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Abstract Background There is a general rise in incidentally found pulmonary nodules (PNs) requiring follow-up due to increased CT use. Biopsy and repeated CT scan are the most useful methods for distinguishing between benign PNs and lung cancer, while they are either invasive or involves radiation exposure. Therefore, there has been increasing interest in the analysis of exhaled volatile organic compounds (VOCs) to distinguish between benign PNs and lung cancer because it’s cheap, noninvasive, efficient, and easy-to-use. However, the exact value of breath analysis in this regard remains unclear. Methods A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-oriented systematic search was performed to include studies that established exhaled VOC-based predictive models to distinguish between benign PNs and lung cancer and reported the exact VOCs used. Data regarding study characteristics, performance of the models, which predictors were incorporated, and methodologies for breath collection and analysis were independently extracted by two researchers. The exhaled VOCs incorporated into the predictive models were narratively synthesized, and those compounds that were reported in > 2 studies and reportedly exhibited consistent associations with lung cancer were considered key breath biomarkers. A quality assessment was independently performed by two researchers using both the Newcastle-Ottawa Scale (NOS) and the Prediction Model Risk of Bias Assessment Tool (PROBAST). Results A total of 11 articles reporting on 46 VOC-based predictive models were included. The majority relied solely on exhaled VOCs (n = 44), while two incorporated VOCs, demographical factors, and radiological signs. The variation in the sensitivity, specificity, and AUC indicators of the models that incorporated multiple factors was lower compared with those of the models that relied solely on exhaled VOCs. A total of 84 VOCs were incorporated. Of these, 2-butanone, 3-hydroxy-2-butanone, and 2-hydroxyacetaldehyde were identified as key predictors that had significantly higher concentrations in the exhaled breath samples of patients with lung cancer. Substantial heterogeneity was observed in terms of the modeling and validation methods used, as well as the approaches to breath collection and analysis. Many of the reports were missing certain key pieces of clinical and methodological information. Conclusions Although exhaled VOC-based models for predicting cancer risk might be a conceivable role as monitoring tools for PNs risk, there has been little overall change in the accuracy of these tests over time, and their role in routine clinical practice has not yet been established. Clinical trial number PROSPERO registration number CRD42023381458.

Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells. Mechanistically, Dem binds to the deubiquitinating enzyme USP22 and promotes its degradation, resulting in increased ubiquitination and degradation of PD-L1 through the proteasome pathway. In addition, Dem increased the activity of cytotoxic T cells and reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in tumor-infiltrating lymphocytes (TILs), thereby activating the tumor immune microenvironment and inhibiting the growth of subcutaneous MC38 tumors in C57BL/6 mice. Moreover, we also found that the combination of Dem and CTLA4 antibodies can further improve the efficacy of antitumor therapy. Our study reveals the mechanism by which Dem promotes PD-L1 degradation and suggests that the combination of Dem and CTLA4 antibodies may improve the efficacy of immunotherapy.

Abstract Simplified rapid hydration has been proven to be non-inferior to standard hydration in preventing contrast-associated acute kidney injury among chronic kidney disease patients undergoing coronary angiography. The current investigation aimed to further confirm the feasibility and safety of the newly proposed hydration method-simplified rapid hydration (SH) in each risk stratification by Mehran risk score (MRS). Eligible patients (n = 954) randomized to the SH group and standard hydration group were allocated into 2 groups based on MRS: low to moderate-risk and high to very high-risk groups. Primary endpoints were the incidence of contrast-associated acute kidney injury (CA-AKI) and acute heart failure (AHF) (SH vs standard hydration). Secondary endpoints included serum creatinine (Scr), blood urea nitrogen (BUN), cystatin-C (Cys-C), and C-reactive protein (CRP) at 24 h, 48 h, and 72 h after PCI procedure, and the incidence of major adverse cardiac events (MACE). MRS was associated with a higher incidence of CA-AKI (OR = 1.101, 95%CI 1.049–1.156, P

Abstract Background Endonucleases play a crucial role in plant growth and stress response by breaking down nuclear DNA. However, the specific members and biological functions of the endonuclease encoding genes in wheat remain to be determined. Results In this study, we identified a total of 26 TaENDO family genes at the wheat genome-wide level. These genes were located on chromosomes 2 A, 2B, 2D, 3 A, 3B, and 3D and classified into four groups, each sharing similar gene structures and conserved motifs. Furthermore, we identified diverse stress-response and growth-related cis-elements in the promoter of TaENDO genes, which were broadly expressed in different organs, and several TaENDO genes were significantly induced under drought and salt stresses. We further examined the biological function of TaENDO23 gene since it was rapidly induced under drought stress and exhibited high expression in spikes and grains. Subcellular localization analysis revealed that TaENDO23 was localized in the cytoplasm of wheat protoplasts. qRT-PCR results indicated that the expression of TaENDO23 increased under PEG6000 and abscisic acid treatments, but decreased under NaCl treatment. TaENDO23 mainly expressed in leaves and spikes. A kompetitive allele-specific PCR (KASP) marker was developed to identify single nucleotide polymorphisms in TaENDO23 gene in 256 wheat accessions. The alleles with TaENDO23-HapI haplotypes had higher grain weight and size compared to TaENDO23-HapII. The geographical and annual frequency distributions of the two TaENDO23 haplotypes revealed that the elite haplotype TaENDO23-HapI was positively selected in the wheat breeding process. Conclusion We systematically analyzed the evolutionary relationships, gene structure characteristics, and expression patterns of TaENDO genes in wheat. The expression of TaENDO23, in particular, was induced under drought stress, mainly expressed in the leaves and grains. The KASP marker of TaENDO23 gene successfully distinguished between the wheat accessions, revealing TaENDO23-HapI as the elite haplotype associated with improved grain weight and size. These findings provide insights into the evolution and characteristics of TaENDO genes at the genome-wide level in wheat, laying the foundation for further biological analysis of TaENDO23 gene, especially in response to drought stress and grain development.

Objective To establish and improve the emergency recruitment strategy of voluntary blood donors under public health emergencies in Shenzhen and verify its effectiveness. Methods Blood donor recruitment strategies under routine, emergency and combined situation were developed. The blood collection data from 2017 to 2019 before the outbreak of COVID-19 pandemic was used as the control group, and those from 2020 to 2022 after the outbreak was used as the experimental group, and the feasibility and effectiveness of this emergency recruitment strategy was confirmed through statistical analysis of key indicators of blood collection and supply. Results Through the application of the emergency recruitment strategy for blood donors in Shenzhen under public health emergencies, statistical analysis of the experimental group and the control group showed a year-on-year increase of 14.11%(73 647.25/521 855.5) in whole blood collection, 42.33%(28 891.47/68 250.95) in platelet collection, 0.33%(529/161 033) in first-time donors, 33.25%(3 154/9 487) in repeated donors and 16.78%(32 585/194 149) in the number of 400 mL donors. The inventory of various types of red blood cell maintained between 6-18 days. After the implementation of the emergency recruitment strategy the blood donation population has shown characteristics as younger age, localization, increased repeated donation and a higher proportion of donors with college education or above. Conclusion The emergency recruitment strategy of blood donors under public health emergencies is feasible and effective, which can quickly and efficiently improve the blood recruitment ability.

Guvermectin, a purine nucleoside natural product produced by the genus Streptomyces, has recently been registered as a new biopesticide to boost rice yield. Despite its economic and agricultural significance, the regulatory mechanisms of guvermectin biosynthesis remain essentially unknown, hindering industrial production and widespread agricultural application. Here, we examined the roles of two LacI family regulators, gvmR and gvmR2, located within and adjacent to the guvermectin biosynthesis cluster, respectively, in guvermectin production in Streptomyces caniferus NEAU6. GvmR activated the expression of the guvermectin cluster by binding to the promoters of gvmR, gvmA, and O1, while GvmR2 repressed the guvermectin cluster via competitive binding to promoters containing GvmR-binding sites, specifically, a 14-bp palindromic sequences: 5′-RTCATWCGYATGAY-3′ (R = G/A, W = A/T, Y = T/C). Moreover, GvmR indirectly activates the expression of gvmR2 while GvmR2 feedback inhibits gvmR transcription, suggesting a functional interaction between the two regulators for coordinating guvermectin production. Overexpression of gvmR via the T7 RNA polymerase-T7 promoter system in the gvmR2 mutant significantly elevated guvermectin production by 125 % (from 631 mg L−1 to 1422 mg L−1), compared to the parental strain NEAU6. This suggested that combinatorial manipulation of gvmR and gvmR2 is useful for improving guvermectin production. These findings enrich our knowledge of the regulatory network for guvermectin biosynthesis, and offer key targets and effective strategies for high-titer guvermectin production.

Abstract Underground wastewater treatment plants (U-WWTPs) have emerged as a novel paradigm for urban wastewater pollutants management, offering benefits such as alleviating the Not-in-my-backyard (NIMBY) effect and utilizing land resources efficiently. China stands at the forefront, witnessing swift advancements in U-WWTP technology and deployment. However, the absence of a thorough understanding of their geographical distribution and operational characteristics could lead to misaligned planning and construction, resulting in inefficient resource allocation and treatment capacities for urban wastewater treatment. This dataset provides an up-to-date overview of the spatial distribution, process selection, and discharge standards for all U-WWTPs in China (with a total number of 201) constructed since 1995. To enhance comparative analysis, the dataset has been supplemented with information on conventional aboveground wastewater treatment plants (A-WWTPs), comprising a total of 2464 records, which enriches a more comprehensive evaluation of different wastewater treatment approaches. Utilizing this dataset can provide essential data support for the strategic management of urban wastewater systems and serve as a valuable reference for the paradigmatic renovation of existing wastewater treatment plants.

Abstract The effect of circumference and displacement of the third fracture fragment on fracture healing after intramedullary nailing of femoral shaft fractures with a third fracture fragment was investigated. A retrospective cohort study was conducted to analyze the data of 142 patients who suffered femoral shaft fractures with a third fracture fragment and were admitted to the First People’s Hospital of Lianyungang from February 2016 to December 2021. According to the circumference of the third fracture fragments, these were divided into three types of type 1: 71 cases; type 2: 52 cases; and type 3: 19 cases. On the basis of the diaphyseal diameter, the degree of displacement of the third fracture fragment was classified into three degrees of degree I: 95 cases; degree II: 31 cases; and degree III: 16 cases. Postoperative follow-up was performed to compare the fracture healing rate, healing time, and the modified Radiographic Union Scale for Tibia (mRUST) at 9th month after surgery in each group. All 142 patients were followed up after operation, with an average of (14.7 ± 4.1) months, and the overall healing rate was 73.4%. When the third fracture fragments were displaced in degree II and III, the mRUST score at 9th month in the type 1 group was higher than that in the type 2 and 3 groups (P = 0.017). Logistic regression analysis showed that greater displacement of third fracture fragments and greater circumference were associated with lower fracture healing rates (P

Abstract Breast muscle growth rate and intramuscular fat (IMF) content show apparent differences between fast-growing broilers and slow-growing indigenous chickens. However, the underlying genetic basis of these phenotypic characteristics remains elusive. In this study, we investigate the dynamic alterations of three-dimensional genome architecture and chromatin accessibility in breast muscle across four key developmental stages from embryo to starter chick in Arbor Acres (AA) broilers and Yufen (YF) indigenous chickens. The limited breed-specifically up-regulated genes (Bup-DEGs) are embedded in breed-specific A compartment, while a majority of the Bup-DEGs involving myogenesis and adipogenesis are regulated by the breed-specific TAD reprogramming. Chromatin loops allow distal accessible regions to interact with myogenic genes, and those loops share an extremely low similarity between chicken with different growth rate. Moreover, AA-specific loop interactions promote the expression of 40 Bup-DEGs, such as IGF1, which contributes to myofiber hypertrophy. YF-specific loop interactions or distal accessible regions lead to increased expression of 5 Bup-DEGs, including PIGO, PEMT, DHCR7, TMEM38B, and DHDH, which contribute to IMF deposition. These results help elucidate the regulation of breast muscle growth and IMF deposition in chickens.

Abstract Background The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking. Results In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn’s disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models. Conclusions Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract

Abstract Adebrelimab, a novel anti‐PD‐L1 antibody, has been approved by the National Medical Products Administration of China as an intravenous infusion for use in combination with carboplatin and etoposide as first‐line treatment for extensive‐stage small‐cell lung cancer in 2023. A two‐compartment model with empirical time‐varying CL for adebrelimab was established based on data from 263 patients receiving body weight‐based doses from two clinical studies. Significant covariate effects of baseline body weight, albumin levels, tumor size, neutrophil counts, and presence of anti‐drug antibodies were identified on CL of debrelimab, none of which were clinically significant or warranted dose adjustment. The degree of decrease in CL was higher in patients who responded to treatment with adebrelimab than in non‐responders. Adebrelimab exposures (AUC, Ctrough, or Cmax) were not identified as a statistically significant factor related to efficacy or safety endpoint in the exposure–response analysis. Distribution of simulated exposure metrics from the flat dose regimen (1200 mg q3w) was similar to the marketed weight‐based dosing regimen (20 mg/kg q3w), supporting the alternative flat dose regimen in the clinic.

Abstract Immune checkpoint blockade (ICB) necessitates a thorough understanding of intricate cellular interactions within the tumor microenvironment (TME). Mesenchymal stromal cells (MSCs) play a pivotal role in cancer generation, progression, and immunosuppressive tumor microenvironment. Within the TME, MSCs encompass both resident and circulating counterparts that dynamically communicate and actively participate in TME immunosurveillance and response to ICB. This review aims to reevaluate various facets of MSCs, including their potential self-transformation to function as cancer-initiating cells and contributions to the creation of a conducive environment for tumor proliferation and metastasis. Additionally, we explore the immune regulatory functions of tumor-associated MSCs (TA-MSCs) and MSC-derived extracellular vesicles (MSC-EVs) with analysis of potential connections between circulating and tissue-resident MSCs. A comprehensive understanding of the dynamics of MSC-immune cell communication and the heterogeneous cargo of tumor-educated versus naïve MSCs may unveil a new MSC-mediated immunosuppressive pathway that can be targeted to enhance cancer control by ICB.

Abstract With the growing awareness of environmental issues available across various media platforms, consumers, particularly the younger generation, are more conscious of their consumption and its impact on the environment. This trend can be observed in the surging demand for environmentally friendly and animal-test-free products on the market. However, despite the young consumer group’s critical role in the marketplace, existing research in this area remains limited, demanding further investigation. Recognising the significance of this trend, this study employs a two-stage partial least squares structural equation modelling-artificial neural network (PLS-SEM-ANN) approach to analyse the antecedents influencing green consumption among young Chinese consumers. This study proposes a conceptual research model that extends the norm activation model (NAM) by analysing 366 self-reported questionnaires. The first-stage PLS-SEM results reveal significant positive correlations between personal norms (PN), environmental knowledge (EK), information availability (IA), social norms (SN) and green consumption intention (GCI). However, face consciousness (FC) was found to have no significant effect on GCI. The second-stage ANN sensitivity analysis shows that PN emerged as the most influential factor on GCI, followed by IA, SN, and EK. This ranking diverges from the PLS-SEM results, suggesting potential hidden nonlinear relationships between IA, SN, EK and GCI. Among the significant predictors of PN, the ascription of responsibility (AR) ranks first, followed by an awareness of consequence (AC) and SN. With its unique two-stage PLS-SEM-ANN approach to green consumption among young consumers, this study offers valuable insights for both marketers and researchers. Marketers gain a new tool to predict GCI more effectively, while researchers can explore the intricate interplay of factors shaping sustainable consumption choices. Methodologically, the present study is one of the few that applies extended NAM using two-stage PLS-SEM-ANN in the context of green consumption.

The anti-detection capabilities of adversarial malware examples have drawn the attention of antivirus vendors and researchers. In black-box scenarios where internal information of the target model cannot be accessed, with the ability of the reinforcement learning (RL) agents to adjust strategies based on the feedback from the environment, existing RL-based methods enable evasion of Windows PE malware detectors. However, obtaining evasion rewards as positive feedback in the black-box setting proves challenging, resulting in low training efficiency. To address this issue, we introduce the intrinsic curiosity reward into the framework to motivate the agent to explore unknown state spaces and learn effective evasion strategies. Additionally, we employ the generative adversarial network (GAN) to obtain varying synthetic data, which replaces random or benign bytes as adversarial payloads for the agent's action content, improving attack capabilities and reducing the risk of hard-coded adversarial perturbations being anchored. We compare the attack performance with other RL-based baseline methods, and experimental results show that our framework is more flexible and effective, achieving a 63%-85% attack success rate against EMBER, FireEye and MalConv. Even if defensive measures are taken, the proposed method still has a certain attack capability, and the success rate remains between 48%-67%.

Plasmid-mediated tigecycline resistance genes, notably the tet(X) and tmexCD-toprJ genes, have garnered considerable attention due to their transferability. This study aims to investigate the prevalence and resistance mechanisms associated with tet(X) and tmexCD-toprJ in flies, which are important reservoirs of antimicrobial resistance genes. A total of 52 tigecycline resistant bacterial isolates were collected, among which 40 (76.9 %) and 12 (23.1 %) were positive for tet(X) and tmexCD-toprJ, respectively. Tigecycline resistant bacteria were isolated from diverse geographical locations in China, with tet(X4)-positive Escherichia coli and tmexCD1-toprJ1-positive Klebsiella pneumoniae dominant among the isolates. The prevalence of tet(X) in rural area was significantly higher than that in urban area (2.7 % vs. 0.3 %; P 0.05). Most tet(X)-positive strains (n = 40, 100.0 %), and 11(91.7 %) of the tmexCD1-toprJ1-positive strains exhibited multi-drug resistance. The IncFIB(Mar)/IncHI1B hybrid plasmid carrying tmexCD1-toprJ1 was identified by whole-genome sequencing analysis, which dominated the transmission of tmexCD1-toprJ1 in K. pneumoniae. Genetic context analysis showed that tmexCD1-toprJ1 was related locally to IS26, and IS26 may exacerbate the spread of tmexCD1-toprJ1 in different bacteria. In addition, the genetic structure of tmexCD1-toprJ1 also contains several antimicrobial resistance genes, including aph(3′)-Ic, sul1, blaDHA-1, blaCTX-M−5, etc., conferring resistance to aminoglycosides, sulfonamides, and carbapenems. This study provides insights into the epidemiology and transmission dynamics of tigecycline resistance genes, informing targeted intervention strategies to mitigate antimicrobial resistance dissemination.

Traditional Chinese Medicine (TCM) formulations serve as a multi-component pharmacological combination therapy with various potential targets and have collected extensive knowledge regarding the in vivo efficacy of treating cardiovascular disorders in clinical practice for thousands of years. However, the obscurity of the chemicals and the molecular mechanisms are impediments to their continued growth and globalization. Therefore, new modern medications based on the combination of beneficial TCM components with precise clinical efficacy are required. The goal of this study was to find the best combination of Achyranthes bidentata Blume (AB) and Paeonia lactiflora Pall. (PL) for hypertension with liver yang hyperactivity (HLYH). The integrated research consisting of principal component analysis (PCA), metabolomics, microbiology, and weighted correlation network analysis (WGCNA) were used to find the optimal combination of AB-PL combinations and reveal the mechanism of action. The result showed AB-PL (2:3) had a substantial protective impact on HLYH, as shown by lower blood pressure, improved liver yang hyperactivity, reduced cardiac remodeling and malondialdehyde (MDA), and increased NO content. Furthermore, the essential elements for AB-PL reducing hypertension may be related to 135 metabolites and 23 microorganisms. In conclusion, our findings support the efficacy of herbal remedies in the treatment of hypertension and provide some pharmacological evidence for the ongoing development of novel modern Chinese drugs for cardiovascular disorders.

The ongoing high occurrence of harmful infectious diseases significantly threatens human health. Existing methods used to control such diseases primarily involve targeting the pathogens, usually neglecting the vital role of host factors in disease advancement. Gamma delta (γδ) T cells act as a bridge between innate and adaptive immunity, playing a crucial role in combating pathogen invasion. Among these γδT cell subsets, which are categorized based on T cell receptor delta variable expression patterns, V delta (δ) 1+ T cells possess unique recognition abilities and regulatory characteristics and actively engage in various immune responses. The differentiation, development, and immune reactivity of Vδ1+ T cells are closely associated with the initial and progressive stages of infectious diseases. This article provides an overview of the classification, distribution, differentiation, and development of Vδ1+ T cells and their mechanisms in combating pathogenic infections, offering new insights for disease diagnosis and treatment.

Abstract Background Although RANK‐LRANK interaction is essential for osteoclastogenesis, the mechanisms by which cancer cells invade bone tissues and initiate osteolytic metastasis remain unclear. Here, we show that the hyperactivation of RelB fosters prostate cancer (PCa) osteolytic metastasis by coordinating interleukin‐8 (IL‐8) and calcium‐binging protein A4 (S100A4). Methods The factors promoting PCa bone metastasis were investigated in sera from PCa patients and tumour tissues derived from nude mice using immunohistochemical analysis and enzyme‐linked immunosorbent assays (ELISA). Cell mobility and mineralization were quantified using BioStation CT and Osteolmage assay. The relative cistrome was investigated in advanced PCa cells by standard transcriptional analyses, including the luciferase reporter response, site‐directed mutagenesis, and chromatin immunoprecipitation (ChIP) assay. PCa cell‐initiated tumour formation, expansion, and bone metastasis were validated in mice using multiple approaches, including orthotopic, intraskeletal, and caudal arterial implantation models. Results IL‐8 and S100A4 correlated with patient Gleason scores and bone metastasis. RelB upregulated IL‐8, facilitating androgen receptor (AR)‐independent growth. RelB‐Sp1 interaction enhanced epithelial‐mesenchymal transition (EMT) by activating Snail and Twist. RelB‐NFAT1c super‐enhancer upregulated S100A4 in the organization of the cytoskeleton and bone metastasis. The RelB‐IL‐8‐S100A4 signalling axis was confirmed to promote osteolytic metastasis in nude mice. Conclusion RelB‐IL‐8 reciprocally promoted EMT by activating inflammatory signalling and inactivating AR signalling. IL‐8 is essential for provoking PCa metastasis but insufficient to drive bone metastasis. IL‐8‐S100A4 cooperation was necessary for metastatic cells to target the bone. Highlights RelB activates inflammatory signalling by upregulating IL‐8 and suppressing AR. RelB upregulates S100A4 by cooperating with NFATC1. IL‐8 boosts EMT by activating Snail 1 and Twist 1, and S100A4 exacerbates osteolytic metastasis via calcium consumption. RelB harnesses IL‐8 and S100A4 to drive PCa osteolytic metastasis.

AimsEpigenetics has significantly evolved and emerged as important players in the pathogenesis of neurodegenerative diseases. However, a scientometric synthesis of such changes over time is currently lacking.MethodsWe conducted a comprehensive search of the Web of Science Core Collection from inception until November 5, 2022, using appropriate keywords. Our primary objective was to employ scientometric analysis to depict changes in keywords over time and to assess the structure and credibility of clusters. Additionally, we examined the network of research (countries, institutions, and authors) using CiteSpace and VOSviewer.ResultsWe identified 25 clusters with well-structured networks (Q = 0.82) and highly credible clustering (S = 0.91) from 16,181 articles published between 1999 and 2022. Our findings are as follows: (a) the literature and research interest concerning the epigenetics of neurodegenerative diseases are continuously growing; (b) the three most productive countries are the USA, China, and Germany; (c) international collaborative relationships exist, alongside small, isolated collaboration networks of individual institutions.ConclusionThe number and impact of global publications on the epigenetics of neurodegenerative diseases have expanded rapidly over the past 20 years. This review provides valuable guidelines for researchers interested in neurodegenerative diseases research.

ABSTRACT: Femoral head necrosis (FHN) in broilers is a common leg disorder in intensive poultry farming, giving rise to poor animal health and welfare. Abnormal mechanical stress in the hip joint is a risk factor for FHN, and articular cartilage is attracting increasing attention as a cushion and lubrication structure for the joint. In the present study, broilers aged 3 to 4 wk with FHN were divided into femoral head separation (FHS) and femoral head separation with growth plate lacerations (FHSL) groups, with normal broilers as control. The features of the hip joint, bone, and cartilage were assessed in FHN progression using devices including computed tomography (CT), atomic force microscope (AFM), and transmission electron microscopy (TEM). Broilers with FHN demonstrated decreased bone mechanical properties, narrow joint space, and thickened femoral head stellate structures. Notably, abnormal cartilage morphology was observed in FHN-affected broilers, characterized by increased cartilage thickness and rough cartilage surfaces. In addition, as FHN developed, cartilage surface friction and friction coefficient dramatically increased, while cartilage modulus and stiffness decreased. The ultramicro-damage occurred in chondrocytes and the extracellular matrix (ECM) of cartilage. Cell disintegration, abnormal mitochondrial accumulation, and oxidative stress damage were observed in chondrocytes. A notable decline in cartilage collagen content was observed in ECM during the initial stages of FHN, accompanied by a pronounced reduction in collagen fiber diameter and proteoglycan content as FHN progressed. Furthermore, the noticeable loosening of the collagen fiber structure and the appearance of type I collagen were noted in cartilage. In conclusion, there was a progressive decrease in bone quality and multifaceted damage of cartilage in the femoral head, which was closely linked to the severity of FHN in broilers.

Abstract Seven in absentia proteins, which contain a conserved SINA domain, are involved in regulating various aspects of wheat (Triticum aestivum L.) growth and development, especially in response to environmental stresses. However, it is unclear whether TaSINA family members are involved in regulating grain development until now. In this study, the expression pattern, genomic polymorphism, and relationship with grain‐related traits were analyzed for all TaSINA members. Most of the TaSINA genes identified showed higher expression levels in young wheat spikes or grains than other organs. The genomic polymorphism analysis revealed that at least 62 TaSINA genes had different haplotypes, where the haplotypes of five genes were significantly correlated with grain‐related traits. Kompetitive allele‐specific PCR markers were developed to confirm the single nucleotide polymorphisms in TaSINA101 and TaSINA109 among the five selected genes in a set of 292 wheat accessions. The TaSINA101‐Hap II and TaSINA109‐Hap II haplotypes had higher grain weight and width compared to TaSINA101‐Hap I and TaSINA109‐Hap I in at least three environments, respectively. The qRT‐PCR assays revealed that TaSINA101 was highly expressed in the palea shell, seed coat, and embryo in young wheat grains. The TaSINA101 protein was unevenly distributed in the nucleus when transiently expressed in the protoplast of wheat. Three homozygous TaSINA101 transgenic lines in rice (Oryza sativa L.) showed higher grain weight and size compared to the wild type. These findings provide valuable insight into the biological function and elite haplotype of TaSINA family genes in wheat grain development at a genomic‐wide level.

Changes in gluten during the freezing process could cause a deterioration in dough quality, which would be solved by electrostatic field treatment. This paper investigated the effects of electrostatic field assisted freezing (EFAF) on the functional properties, structural characteristics and aggregation behavior of gluten. The results showed that EFAF improved the functional properties of gluten with enhanced water holding, emulsifying and foaming properties. When the electrostatic field was applied, the α-helix content and g-g-g conformation of gluten proteins increased with a maximum of 27.50 % and 40.05 %, respectively, which were significantly different from the control (P

The wheel-rail wear was predicted for modern trams with independently rotating wheelset running on a groove-shaped rail. The tram vehicle-track coupled dynamics model, considering the wheel-rail multi-point contact, was developed using software UM to evaluate the dynamic responses of the vehicle and track. Hertz contact theory, the FastSim algorithm, and Archard material wear model were used to solve the normal contact stress, tangential contact stress, and wheel-ail wear, respectively. The wheel and rail profiles were updated when the wear depth reached to 0.1 mm. In calculation, the wheel and rail wear was calculated and analyzed separately. The results of groove rail and independently rotating wheelset wear predicted by this model coincided with relevant literature, which proved the effectiveness of this model. The wheel and rail wear characteristics of modern trams passing through curved tracks with small radii and the influence of wheel-rail friction coefficient on wheel and rail wear were calculated and analyzed using this model. The results show that the wheel and rail wear on the circular curve and the rear transition curve is more intense. The wheel wear is the most intense on circular curve while the rail wear is on the rear transition curve. The wear of inner and outer rails and wheels of wheelset one increases with the increase of wheel-rail friction coefficient while the wear of inner and outer wheels of wheelset three have no obvious change. The wear of the inner and outer rails is the most intense at the gauge corner position while is the lightest at the guard rail. The wear of wheelset one is more intense than that of wheelset three and the inner wheel wear is more intense than that of the outer wheel. The present analysis contributes to improve the life of tram wheel and rail and reduce the frequency of wheel-rail maintenance during operation.

IntroductionEchinococcus granulosus, known as cystic echinococcosis, is a prominent zoonotic parasitic disease of significant global concern. The definitive hosts serves as the primary reservoir for the transmission of echinococcosis, as well as a main factor in the prevention and control of the disease. Unfortunately, there is currently no commercially available vaccine for these hosts. Nevertheless, DNA vaccines show potential as a feasible strategy for the control and management of parasitic diseases.MethodsIn this study, the EgM123 antigen was selected for its well-documented immunogenic properties to develop a DNA vaccine aimed at combating E. granulosus infection in canines.ResultsThe results showed a marked increase in IgG levels in the group vaccinated with pVAX1-EgM123 DNA compared to the PBS group. Additionally, the cytokines IL-1, IFN-γ, IL-4, and IL-6 were significantly upregulated in the pVAX1-EgM123 DNA vaccine group. Furthermore, in comparison to the PBS control group, the EgM123 DNA vaccine group exhibited a notable 87.85% reduction in worm burden and a 65.00% inhibition in segment development.DiscussionThese findings indicate that the pVAX1-EgM123 DNA vaccine shows promising immunogenicity, successfully eliciting a targeted immune response in canines. Moreover, it significantly diminishes the worm burden and hinders the progression of tapeworms in the pVAX1-EgM123 DNA vaccine group. These findings suggest that the pVAX1-EgM123 DNA vaccine holds promise as a potential candidate vaccine for combating E. granulosus infection in dogs.

BackgroundCMRtools is a software package that can be used to measure T2* values to diagnose liver iron overload, however, its accuracy in terms is affected by multiple factors, including goodness-of-fit (R2 value), the number of echo time (TE) images, and the liver iron concentration (LIC). To investigate the effects of the R2 value, the number of TE images, and the LIC on the accuracy of CMRtools software for measuring T2* values to diagnose liver iron overload (LIO).Materials and methodsCMRtools software was used to measure liver T2* values among 108 thalassemia patients via the truncation method, and the R2 values, the number of TE images, and T2* values were recorded. These values were subsequently converted into liver iron concentration (LICT) values. The LICF (derived from MRI-R2/FerriScan) was used as a reference, and the diagnostic accordance rate (DAR) was compared between R2 value subgroups, between TE image number subgroups, and between LIC subgroups.ResultsThe greater the R2 value was, the greater the standardized DAR (SDAR) was (p 0.05). However, the relationship between TE image number subgroups and SDAR was analysed using Spearman’s correlation, and it was found to be positively correlated (rs = 0.729, p = 0.017). The SDAR are not identical between each LIC subgroup (p > 0.05), furthermore, the relationship between LIC subgroup and SDAR was found irrelevant (p = 0.747).ConclusionThe accuracy of CMRtools software for diagnosing LIO in patients with thalassemia can be improved by artificially controlling the number of TE images to be fitted and selecting higher R2 values.

IntroductionChemotherapy-induced cardiotoxicity poses a significant challenge in the treatment of breast cancer, potentially compromising both the efficacy of cancer therapy and cardiac health of patients. This study aimed to enhance the early detection of cardiotoxic effects by integrating advanced imaging modalities and biomarker analysis, thereby facilitating timely interventions to mitigate cardiac risk.MethodsA prospective cohort design was employed, enrolling breast cancer patients scheduled for potentially cardiotoxic chemotherapy regimens. The study utilized a comprehensive diagnostic toolkit, including echocardiography with strain imaging, cardiac MRI, and serial measurements of cardiac biomarkers such as high-sensitivity troponins and natriuretic peptides.ResultsThe analysis revealed that subtle changes in myocardial strain parameters and early biomarker elevations were predictive of subsequent declines in left ventricular function, preceding conventional echocardiographic evidence of cardiotoxicity. Logistic regression analysis highlighted the additive predictive value of integrating biomarker data with advanced imaging findings to identify patients with the highest risk of significant cardiotoxicity.DiscussionThe study concluded that an integrated diagnostic approach, combining detailed imaging assessments with sensitive biomarker analysis, offers a superior strategy for the early detection of chemotherapy-induced cardiotoxicity in breast cancer patients. This proactive diagnostic strategy empowers clinicians to tailor cancer therapy more precisely, balancing oncologic efficacy with cardiovascular safety and underscores the importance of a multidisciplinary approach in the management of patients undergoing potentially cardiotoxic chemotherapy.

Randomized clinical trials (RCTs) of PCSK9 monoclonal antibody(mAb) specifically for Chinese patients have been limited. This multi-center RCT is to clarify the efficacy and safety of a novel mAb, Ebronucimab, in Chinese patients. Patients diagnosed with primary hypercholesterolemia, including Heterozygous Familial Hypercholesterolemia, or mixed dyslipidemia, were categorized by ASCVD risk and randomly assigned at a ratio of 2:1:2:1 to receive Ebronucimab 450 mg or matching placebo every 4 weeks (Q4W), or Ebronucimab 150 mg or matching placebo every 2 weeks (Q2W). The primary outcome was the percentage change of LDL-C from baseline to week 12 for all groups. The least squares mean reduction difference (95 %CI) in LDL-C from baseline to week 12 of Ebronucimab 450 mg Q4W and Ebronucimab 150 mg Q2W groups versus the placebo group was −59.13 (-64.103, −54.153) (Adjusted p

Abstract Background Ubiquitination is an important regulatory step of selective protein degradation in the plant UPS (ubiquitin–proteasome system), which is involved in various biological processes in eukaryotes. Ubiquitin-conjugating enzymes play an intermediate role in the process of protein ubiquitination reactions and thus play an essential role in regulating plant growth and response to adverse environmental conditions. However, a genome-wide analysis of the UBC gene family in wheat (Triticum aestivum L.) has not yet been performed. Results In this study, the number, physiochemical properties, gene structure, collinearity, and phylogenetic relationships of TaUBC family members in wheat were analyzed using bioinformatics methods. The expression pattern of TaUBC genes in different tissues/organs and developmental periods, as well as the transcript levels under abiotic stress treatment, were analyzed using RNA-Seq data and qRT-PCR. Meanwhile, favorable haplotypes of TaUBC25 were investigated based on wheat resequencing data of 681 wheat cultivars from the Wheat Union Database. The analyses identified a total of 93 TaUBC family members containing a UBC domain in wheat genome. These genes were unevenly distributed across 21 chromosomes, and numerous duplication events were observed between gene members. Based on phylogenetic analysis, the TaUBC family was divided into 13 E2 groups and a separate UEV group. We investigated the expression of TaUBC family genes under different tissue/organ and stress conditions by quantitative real-time PCR (qRT-PCR) analysis. The results showed that some TaUBC genes were specifically expressed in certain tissues/organs and that most TaUBC genes responded to NaCl, PEG6000, and ABA treatment with different levels of expression. In addition, we performed association analysis for the two haplotypes based on key agronomic traits such as thousand-kernel weight (TKW), kernel length (KL), kernel weight (KW), and kernel thickness (KT), examining 122 wheat accessions at three environmental sites. The results showed that TaUBC25-Hap II had significantly higher TKW, KL, KW, and KT than TaUBC25-Hap I. The distribution analysis of haplotypes showed that TaUBC25-Hap II was preferred in the natural population of wheat. Conclusion Our results identified 93 members of the TaUBC family in wheat, and several genes involved in grain development and abiotic stress response. Based on the SNPs detected in the TaUBC sequence, two haplotypes, TaUBC25-Hap I and TaUBC25-Hap II, were identified among wheat cultivars, and their potential value for wheat breeding was validated by association analysis. The above results provide a theoretical basis for elucidating the evolutionary relationships of the TaUBC gene family and lay the foundation for studying the functions of family members in the future.

Abstract Background Antimicrobial resistance (AMR) is a major threat to children’s health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making. Methods We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii. Conclusions mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST.

Abstract Background Carbapenem-resistant Escherichia coli (CREC) has been considered as WHO priority pathogens, causing a great public health concern globally. While CREC from patients has been thoroughly investigated, the prevalence and underlying risks of CREC in healthy populations have been overlooked. Systematic research on the prevalence of CREC in healthy individuals was conducted here. We aimed to characterize CREC collected from healthy populations in China between 2020 and 2022 and to compare the genomes of CREC isolates isolated from healthy individuals and clinical patients. Methods We present a nationwide investigation of CREC isolates among healthy populations in China, employing robust molecular and genomic analyses. Antimicrobial susceptibility testing, whole-genome sequencing, and bioinformatics were utilized to analyze a cohort of CREC isolates (n = 113) obtained from fecal samples of 5 064 healthy individuals. Representative plasmids were extracted for third-generation nanopore sequencing. We previously collected 113 non-duplicate CREC isolates (59 in 2018, 54 in 2020) collected from ICU patients in 15 provinces and municipalities in China, and these clinical isolates were used to compare with the isolates in this study. Furthermore, we employ comparative genomics approaches to elucidate molecular variations and potential correlations between clinical and non-clinical CREC isolates. Results A total of 147 CREC isolates were identified from 5 064 samples collected across 11 provinces in China. These isolates were classified into 64 known sequence types (STs), but no dominant STs were observed. In total, seven carbapenemase genes were detected with bla NDM-5 (n = 116) being the most prevalent one. Genetic environments and plasmid backbones of bla NDM were conserved in CREC isolated from healthy individuals. Furthermore, we compared clinical and healthy human-originated CRECs, revealing noteworthy distinctions in 23 resistance genes, including bla NDM-1, bla NDM-5, and bla KPC (χ 2 test, p

Abstract Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

Abstract Background Gastric cancer is currently estimated to be the fifth leading common cancer in the world, and responsible for about one million new cases and an estimated 769,000 cancer-related deaths each year. WFDC21P is long non-coding RNA and has been reported to play critical roles in serval types of cancer. Our research aims to investigate the biological effects and molecular mechanism of WFDC21P in gastric cancer. Methods Datasets (GSE53137, GSE58828, and GSE109476) in GEO database were used to screen differential expressed lncRNAs in gastric cancer by online GEO2R analysis tool. Quantitative RT-PCR was used to verify the above prediction in ten pairs of gastric cancer and corresponding paracancerous tissues. Pan-cancer analysis was used to analyze the expression of WFDC21P in different types of cancer. Small interfering RNAs were used to WFDC21P knockdown. CCK-8 and colony formation assays were used to measure the proliferation and tumorigenesis abilities. Wound healing and Transwell assay were used to detect the migration and invasion abilities. Proteins that interact with WFDC21P were predicted by catRAPID database. RNA pull down and RNA Immunoprecipitation were used to confirm the interaction. Western blotting was used to detect the key proteins level in calcium homeostasis signaling pathway. Loss-of-function and rescue assays were used to evaluate the biological function of SEC63 at the background of WFDC21P silencing. Results WFDC21P was upregulated in gastric cancer tissues and cell lines. WFDC21P downregulation suppressed proliferation, tumorigenesis, migration, invasion, and promoted apoptosis in gastric cancer. SEC63 protein had the capability to bind with WFDC21P and the expression of SEC63 was regulated by WFDC21P. SEC63 was also upregulated in gastric cancer and exerted effects during tumor growth and metastasis. Conclusions This study confirmed that lncRNA WFDC21P aggravated gastric cancer malignant behaviors by interacting with SEC63 to regulate the calcium homeostasis signaling pathway.

To study the effect of resting on the quality of frozen dough, the changes in the moisture state of the dough during the resting process (0, 30, 60, 90, 120 min), the moisture distribution of dough and their effects on ice crystal distribution, microstructure, and creep recovery characteristics after dough freezing were investigated. The results showed that the freezable water content in the dough was decreased by 0.96% with the extension of the resting time. The pores and number of ice crystals formed in the dough during the freezing process gradually decreased and the distribution of ice crystals became more and more uniform. The average pore area decreased from 22.65 to 11.80 with the extension of the resting time from 0 min to 120 min, and the number of pores decreased from 22.65 to 11.80 with the extension of the resting time. The maximum creep flexibility Jmax increased significantly (P

Abstract Background Trigeminal nerve injury is one of the most serious complications in oral clinics, and the subsequent chronic orofacial pain is a consumptive disease. Increasing evidence demonstrates long non-coding RNAs (lncRNAs) play an important role in the pathological process of neuropathic pain. This study aims to explore the function and mechanism of LncRNA Anxa10-203 in the development of orofacial neuropathic pain. Methods A mouse model of orofacial neuropathic pain was established by chronic constriction injury of the infraorbital nerve (CCI-ION). The Von Frey test was applied to evaluate hypersensitivity of mice. RT-qPCR and/or Western Blot were performed to analyze the expression of Anxa10-203, DHX30, and MC1R. Cellular localization of target genes was verified by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect the interaction between the target molecules. Electrophysiology was employed to assess the intrinsic excitability of TG neurons (TGNs) in vitro. Results Anxa10-203 was upregulated in the TG of CCI-ION mice, and knockdown of Anxa10-203 relieved neuropathic pain. Structurally, Anxa10-203 was located in the cytoplasm of TGNs. Mechanistically, Mc1r expression was positively correlated with Anxa10-203 and was identified as the functional target of Anxa10-203. Besides, Anxa10-203 recruited RNA binding protein DHX30 and formed the Anxa10-203/DHX30 complex to enhance the stability of Mc1r mRNA, resulting in the upregulation of MC1R, which contributed to the enhancement of the intrinsic activity of TGNs in vitro and orofacial neuropathic pain in vivo. Conclusions LncRNA Anxa10-203 in the TG played an important role in orofacial neuropathic pain and mediated mechanical allodynia in CCI-ION mice by binding with DHX30 to upregulate MC1R expression. Graphical Abstract The up-regulated lncRNA Anxa10-203 in the trigeminal ganglion of CCI-ION mice interacts with DHX30 to contribute to the excitability of TG neurons and orofacial pain by enhancing Mc1r mRNA stability.

High solid anaerobic digestion (HSAD) achieves the benefits of high volumetric loading rates and lower reject water production, which, however, results in much more concentrated reject water with a remarkable increase in organics and nitrogen compared with that from conventional AD with low solid content. The high concentrations of ammonium (2000–3500 mg/L) and COD (3000–4000 mg/L) were reported to exert inhibition on anammox bacteria (AnAOB), posing challenges to the application of the partial nitritation/anammox (PN/A). To date, no cases of PN/A process start-up for sludge HSAD reject water were reported. This study demonstrated the start-up process of a 480 m3/d PN/A project without anammox sludge inoculation and treating HSAD reject water from a centralized dewatered sludge treatment plant. The project did not construct new infrastructures but utilized previously constructed tanks to upgrade the process from existing short-cut nitrification-denitrification to a two-stage PN/A process. Although no external anammox sludge inoculation was performed to save seeding sludge cost, the start-up was successfully achieved in about 9 months (273 days) based on a three-step method of “AnAOB enrichment - sludge acclimation - capacity doubling”. During start-up, the relative abundance of AnAOB (Candidatus_Kuenenia) increased from near zero to 12.0%. After start-up, the total inorganic nitrogen (TIN) removal load reached 0.74 kgN/(m3•d), with a total nitrogen removal efficiency of over 90%. Compared to the traditional nitrification-denitrification process, the PN/A process remarkably reduces the addition of organic chemicals and aeration energy consumption, saving approximately 4.2 million yuan (RMB) in operational costs annually. In summary, this research provides a full-scale reference for the start-up of the PN/A process treating sludge HSAD reject water.

IntroductionUnderstory removal is frequently used to relieve the renewal pressure on trees and promote the growth capability of trees for maintaining community stability, while the lack of previous study on temperate forests limits our assessment of the effectiveness of this essential management measurement.MethodsIn this study, we calculated the niche characteristics and interspecific association of main understory species and community stability in temperate forests [original broad-leaved Korean pine forest (BKF), Betula platyphylla secondary forest (BF), and Larix gmelinii plantation (LF)] after understory removal for characterizing the resource utilization capacity of the regeneration trees.ResultsDuring the restoration stage, the niche breadth of understory plants with similar habits varied across stands and layers; regeneration tree species with heliophile and semishade occupied a larger niche in BKF and LF, while it was the opposite in LF. Niche overlap among heliophile regeneration trees increased in both BKF and BF, but not in LF. The interspecific association among main species revealed that the distribution of each species was independent and the interspecific association was loose and it varied in different forests and different light-demanding species with regeneration trees. The stability of shrub communities in BF and LF improved whereas that of BKF declined, while that of the herb communities of corresponding forests showed the opposite state.DiscussionOur study demonstrated that the effectiveness of understory removal depends on species’ ecological habits, which enhances the renewal and resource utilization capacity of regeneration tree species in temperate forests and shrub community stability in BF and LF.

Background and purposeImmunotherapy, with or without radiotherapy (iRT or ICIs-nonRT), is the standard treatment for non–small cell lung cancer (NSCLC). Nonetheless, the response to the treatment varies among patients. Given the established role of aspartate aminotransferase/alanine transaminase (AST/ALT) ratio in predicting cancer prognosis, we sought to identify whether the pre-treatment AST/ALT ratio has the potential to serve as a prognostic factor for NSCLC patients receiving ICIs-nonRT and iRT.Materials and methodsWe retrospectively analyzed NSCLC patients who received immunotherapy between April 2018 and March 2021. Patients were classified into iRT group and ICIs-nonRT group and further classified based on AST/ALT ratio cut-off values. The Kaplan-Meier (KM) method estimated the time-to-event endpoints (progression-free survival (PFS) and overall survival (OS)ResultsOf the cohort, 239 underwent ICIs-nonRT and 155 received iRT. Higher AST/ALT ratios correlated with worse outcomes in the ICIs-nonRT group but indicated better outcomes in those who received iRT. Multivariate analysis validated AST/ALT ratio as an independent prognostic factor. For AST/ALT ratios between 0.67-1.7, both ICIs-nonRT and iRT yielded similar treatment outcomes; with AST/ALT ratios greater than 1.7, iRT could be a more favorable treatment option (P=0.038). Conversely, for ratios less than 0.67, ICIs-nonRT could be a more favorable treatment option (P=0.073).ConclusionsThe pre-treatment AST/ALT ratio demonstrates potential as a prognostic marker for treatment outcomes in NSCLC patients receiving either ICIs-nonRT or iRT. This finding could help guide clinicians in selecting more effective treatment protocols, thereby enhancing patient prognosis.

Objective: To observe the morphological characteristics of posterior scleral staphyloma (PSS) with or without macular retinoschisis (MRS) using optical coherence tomography (OCT). Additionally, the incidence and severity of other pathologic myopic maculopathy associated with posterior scleral staphyloma was also evaluated. Methods: General information and OCT imaging data from 440 patients with posterior scleral staphyloma (PSS) and the PSS curvature > 20×10−3 μm–1 were collected. These patients visited the Department of Ophthalmology at the First Affiliated Hospital of Harbin Medical University from January 2013 to June 2021. The obtained OCT images of PSS were analyzed using the Image J software to measure the curvature along the Bruch's membrane. The measured curvature was divided into four levels using the quartile method. The classification of macular retinoschisis (MRS) was based on the anatomical structure of the retina and the location of macular retinoschisis. Patients with PSS accompanied by MRS were assigned to the MRS group, while PSS patients without MRS were assigned to the non-MRS group. Additionally, typical OCT changes in other pathologic myopic maculopathy diseases, such as myopic choroidal neovascularization (mCNV), myopic traction maculopathy (MTM), and myopic foveoschisis (MF), were recorded and evaluated. Results: A total of 615 eyes (328 right eyes, 287 left eyes) from 440 patients (80 males and 360 females) were recruited in this study. The MRS group consisted of 159 patients (36.1%) with 190 eyes (30.9%), while the non-MRS group consisted of 281 patients (63.9%) with 425 eyes (69.1%). Both groups had a significantly higher proportion of female patients compared to male patients, and the right eye was more commonly affected than the left eye. In the MRS group, the prevalence of MRS increased progressively with the severity of PSS. Among the common posterior pole diseases, epiretinal membrane had the highest prevalence (33.2%), while lamellar macular hole had the lowest prevalence (5.3%). In the non-MRS group, the proportion of PSS in each group decreased progressively (except for an equal prevalence in the third and fourth levels) with increasing severity of PSS. Among the common posterior pole diseases, choroidal neovascularization had the highest prevalence (41.4%), while lamellar macular hole had the lowest prevalence (6.5%). When comparing the two groups, there were no significant differences in age, gender, and eye distribution. The MRS group had a higher prevalence of macular schisis, retinal detachment, and dome-shaped macula (17.9%, 14.2%, 14.8%) compared to the non-MRS group (11.3%, 9.2%, 9.6%). The non-MRS group had a significantly higher prevalence of choroidal neovascularization (41.4%) compared to the MRS group (12.6%), while there were no significant differences in the prevalence of epiretinal membrane and lamellar macular hole between the two groups. Conclusion: The prevalence of MRS increased progressively with the severity of PSS, and the MRS occurrence was positively correlated with PSS, which indicated that PSS may lead to MRS, while the proportion of PSS in each group decreases gradually with the severity of PSS in the non-MRS group decreased progressively (except for an equal prevalence in the third and fourth levels). In the MRS group, outer macular retinoschisiss were most relevant to posterior scleral staphyloma, and the prevalence of macular holes and retinal detachments was higher in the MRS group compared to the non-MRS group, indicating that MRS may further turn into complications such as macular holes and retinal detachments, which can significantly affect vision or lead to blindness. The prevalence of choroidal neovascularization (CNV) was significantly higher in the non-MRS group compared to the MRS group, suggesting that PSS with lower severity is more prone to develop into CNV. Dome-shaped macula (DSM) seems to play a protective role in the development of pathologic myopia, and abnormal changes in posterior scleral staphyloma curvature may be an important factor affecting the development and shape of DSM.

This study aims to elucidate the mechanism underlying the reduced jejunal injury in PEDV-challenged piglets after oral administration of puerarin and poria cocos polysaccharides combination (PR + PCP, PP). Results showed that the PEDV challenge caused damage to the small intestine by injuring the villi and inducing redox imbalance which exacerbated the diarrhea of piglets, while PP administration trended to reduce the PEDV infection-caused diarrhea in piglets by alleviating the jejunal injury and restoring the redox balance. Further proteomics and qPCR results showed that PP could significantly reduce the decline of the protein and mRNA levels of gene SDSL inhibiting cellular autophagy in PEDV-infected jejunum of piglets. The immunofluorescence results showed that the autophagy levels of the jejunum expressing low SDSL caused by PEDV infection in the PEDV group were significantly higher than those of the jejunum expressing higher levels of SDSL caused by PP administration in the PP + PEDV group. These results showed that PEDV infection caused jejunal excessive autophagy in piglets by reducing the expression level of SDSL. However, the restoration of the expression level of SDSL significantly reduced the PEDV infection-caused jejunal excessive autophagy in piglets, leading to a decrease in jejunal injury. Therefore, PP administration can alleviate the excessive autophagy-caused jejunal injury by increasing SDSL levels in PEDV-infected piglets. This result suggests that PP can be used as a potential feed additive to prevent PEDV infection.

Accumulating evidence strongly support the key role of NLRP3-mediated pyroptosis in the pathogenesis and progression of vascular endothelial dysfunction associated with diabetes mellitus. Various studies have demonstrated that the activation or upregulation of Silent Information Regulation 2 homolog 2 (SIRT2) exerts inhibitory effect on the expression of NLRP3. Although 1,8-cineole has been found to protect against endothelial dysfunction and cardiovascular diseases, its role and mechanism in diabetic angiopathy remain unknown. Therefore, the aim of this study was to investigate the ameliorative effect of 1,8-cineole through SIRT2 on pyroptosis associated with diabetic angiopathy in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanism. The findings revealed that 1,8-cineole exhibited a protective effect against vascular injury and ameliorated pathological alterations in the thoracic aorta of diabetic mice. Moreover, it effectively mitigated pyroptosis induced by palmitic acid-high glucose (PA-HG) in HUVECs. Treatment with 1,8-cineole effectively restored the reduced levels of SIRT2 and suppressed the elevated expression of pyroptosis-associated proteins. Additionally, our findings demonstrated the occurrence of NLRP3 deacetylation and the physical interaction between NLRP3 and SIRT2. The SIRT2 inhibitor AGK2 and siRNA-SIRT2 effectively attenuated the effect of 1,8-cineole on NLRP3 deacetylation in HUVECs and compromised its inhibitory effect against pyroptosis in HUVECs. However, overexpression of SIRT2 inhibited PA-HG-induced pyroptosis in HUVECs. 1,8-Cineole inhibited the deacetylation of NLRP3 by regulating SIRT2, thereby reducing pyroptosis in HUVECs. In conclusion, our findings suggest that PA-HG-induced pyroptosis in HUVECs plays a crucial role in the development of diabetic angiopathy, which can be mitigated by 1,8-cineole.

Abstract Targeting the programmed cell death 1/programmed cell death ligand 1 (PD‐1/PD‐L1) pathway has been identified as a successful approach for tumor immunotherapy. Here, we identified that the small molecule 5,7,4′‐trimethoxyflavone (TF) from Kaempferia parviflora Wall reduces PD‐L1 expression in colorectal cancer cells and enhances the killing of tumor cells by T cells. Mechanistically, TF targets and stabilizes the ubiquitin ligase HMG‐CoA reductase degradation protein 1 (HRD1), thereby increasing the ubiquitination of PD‐L1 and promoting its degradation through the proteasome pathway. In mouse MC38 xenograft tumors, TF can activate tumor‐infiltrating T‐cell immunity and reduce the immunosuppressive infiltration of myeloid‐derived suppressor cells and regulatory T cells, thus exerting antitumor effects. Moreover, TF synergistically exerts antitumor immunity with CTLA‐4 antibody. This study provides new insights into the antitumor mechanism of TF and suggests that it may be a promising small molecule immune checkpoint modulator for cancer therapy.

ABSTRACT Clostridium perfringens has emerged as a growing public health concern due to its ability to cause various infections and its increasing resistance to antibiotics. To assess its current epidemiology in clinical settings, we conducted a survey involving 426 healthy individuals and 273 ICU inpatients at a provincial hospital in China. Our findings revealed a high prevalence of C. perfringens in healthy individuals (45.77%, 95% CI: 41.0%–50.6%) and ICU patients (12.82%, 95% CI: 9.1%–17.4%). The identified 220 C. perfringens isolates displayed substantial resistance to erythromycin (57.9%), clindamycin (50.7%), and tetracycline (32.0%), primarily attributed to the presence of erm(Q) (54.4%), lnu(P) (13.8%), tetB(P) (83.6%), and tetA(P) (66.7%). Notably, C. perfringens isolates from this particular hospital demonstrated a high degree of sequence type diversity and phylogenic variation, suggesting that the potential risk of infection primarily arises from the bacteria’s gut colonization rather than clonal transmissions within the clinical environment. This study provides an updated analysis of the current epidemiology of C. perfringens in healthy individuals and ICU patients in China and emphasizes the need to optimize intervention strategies against its public health threat.IMPORTANCEClostridium perfringens is a bacterium of growing public health concern due to its ability to cause infections and its increasing resistance to antibiotics. Understanding its epidemiology in clinical settings is essential for intervention strategies. This study surveyed healthy individuals and ICU inpatients in a provincial hospital in China. It found a high prevalence of C. perfringens, indicating infection risk. The isolates also showed significant antibiotic resistance. Importantly, the study revealed diverse sequence types and phylogenetic variation, suggesting infection risk from intestinal colonization rather than clonal transmission in hospitals. This analysis emphasizes the need to optimize intervention strategies against this public health threat.

Abstract The rhomboid‐like (RBL) gene encodes serine protease, which plays an important role in the response to cell development and diverse stresses. However, genome‐wide identification, expression profiles, and haplotype analysis of the RBL family genes have not been performed in wheat (Triticum aestivum L.). This study investigated the phylogeny and diversity of the RBL family genes in the wheat genome through various approaches, including gene structure analysis, evolutionary relationship analysis, promoter cis‐acting element analysis, expression pattern analysis, and haplotype analysis. The 41 TaRBL genes were identified and divided into five subfamilies in the wheat genome. RBL family genes were expanded through segmented duplication and purification selection. The cis‐element analysis revealed their involvement in various stress responses and plant development. The results of RNA‐seq and quantitative real‐time‐PCR showed that TaRBL genes displayed higher expression levels in developing spike/grain and were differentially regulated under polyethylene glycol, NaCl, and abscisic acid treatments, indicating their roles in grain development and abiotic stress response. A kompetitive allele‐specific PCR molecular marker was developed to confirm the single nucleotide polymorphism of TaRBL14a gene in 263 wheat accessions. We found that the elite haplotype TaRBL14a‐Hap2 showed a significantly higher 1000‐grain weight than TaRBL14a‐Hap11 in at least three environments, and the TaRBL14a‐Hap2 was positively selected in wheat breeding. The findings will provide a good insight into the evolutionary and functional characteristics of the TaRBL genes family in wheat and lay the foundation for future exploration of the regulatory mechanisms of TaRBL genes in plant growth and development, as well as their response to abiotic stresses.

This study aimed to depict the mineral deposition on the cellulose extracted from mineral-rich Lycium barbarum L. leaves by the basic base/acid treatment. Alkali treatment made the cellulose fluffy, and the leaf phytoliths changed to liquid silicon, depositing onto the fluffy cellulose in crystalline forms, with the mineral content (mainly Si, Ca, and Al) reaching 9.41 % in cellulose after 24 h alkali treatment. Acid treatment decreased the deposited minerals affecting the cellulose crystallinity. Sulfuric acid (SA) mainly eroded the cellulosic amorphous zone and the attached minerals, and crystallized minerals (mainly quartz-SiO2) remained in the crystalline zone, increasing the cellulose crystallinity (66.8 %). Hydrofluoric acid (HF) indiscriminately removed nearly all minerals regardless of crystalline and amorphous zones, thus lowering the crystallinity. Further application research showed that the ability of the SA-refining cellulose to stabilize emulsion (89.8 %) was much stronger than that of the HF counterpart (62.6 %), and the mineral-relevant cellulose crystallinity determined the emulsion stability. These findings might help in understanding the impact of the basic extraction on cellulosic mineralization and quality and shed light on the development of novel functional cellulose.

Background: The GIMAP family genes play a key role in immune function. Increasing evidence suggests that GIMAP genes were implicated in the tumorigenesis of lung adenocarcinoma (LUAD). This study aimed to investigate the clinical significance of GIMAP family genes in LUAD. Methods: In this study, we explored the expression, mutation, prognostic value of GIMAP family genes and the correlation with immune microenvironment in LUAD. We further investigated the relationship between GIMAP family genes expression and immunotherapy response in GEO LUAD and melanoma cohorts. Results: Among the GIMAP family genes, the expression levels of GIMAP1, GIMAP2, GIMAP4, GIMAP5, GIMAP6, GIMAP7, and GIMAP8 were significantly lower in LUAD tumor tissues than normal tissues. Most GIMAP genes were closely related to age, tumor grade and T stage, but not significantly related to sex, N stage and M stage. In the overall population, patients with high expression of GIMAP family genes had a significant longer overall survival (OS). GO and KEGG enrichment analysis showed that GIMAP family genes were highly enriched in immune-related biological process. The expression of GIMAP family genes was positively correlated with immune cell infiltration and immune checkpoint molecules. Furthermore, high expression of GIMAP family genes were correlated with therapeutic response to immunotherapy in LUAD and melanoma patients. Conclusion: In this study, we identified that GIMAP family genes were significantly associated with immune cell infiltration and immune checkpoint molecules. They potentially play a critical role in anti-tumor immunity and serve as immunotherapy biomarkers.

Sodium-ion batteries (SIBs) with low cost and high safety are considered as an electrochemical energy storage technology suitable for large-scale energy storage. Hard carbon, which is inexpensive and has both high capacity and low sodium storage potential, is regarded as the most promising anode for commercial SIBs. However, the commercialization of hard carbon still faces technical issues of low initial Coulombic efficiency, poor rate performance, and insufficient cycling stability, due to the intrinsically irregular microstructure of hard carbon. To address these challenges, the rational design of the hard carbon microstructure is crucial for achieving high-performance SIBs, via gaining an in-depth understanding of its structure–performance correlations. In this context, our review firstly describes the sodium storage mechanism from the perspective of the hard carbon microstructure's formation. We then summarize the state-of-art development of hard carbon, providing a critical overview of emergence of hard carbon in terms of precursor selection, microstructure design, and electrolyte regulation to optimize strategies for addressing practical problems. Finally, we highlight directions for the future development of hard carbon to achieve the commercialization of high-performance SIBs. We believe this review will serve as basic guidance for the rational design of hard carbon and stimulate more exciting research into other types of energy storage devices.

We aimed to explore the effect of salidroside (SAL) on meat quality, antioxidant capacity, and lipid metabolism in broilers. The results demonstrated that SAL significantly reduced the yellowness (b*), shear force, cooking loss, drip loss, MDA, TBARS, and carbonyl content in breast (P

ABSTRACT: Objectives: Earthworms are one of the key components of soil, and they play a crucial role in the transformation of various nutrients and pollutants in the soil. The purpose of this study is to characterize the NDM-1-producing C. freundii isolated from soil-dwelling earthworms near a hospital, exploring their potential role as carriers of carbapenem-resistant genes. Methods: Isolates were isolated from the intestines of earthworms and identified by MALDI-TOF MS. The presence of NDM enzyme was verified through the CARBA-5 Assay. Whole genome sequencing was conducted using the Illumina NovaSeq PE150 platform. Antimicrobial susceptibility testing and conjugation experiment were performed for phenotypic analysis. Results: This isolate exhibited a multidrug-resistant profile, including resistance to imipenem, meropenem, and ertapenem and successfully transferred blaNDM-1 gene to Escherichia coli. Whole genomic sequencing showed that blaNDM-1 gene was located on an IncFIIY-type plasmid. Phylogenetic analysis revealed a close relationship between the QY221001 strain obtained from earthworms and the human isolate F2021 in the NCBI database, both of which were collected in Hangzhou, China. Conclusion: To our knowledge, this is the first report of an NDM-1-producing bacteria isolated from the intestine of an earthworm. Our finding suggested that earthworms could be a potential reservoir of carbapenem resistance genes, emphasizing the importance of enhanced environmental monitoring of antimicrobial resistance.

Abstract Background IMP-producing Klebsiella spp. (IMPKsp) strains have spread globally, including in China. Currently, the prevalence and genomic characterization of IMPKsp is largely unknown nationwide. Here we aimed to provide a general overview of the phenotypic and genomic characteristics of IMPKsp strains. Methods 61 IMPKsp strains were obtained from 13 provinces in China during 2016-2021. All strains were tested for their susceptibility to antimicrobial agents by the microdilution broth method and sequenced with Illumina next-generation sequencing. We performed conjugation experiments on thirteen representative strains which were also sequenced by Oxford nanopore sequencing technology to characterize bla IMP-encoding plasmids. Results We find that all IMPKsp strains display multidrug-resistant (MDR) phenotypes. All strains belong to 27 different STs. ST307 emerges as a principal IMP-producing sublineage. bla IMP-4 is found to be the major isoform, followed by bla IMP-38. Seven incompatibility types of bla IMP-encoding plasmids are identified, including IncHI5 (32/61, 52.5%), IncN-IncR (10/61, 16.4%), IncFIB(K)-HI1B (7/61, 11.5%), IncN (5/61, 8.2%), IncN-IncFII (2/61, 3.3%), IncFII (1/61, 1.6%) and IncP (1/61, 1.6%). The strains carrying IncHI5 and IncN plasmids belong to diverse ST types, indicating that these two plasmids may play an important role in the transmission of bla IMP genes among Klebsiella spp. strains. Conclusions Our results highlight that multi-clonal transmission, multiple genetic environments and plasmid types play a major role in the dissemination process of bla IMP genes among Klebsiella spp. IncHI5 type plasmids have the potential to be the main vectors mediating the spread of the bla IMP genes in Klebsiella spp.