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Abstract Background Tuberculous meningitis (TBM) is a severe central nervous system (CNS) infection with a challenging diagnosis due to inadequate detection methods. This study evaluated current clinical detection methods and their applicability. Methods A cohort of 514 CNS infection patients from 2018 to 2020 was studied. Data on general demographics, Cerebrospinal Fluid (CSF) analysis, epidemiology, and clinical outcomes were collected. TBM patients were identified, and the sensitivities of mmetagenomic next-generation sequencing (NGS), GeneXpert, and microbial culture were compared. Kappa statistic assessed the consistency between methods. Results Among the patients involved, TBM (29%) and neurosyphilis (25%) were the two most prevalent CNS infections. CSF analysis indicated that 76% of patients had leukocytosis, suggesting a potential CNS inflammation. In TBM cases, 92.5% had elevated CSF protein and leukocyte counts. Moreover, the percentage of positive mNGS results was 55.6%. GeneXpert and MTB cultures alone had lower sensitivity, but combined use resulted in a 53.4% positive rate. Conclusions This study highlights the high sensitivity of mNGS, comparable to GeneXpert and MTB culture. The combined methods are cost-effective and straightforward, and can partially substitute for mNGS, offering valuable alternatives for TBM diagnosis and providing insights into multiple diagnostic strategies in clinical practice.

Facing the dual pressure of eutrophication control and global phosphorus scarcity, the efficient removal and recovery of phosphate from wastewater has attracted growing attention in recent years. Herein, an efficient nanocomposite (nCaO2-BFS) was successfully synthesized through a facile coprecipitation method by loading nano-calcium peroxide (nCaO2) onto blast furnace slags (BFS) and used for phosphate removal and recovery from wastewater. Based on the preliminary screening of as-prepared nCaO2-BFS sorbents regarding phosphate removal efficiency, the nCaO2-BFS nanocomposite prepared with a CaCl2-to-BFS mass ratio of 0.6:1, NH3·H2O amount of 20 mL, and H2O2 amount of 12 mL was selected for further characterization and phosphate elimination. Results showed that the developed nCaO2-BFS sorbent exhibits a superior adsorption capacity of 67.48 mg·g-1, a broadly applicable pH range from 4 to 10, and strong selectivity for phosphate in the presence of competing anions including Cl-, NO3-, SO42-, HCO3-, and CO32-. Mechanistically, surface precipitation and inner-sphere complexation via ligand exchange were identified as the primary sorption mechanism for nCaO2-BFS in capturing phosphate. The plant growth test confirmed that the phosphate-laden nCaO2-BFS sorbent could be used as a slow-release fertilizer to promote the growth of Brassica rapa L. Therefore, applying nCaO2-BFS appears to be a promising method for remediating excessive phosphate and recovering the non-renewable phosphorus resource.

Abstract Large language models have achieved outstanding performance on various downstream tasks with their advanced understanding of natural language and zero-shot capability. However, they struggle with knowledge constraints, particularly in tasks requiring complex reasoning or extended logical sequences. These limitations can affect their performance in question answering by leading to inaccuracies and hallucinations. This paper proposes a novel framework called KnowledgeNavigator that leverages large language models on knowledge graphs to achieve accurate and interpretable multi-hop reasoning. Especially with an analysis-retrieval-reasoning process, KnowledgeNavigator searches the optimal path iteratively to retrieve external knowledge and guide the reasoning to reliable answers. KnowledgeNavigator treats knowledge graphs and large language models as flexible components that can be switched between different tasks without additional costs. Experiments on three benchmarks demonstrate that KnowledgeNavigator significantly improves the performance of large language models in question answering and outperforms all large language models-based baselines.

Abstract Background The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

Abstract The risk of cholangitis after ERCP implantation in malignant obstructive jaundice patients remains unknown. To develop models based on artificial intelligence methods to predict cholangitis risk more accurately, according to patients after stent implantation in patients’ MOJ clinical data. This retrospective study included 218 patients with MOJ undergoing ERCP surgery. A total of 27 clinical variables were collected as input variables. Seven models (including univariate analysis and six machine learning models) were trained and tested for classified prediction. The model’ performance was measured by AUROC. The RFT model demonstrated excellent performances with accuracies up to 0.86 and AUROC up to 0.87. Feature selection in RF and SHAP was similar, and the choice of the best variable subset produced a high performance with an AUROC up to 0.89. We have developed a hybrid machine learning model with better predictive performance than traditional LR prediction models, as well as other machine learning models for cholangitis based on simple clinical data. The model can assist doctors in clinical diagnosis, adopt reasonable treatment plans, and improve the survival rate of patients.

YB1 (Y box binding protein 1), a multifunctional protein capable of binding to DNA/RNA, is present in most cells and acts as a splicing factor. It is involved in numerous cellular processes such as transcription, translation, and DNA repair, significantly affecting cell proliferation, differentiation, and apoptosis. Abnormal expression of this protein is closely linked to the formation of various malignancies (osteosarcoma, nasopharyngeal carcinoma, breast cancer, etc.). This review examines the multifaceted functions of YB1 and its critical role in osteosarcoma progression, providing new perspectives for potential therapeutic strategies.

The objective of this study was to reveal the antibacterial mode of action of garviecin LG34 against S. aureus CICC 21600 and L. monocytogenes CICC 21633 and measure the inhibitions on these two foodborne pathogenic bacteria in milk. Antibacterial mechanism of garviecin LG34 was ascertained by its effect on the efflux of Potassium (K+) ions, extracellular electrical conductivity, UV-absorbing substances, potential across the membrane (ΔΨ), and cell permeability. The inhibition of garviecin LG34 against S. aureus CICC 21600 and L. monocytogenes CICC 21600 in milk was studied by viable counting method. Supplementation with 160 AU/ml of garviecin LG34 had a bactericidal effect on S. aureus CICC 21600 and L. monocytogenes CICC 21633. A total of 80, 160, and 320 AU/ml of garviecin LG34 resulted in the effusion of potassium ion and UV-absorbing substances, the leakage of cellular electrolytes, and the dissipation of electrical potential across the membrane of these two food-borne bacteria and showed a dose-dependent. Moreover, the increase in cell permeability of both strains was observed by flow cytometer after cells treated with 160 AU/ml of garviecin LG34. Garviecin LG34 significantly inhibited the growth of these two food-borne bacteria in milk, especially in skimmed milk. Garviecin LG34 could cause pore formation, intracellular materials release, and permeability increase of S. aureus CICC 21600 and L. monocytogenes CICC 21633, and could be applied to milk as bio-preservative.

Abstract Obesity, caused V̇ by a long‐term high‐fat diet, is a risk factor for insulin resistance and nonalcoholic fatty liver disease (NAFLD). The gut microbiota plays an important role in NAFLD development by producing lipopolysaccharides (LPS). Isoleucine (ILE), as one of the branched‐chain amino acids (BCAAs), has a negative effect on glucose and lipid metabolism in obese mice. Therefore, we speculated that isoleucine‐restricted diets could prevent high‐fat diet‐induced insulin resistance and NAFLD. For this purpose, 30 C57BL/6J mice received a control check diet (CK), a high‐fat diet (HFD), and a isoleucine‐restricted diet (IR) for 12 weeks, respectively. The current study revealed that IR diets reversed HFD‐induced weight gain, increased fasting glucose levels, and lipid metabolism disorder. Furthermore, IR diets attenuated HFD‐induced hepatic inflammation by regulating the LPS/TLR4/NF‐κB signaling pathway. Moreover, hepatic insulin resistance and gluconeogenesis disorder were significantly improved by IR diets. In addition, IR diets reshaped HFD‐induced gut microbiota imbalance, reflected in decreasing the proportion of Proteobacteria phylum and LPS contents. Taken together, our studies support that restricting isoleucine in high‐fat diets was a novel means of preventing obesity‐induced NAFLD and insulin resistance.

In this work, the gastrointestinal digestive outcome of Tremella fuciformis polysaccharide (TFP) was examined using in vitro simulated experiments, together with its effect on the intestinal microbiota. TFP did not significantly alter during the stage of oral digestion, according to an in vitro digestion investigation. Nevertheless, glycosidic connections of TFP were broken throughout the intestinal and stomach digesting phases, which resulted in the dissociation of macromolecular aggregates, a marked rise in decreasing sugar content (CR), as well as a drop in molecular weight (Mw). Additionally, microbial community analysis following fecal fermentation in vitro indicated that TFP might control the alpha and beta diversity of gut microbiota and change the genus- and phylum-level community composition. It increased the abundance of beneficial bacteria including Megasphaera, Phascolarctobacterium, and Bacteroides, and suppressed the growth of harmful bacteria like Escherichia-shigella and Fusobacterium, thus contributing to maintaining gut homeostasis. These results suggested that TFP could have a positive impact on health through enhancing the gut microbiota environment, giving a theoretical basis for its use as a prebiotic.

Abstract Background The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. Methods Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT–PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT–PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models. Results ERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors. Conclusions The ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors.

Abstract Background Body weight and size are important economic traits in chickens. While many growth-related quantitative trait loci (QTLs) and candidate genes have been identified, further research is needed to confirm and characterize these findings. In this study, we investigate genetic and genomic markers associated with chicken body weight and size. This study provides new insights into potential markers for genomic selection and breeding strategies to improve meat production in chickens. Methods We performed whole-genome resequencing of and Wenshang Barred (WB) chickens (n = 596) and three additional breeds with varying body sizes (Recessive White (RW), WB, and Luxi Mini (LM) chickens; (n = 50)). We then used selective sweeps of mutations coupled with genome-wide association study (GWAS) to identify genomic markers associated with body weight and size. Results We identified over 9.4 million high-quality single nucleotide polymorphisms (SNPs) among three chicken breeds/lines. Among these breeds, 287 protein-coding genes exhibited positive selection in the RW and WB populations, while 241 protein-coding genes showed positive selection in the LM and WB populations. Genomic heritability estimates were calculated for 26 body weight and size traits, including body weight, chest breadth, chest depth, thoracic horn, body oblique length, keel length, pelvic width, shank length, and shank circumference in the WB breed. The estimates ranged from 0.04 to 0.67. Our analysis also identified a total of 2,522 genome-wide significant SNPs, with 2,474 SNPs clustered around two genomic regions. The first region, located on chromosome 4 (7.41-7.64 Mb), was linked to body weight after ten weeks and body size traits. LCORL, LDB2, and PPARGC1A were identified as candidate genes in this region. The other region, located on chromosome 1 (170.46-171.53 Mb), was associated with body weight from four to eighteen weeks and body size traits. This region contained CAB39L and WDFY2 as candidate genes. Notably, LCORL, LDB2, and PPARGC1A showed highly selective signatures among the three breeds of chicken with varying body sizes. Conclusion Overall this study provides a comprehensive map of genomic variants associated with body weight and size in chickens. We propose two genomic regions, one on chromosome 1 and the other on chromosome 4, that could helpful for developing genome selection breeding strategies to enhance meat yield in chickens.

Abstract High‐fat diets (HFDs) trigger oxidative stress, insulin resistance (IR), and inflammatory responses in the body, leading to cognitive dysfunction. This study aimed to elucidate the effects of nuciferine on HFD‐induced IR and cognitive impairment in the central nervous system of obese mice and further identify the possible underlying mechanisms. In behavioral experiments, nuciferine administration increased the total distance moved, the number of times mice entered the open arm, the duration of open dwell time, and the number of alternations while shortening the latency to escape. Nuciferine suppressed HFD‐induced synaptic structure damage, as evidenced by the increased expressions of neurotrophic factor BDNF and synaptic function proteins SYN, SNAP‐25, and PSD‐95. In addition, nuciferine effectively ameliorated HFD‐induced IR by IRS/PI3K/AKT pathway, alleviated HFD‐induced neurological damage through AMPK/SIRT1 pathway, and improved cognitive impairment via the Aβ‐tau‐neuroinflammation axis. Therefore, nuciferine could be a new food‐derived neuroprotective agent to counteract HFD‐induced damage.

Men who have sex with men and people living with HIV are disproportionately affected in the 2022 multi-country monkeypox epidemic. The smallpox vaccine can induce cross-reactive antibodies against the monkeypox virus (MPXV) and reduce the risk of infection. Data on antibodies against MPXV induced by historic smallpox vaccination in people with HIV are scarce. In this observational study, plasma samples were collected from people living with and without HIV in Shenzhen, China. We measured antibodies binding to two representative proteins of vaccinia virus (VACV; A27L and A33R) and homologous proteins of MPXV (A29L and A35R) using an enzyme-linked immunosorbent assay. We compared the levels of these antibodies between people living with and without HIV. Stratified analyses were performed based on the year of birth of 1981 when the smallpox vaccination was stopped in China. Plasma samples from 677 people living with HIV and 746 people without HIV were tested. A consistent pattern was identified among the four antibodies, regardless of HIV status. VACV antigen-reactive and MPXV antigen-reactive antibodies induced by historic smallpox vaccination were detectable in the people born before 1981, and antibody levels reached a nadir during or after 1981. The levels of smallpox vaccine-induced antibodies were comparable between people living with HIV and those without HIV. Our findings suggest that the antibody levels against MPXV decreased in both people living with and without HIV due to the cessation of smallpox vaccination.

The k-nearest neighbor algorithm is a powerful classification method. However, its classification performance will be affected in small-size samples with existing outliers. To address this issue, a pre-averaged pseudo nearest neighbor classifier (PAPNN) is proposed to improve classification performance. In the PAPNN rule, the pre-averaged categorical vectors are calculated by taking the average of any two points of the training sets in each class. Then, k-pseudo nearest neighbors are chosen from the preprocessed vectors of every class to determine the category of a query point. The pre-averaged vectors can reduce the negative impact of outliers to some degree. Extensive experiments are conducted on nineteen numerical real data sets and three high dimensional real data sets by comparing PAPNN to other twelve classification methods. The experimental results demonstrate that the proposed PAPNN rule is effective for classification tasks in the case of small-size samples with existing outliers.

Estimating crop yield prior to harvest plays a crucial role in agricultural decision making. Machine learning models that use remote sensing (RS) data can provide quick and early estimates of crop yield. Previously, timeseries gross primary production (GPP) synthesized from RS data has been employed in agricultural applications. However, relevant research on using GPP data and deep learning models in crop yield prediction is scarce. The aim of this study was to assess the capability of MODIS-derived GPP data and deep transfer learning to predict crop yield. We developed and trained deep neural network (DNN), one-dimensional convolutional neural network (1D-CNN), and gated recurrent unit (GRU) models to predict county-level corn and soybean yields. Then we evaluated the performance of crop-type and location transfer learning strategies in crop yield prediction. The results of this study can be summarized as follows: (1) GPP data and deep transfer learning have the potential to predict crop yield with reasonable prediction accuracy; (2) in the context of transfer learning, crop-type transfer learning produced a coefficient of determination (R2) ranging from 0.521 to 0.784 for soybean and from 0.644 to 0.903 for corn. Meanwhile, location transfer learning yielded R2 values ranging from 0.690 to 0.931 for the Great Plains (GP) climatic zone and 0.480 to 0.801 for the Eastern Temperate Forest (ETF) climatic zone; and (3) For corn and soybean yield predictions, the 1D-CNN model (R2 = 0.864 for corn and 0.750 for soybean) outperformed the DNN and GRU models. Our results reveal that MODIS-derived GPP data and deep transfer learning can be used to effectively predict county-level crop yield.

Antibodies perform both neutralizing and non-neutralizing effector functions that protect against certain pathogen-induced diseases. A human antibody directed at the SARS-CoV-2 Spike N-terminal domain (NTD), DH1052, was recently shown to be non-neutralizing, yet it protected mice and cynomolgus macaques from severe disease. The mechanisms of NTD non-neutralizing antibody-mediated protection are unknown. Here we show that Fc effector functions mediate NTD non-neutralizing antibody (non-nAb) protection against SARS-CoV-2 MA10 viral challenge in mice. Though non-nAb prophylactic infusion did not suppress infectious viral titers in the lung as potently as neutralizing antibody (nAb) infusion, disease markers including gross lung discoloration were similar in nAb and non-nAb groups. Fc functional knockout substitutions abolished non-nAb protection and increased viral titers in the nAb group. Fc enhancement increased non-nAb protection relative to WT, supporting a positive association between Fc functionality and degree of protection from SARS-CoV-2 infection. For therapeutic administration of antibodies, non-nAb effector functions contributed to virus suppression and lessening of lung discoloration, but the presence of neutralization was required for optimal protection from disease. This study demonstrates that non-nAbs can utilize Fc-mediated mechanisms to lower viral load and prevent lung damage due to coronavirus infection.

Abstract Reactive oxygen species (ROS)‐mediated oxidative stress and apoptosis contribute to the pathogenesis and pathological conditions of various diseases induced by food and environmental pollutants. Myricetin and dihydromyricetin, as natural flavonoids, can counteract oxidative damage, apoptosis, and associated diseases. Molecular docking analysis, ELISA, fluorescence spectroscopy, and Western blot techniques were applied to examine the potential of the two flavonoids as effective therapeutics for ROS‐mediated diseases and the mechanism(s) underlying their protective effects against ethanol/H2O2‐induced damage. In Kunming mice and HepG2 cells, myricetin and dihydromyricetin inhibited ethanol/H2O2‐induced liver damage, ROS accumulation, and oxidative stress and apoptosis. Molecular docking showed that myricetin and dihydromyricetin interacted with JNK1 via hydrophobic interactions and hydrogen bonds, thereby exerting their protective effects. The significant differences in their binding patterns to JNK1 resulted from the different bond types between C2 and C3 on their C ring. Myricetin and dihydromyricetin likely protected liver injury via counteracting ROS/JNK1‐mediated oxidative stress and apoptosis. The finding that the suppression of ROS‐mediated oxidative stress and apoptosis by flavonoids via interacting with functional proteins, such as kinase, may represent an alternative strategy for treating excessive ROS‐induced health problems.

ABSTRACT: Compared to high-yield commercial laying hens, Chinese indigenous chicken breeds have poor egg laying capacity due to the lack of intensive selection. However, as these breeds have not undergone systematic selection, it is possible that there is a greater abundance of genetic variations related to egg laying traits. In this study, we assessed 5 egg number (EN) traits at different stages of the egg-laying period: EN1 (from the first egg to 23 wk), EN2 (from 23 to 35 wk), EN3 (from 35 to 48 wk), EN4 (from the first egg to 35 wk), and EN5 (from the first egg to 48 wk). To investigate the molecular mechanisms underlying egg number traits in a Chinese local chicken breed, we conducted a genome-wide association study (GWAS) using data from whole-genome sequencing (WGS) of 399 Laiwu Black chickens. We obtained a total of 3.01 Tb of raw data with an average depth of 7.07 × per individual. A total of 86 genome-wide suggestive or significant single-nucleotide polymorphisms (SNP) contained within a set of 45 corresponding candidate genes were identified and found to be associated with stages EN1-EN5. The genes vitellogenin 2 (VTG2), lipase maturation factor 1 (LMF1), calcium voltage-gated channel auxiliary subunit alpha2delta 3 (CACNA2D3), poly(A) binding protein cytoplasmic 1 (PABPC1), programmed cell death 11 (PDCD11) and family with sequence similarity 213 member A (FAM213A) can be considered as the candidate genes associated with egg number traits, due to their reported association with animal reproduction traits. Noteworthy, results suggests that VTG2 and PDCD11 are not only involved in the regulation of EN3, but also in the regulation of EN5, implies that VTG2 and PDCD11 have a significant influence on egg production traits. Our study offers valuable genomic insights into the molecular genetic mechanisms that govern egg number traits in a Chinese indigenous egg-laying chicken breed. These findings have the potential to enhance the egg-laying performance of chickens.

The oxidative damage induced by oxidized low-density lipoprotein (ox-LDL) plays a pivotal role in the development of atherosclerosis. In this study, we investigated the protective effects of quercetin, a plant-derived flavonoid, against ox-LDL-induced damage in human umbilical vein endothelial cells (HUVECs) by mitigating oxidative stress. Our findings demonstrate that quercetin substantially enhances cell viability by attenuating oxidative stress induced by ox-LDL (the cell viability increased from 48 % to 89 %). Notably, this process is intricately regulated by the MALAT1/miR-494–3p/PTEN axis. In HUVECs exposed to ox-LDL, interventions such as knocking down MALAT1 or overexpressing miR-494–3p result in increased cell viability and reduced accumulation of reactive oxygen species (ROS), akin to the protective effect observed with quercetin pretreatment. Through further exploration using molecular biological technique, MALAT1 was confirmed to interact with miR-494–3p and serve as a competing endogenous RNA (ceRNA). These results, for the first time, underscore the involvement of the MALAT1/miR-494–3p/PTEN axis in quercetin's protective action against ox-LDL-induced oxidative stress. Our research provides compelling evidence supporting quercetin as a potential candidate for anti-atherosclerotic therapy. Furthermore, it offers fresh insights into the pathogenesis of atherosclerosis and potential strategies for intervention in this condition.

Abstract Background Detecting pathogens in pediatric central nervous system infection (CNSI) is still a major challenge in medicine. In addition to conventional diagnostic patterns, metagenomic next-generation sequencing (mNGS) shows great potential in pathogen detection. Therefore, we systematically evaluated the diagnostic performance of mNGS in cerebrospinal fluid (CSF) in pediatric patients with CNSI. Methods Related literature was searched in the Web of Science, PubMed, Embase, and Cochrane Library. We screened the literature and extracted the data according to the selection criteria. The quality of included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the certainty of the evidence was measured by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) score system. Then, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odd’s ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) were estimated in Stata Software and MetaDisc. Subgroup analyses were performed to investigate the potential factors that influence the diagnostic performance. Results A total of 10 studies were included in the meta-analysis. The combined sensitivity was 0.68 (95% confidence interval [CI]: 0.59 to 0.76, I 2 = 66.77%, p

Abstract Viral infections in plants pose major challenges to agriculture and global food security in the twenty-first century. Plants have evolved a diverse range of specialized metabolites (PSMs) for defenses against pathogens. Although, PSMs-mediated plant-microorganism interactions have been widely discovered, these are mainly confined to plant-bacteria or plant-fungal interactions. PSM-mediated plant-virus interaction, however, is more complicated often due to the additional involvement of virus spreading vectors. Here, we review the major classes of PSMs and their emerging roles involved in antiviral resistances. In addition, evolutionary scenarios for PSM-mediated interactions between plant, virus and virus-transmitting vectors are presented. These advancements in comprehending the biochemical language of PSMs during plant-virus interactions not only lay the foundation for understanding potential co-evolution across life kingdoms, but also open a gateway to the fundamental principles of biological control strategies and beyond. Graphical Abstract The putative co-evolutionary triad of plant metabolites (PSM) mediated interactions between plant, viruses and their insect vectors. This dynamic trio is depicted through the interplay represented by pink and green arrows, signifying the PSM mediated bidirectional interactions occurring between the virus, the host plant, and the vector.

Abstract High‐fat diets (HFDs) can trigger lipid accumulation, insulin resistance, and inflammatory responses in the body, causing glucose and lipid metabolism dysfunction. This study aimed to explore the role of nuciferine on HFD‐induced disorders of glucose and lipid metabolism in obesity mice models, and further to identify the possible underlying mechanisms. In our experiments, nuciferine effectively ameliorated HFD‐induced insulin resistance by IRS/PI3K/AKT pathway, and alleviated HFD‐induced lipid accumulation via AMPK‐mediated regulation of FAS and ATGL expression. Nuciferine also suppressed HFD‐induced intestinal pathological damage, as evidenced by the improvement of intestinal barrier integrity and the increasing in expressions of tight junction proteins of claudin, ZO‐1, and occludin. In addition, 16S rRNA gene sequencing of the fecal microbiota suggested that nuciferine changed the diversity and the composition of gut microbiota in HFD‐fed mice. Nuciferine decreased the ratio of Firmicutes/Bacteroidetes, the relative abundance of LPS‐producing genus Desulfovibrio and the bacteria which involved in lipid metabolism. In summary, nuciferine ameliorated the disorders of glucose and lipid metabolism in obese mice via balancing the gut–liver axis.

Abstract Background In this study, we explored the characteristics and causes of freckle formation. We collected 15 normal and freckled eggs each for eggshell index testing and hypothesized that the structure and function of the uterus would have a direct effect on freckled egg production given that eggshells are formed in the uterus. To test this hypothesis, we collected uterine tissue from laying hens (418 days of age) that laid normal (Group C, n = 13) and freckled (Group T, n = 16) eggs for 7 consecutive days. Results When we examined the eggshell quality, we found that the L value was significantly lower (P 0.05). There was no significant difference (P > 0.05) between the transverse and longitudinal diameters of the eggs in each group.We then performed histopathology and transcriptome analyses on the collected tissue. When compared with group C, uterine junctional epithelial cells in group T showed significant defects and cilia loss, and epithelial tissue was poorly intact. From transcriptomics, genes that met (|log2FC|) ≥ 1 and P

Heat stress poses a significant challenge to livestock farming, particularly affecting the health and productivity of high-yield dairy cows. This study develops a machine learning framework aimed at predicting the core body temperature (CBT) of dairy cows to enable more effective heat stress management and enhance animal welfare. The dataset includes 3005 records of physiological data from real-world production environments, encompassing environmental parameters, individual animal characteristics, and infrared temperature measurements. Employed machine learning algorithms include elastic net (EN), artificial neural networks (ANN), random forests (RF), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and CatBoost, alongside several optimization algorithms such as Bayesian optimization (BO) and grey wolf optimizer (GWO) to refine model performance through hyperparameter tuning. Comparative analysis of various feature sets reveals that the feature set incorporating the average infrared temperature of the trunk (IRTave_TK) excels in CBT prediction, achieving a coefficient of determination (R2) value of 0.516, mean absolute error (MAE) of 0.239 °C, and root mean square error (RMSE) of 0.302 °C. Further analysis shows that the GWO–XGBoost model surpasses others in predictive accuracy with an R2 value of 0.540, RMSE as low as 0.294 °C, and MAE of just 0.232 °C, and leads in computational efficiency with an optimization time of merely 2.41 s—approximately 4500 times faster than the highest accuracy model. Through SHAP (SHapley Additive exPlanations) analysis, IRTave_TK, time zone (TZ), days in lactation (DOL), and body posture (BP) are identified as the four most critical factors in predicting CBT, and the interaction effects of IRTave_TK with other features such as body posture and time periods are unveiled. This study provides technological support for livestock management, facilitating the development and optimization of predictive models to implement timely and effective interventions, thereby maintaining the health and productivity of dairy cows.

The southern catfish (Silurus meridionalis) is an economically important carnivorous freshwater fish in China. In this study, we compared the properties of skin collagen from southern catfish fed with raw food (RF) and cooked food (CF). The skin collagen yield in the RF group (8.66 ± 0.11%) was significantly higher than that of the CF group (8.00 ± 0.27%). SDS-PAGE, circular dichroism spectroscopy, and FTIR analyses revealed that the collagen extracted from southern catfish skin in both groups was type I collagen, with a unique triple helix structure and high purity. The thermal denaturation temperature of collagen in the RF group (35.20 ± 0.11 °C) was significantly higher than that of the CF group (34.51 ± 0.25 °C). The DPPH free radical scavenging rates were 68.30 ± 2.41% in the RF collagen and 61.78 ± 3.91% in the CF collagen, which was higher than that found in most fish collagen. Both the RF and CF groups had high ability to form fibrils in vitro. Under the same conditions, the CF group exhibited faster fibril formation and a thicker fibril diameter (p < 0.05). In addition, the RF group exhibited significantly higher expression of col1a1 compared to the CF group. These results indicated that feeding southern catfish raw food contributed to collagen production, and the collagen from these fish may have potential in biomaterial applications.

Vertically loaded anchors (VLAs) are widely used as mooring foundations in marine environments. Their working conditions typically involve deep-sea seabed, frequently subjected to cyclic loads induced by wind, waves, and currents. Therefore, understanding the mechanical properties of VLAs under cyclic loading is essential for ensuring the safety of mooring systems. This paper summarizes the current research status on the mechanical properties of VLAs under cyclic loading, analyzing the mechanisms by which cyclic loads affect these properties. Additionally, it reviews and summarizes the research methods applied to studying VLAs under cyclic loading, discussing the issues inherent in various methodologies. Finally, it provides an outlook on future research into VLAs under cyclic loading, laying the groundwork for subsequent studies on the bearing mechanisms of novel VLAs, such as the double-plate vertically loaded anchor (DVLA), under cyclic loading.

Producing translucent eggs has been found to reduce the quality and safety of the eggs, as well as the demand from consumers. However, the intestinal function and the molecular mechanism for the production of translucent eggs remain uncertain. A total of 120 eggs from 276-day-old Jining Bairi were divided into two groups based on eggshell translucence: the translucent egg group (group T) and the normal group (group C). Group T exhibited thicker eggshells and a lower egg yolk color. Subsequently, we divided the chickens into translucent and normal groups based on their egg quality. We then assessed the plasma biochemical index, intestinal morphology and structure, enzyme activity, and antioxidant capacity of the hens producing translucent eggs compared to those producing normal eggs. The results showed that the ratio of duodenal villus length to crypt depth, succinate dehydrogenase (SDH) activity, chymotrypsin, total ATPase (T-ATPase), alkaline phosphatase (AKP), and glutathione peroxidase (GSH-Px) activities were decreased in the hens produced translucent eggs (p < 0.05), but malondialdehyde (MDA) content was increased (p < 0.05); jejunal lipase activity, Na+K+-ATPase activity, total antioxidant capacity (T-AOC), and GSH-Px activities were decreased (p < 0.05) in group T; ileal amylase and Ca2+Mg2+-ATPase activities were also decreased (p < 0.05) in group T. In addition, we identified a total of 471 differentially expressed genes (DEGs) in duodenal tissue, with 327 up-regulated genes and 144 down-regulated genes (|log2FC| ≥ 1 and p < 0.05). Enrichment analysis showed that the up-regulated genes, such as GSTT1, GSTO2, and GSTA3, were mostly enriched in metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450, and oxidative phosphorylation pathways. The results of our study indicate that plasma lipid metabolism disorder, decreased intestinal antioxidant capacity, and altered intestinal metabolism capabilities may influence the formation of translucent eggs.

Th2-high asthma is characterized by elevated levels of type 2 cytokines, such as interleukin 13 (IL-13), and its prevalence has been increasing worldwide. Ferroptosis, a recently discovered type of programmed cell death, is involved in the pathological process of Th2-high asthma; however, the underlying mechanisms remain incompletely understood. In this study, we demonstrated that the serum level of malondialdehyde (MDA), an index of lipid peroxidation, positively correlated with IL-13 level and negatively correlated with the predicted forced expiratory volume in 1 s (FEV1%) in asthmatics. Furthermore, we showed that IL-13 facilitates ferroptosis by upregulating of suppressor of cytokine signaling 1 (SOCS1) through analyzing immortalized airway epithelial cells, human airway organoids, and the ovalbumin (OVA)-challenged asthma model. We identified that signal transducer and activator of transcription 6 (STAT6) promotes the transcription of SOCS1 upon IL-13 stimulation. Moreover, SOCS1, an E3 ubiquitin ligase, was found to bind to solute carrier family 7 member 11 (SLC7A11) and catalyze its ubiquitinated degradation, thereby promoting ferroptosis in airway epithelial cells. Last, we found that inhibiting SOCS1 can decrease ferroptosis in airway epithelial cells and alleviate airway hyperresponsiveness (AHR) in OVA-challenged wide-type mice, while SOCS1 overexpression exacerbated the above in OVA-challenged IL-13-knockout mice. Our findings reveal that the IL-13/STAT6/SOCS1/SLC7A11 pathway is a novel molecular mechanism for ferroptosis in Th2-high asthma, confirming that targeting ferroptosis in airway epithelial cells is a potential therapeutic strategy for Th2-high asthma.

Abstract Hyperuricemia as one of the key factors for gout, and quercetin could reduce the uric acid (UA) content. However, the mechanism of quercetin reduces UA content is still uncovered. Herein, we found quercetin can reduce UA content, induce antioxidant enzyme activity, inhibit the enzyme activity of xanthine oxidase (XOD) in hyperuricemia mice. Moreover, the UA reabsorption was also significantly reduced in the kidney and the kidney inflammation was alleviated by quercetin in hyperuricemia mice. Meanwhile, the protein level of ATP‐binding cassette super‐family G member 2 (ABCG2) was markedly induced and the protein levels of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were significantly repressed by quercetin in hyperuricemia mice and HK‐2 cells and by quercetin‐3‐O‐glucuronide in HK‐2 cells. Additionally, the docking mode indicated that quercetin is stable bound to the active site of XOD. Overall, the data reveal that quercetin alleviates hyperuricemia by repressing the activity of XOD, reducing the UA absorption via enhancing ABCG2 expression, and repressing URAT1 and GLUT9 expression.

Abstract Intramedullary tumors are a class of central nervous system tumors with an incidence of 2 to 4%. As they are located very deep and frequently cause postoperative neurological complications, surgical resection is difficult. In recent years, many surgeons have performed electrophysiological monitoring to effectively reduce the occurrence of postoperative neurological complications. Modern electrophysiological monitoring technology has advanced considerably, leading to the development of many monitoring methods, such as SSEPs, MEPs, DCM, and EMG, to monitor intramedullary tumors. However, electrophysiological monitoring in tumor resection is still being studied. In this article, we discussed the different monitoring methods and their role in monitoring intramedullary tumors by reviewing previous studies. Intratumorally tumors need to be monitored for a summary of the condition of the patient. Only by using various monitoring methods flexibly and through clear communication between surgeons and neurophysiological experts can good decisions be made during surgery and positive surgical results be achieved.

Abstract Background Egg laying rate (LR) is associated with a clutch, which is defined as consecutive days of oviposition. The clutch trait can be used as a selection indicator to improve egg production in poultry breeding. However, little is known about the genetic basis of clutch traits. In this study, our aim was to estimate genetic parameters and identify quantitative trait single nucleotide polymorphisms for clutch traits in 399 purebred Laiwu Black chickens (a native Chinese breed) using a genome-wide association study (GWAS). Methods In this work, after estimating the genetic parameters of age at first egg, body weight at first egg, LR, longest clutch until 52 week of age, first week when the longest clutch starts, last week when the longest clutch ends, number of clutches, and longest number of days without egg-laying until 52 week of age, we identified single nucleotide polymorphisms (SNPs) and potential candidate genes associated with clutch traits in Laiwu Black chickens. The restricted maximum likelihood method was used to estimate genetic parameters of clutch pattern in 399 Laiwu Black hens, using the GCTA software. Results The results showed that SNP-based heritability estimates of clutch traits ranged from 0.06 to 0.59. Genotyping data were obtained from whole genome re-sequencing data. After quality control, a total of 10,810,544 SNPs remained to be analyzed. The GWAS revealed that 421 significant SNPs responsible for clutch traits were scattered on chicken chromosomes 1–14, 17–19, 21–25, 28 and Z. Among the annotated genes, NELL2, SMYD9 , SPTLC2, SMYD3 and PLCL1 were the most promising candidates for clutch traits in Laiwu Black chickens. Conclusion The findings of this research provide critical insight into the genetic basis of clutch traits. These results contribute to the identification of candidate genes and variants. Genes and SNPs potentially provide new avenues for further research and would help to establish a framework for new methods of genomic prediction, and increase the accuracy of estimated genetic merit for egg production and clutch traits.

Abstract Cadmium (Cd) is a heavy metal toxic that can cause health problems including lung injury. This study was set out to meet the growing demand for effective treatment of lung diseases and explore the mechanism of caffeic acid phenethyl ester (CAPE, a natural phenolic acid) protect against Cd‐caused lung damage. In this study, CAPE significantly increased mice body weight, decreased lung W/D ratio, and alleviated histomorphological injury. CAPE mitigated CdCl2‐induced oxidative stress through Nrf2/HO‐1/NQO1 pathway, suppressed inflammation via MyD88/NF‐κB pathway, and alleviated apoptosis by modulating apoptosis mediators. CAPE also inhibited the CdCl2‐caused decreasing of TLR4 level and the increasing of miR‐182‐5p level, which is achieved by miR‐182‐5p sponging TLR4. Collectively, miR‐182‐5p is involved in CAPE against CdCl2‐caused lung damage by targeting TLR4. MiR‐182‐5p/TLR4 is a new pathway for inhibiting oxidative stress, apoptosis, and inflammation in CAPE‐mediated lung protection, which provides a novel avenue for treatment therapies.

The land-based recirculating aquaculture system (RAS) has been widely applied to fish farming as a new eco-friendly culture model. This system consists of circular culture tanks on land integrated with water treatment and recycling systems. This study investigated the growth performance of juvenile gibel carp (Carassius gibelio) cultured at high stocking density (HSD, 0.3 kg/m3) and low stocking density (LSD, 0.15 kg/m3) conditions in RAS, and evaluated the comprehensive economic profit of RAS. The body weight, body length, weight gain rate, and condition factor of gibel carp in the LSD group were significantly higher than those in the HSD group (p < 0.05). The feed conversion ratio increased significantly in the HSD group (p < 0.05). A histological analysis revealed a significantly higher density of white muscle fibers in the LSD group (p < 0.05). Relative mRNA expression levels showed that ubiquitin–proteasome system (UPS)-related genes, ub, psma2, and mafbx, were significantly expressed in the HSD group, while the s6k1 expression was elevated in the LSD group (p < 0.05). The mRNA expression levels of keap1 and hsp70 in the dorsal muscle were significantly higher in the HSD group (p < 0.05). Throughout the rearing period, the water temperature remained consistent between the two density groups. The pH value gradually decreased and the dissolved oxygen levels in the HSD group were generally lower than in the LSD group. The nitrite nitrogen (NO2−-N) content was higher in the HSD group. Compared to the LSD group, the return on investment was significantly lower in the HSD group. In conclusion, the water quality and growth rates of juvenile gibel carp were better in the LSD group. An appropriate stocking density improved the growth performance and aquaculture economic efficiency.

This study examined the spoilage potential of specific spoilage organisms on the degradation of adenosine triphosphate (ATP)-related compounds in vacuum-packed refrigerated large yellow croaker. The total viable count (TVC), ATP-related compounds and related enzymes of vacuum-packed refrigerated large yellow croaker inoculated with different bacteria (Pseudomonas fluorescens and Shewanella putrefaciens) were characterized using the spread plate method, high-performance liquid chromatography and assay kits, respectively. Results indicated that the TVC for both control and Shewanella putrefaciens groups reached spoilage levels at days 9 and 15, respectively. The changes of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and adenosine deaminase activity across all groups showed no significant difference attributable to microbial growth. The results suggested that ATP to inosine monophosphate (IMP) degradation primarily occurs via fish’s endogenous enzymes, with minimal microbial involvement. On day 12, the IMP content in fillets inoculated with Pseudomonas fluorescens (0.93 μmol/g) was half higher than in those inoculated with Shewanella putrefaciens (0.57 μmol/g). Both spoilage organisms facilitated IMP degradation, with Shewanella putrefaciens making a more substantial contribution. Analysis of K values and correlation coefficients revealed that Shewanella putrefaciens was the primary factor in the freshness loss of refrigerated vacuum-packed large yellow croaker. These findings offer a reference for understanding quality changes in refrigerated large yellow croaker, especially regarding umami degradation at the microbial level.

Self-supervised monocular depth estimation can exhibit excellent performance in static environments due to the multi-view consistency assumption during the training process. However, it is hard to maintain depth consistency in dynamic scenes when considering the occlusion problem caused by moving objects. For this reason, we propose a method of self-supervised self-distillation for monocular depth estimation (SS-MDE) in dynamic scenes, where a deep network with a multi-scale decoder and a lightweight pose network are designed to predict depth in a self-supervised manner via the disparity, motion information, and the association between two adjacent frames in the image sequence. Meanwhile, in order to improve the depth estimation accuracy of static areas, the pseudo-depth images generated by the LeReS network are used to provide the pseudo-supervision information, enhancing the effect of depth refinement in static areas. Furthermore, a forgetting factor is leveraged to alleviate the dependency on the pseudo-supervision. In addition, a teacher model is introduced to generate depth prior information, and a multi-view mask filter module is designed to implement feature extraction and noise filtering. This can enable the student model to better learn the deep structure of dynamic scenes, enhancing the generalization and robustness of the entire model in a self-distillation manner. Finally, on four public data datasets, the performance of the proposed SS-MDE method outperformed several state-of-the-art monocular depth estimation techniques, achieving an accuracy (δ1) of 89% while minimizing the error (AbsRel) by 0.102 in NYU-Depth V2 and achieving an accuracy (δ1) of 87% while minimizing the error (AbsRel) by 0.111 in KITTI.

To study the classification, identification, and discrimination between different geographical populations of Triplophysa yarkandensis and explore the related otolith morphology and fish life history, this study statistically analyzed the morphological otolith indices and fish bodies of 734 T. yarkandensis from the Yarkand River, Hotan River, and Tarim River using otolith morphology and fish ecology methods. The results showed that otoliths were small in T. yarkandensis, approximately elliptic, thicker in the middle, gradually thinning to the outer edge, and with a prominent protrusion in the center of the external surface. Otolith length was obviously larger than otolith width while the excisural notch was not obvious, wherein the rostrum was developed, the ventral otolith edge was smooth with a shallow arc, and the otolith dorsal had a crest-like ridge. No significant difference between left and right lapillus morphology was observed (P > 0.05). The otolith morphological indices followed a logarithmic function with the body length and weight (R2=0.48~0.62). It reflects the ontogenetic adaptation to the environment, and migration behavior mainly affects the relationship between otolith morphology and fish body morphology. The SHAPE software was used to extract the outer otolith contour of T. yarkandensis, revealing morphological differences between T. yarkandensis populations. The parameter with the largest discriminant coefficient, i.e., the one in which the morphological difference has the greatest significant effect, was screened. Therewith, the discriminant formula was set up to calculate the discriminant accuracy. Discriminant analysis between groups using fish morphology, otolith morphometry and elliptical Fourier analysis, respectively. The discriminant accuracy of the Hotan River and Tarim River populations was 96.0%, 61.4%, and 82.2%; the Yarkand River and Hotan River was 93.0%, 79.5%, and 87.9%; the Yarkand River and Tarim River populations was 96.5%, 77.5%, and 86.8%. Environmental factors such as water temperature, spatial niche adaptation, and habitat depth were the main causes of the otolith morphological changes, also affecting the behavior characteristics of typical T. yarkandensis life history, especially fish migration. In this study, the T. yarkandensis was found to live in high altitude, low habitat temperature, and high salinity and alkaline waters, so the fish body growth and the elements deposition rate onto otoliths were low. T. yarkandensis belongs to the sub-cold water and benthic fish group, which only enters deep water during overwintering in winter. In other seasons, it swims along the edge and rests in shallow depth waters, so the otolith grows slowly and has a small size. The relationship between otolith and body growth reflected the T. yarkandensis ontogenetic adaptability to its habitat. As the T. yarkandensis residence time is short in the migration area, mineral elements in the water body cannot be rapidly deposited in a short period of time, and the accelerated body growth is not completely reflected in the otolith growth. Therefore, the short-distance migration behavior under habitat fragmentation mainly affects the correlation between otolith and fish growth in T. yarkandensis. The fish otolith morphology is highly species-specific and population-specific. T. yarkandensis otolith morphology was significantly different among the geographically different populations (P < 0.05). In this study, the accuracy rate (> 90.0%) was slightly higher than that of elliptic Fourier analysis (> 80.0%), both of which could be used as the discrimination basis parameter. However, the traditional fish otolith morphology is easy to record, as repetitive operations are robust and less affected by the environment, especially in the contents of a carnivorous fish feeding analysis; therefore, vertebrate paleontology explore has a useful application prospect in these aspects. Moreover, it could serve as an effective tool to identify fish intraspecific differences in the case of growth restriction or bodily injury. Therefore, it is of great research value to introduce the otolith morphology into the population identification of T. yarkandensis. This study explored the T. yarkandensis morphological characteristics and compared otolith morphologies to effectively identify the geographically different population, co-relating otolith shape with T. yarkandensis growth (i.e., body length and quality) and resource management, providing theoretical support to further researches about the composition and migratory population growth. The T. yarkandensis intraspecies differences in different rivers were also compared concerning fish body morphology, otolith measurements, and elliptic Fourier analysis, providing strong evidence for traditional morphological classification. The effective utilization and cost control of incomplete fish samples was greatly favored by this study. Otolith morphology was applied for the first time in the classification and population identification of T. yarkandensis, which laid a foundation for the development and research of its microchemical features and life history strategy, presenting a reference for further identification and evolutionary classification of Triplophysa, strengthening the taxonomic foundation of aquatilia, and providing scientific basis for protecting the plateau fishery germplasm resources.

Abstract Quantification of the cardiac function is vital for diagnosing and curing the cardiovascular diseases. Left ventricular function measurement is the most commonly used measure to evaluate the function of cardiac in clinical practice, how to improve the accuracy of left ventricular quantitative assessment results has always been the subject of research by medical researchers. Although considerable efforts have been put forward to measure the left ventricle (LV) automatically using deep learning methods, the accurate quantification is yet a challenge work as a result of the changeable anatomy structure of heart in the systolic diastolic cycle. Besides, most methods used direct regression method which lacks of visual based analysis. In this work, a deep learning segmentation and regression task-unified network with transformer and spatial–temporal convolution is proposed to segment and quantify the LV simultaneously. The segmentation module leverages a U-Net like 3D Transformer model to predict the contour of three anatomy structures, while the regression module learns spatial–temporal representations from the original images and the reconstruct feature map from segmentation path to estimate the finally desired quantification metrics. Furthermore, we employ a joint task loss function to train the two module networks. Our framework is evaluated on the MICCAI 2017 Left Ventricle Full Quantification Challenge dataset. The results of experiments demonstrate the effectiveness of our framework, which achieves competitive cardiac quantification metric results and at the same time produces visualized segmentation results that are conducive to later analysis.

Abstract Background Metabolic derangements and systemic inflammation are related to the progression of colorectal cancer (CRC) and the prognoses of these patients. The survival of stage II and III CRC patients existed considerable heterogeneity highlighting the urgent need for new prediction models. This study aimed to develop and validate prognostic nomograms based on preoperative serum liver enzyme as well as evaluate the clinical utility. Methods A total of 4014 stage II/III primary CRC patients pathologically diagnosed from January 2007 to December 2013 were included in this study. These patients were randomly divided into a training set (n = 2409) and a testing set (n = 1605). Univariate and multivariate Cox analyses were used to select the independent factors for predicting overall survival (OS) and disease-free survival (DFS) of stage II/III CRC patients. Next, nomograms were constructed and validated to predict the OS and DFS of individual CRC patients. The clinical utility of nomograms, tumor-node-metastasis (TNM), and the American Joint Committee on Cancer (AJCC) system was evaluated using time-dependent ROC and decision curve analyses. Results Among seven preoperative serum liver enzyme markers, aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) was identified as an independent factor for predicting both OS and DFS of stage II/III CRC patients. The nomograms incorporated De Ritis ratio and significant clinicopathological features achieved good accuracy in terms of OS and DFS prediction, with C-index of 0.715 and 0.692, respectively. The calibration curve showed good agreement between prediction by nomogram and actual observation. The results of time-dependent ROC and decision curve analyses suggested that the nomograms had improved discrimination and greater clinical benefits compared with TNM and AJCC staging. Conclusions De Ritis ratio was an independent predictor in predicting both the OS and DFS of patients with stage II/III CRC. Nomograms based on De Ritis ratio and clinicopathological features showed better clinical utility, which is expected to help clinicians develop appropriate individual treatment strategies for patients with stage II /III CRC.

As a key component of plant nitrogen-fixing enzymes and a variety of human coenzyme factors, molybdenum (Mo) plays an essential role in supporting both plant growth and human health. Soil is a key medium for the cycling of Mo in the biosphere. However, the driving anthropogenic and natural factors governing the spatial distribution of Mo in soil and their interactions are not well understood. To determine the factors that affect the spatial patterns of Mo in topsoil, 6980 samples were collected from the Longitudinal Range–Gorge Region (Linshui County, Sichuan Province, China). In this area, tall mountains are adjacent to deep valleys. Topsoil with enriched Mo is mostly distributed in mountainous areas. The most important factors influencing Mo in topsoil are soil parent materials (q = 0.482), altitude (q = 0.256), and soil type (q = 0.259). There are synergistic effects among the various driving factors [q(X1 ∩ X2) > Max[q(X1), q(X2)]]. The Geodetector model was used to validate the magnitude of the interaction effects. The contribution to interacting factors is nonlinearly enhanced when the contribution of a single factor was low (any two factors of aspect, road distance, land use type, and S). The contribution to interacting factors is enhanced bidirectionally when the contribution of a single factor was high (any two factors of altitude, soil type, soil parent material, OM, and TFe2O3). When the contribution of one factor is high and the other is low, the contributing to interacting factors is mostly enhanced bidirectionally and a few are nonlinearly enhanced.

ABSTRACT: The objective of this study was to investigate the effect of Lactobacillus salivarius (L. salivarius) SNK-6 supple-mentation on the laying performance, egg quality, blood parameters, intestinal morphology, and cecal microbial community of laying hens. A total of 432 healthy 30-wk-age laying hens were randomly divided into 3 groups with 6 replicates under the same husbandry and dietary regimes: control (CON); 2.0 × 108 CFU/kg L. salivarius supplementation (T1); 2.0 × 109 CFU/kg L. salivarius supplementation (T2). The experiment lasted for 10 wk. The results indicated that the supplementation resulted in a significant reduction in the broken egg and unqualified egg ratios, and a significant increase in the eggshell strength, eggshell relative weight, albumen height, and Haugh units (P < 0.05). The L. salivarius-treated hens exhibited significantly reduced serum malondialdehyde levels (P < 0.05); significantly increased total protein, phosphorus, calcitonin, and immunoglobulin M (P < 0.05); significantly increased cecal secretory immunoglobulin A concentration (P < 0.05); significantly improved villus height (VH) in the duodenum and VH to crypt depth ratio in the jejunum (P < 0.05). The serum globulin and interleukin-1β, immunoglobulin G concentrations, and catalase activity significantly increased in T2 (P < 0.05). Furthermore, the serum interferon-α level in T1 was significantly higher than that of the CON (P < 0.05). The intestinal barrier-related mRNA gene ZO-1, CLDN1, and MUC2 expression in the jejunum was significantly upregulated in the T1 and T2 groups (P < 0.05). The Firmicutes/Bacteroidetes ratio was higher and the relative abundances of Flavonifractor and Clostridiales_noname were significantly higher in the T1 group (P < 0.05). In conclusion, dietary supplementation with L. salivarius SNK-6 may improve hen egg quality, serum antioxidant capacity, immune function, and intestinal health.

Non-invasive ultrasound neuromodulation (USNM) is a powerful tool to explore neural circuits and treat neurological disorders. Due to the heterogeneity of the skull and regional variations in modulation and treatment objectives, it is necessary to develop an efficient and spatially controllable neuromodulation approach. Recently, transcranial focused ultrasound (tFUS) combined with external biomicro/nanomaterials for brain stimulation has garnered significant attention. This study focused on tFUS combined with perfluoropentane (PFP) nanodroplets (NDs) to improve the efficacy and spatial controllability of USNM. The developed two-stage variable pulse tFUS sequence that include the acoustic droplet vaporization (ADV) pulse for vaporizing PFP NDs into microbubbles (MBs) and the USNM sequence for inducing mechanical oscillations of the formed MBs to enhance neuronal activity. Further, adjusting the acoustic pressure of the ADV pulse generated the controllable vaporization regions, thereby achieving spatially controllable neuromodulation. The results showed that the mean densities of c-fos+ cells expression in the group of PFP NDs with ADV (109 ± 19 cells/mm2) were significantly higher compared to the group without ADV (37.34 ± 8.24 cells/mm2). The acoustic pressure of the ADV pulse with 1.98 MPa and 2.81 MPa in vitro generated the vaporization regions of 0.146 ± 0.032 cm2 and 0.349 ± 0.056 cm2, respectively. Under the same stimulation conditions, a larger vaporization region was also obtained with higher acoustic pressure in vivo, inducing a broader region of neuronal activation. Therefore, this study will serve as a valuable reference for developing the efficient and spatially controllable tFUS neuromodulation strategy.

BackgroundHuman immunodeficiency virus (HIV)-positive patients with anal condyloma acuminata (CA) present an increased risk of anal cancer progression associated with oncogenic human papillomavirus (HPV) infection. It is essential to explore determinants of anal infection by oncogenic HPV among HIV-positive patients with CA.MethodsA retrospective cohort study was performed in HIV-positive patients with CA between January 2019 to October 2021 in Shenzhen, Southeast China. Exfoliated cells were collected from CA lesions and the anal canal of HPV genotypes detected by fluorescence PCR. Unconditional logistic regression analysis was used to probe associations of independent variables with oncogenic HPV infection.ResultsAmong HIV-positive patients with CA, the most prevalent oncogenic genotypes were HPV52 (29.43%), HPV16 (28.93%), HPV59 (19.20%), and HPV18 (15.96%). Risk of oncogenic HPV infection increased with age at enrollment (COR: 1.04, 95% CI: 1.01–1.07, p = 0.022). In the multivariable analysis, age ≥ 35 years (AOR: 2.56, 95% CI: 1.20–5.70, p = 0.02) and history of syphilis (AOR: 3.46, 95% CI: 1.90–6.79, p

Abstract Background Lymph node metastasis risk stratification is crucial for the surgical decision‐making of thyroid cancer. This study investigated whether the integrated gene profiling (combining expression, SNV, fusion) of Fine‐Needle Aspiration (FNA) samples can improve the prediction of lymph node metastasis in patients with papillary thyroid cancer. Methods In this retrospective cohort study, patients with papillary thyroid cancer who went through thyroidectomy and central lymph node dissection were included. Multi‐omics data of FNA samples were assessed by an integrated array. To predict lymph node metastasis, we built models using gene expressions or mutations (SNV and fusion) only and an Integrated Risk Stratification (IRS) model combining genetic and clinical information. Blinded histopathology served as the reference standard. ROC curve and decision curve analysis was applied to evaluate the predictive models. Results One hundred and thirty two patients with pathologically confirmed papillary thyroid cancer were included between 2016–2017. The IRS model demonstrated greater performance [AUC = 0.87 (0.80–0.94)] than either expression classifier [AUC = 0.67 (0.61–0.74)], mutation classifier [AUC = 0.61 (0.55–0.67)] or TIRADS score [AUC = 0.68 (0.62–0.74)] with statistical significance (p 1 cm, AUC = 0.88 (0.79–0.97)] and small nodule [≤1 cm, AUC = 0.84 (0.74–0.93)] subgroups. The genetic risk factor showed independent predictive value (OR = 10.3, 95% CI:1.1–105.3) of lymph node metastasis in addition to the preoperative clinical information, including TIRADS grade, age, and nodule size. Conclusion The integrated gene profiling of FNA samples and the IRS model developed by the machine‐learning method significantly improve the risk stratification of thyroid cancer, thus helping make wise decisions and reducing unnecessary extensive surgeries.

Claudin18.2 (CLDN18.2) is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer. It has been identified as a promising target and a potential biomarker to diagnose tumor, evaluate efficacy, and determine patient prognosis. TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2. In this study, we constructed a solid target radionuclide zirconium-89 (89Zr) labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines. The [89Zr]Zr-desferrioxamine (DFO)-TST001 showed high radiochemical purity (RCP, >99%) and specific activity (24.15 ± 1.34 GBq/μmol), and was stable in 5% human serum albumin, and phosphate buffer saline (>85% RCP at 96 h). The EC50 values of TST001 and DFO-TST001 were as high as 0.413 ± 0.055 and 0.361 ± 0.058 nM (P > 0.05), respectively. The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors (1.11 ± 0.02 vs. 0.49 ± 0.03, P = 0.0016) 2 days post injection (p.i.). BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i. with [89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups. Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive (+++) for CLDN18.2, while those in the BGC823 group did not express CLDN18.2 (−). The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice (2.05 ± 0.16 %ID/g) than BGC823 mice (0.69 ± 0.02 %ID/g) and blocking group (0.72 ± 0.02 %ID/g). A dosimetry estimation study showed that the effective dose of [89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq, which is within the range of acceptable doses for nuclear medicine research. Taken together, these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.

The motor imagery brain-computer interface has always been the focus of scholars.But traditional system cannot accurately extract significant signals and has low classification accuracy.To overcome such difficulty, a new Transformer model was proposed based on the auto-encoder (AE).The filter bank common spatial pattern (FBCSP) was used to extract the features of multiple frequency bands, and the AE was exploited to obtain the dimensionality-reduced feature matrix.Finally, it considered the influence of the global signal features by the position encoding of the Transformer model and considered the internal correlation of the feature matrix by using the multi-head self-attention mechanism.By comparison with the traditional K-nearest neighbors (KNN) system based on linear discriminant analysis (LDA), the experimental results validates that the classification effect of AE+Transformer model is better than that of LDA+KNN system.It shows that the improved algorithm is suitable for the binary classification of motor imagery.

Abstract Background Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. Methods We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. Results In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. Conclusions Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.

Abstract Background As one of the most devastating cancers, head and neck squamous cell carcinoma (HNSCC) has a short survival time and poor prognosis. Pescadillo ribosomal biogenesis factor 1 (PES1) plays a critical role in the progression of numerous cancers. However, its role and underlying mechanisms in HNSCC remain unclear. Methods A variety of bioinformatic approaches were used to identify the expressions, prognostic and diagnostic value of PES1 in HNSCC. qRT‐PCR, immunofluorescence (IF) assay, western blotting and immunohistochemical (IHC) were used to evaluate the expression of PES1 in HNSCC cell lines and clinical tissues. PES1 was knocked down in TU177 and FaDu cells which have high PES1 expression. The effects of PES1 on cell proliferation and tumour growth in HNSCC were elevated by colony formation, CCK8 assays and tumorigenicity assay in nude mice. The effects on cisplatin (CDDP) sensitivity upon silencing of PES1 were assessed using a patient‐derived xenograft (PDX) model. Results PES1 expression was an independent prognostic factor for HNSCC and negatively associated with the overall survival rate. Silencing of PES1 reduces HNSCC cell proliferation and tumour growth. Moreover, PES1 inhibition significantly sensitises HNSCC cells to cisplatin. Furthermore, we found a PES1 has a high correlation with c‐Myc and plays an essential role in the tumour immune microenvironment. Conclusion Our findings suggest that PES1 is associated with tumour growth and drug resistance and served as a potential cancer marker for diagnosis and a putative therapeutic target for HNSCC.

Abstract Background The number of human rabies cases caused by pet dogs in Guangzhou has been decreasing after years of comprehensive interventions. Consequently, attacks by stray dogs become a major issue in rabies control. Objectives To share our experience of successfully dealing with rabies to provide some inspiration for prevention and control in countries and regions affected by it. Methods A multidisciplinary One Health response was initiated to control this outbreak. Rabies virus was detected by PCR in the brain tissue of the associated stray dog. The sequences were aligned with reference sequences downloaded from GenBank using ClustalX. The maximum likelihood method implemented in MEGA 5.0 software package was used in a phylogenetic analysis of the aligned sequences. Results Twelve patients with exposure to the stray dog were identified in the field investigation. Rabies vaccines and immunoglobulin were administered to all patients within 48 h. After 1 year of follow‐up, no exposed patients showed symptoms. Maximum likelihood analysis of the nucleotide sequences obtained from the PCR products indicated that the rabies virus in the dog was closely related to isolates from neighbouring provinces of Guangdong as well as those from surrounding countries of China. Conclusions Multidisciplinary One Health intervention is effective not only in the control of rabies but also in rapid emergency responses to attacks by rabid stray dogs.

With the global aging population, addressing prevalent age-related conditions such as osteoporosis and sarcopenia is crucial. Traditional nutritional strategies focusing on single nutrients like calcium, vitamin D, or protein have limitations, prompting a nuanced exploration of the relationship between aging, nutrition, and musculoskeletal health. This cross-sectional study examines the complex interplay between dietary intake of macronutrients, common micronutrients, and water, as well as their association with musculoskeletal health in adults aged 50 to 80 years, using U.S. National Health and Nutrition Examination Survey data (NHANES). Employing multiple linear regression, restricted cubic splines, weighted quantile sum (WQS), and quantile-based g-computation (QGC) regression models, our initial analysis using the WQS model revealed that a one-quartile increase in mixed macronutrient intake was associated with a significant 0.009 unit increase in bone mineral density (BMD) and a 0.670 unit increase in grip strength, while a similar increase in mixed micronutrient intake showed a 0.007 unit increase in BMD and a 0.442 unit increase in grip strength. Our findings highlight the importance of a balanced dietary approach in promoting musculoskeletal health in the elderly, offering holistic strategies for overall well-being.

Two novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (YPF and LLLP) were discovered from goat milk protein by peptidomics, in silico analysis, and in vitro assessment. A total of 698 peptides (50 = 368.54 ± 12.97 μM and 213.99 ± 0.64 μM) and in situ (IC50 = 159.46 ± 17.40 μM and 154.96 ± 8.41 μM) DPP-IV inhibitory capacities, and their inhibitory mechanisms were further explored by molecular docking. Our study showed that the formation of strong non-bonding interactions with the core residues from the pocket of DPP-IV (such as ARG358, PHE357, GLU205, TYR662, TYR547, and TYR666) might primarily account for the DPP-IV inhibitory activity of two identified peptides. Overall, the two novel DPP-IV inhibitory peptides rapidly identified in this study can be used as functional food ingredients for the control of diabetes.