on weekend metro usage.MethodUsing multi-source datasets in Shanghai, this study applies Gradient Boosting Decision Trees (GBDT), a nonlinear machine learning approach to estimate the non-linear and threshold effects of the built environment on weekend metro ridership.ResultsResults show that land use mixture, distance to CBD, number of bus line, employment density and rooftop density are top five most important variables by both relative importance analysis and Shapley additive explanations (SHAP) values. Employment density and distance to city center are top five important variables by feature importance. According to the Partial Dependence Plots (PDPs), every built environment variable shows non-linear impacts on weekend metro ridership, while most of them have certain effective ranges to facilitate the metro usage. Maximum weekend ridership occurs when land use mixture entropy index is less than 0.7, number of bus lines reaches 35, rooftop density reaches 0.25, and number of bus stops reaches 10.ImplicationResearch findings can not only help government the non-linear and threshold effects of the built environment in planning practice, but also benefit public health by providing practical guidance for policymakers to increase weekend metro usage with station-level built environment optimization.

BackgroundAsparaginase is a critical component of chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but its use is often complicated by asparaginase-associated pancreatitis (AAP). Genetic predispositions, such as variants in the SPINK1 gene, have been linked to an increased risk of pancreatitis. However, the role of genetic factors in relation to asparaginase treatment remains incompletely understood, partly because mutations in pancreatitis-causing genes are rarely found in pediatric ALL.Case descriptionA four-year and three-month-old Chinese girl was admitted to our hospital due to fever for half a day, with no history of significant prior medical history. Initial blood tests revealed hematological abnormalities, including leukopenia, anemia, and thrombocytosis. Bone marrow aspiration identified 81.5% blast cells with B-lymphocyte morphology and immunophenotype, leading to a diagnosis of B-cell acute lymphoblastic leukemia (B-ALL). The patient began treatment under the CCCG-ALL-2015 protocol, which included PEG-asparaginase (PEG-asp). On day 10 of induction, she developed AAP, which was primarily characterized by severe epigastric pain and elevated serum amylase. Despite effective symptom management with analgesics and anti-inflammatory therapy, AAP recurred following administration of L-asparaginase (L-asp). Genetic analysis revealed a heterozygous SPINK1 c.194 + 2T>C variant (rs148954387), a well-known pathogenic variant associated with increased susceptibility to pancreatitis. Sanger sequencing confirmed that the SPINK1 variant was inherited from her asymptomatic mother. The patient's AAP was managed conservatively, and an asparaginase-free regimen ultimately achieved complete remission without recurrence of pancreatitis.ConclusionsThe identification of the SPINK1 c.194 + 2T>C variant, which is recognized as pathogenic, provides valuable information for understanding the heightened risk of AAP in our pediatric ALL patient. Our case underscores the potential role of genetic predisposition in the development of AAP and highlights the importance of considering genetic screening prior to asparaginase therapy in pediatric ALL patients to identify those at increased risk.

Objectives: The epidemical and clinical features of distinct hantavirus infections exhibit heterogeneity. However, the evolving epidemics and distinct determines of the two hantavirus infections remain uncertain. Methods: Data on hemorrhagic fever with renal syndrome (HFRS) cases and genotyping were collected from multiple sources to explore the distribution dynamics of different endemic categories. Four modelling algorithms were used to examine the relationship between infected hantavirus genotypes in HFRS patients, as well as assess the impacts of urbanization-related factors on HFRS incidence. Results: The number of cities dominated by Hantaan (HTNV) and Seoul (SEOV) viruses was projected to decrease between two phases, while the mixed endemic cities increased. Patients with SEOV infection predominantly presented gastrointestinal symptoms. The modeling analysis revealed that built-up land and real GDP demonstrated the highest contribution to HTNV and SEOV infections, respectively. The impact of nightlight index and park green land was more pronounced in HTNV-dominant cities, while cropland, impervious surface, and floor space of commercialized buildings sold contributed more to HFRS incidence in SEOV-dominant cities. Conclusions: Our findings fill a gap for the three endemic categories of HFRS, which may guide the development of targeted prevention and control measures under the conditions of urbanization development.

ABSTRACT: Environmental pollution poses a significant challenge to the poultry industry, leading to substantial losses and adverse effects on the health, production, and performance of avian species. In recent years, there has been growing interest in exploring natural compounds with potential protective effects against cadmium (Cd)-induced toxicity. Luteolin (LUT), a flavonoid found in various plants, has been studied for its antioxidant, anti-inflammatory, and cytoprotective properties. In this study, Su green shell grass chickens were divided into 4 groups: control, LUT (150 mg LUT), Cd (100 mg CdCl2), and Cd + LUT (100 mg CdCl2 + 150 mg LUT) groups for 1 month, respectively. The present study revealed that LUT maintained the morphology and functional activity of the liver and intestine. LUT alleviated Cd-induced impairment in the liver and intestinal biochemical indicators, suppressed Cd-induced liver fibrosis, mitigated liver and intestinal tissue damage. Additionally, LUT reduced oxidative stress and regulated the Cd-induced impairment in trace elements of the liver and intestine. Furthermore, LUT reduced Cd-induced liver inflammation, restored Cd-induced intestinal barrier function, and normalized Cd-induced serum proteins, including changes in the content of glutamyltranspeptidase. Moreover, LUT maintained Cd-induced disruption of gut microbiota and alleviated bacterial dysbiosis. Overall, these findings suggest that LUT holds promise as a potential therapeutic agent for mitigating the adverse effects of Cd-induced toxicity in poultry, by preserving liver and intestinal health, reducing oxidative stress, inflammation, and restoring gut microbiota balance.

ABSTRACT: A recently discovered environmental contaminant, microplastics (MP) are capable of amassing within the body and pose a grave threat to the health of both humans and animals. It is widely acknowledged that the combination of cadmium (Cd), a hazardous heavy metal, and microplastics produces synergistic deleterious effects. Nevertheless, the mechanism by which co-exposure to polyvinyl chloride microplastics (PVC-MP) and Cd damages the liver of avian females is unknown. Globally prevalent and the subject of extensive research in mammals, nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition. However, the mechanisms underlying injury to the avian digestive system caused by NAFLD remain unknown. Two months of co-exposure to Cd and PVC-MPs, pure water, solitary Cd exposure, single microplastics exposure, and pure water were administered to female Muscovy ducks in this study. The objective of this research was to examine whether the co-exposure of duck liver to PVC-MPs and Cd-induced oxidative stress resulted in NAFLD and subsequent apoptosis of hepatic cells. The study's findings showed that hepatocyte shape and functional activity were negatively impacted by PVC-MP and Cd buildup in liver tissues. Reduced liver organ coefficients, increased alanine aminotransferase (ALT) content, and ultrastructural damage to hepatocyte nuclei and mitochondria are indicators of this. These results point to a possible impairment in liver function. phosphoenolpyruvate carboxykinase 1 (PCK1) deficiency activates the protein kinase B/phosphatidylinositol 3-kinase (PI3K/AKT) pathway in the livers of female reproductive ducks that have been damaged by oxidative stress. This stimulation induces lipid deposition, fibrosis, and glycogen accumulation, which ultimately results in hepatocyte apoptosis. In summary, our research provides evidence that PVC-MPs cause oxidative harm to the liver, which subsequently results in fibrosis of liver tissue, hepatic glucolipid metabolism, and ultimately apoptosis.

Non-structural protein 2 (NSP2) of PRRSV is highly variable and plays crucial roles in the virus's life cycle. To elucidate the function of NSP2 during PRRSV infection, we identified SH3KBP1 as an NSP2-interacting host protein using mass spectrometry. Exogenous SH3KBP1 expression significantly inhibited PRRSV replication by enhancing IFN-I and related ISGs production. Conversely, SH3KBP1 knockdown promoted viral replication by downregulating IFN-I and ISGs levels. In vivo experiments revealed that Sh3kbp1-/- mice were more susceptible to VSV infection, exhibiting reduced serum IFN-β levels. Further investigation showed that SH3KBP1 enhances RIG-I signal transduction by increasing K63-linked polyubiquitination through interaction with the E3 ubiquitin ligase TRIM25. We also found that PRRSV infection and NSP2 overexpression induce the autophagic degradation of SH3KBP1, counteracting the host's innate immune response. A critical interaction site was identified within the third polyproline-arginine motif in NSP2 (453PVPAPR458). Recombinant PRRSV lacking this motif displayed reduced virulence and decreased SH3KBP1 degradation. This study advances our understanding of how PRRSV interferes with the host immune response and offers valuable insights for developing novel attenuated vaccines against PRRSV.

Objective: Acute lower gastrointestinal bleeding is a common emergency in gastroenterology. Currently, there is insufficient information to predict adverse outcomes in patients with acute lower gastrointestinal bleeding. Our study aimed to compare the effectiveness of the clinical risk scores currently utilized and their ability to predict significant outcomes in lower gastrointestinal bleeding. Methods: We conducted a prognostic study of patients hospitalized for acute lower gastrointestinal bleeding who underwent colonoscopy or angiography at a single-center hospital between January 2015 and October 2023. Adverse outcomes associated with ALGIB included rebleeding, blood transfusion, hemostatic interventions, and in-hospital death. We calculated three risk scores at admission (Oakland, Birmingham, SALGIB). We measured the accuracy of these scores using the area under the receiver operating characteristic curve (AUC) and compared them with DeLong's test. Results: 222 patients with confirmed lower gastrointestinal bleeding (aged 64 years, 53–75) were finally included. The most common diagnoses were colorectal cancer (28 %) and hemorrhoids (14 %). The Oakland score, Birmingham score, and SALGIB score displayed comparable performance in predicting any adverse outcome (AUC = 0.54, 0.53, 0.55). However, none of the scores were able to sufficiently discriminate rebleeding, blood transfusion, or hemostatic intervention. Using the Youden index, cutoff points for predicting undesired results were identified for the Oakland score at 13, Birmingham score at 3, and SALGIB score at 2. Conclusions: None of the three scores demonstrated satisfactory discrimination for adverse outcomes. Therefore, it is necessary to develop novel risk stratification scores with higher performance to improve risk stratification in acute lower gastrointestinal bleeding.

Introduction Late-life depression (LLD) is a global public health issue, often accompanied by cognitive impairments that can exacerbate the severity of depression and impair social functioning. Despite being a well-established treatment for LLD, the suitability of problem-solving therapy (PST) for individuals with LLD and varying degrees of cognitive impairments warrants further investigation. This paper presents the protocol for a systematic review and meta-analysis of randomised controlled trials (RCTs) aimed at evaluating the effectiveness and acceptability of PST for this specific demographic.Methods/analysis Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we will conduct a systematic review to synthesise existing research on PST for individuals in this demographic. We will comprehensively search multiple databases and sources, including PubMed, EMBASE, the Cochrane Database and APA PsycNET from inception to October 2023, without language, publication year or type restrictions. Relevant studies will be manually screened from the references. Only RCTs involving PST for LLD will be included. The primary efficacy outcome will be the standardised mean difference in total scores on continuous depression severity scales across different comparison arms. Data extraction will be conducted independently by two reviewers (CH and J-JW), and methodological rigour will be assessed using the Cochrane Risk of Bias assessment tool. Subgroup and sensitivity analyses will be performed to investigate the impact of concomitant cognitive impairments and to evaluate the robustness of the findings.Ethics and dissemination The meta-analysis project is expected to be ethically unproblematic and does not require approval from a research ethics committee. The results of this study will be shared through articles in scholarly peer-reviewed journals and presentations in various formats, both print and digital.PROSPERO registration number CRD42023473782

IntroductionPatients on maintenance hemodialysis (MHD) were more vulnerable to and had a higher mortality during the COVID-19 pandemic. As angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine S1 member 2 (TMPRSS2) played crucial roles in viral entry into the human host cells, we therefore investigated in the MHD patients whether their plasma levels were associated with susceptibility to the COVID-19.MethodsBlood samples were collected from the patients in our then COVID-19 free center immediately upon lifting of the stringent quarantine measures in early December of 2022 and infection situation was observed within the following 2 weeks. Plasma levels of the soluble ACE2 (sACE2), ACE (sACE) and TMPRSS2 (sTMPRSS2) were measured with ELISA method. Data were stepwisely tested for independent effect, relevant role and synergistic action on the susceptibility by multiple logistic regression, receiver operating characteristic curve and multiple dimensionality reduction (MDR) method, respectively.ResultsAmong the 174 eligible patients, 95 (54.6%) turned COVID-19 positive with a male to female ratio of 1.57 during the observation period. Comparing with the uninfected, the infected had significantly higher sACE2 and lower sTMPRSS2 levels upon comparable sACE concentration. Besides the sACE2, factors associated with susceptibility were vintage and individual session time of the hemodialysis, smoking and comorbidity of hepatitis, whereas lymphocyte counts showed a tendency (p = 0.052). Patients simultaneously manifesting higher sACE2 level and lower lymphocyte counts had an increased infection risk as confirmed by the MDR method.ConclusionBy sorting out the susceptible ones expeditiously, this algorithmic approach may help the otherwise vulnerable MHD patients weather over future wave of COVID-19 variants or outbreak of other viral diseases.

ObjectiveThe present study sought to evaluate the relationship between age-related cataracts, a prevalent ocular condition among the elderly, and the occurrence of depressive symptoms within a cohort of Chinese adults residing in Anhui, China.MethodsA survey involving 252 Chinese individuals aged 65 years and older was conducted at Lu’an People’s Hospital. Depressive symptoms were assessed using the Hamilton Depression Scale (HAMD) consisting of 17 items, while age-related cataracts were clinically classified according to the Lens Opacities Classification System (LOCS) III. Depressive symptoms were identified by a HAMD score exceeding 7. Logistic regression analyses were employed to determine the odds ratios (OR) and 95% confidence intervals (CI) pertaining to the association between age-related cataracts and depressive symptoms.ResultsCataract patients aged 65 years and older had significantly higher scores of depressive symptoms than those under 65 years (mean scores of 8.17 ± 3.26 versus 5.18 ± 1.86, p

Abstract The North Pacific is known with iron limitation for phytoplankton growth in the subarctic region and nitrogen limitation in the subtropical gyre. Although the growth rate of phytoplankton is determined by the concentration of limiting nutrient, the supply ratio of iron to nitrogen is suggested to be essential to this biogeographic pattern. However, the underlying dynamics determining the ratio remain largely unknown. We investigated mechanisms of dissolved iron (dFe) and nitrate (NO3−) transport to the euphotic zone of the North Pacific using an eddy‐resolvable biogeochemical model. We show that lateral advection and atmospheric deposition are dominant drivers for dFe transport, resulting in high Fe:N supply ratio in both subarctic and subtropical regions. Conversely, significant vertical supplies of NO3− through upwelling and diffusion processes markedly reduce the supply ratio in the subarctic region. These dynamics combined lead to high Fe:N supply ratio in the gyre and low ratio in the subarctic, ultimately driving high nitrogen fixation condition in the gyre and the iron‐limited phytoplankton growth condition in the subarctic region.

Historical cultural heritage sites are valuable for all of mankind, as they reflect the material and spiritual wealth of by nations, countries, or specific groups during the development of human civilization. The types and functions of microorganisms that form biofilms on the surfaces of architectural heritage sites influence measures to preserve and protect these sites. These microorganisms contribute to the biocorrosion of architectural heritage structures through the cycling of chemical elements. The ancient city wall of Shou County is a famous architectural and cultural heritage site from China’s Song Dynasty, and the protection and study of this site have substantial historical and cultural significance. In this study, we used metagenomics to study the microbial diversity and taxonomic composition of the Song Dynasty city wall in Shou County, a tangible example of Chinese cultural heritage. The study covered three main topics: (1) examining the distribution of bacteria in the biofilm on the surfaces of the Song Dynasty city wall in Shou County; (2) predicting the influence of bacteria involved in the C, N, and S cycles on the corrosion of the city wall via functional gene analysis; and (3) discussing cultural heritage site protection measures for biocorrosion-related bacteria to investigate the impact of biocorrosion on the Song Dynasty city wall in Shou County, a tangible example of Chinese cultural heritage. The study revealed that (1) the biofilm bacteria mainly belonged to Proteobacteria, Actinobacteria, Cyanobacteria, Bacteroidetes, and Firmicutes, which accounted for more than 70% of the total bacteria in the biofilms. The proportion of fungi in the microbial community of the well-preserved city wall was greater than that in the damaged city wall. The proportion of archaea was low—less than 1%. (2) According to the Shannon diversity index, the well-preserved portion of the ancient city wall had the highest diversity of bacteria, fungi, and archaea, and bacterial diversity on the good city wall was greater than that on the corroded city wall. (3) Bray–Curtis distances revealed that the genomes of the two good city walls were similar and that the genomes of the corroded city wall portions were similar. Researchers also detected human intestine-related bacteria in four locations on the city walls, with the proportion of these bacteria in the microbial community being greater on good city walls than on bad city walls. (4) KEGG functional analysis revealed that the energy metabolism and inorganic ion transport activities of the bacterial community on the corroded city wall were greater than those of the good city wall. (5) In the carbon cycle, the absence of active glycolysis, the ED pathway, and the TCA cycle played significant roles in the collapse of the east city wall. (6) The nitrogen cycling processes involved ammonia oxidation and nitrite reduction to nitrate. (7) In the sulfur cycle, researchers discovered a crucial differential functional gene, SoxY, which facilitates the conversion of thiosulfate to sulfate. This study suggests that, in the future, biological approaches can be used to help cultural heritage site protectors achieve targeted and precise protection of cultural relics through the use of microbial growth inhibition technology. The results of this study serve as a guide for the protection of cultural heritage sites in other parts of China and provide a useful supplement to research on the protection of world cultural heritage or architectural heritage sites.

Background The reproductive ability of male giant pandas has been a major complicating factor in the ex-situ conservation of the species. While it is well known that the testis produces sperm and secretes androgens, a process that requires precise regulation of various proteins, at present, there has been no systematic study on the composition of proteins in the testis of the giant pandas. Therefore, this study aims to apply proteomics to explore the regulation of proteins in the testes of giant pandas. Methods Samples from the testes of three giant pandas (22 years, 18 years, 8 days) were studied to assess the protein’s function. A label-free quantitative method was used to isolate testicular proteins from each male, 139,039 peptides and 11,435 proteins were obtained. Results Gene Ontology (GO) annotates most of the proteins involved in the processes of protein phosphorylation, oxidation-reduction, proteolysis, and signal transduction. KEGG pathway indicated that most of the proteins were involved in the pathway of signal transduction, transport, and catabolism. The protein kinase and WD40 repeats were involved in protein-protein interaction, which in turn regulates gene expression in the testicular tissue of giant pandas. Conclusions This study is the first to conduct an in-depth proteomic analysis of testicular tissue in giant pandas. The results revealed the important role of proteins in testicular tissue on spermatogenesis, testosterone production, and testicular microenvironment, providing clues for further research on male giant panda reproduction.

Background: Z-DNA-binding protein 1 (ZBP1) is a critical Z-DNA- and Z-RNA-binding protein. However, its diagnostic and prognostic significance, as well as its functions in clear cell renal cell carcinoma (ccRCC), are not well understood. Materials and methods: Paired and unpaired differential expression analyses of ZBP1 were performed in pan-cancer cells. Receiver operating characteristic (ROC) curves and survival analyses were used to evaluate the clinical significance of ZBP1. Functional enrichment and immune infiltration analyses were used to explore the mechanisms underlying ZBP1 expression. Western blotting, qRT-PCR, CCK-8, and colony formation assays were used to investigate the potential function of ZBP1 in ccRCC cells. Molecular docking was utilized to identify drugs targeting ZBP1. Results: ZBP1 was highly expressed in ccRCC, demonstrating significant diagnostic and prognostic value. ZBP1 mRNA expression correlated with TNM stage, pathologic stage, and histologic grade. Functional enrichment analyses indicated that ZBP1 is involved in multiple immune processes. Moreover, ZBP1 mRNA expression was positively correlated with the infiltrating levels of T cells and cytotoxic cells, and negatively correlated with the infiltrating levels of mast cells and Th17 cells in ccRCC. Biological experiments confirmed that ZBP1 promotes ccRCC cell proliferation. Molecular docking studies identified rucaparib as a potential drug targeting ZBP1. Conclusion: Our research findings suggest that targeting ZBP1 could represent a novel therapeutic approach to inhibit the progression of ccRCC.

BackgroundIncreased oxidative stress due to aging can lead to increased bone loss. The most abundant form of vitamin E, namely α-tocopherol, has high antioxidant properties and biological activity; however, its effect on osteoporosis has not been well studied in humans. We aimed to investigate the association between dietary vitamin E (α-tocopherol) and osteoporosis among older adults in the United States.MethodsThis cross-sectional study analyzed data on older adults in the United States aged ≥50 years from the 2007–2010, 2013–2014 and 2017–2020 pre-pandemic cycles of the National Health and Nutrition Examination Survey. Sample-weighted multivariate regression models were used, with adjustments for relevant confounders.ResultsThis study comprised 5,800 individuals with available data on dietary intake and bone mineral density of hip and spine. The mean participant age was 61.4 (standard deviation, 8.7) years, and approximately 9.9% had osteoporosis. High vitamin E intake was significantly associated with a reduced risk of osteoporosis (odds ratio, 0.96, 95% confidence interval, 0.93–0.98). In addition, there was evidence of interaction between dietary vitamin E and prior fracture on preventing osteoporosis.ConclusionsOur study indicated a linear association between dietary vitamin E levels and osteoporosis in an older population in the United States. Further research is required to explore the potential effects of different forms of vitamin E on osteoporosis.

Abstract The mTOR inhibitor everolimus has been approved as a sequential or second‐line therapy for renal cell carcinoma (RCC). However, the development of drug resistance limits its clinical applications. This study aims to address the challenge of everolimus resistance and provide new insights into the treatment of advanced RCC. Here, the cytotoxicity of the DNA methyltransferase 1 (DNMT1) inhibitor SGI‐1027 in inducing cell vacuolation and methuosis is discovered and demonstrated for the first time. Additionally, SGI‐1027 exerts synergistic effects with everolimus, as their combination suppresses the growth, migration, and invasion of renal cancer cells. Mechanistically, apoptosis and GSDME‐dependent pyroptosis triggered by lysosomal membrane permeability (LMP) are observed. The upregulation of GSDME expression and increased lysosomal activity in renal cancer cells provide a therapeutic window for the combination of these two drugs to treat renal cancer. The combination treatment exhibits effective anti‐tumor activity and is well tolerated in a subcutaneous tumor model. Overall, this study validates and reveals the specific cytotoxicity property of SGI‐1027 and its potent synergistic effect with everolimus, offering new insights into advanced RCC therapy and everolimus‐resistance overcoming.

Objectives Diagnosis and assessment of chronic obstructive pulmonary disease (COPD) rely extensively on spirometry, which necessitates patient cooperation. The clinical value of impulse oscillometry (IOS) as a non-volitional method in patients with COPD remains uncertain.Design This retrospective observational study was conducted using patient data from between January 2014 and December 2015.Setting Five public hospitals in China: West China Hospital, Nuclear Industry 416 Hospital, Suining Central Hospital, Affiliated Hospital, Medical College of Chengdu University and 363 Hospital.Participants The study included 6307 participants aged>40 years, comprising 2109 COPD patients and 4198 general non-COPD individuals, according to the Global Initiative for Obstructive Lung Disease (GOLD) spirometry standard. Participants with lung cancer, pulmonary tuberculosis, pneumonia or those who underwent lung resection were excluded from the study.Outcome measures and analysis Demographic data, spirometry results and IOS results were collected. Spearman’s correlation analysis was used to examine the correlation between the IOS and spirometry parameters. Receiver operating characteristic curve analysis was used to evaluate the IOS performance in COPD diagnosis and severity staging.Results Patients with COPD exhibited significant increases in Z5, R5, R20, R5−R20, Fres and Rp, but a decrease in X5 compared with non-COPD subjects (p

Massive and diversified distributed energy resources (DERs) have great potential for improving the flexibility of power system operations. However, given the wide distribution, small capacity, and variable ownership subject characteristics of DERs, virtual power plants (VPPs) are suitable for aggregating the flexible DERs for participation in the wholesale energy market. Extant studies have focused on obtaining bidding strategies in multiple electricity markets. However, there are shortcomings in the relevant market mechanisms and temporal relationships for participating in energy and ancillary service markets. This work proposes a joint market temporal rolling bidding strategy for VPPs in the wholesale market based on real unified electricity market mechanisms in the southern region of China. Accordingly, the proposed method enhances the market-oriented operational profits of VPPs.

ABSTRACT Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens.IMPORTANCEOur study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

BackgroundStigma, anxiety and depressive symptoms are highly prevalent in parents of children with autism spectrum disorder (ASD) and may have a detrimental impact on the rehabilitation and treatment of children with ASD, ultimately leading to more behavioral issues and higher rates of disability. Therefore, the purpose of this study was to identify the association between general self-efficacy, courtesy stigma, and anxiety and depressive symptoms, and to further discuss whether general self-efficacy moderated the association between courtesy stigma and anxiety and depressive symptoms in parents of children with ASD.MethodsA total of 409 parents of children with ASD from Lianyungang, Jiangsu Province, Eastern China participated in a cross-sectional survey. A structured questionnaire was used to collect sociodemographic characteristics, courtesy stigma, general self-efficacy, anxiety symptoms, and depressive symptoms. Hierarchical multiple regression was used to assess the associations of courtesy stigma, general self-efficacy and courtesy stigma × general self-efficacy interaction with anxiety and depressive symptoms. Simple slope analysis was used to visualize the interaction.ResultsThe courtesy stigma of parents of children with ASD was positively correlated with anxiety (B = 0.374, P < 0.001) and depressive symptoms (B = 0.366, P < 0.001). General self-efficacy was negatively correlated with anxiety (B = -0.200, P < 0.001) and depressive symptoms (B = -0.210, P < 0.001). The association between courtesy stigma and anxiety symptoms was different in the high (1 standard deviation (SD) above the mean, b = 0.258, standard error (SE) = 0.056, t = 4.567, P < 0.001) and low (1 SD below the mean, b = 0.470, SE = 0.053, t = 8.870, P < 0.001) groups of general self-efficacy. In addition, the association between courtesy stigma and depressive symptoms was also different in the high (1 SD above the mean, b = 0.241, SE = 0.056, t = 4.268, P < 0.001) and low (1 SD below the mean, b = 0.469, SE = 0.053, t = 8.844, P < 0.001) groups of general self-efficacy.ConclusionsGeneral self-efficacy could moderate the impact of courtesy stigma on anxiety and depressive symptoms. Therefore, among parents of children with ASD who experienced high courtesy stigma, enhancing general self-efficacy could be an effective strategy to reduce anxiety and depressive symptoms in this population.

IntroductionThe rapid evolution of online health services (OHS) has significantly improved healthcare accessibility. However, the impact of air pollution on individuals’ willingness to engage with OHS remains underexplored in the existing literature. This study addresses this gap by investigating how air pollution threats influence the intention to use OHS, grounded in Protection Motivation Theory (PMT) and Rational Choice Theory (RCT).MethodsUsing cross-sectional survey data, a theoretical model was developed and tested to examine the relationships between threat appraisal, coping appraisal, perceived benefits, perceived costs, and OHS usage intentions.ResultsThe findings indicate that threat appraisal, coping appraisal, and perceived benefits positively affect the intention to use OHS, while perceived costs negatively impact usage intention. Additionally, age significantly moderates the relationship between coping appraisal and the intention to use OHS.DiscussionThis study extends the application of PMT and RCT in the context of OHS. It provides valuable insights into the factors influencing users’ intentions to utilize these services, with implications for improving OHS adoption in environments affected by air pollution.

Summary: A study was conducted to investigate whether an integrated management (IM) model led by public healthcare providers is effective in reducing cardiovascular disease (CVD)-specific and all-cause mortality rates in low-income rural populations with hypertension. The study recruited 14,234 patients with hypertension aged 18 years or older and allocated them to either an IM group or a usual care (UC) group. During a median follow-up of 48.0 months, the incidences of CVD-specific and all-cause deaths were lower in the IM group than in the UC group. The hazard ratios for CVD-specific mortality and all-cause mortality among patients in the IM group were 0.60 and 0.62, respectively. The results showed that the IM model led by public health providers resulted in clinically significant reductions in CVD-specific and all-cause mortality rates in low-income rural populations with hypertension.

This study aimed to investigate the effect of ultrasound treatment times (30 min and 60 min) and levels of quinoa protein (QPE) addition (1 % and 2 %) on the quality of Chinese style reduced-salt pork meatballs, commonly known as lion’s head. The water-holding capacity (WHC), gel and rheology characteristics, and protein conformation were assessed. The results indicated that extending the ultrasound treatment time and elevating the quinoa protein content caused conspicuous improvements (P

Benign prostatic hyperplasia (BPH) is one of the major chronic complications of type 2 diabetes mellitus (T2DM), and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH. The profiles of sex steroid hormones are simultaneously quantified by LC–MS/MS in the clinical serum of patients, including simple BPH patients, newly diagnosed T2DM patients, T2DM complicated with BPH patients and matched healthy individuals. The G protein-coupled estrogen receptor (GPER) inhibitor G15, GPER knockdown lentivirus, the YAP1 inhibitor verteporfin, YAP1 knockdown/overexpression lentivirus, targeted metabolomics analysis, and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH. The homeostasis of sex steroid hormone is disrupted in the serum of patients, accompanying with the proliferated prostatic epithelial cells (PECs). The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals. Elevated 17β-estradiol (E2) is the key contributor to the disrupted sex steroid hormone homeostasis, and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH. Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose (HG)-induced PECs proliferation through the formation of the YAP1-TEAD4 heterodimer. Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells. The anti-proliferative effects of verteporfin, an inhibitor of YAP1, are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells. Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Reduction of the driving range under either cold temperature or real-world running condition has become the biggest challenge for battery electric vehicle (BEV). In this paper, a simulation platform that combines a kinematics model, a thermal management model, and extracted typical running conditions has been established to estimate the energy flows inside the electric vehicle under cold temperature and real-world running condition. Three vehicles have been selected to validate the accuracy of the simulation platform, giving an accuracy between 90.6% and 96.6% according to different running conditions. Under highway running condition, the driving range could be reduced by 54%. Under urban running condition, when the environment temperature drops down to −20°C, the driving range is only 49.1% of that under 20°C. In addition, there could be a 4.4% increase in driving range if the target cabin temperature could be decreased from 28°C to 20°C. According to simulation, the application of motor waste heat recovery, internal gas recirculation, and heat pump, could increase the driving range at −7°C under urban running condition by 3.5%, 2.9%, and 3.9%, indicating a 10.3% improvement in total. This has been validated via experimental test after implementing these three approaches onto the test vehicle.

PurposeTo compare the performance of 99mTc-FAPI-04 SPECT/CT and contrast-enhanced CT (CECT) in the detection of postoperative metastasis in patients with colorectal cancer (CRC).MethodsThe postoperative patients with CRC were consecutively recruited from January 2023 to June 2023, and the enrolled patients completed 99mTc-FAPI-04 SPECT/CT imaging and CECT examination within two weeks. Histopathological analysis and the follow-up results were used as the reference criteria. The location and number of metastatic sites and the detection accuracy between the two imaging methods were compared. The tumor-to-background ratio (TBR) of liver metastasis and lymph node metastasis in 99mTc-FAPI-04 SPECT/CT imaging were also calculated for comparison.ResultsIn total, 19 postoperative CRC patients, including 15 patients with metastasis, were included in this study. In the patient-based analysis, 99mTc-FAPI-04 SPECT/CT showed a significantly higher sensitivity for the detection of metastasis than CECT (93.3% vs. 80.0%, p = 0.038), but both techniques had the same specificity (100%, 4/4). For the lesion-based analysis, the detection rates of metastatic sites were 92.2% (47/51) and 72.5% (37/51) for 99mTc-FAPI-04 SPECT/CT and CECT, respectively, and the difference between them was statistically significant. In the diagnosis of liver metastasis and lymph node metastasis, 99mTc-FAPI-04 SPECT/CT both exceeded CECT. Additionally, the TBR in lymph node metastasis was higher than that in liver metastasis.ConclusionThe findings suggested that 99mTc-FAPI-04 SPECT/CT could detect metastasis more effectively than CECT, especially liver and lymph node metastases, in postoperative CRC patients.

Abstract A long‐held tenet in computer science asserts that the training of deep learning is analogous to an alchemical furnace, and its “black box” signature brings forth inexplicability. For electromagnetic metasurfaces, the related intelligent applications also get stuck into such a dilemma. Although the past 5 years have witnessed a proliferation of deep learning‐based works across complex photonic scenarios, they neglect the already existing but untapped physical laws. Here, the intrinsic correlation between the real and imaginary parts of the spectra are revealed using Kramers–Kronig relations, which is then mimicked by bidirectional information flow in neural network space. Such consideration harnesses the missing spectral connection to extract crucial features effectively. The bidirectional recurrent neural network is benchmarked in metasurface inverse design and compare it with a fully‐connected neural network, unidirectional recurrent neural network, and attention‐based transformer. Beyond the improved accuracy, the study examines the intermediate information products and physically explains why different network structures yield different performances. The work offers explicable perspectives to utilize physical information in the deep learning field and facilitates many data‐intensive research endeavors.

Abstract Dysregulation of the transforming growth factor‐β (TGF‐β) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug‐resistant CSCs. Through a genome‐wide CRISPR activation screen utilizing stem‐like drug‐resistant properties as a readout, the TGF‐β receptor‐associated binding protein 1 (TGFBRAP1) is identified as a TGF‐β‐inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF‐β receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF‐β signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly‐ubiquitination and proteasomal degradation. Moreover, hyperactive TGF‐β signaling in turn up‐regulates TGFBRAP1 expression in drug‐resistant CSC‐like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF‐β signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF‐β signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1‐mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF‐β signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.

Prostate cancer (PCa) is the second most common tumor in men globally. Its etiology has been attributed to multiple factors, including age and ethnicity, with family history identified as a significant risk factor. The role of family history in prostate cancer risk appears to be more extensive than previously thought, with evidence suggesting that prostate cancer and breast cancer may occur concurrently within families. BRCA2 mutations have been linked to an increased risk of prostate cancer, particularly in patients diagnosed with early-onset disease. It is estimated that BRCA2 mutations account for approximately 5% of familial prostate cancer cases. It is noteworthy that cases of prostate cancer in patients with BRCA2 mutations are rare in clinical practice. Here we report a case of prostatitis carcinoma with a mutation in the BRCA2 gene in a patient who underwent robotic-assisted radical prostatectomy for prostatitis carcinoma after medication was not effective. Genetic testing of him, his son, and his daughter showed that they all had mutations in this gene, and it is noteworthy that the type of BRCA2 mutation in his son has never been reported before, which is rare in clinical practice.

The successful launch of the Sentinel-1 satellite in 2014 brought a large amount of free SAR images to researchers and scholars, and its application in the fields of ocean monitoring, land use change, natural disaster monitoring and emergency response is becoming increasingly mature and precise. The main applications of InSAR can be categorized into surface deformation monitoring and DEM generation. Sentinel-1 was initially designed for surface deformation monitoring; thus, there are fewer relevant studies on the use of Sentinel-1 data for DEM extraction. However, as the only SAR satellite whose data are currently free and openly available and whose data are constantly updated, it is highly important to study its sources of error in the DEM generation process and the accuracy of its products. In addition, the SAR data provided by the Sentinel-1 satellite has the advantages of high resolution, all-day, all-weather, providing a large data source for DEM production. Taking the Ankang area as an example, this paper analyzes the influence of the InSAR spatiotemporal baseline, ground cover, terrain factors, SAR imaging and other factors on the accuracy of the Sentinel-1-extracted DEM using multisource ground observation data to validate its feasibility for terrain mapping in complex terrain. Finally, we look forward to how to effectively improve the quality of Sentinel-1 DEM products to provide guidance and a reference for subsequent research on DEM extraction using Sentinel-1 SAR images and designation of Sentinel-1 C satellite’s parameters.