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Abstract Background This study aimed to develop and validate an ultrasound radiomics model for distinguishing invasive ductal carcinoma (IDC) from ductal carcinoma in situ (DCIS) by combining intratumoral and peritumoral features. Methods Retrospective analysis was performed on 454 patients from Chengzhong Hospital. The patients were randomly divided in accordance with a ratio of 8:2 into a training group (363 cases) and validation group (91 cases). In addition, 175 patients from Yanghu Hospital were used as the external test group. The peritumoral ranges were set to 2, 4, 6, 8, and 10 mm. Mann–Whitney U-test, recursive feature elimination, and a least absolute shrinkage and selection operator were used to in the dimension reduction of the radiomics features and clinical knowledge, and machine learning logistic regression classifiers were utilized to construct the diagnostic model. The area under the curve (AUC) of the receiver operating characteristics, accuracy, sensitivity, and specificity were used to evaluate the model performance. Results By combining peritumoral features of different ranges, the AUC of the radiomics model was improved in the validation and test groups. In the validation group, the maximum increase in AUC was 9.7% (P = 0.031, AUC = 0.803) when the peritumoral range was 8 mm. Similarly, when the peritumoral range was only 8 mm in the test group, the maximum increase in AUC was 4.9% (P = 0.005, AUC = 0.770). In this study, the best prediction performance was achieved when the peritumoral range was only 8 mm. Conclusions The ultrasound-based radiomics model that combined intratumoral and peritumoral features exhibits good ability to distinguish between IDC and DCIS. The selection of peritumoral range size exerts an important effect on the prediction performance of the radiomics model.

The present study investigated the effects of supplementing Macleaya cordata extract (MCE) in low-fishmeal or low-protein diet on the growth performance, blood biochemical indices, intestinal morphology, and intestinal microbiota of juvenile largemouth bass. Two control diets were prepared: a low-protein diet (LP-0) containing 360 g/kg fishmeal and 460 g/kg crude protein, and a low-fishmeal diet (LF-0) containing 270 g/kg fishmeal and 500 g/kg crude protein. Then, 500 mg/kg MCE (Sangrovit) was added to the above two diets resulting in LP-500 and LF-500 diets, respectively. Juvenile largemouth bass (initial weight 21.0 ± 1.0 g) were fed the four diets for 60 days. Results showed that supplementing 500 mg/kg MCE in the low-protein diet, but not in the low-fishmeal diet, significantly increased the weight gain of largemouth bass (P

The incidence of gastric cancer remains high and poses a serious threat to human health. Recent comprehensive investigations into amino acid metabolism and immune system components within the tumor microenvironment have elucidated the functional interactions between tumor cells, immune cells, and amino acid metabolism. This study reviews the characteristics of amino acid metabolism in gastric cancer, with a particular focus on the metabolism of methionine, cysteine, glutamic acid, serine, taurine, and other amino acids. It discusses the relationship between these metabolic processes, tumor development, and the body’s anti-tumor immunity, and analyzes the importance of targeting amino acid metabolism in gastric cancer for chemotherapy and immunotherapy.

Abstract Background Our previous study demonstrated that β2-microglobulin (β2M) promoted ER+/HER2– breast cancer survival via the SGK1/Bcl-2 signaling pathway. However, the role of β2M has not been investigated in ER–/HER2+ breast cancer. Here, we aimed to determine the role of β2M in ER–/HER2+ breast cancer. Methods The interaction between β2M and HFE was confirmed by co-immunoprecipitation, mass spectrometry, yeast two-hybrid screening, and His pull-down. The knockdown and overexpression of β2M or HFE were performed in MDA-MB-453 cells, and ERK signaling pathway was subsequently analyzed via western blotting. Apoptotic cells were detected using flow cytometer. β2M, HFE, and p-ERK1/2 were examined in tumor and paired adjacent tissues via immunohistochemistry. Results HFE was found to be an interacting protein of β2M in ER–/HER2+ breast cancer cells MDA-MB-453 by co-immunoprecipitation and mass spectrometry. A yeast two-hybrid system and His-pull down experiments verified that β2M directly interacted with HFE. β2M and HFE as a complex were mainly located in the cytoplasm, with some on the cytomembrane of MDA-MB-453 cells. In addition to breast cancer cells BT474, endogenous β2M directly interacted with HFE in breast cancer cells MDA-MB-453, MDA-MB-231, and MCF-7. β2M activated the ERK signaling pathway by interacting with HFE and induced apoptosis of MDA-MB-453 cells. The expression of HFE and p-ERK1/2 showed significantly high levels in HER2-overexpressing breast cancer tumor tissue compared with adjacent normal tissue, consistent with the results obtained from the cell experiments. Conclusions β2M induced apoptosis of tumor cells via activation of the ERK signal pathway by directly interacting with HFE in HER2-overexpressing breast cancer.

Abstract Background Chronic kidney disease (CKD) is the third most common cause of death after cancer and heart disease. The continuous treatment of children with CKD was greatly challenged during the COVID-19 pandemic, which significantly impacted the CKD children’s prognosis and the caregivers’ psychological status. However, the influence mechanism of socioeconomic status, medical delay duration, traffic pressure, and online consultation duration on caregivers’ hope and psychological resilience still lacks relevant evidence. Methods This study investigated the general social information, hope, and psychological resilience of 247 caregivers with CKD in 13 provinces of China in March 2020. Factor analysis and an exploratory Structural Equation Model ( SEM ) were used to find the best-fit model, and Bootstrapping was used to calculate the 95% CI of indirect effects. Results The factor analysis obtained four common factors, namely, socioeconomic status (annual family income, education, and career stability), medical accessibility (online consultation duration, medical delay duration, and traffic pressure), hope (positive attitude, positive action, and intimate relationship) and psychological resilience (optimism, tenacity, and strength), with the cumulative contribution rate of 65.34%. Bootstrapping obtains the socioeconomic status β = 0.30 (95% CI [0.14, 0.47], P = 0.002), medical accessibility β = 0.31 (95% CI [0.12, 0.47], P = 0.002), and hope β = 0.40 (95% CI [0.27, 0.52], P = 0.002) has a direct impact on psychological resilience of CKD children caregivers, followed by medical accessibility β = 0.20 (95% CI [0.10, 0.38], P = 0.001) and hope β = 0.23 (95% CI [0.16, 0.32], P = 0.001) plays a mediating role between socioeconomic status and psychological resilience. The indirect impact effect β = 0.35 (95% CI [0.25, 0.50], P = 0.001) is greater than the direct impact effect β = 0.30 (95% CI [0.14, 0.47], P = 0.002). Conclusions Sufficient attention should still be given to children with immunodeficiency after the COVID-19 pandemic, such as CKD, to avoid infection of deadly. Secondly, the government should vigorously develop Primary medical institutions to ensure efficient treatment of severe patients in tertiary hospitals; Finally, the professional literacy of medical workers in remote diagnosis and treatment should be improved to enhance the country’s emergency response capacity for similar major public events and the requirements for normalised epidemic prevention and control.

Many biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-β signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.

To deepen our understanding of long-chain fatty acid carbon chain elongation and desaturation in ducks, this study systematically analyzed the transcriptional activities of key gene promoters, including ELOVLs, FADSs, and SCDs. Predictive modeling coupled with statistical analysis revealed a prevalence of binding motifs for transcription factors, particularly those associated with Sp1, NF-1, and C/EBPalpha. Moreover, variation analysis of resequencing data from both wild and domestic ducks, specifically mallards and Pekin ducks, informed targeted mutagenesis within the core promoter regions of ELOVL2, ELOVL5, and ELOVL6. Notably, mutations at positions -56 G>C in ELOVL2, -52 T>C in ELOVL5, and -513 T>C in ELOVL6 significantly diminished transcriptional activity. These findings substantially enhance our understanding of the molecular mechanisms regulating the biosynthesis of long-chain fatty acids in ducks and support future genetic selection initiatives aimed at developing Pekin duck breeds with enhanced nutritional value.

BackgroundThe incidence of stroke in China is approximately 343 per 100,000 people each year, the highest rate worldwide. Hemorrhagic transformation (HT), particularly symptomatic intracerebral hemorrhage (sICH) following acute ischemic stroke (AIS) with or without intravenous thrombolysis (IVT), can lead to rapid neurological deterioration, poor prognosis, and even death. Non-alcoholic fatty liver disease (NAFLD) has been identified as a risk factor for stroke occurrence and associated with poor long-term functional outcomes. Nonetheless, no studies have examined the association between liver fibrosis and HT in AIS patients who underwent IVT.MethodA total of 826 patients with AIS who underwent IVT were included in this study. We calculated nine validated liver fibrosis indices to assess the extent of liver fibrosis. HT was detected by follow-up cranial CT/MRI within 24 h post-IVT and was classified as either hemorrhagic infarction (HI) or parenchymal hematoma (PH). Symptomatic intracranial hemorrhage was defined as a sudden symptomatic neurological deterioration, indicated by an increase in (National Institutes of Health Stroke Scale) NIHSS score of 4 points or more.ResultThe median values of fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aspartate aminotransferase (AST)-platelet ratio index (APRI), Forns index, alanine aminotransferase (ALT)/AST (ARR), AST/ALT ratio-platelet ratio index (AARPRI), fibrosis quotient (FibroQ), and Fibrosis Index were significantly higher, while the fibrosis-5 (FIB-5) was significantly lower in the HT and sICH groups (all P < 0.001). After adjusting for potential confounders, all nine liver fibrosis indices remained associated with HT and sICH. Receiver operating characteristic (ROC) curve analysis revealed that the FibroQ score had the best predictive ability for HT (AUC = 0.707, CI = 0.652–0.762, P < 0.001), while FIB-4 had the best predictive ability for sICH (AUC = 0.802, CI = 0.711–0.892, P < 0.001).ConclusionLiver fibrosis, as validated by FIB-4, mFIB-4, FIB-5, APRI, Forns index, ARR, AARPRI, FibroQ, and Fibrosis Index, was associated with HT and sICH in AIS patients after IVT.

BackgroundHemorrhagic transformation (HT) after intravenous thrombolysis (IVT) with rt-PA can precipitate rapid neurological deterioration, poor prognosis, and even death. The HALP score (hemoglobin, albumin, lymphocyte, and platelet) is a novel indicator developed to reflect both systemic inflammation and the nutritional status of patients. The goal of this study was to reveal the relationship between the HALP score and the risk of HT after IVT in people with acute ischemic stroke (AIS).MethodsA total of 753 patients with AIS were included in this study. Patients were divided into quartiles according to baseline HALP score. The HALP score was calculated as follows: hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). Binary logistic regression was used to reveal the connection between HALP score and HT.ResultsThe baseline HALP score were significantly lower in the HT than non-HT patients (p 49.6), respectively. Moreover, the severity of HT increased with decreasing HALP level (p

Abstract Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4–62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3–99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1–11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

Abstract This study aimed to develop and validate prediction models to estimate the risk of death and intensive care unit admission in COVID-19 inpatients. All RT-PCR-confirmed adult COVID-19 inpatients admitted to Fujian Provincial Hospital from October 2022 to April 2023 were considered. Elastic Net Regression was used to derive the risk prediction models. Potential risk factors were considered, which included demographic characteristics, clinical symptoms, comorbidities, laboratory results, treatment process, prognosis. A total of 1906 inpatients were included finally by inclusion/exclusion criteria and were divided into derivation and test cohorts in a ratio of 8:2, where 1526 (80%) samples were used to develop prediction models under a repeated cross-validation framework and the remaining 380 (20%) samples were used for performance evaluation. Overall performance, discrimination and calibration were evaluated in the validation set and test cohort and quantified by accuracy, scaled Brier score (SbrS), the area under the ROC curve (AUROC), and Spiegelhalter-Z statistics. The models performed well, with high levels of discrimination (AUROCICU [95%CI]: 0.858 [0.803,0.899]; AUROCdeath [95%CI]: 0.906 [0.850,0.948]); and good calibrations (Spiegelhalter-Z ICU : − 0.821 (p-value: 0.412); Spiegelhalter-Z death : 0.173) in the test set. We developed and validated prediction models to help clinicians identify high risk patients for death and ICU admission after COVID-19 infection.

This study investigated the effects of different dilution concentrations of azoxystrobin and thiophanate-methyl on the preservation of postharvest litchi fruit at ambient temperature. By analyzing the physiological indicators of litchi fruit during storage, the optimal fungicide formulation was selected, verified, and dietary exposure assessed thus the preservation method of extending shelf life for litchi at ambient temperature was obtained. The results showed that the litchi fruit treated with a 1600-fold dilution of 25% azoxystrobin (M1600), or a 1600-fold dilution of 25% azoxystrobin mixed with a 700-fold dilution of 70% thiophanate-methyl (M1600+J700) significantly inhibited the respiratory rate of litchi fruit, decreased the relative conductivity of pericarp and decay rate of litchi fruit (P

Abstract Background Steroid-resistant nephrotic syndrome (SRNS) are monogenic in some cases, however, there are still no clear guidelines on genetic testing in the clinical practice of SRNS in children. Methods Three hundred thirty-two children were diagnosed with SRNS, and all children underwent genetic testing, including gene panels and/or whole-exome/genome sequencing (WES/WGS), during treatment. We analysed the relationship between clinical manifestation and genotype, and compared different genetic testing methods’ detection rates and prices. Results In this study, 30.12% (100/332) of children diagnosed with SRNS had monogenic causes of the disease. With 33.7% (122/332) of children achieving complete remission, 88.5% (108/122) received steroids combined with tacrolimus (TAC). In detectability, WES increased by 8.69% (4/46) on gene panel testing, while WGS increased by 4.27% (5/117) on WES, and WES was approximately 1/7 of the price of WGS for every further 1% increase in pathogenicity. Conclusions We verified that steroids combined with TAC were the most effective option in paediatric SRNS. In detection efficiency, we found that WGS was the highest, followed by WES. The panel was the lowest, but the most cost-effective method when considering the economic-benefit ratio, and thus it should be recommended first in SRNS.

The occurrence of mine water inrushes is common and poses significant hazards in various mining areas throughout China. However, the existing regulations lack of specific engineering geological and hydrogeological exploration guidelines tailored to the water inrush from separation layers (WISL). Exploring the methods of engineering geological and hydrogeological exploration and assessment for the WISL can contribute to further enhancing the prevention and control of mine water disasters in China. This paper begins by examining the mechanism behind WISL in coal mines. It analyzes the geological conditions governing the progression of WISL from its inception to full-scale occurrence and categorizes three prevalent types of WISL in China, i.e., dynamic water inrush, hydrostatic water inrush, and mud and sand-carrying water inrush, all originating from separation layers. Subsequently, it identifies “water source”“channel”“force source”and “material source” as pivotal concealed factors dictating the nature and severity of WISL. Then, the concept of a “inrush separation zone” referring to composite stratigraphic layers situated above traditional water-conducting fractured zones is introduced, where the WISL may transpire during mining activities. Furthermore, it presents a method for delineating “inrush separation zone” in coal mines, outlining exploration stages and specifying crucial investigative focal points. The exploration of water damage in upper strata of coal mine should include two stages: first, the exploration of basic engineering geology and hydrogeological conditions of overlying rock should be carried out to evaluate the possibility of water damage in the exploration area and determine the horizon of potential mining overlying rock ; second, regarding the “inrush separation zone” and “source” layer as the exploration target layer, the special investigation of the hidden disaster factors of the upper layer water damage should be conducted to assess the type and intensity of the water damage in the upper layer. The hydrodynamic conditions and the evolution of overburden fractures are investigated during the mining period. Lastly, a comprehensive forecast evaluation model is proposed and constructed on the coordinated evolutionary mechanisms arising from the interaction of causative factors like “water source”“channel”“force source”and “material source”. This model predicts and evaluates the types, locations, and inflows of water inrush at mining faces before operations commence.

Pacific white shrimp (Litopenaeus vannamei) is an important aquaculture shrimp in China and globally due to its high nutritional value and delicious flavors [...]

Abstract Established in 1962, lithium–sulfur (Li–S) batteries boast a longer history than commonly utilized lithium–ion batteries counterparts such as LiCoO2 (LCO) and LiFePO4 (LFP) series, yet they have been slow to achieve commercialization. This delay, significantly impacting loading capacity and cycle life, stems from the long‐criticized low conductivity of the cathode and its byproducts, alongside challenges related to the shuttle effect, and volume expansion. Strategies to improve the electrochemical performance of Li–S batteries involve improving the conductivity of the sulfur cathode, employing an adamantane framework as the sulfur host, and incorporating catalysts to promote the transformation of lithium polysulfides (LiPSs). 2D MXene and its derived materials can achieve almost all of the above functions due to their numerous active sites, external groups, and ease of synthesis and modification. This review comprehensively summarizes the functionalization advantages of MXene‐based materials in Li–S batteries, including high‐speed ionic conduction, structural diversity, shuttle effect inhibition, dendrite suppression, and catalytic activity from fundamental principles to practical applications. The classification of usage methods is also discussed. Finally, leveraging the research progress of MXene, the potential and prospects for its novel application in the Li–S field are proposed.

Objective: To compare the impact of two pesticide dose forms on Blattella germanica (B. germanica)resistance enzymes.The micro-drop technique was utilized on subcultured B. germanica, and the metabolic enzyme activity was assessed.Using spectrophotometry, the relative enzyme activities of B.germanica were determined.Profile analysis was used to compare the enzyme activities of beta-cypermethrin in both nanoemulsion and traditional emulsion forms.Findings: The suppression percentages of the acetylcholinesterase enzyme (AchE), GST, and P450–O demethylases across different pesticide formulations were analyzed using regression equations, yielding F = 31.18, P

Background: To evaluate the efficacy and safety of allogenic CD8 + natural killer T (CD8+ NKT) immunotherapy combined with gefitinib in the treatment of advanced or metastatic EGFR mutant non-small cell lung cancer (NSCLC). Methods: This study is prospective. The NSCLC patients with exon 19 (Ex19del) or exon 21 L858R point mutations, and response to gefitinib treatment were enrolled into the trial to be randomly assigned into the gefitinib arm and the gefitinib/NKT arm. Allogenic CD8+ NKT cells were cultured in vitro and adaptive transferred into the patients via vein in the gefitinib/NKT arm. The primary endpoint was progression-free survival (PFS). Secondary endpoint analysis included time to disease progression (TTP), overall survival (OS), levels of serum tumour markers for carcinoembryonic antigen (CEA) and alanine aminotransferase (ALT) in the blood, the response rate and safety. From July 2017 to June 2021, 19 patients were randomly assigned to the gefitinib arm (n = 8) and the gefitinib/NKT arm (n = 11). Results: The estimated median survival PFS in the gefitinib/NKT arm was significantly longer than that of the gefitinib arm (12 months vs 7 months). Similar results were also observed for the median TTP. Moreover, the gefitinib/NKT arm had better CEA control than the gefitinib arm. Clinical grade 3 adverse reactions occurred in 64% and 39% of patients in the gefitinib/NKT arm and the gefitinib arm, respectively. The most common grade 3 adverse events in the gefitinib/NKT arm included abnormal liver function in 8 cases (73%) and diarrhoea in 1 case (9%), both of which resolved after drug intervention. Conclusion: The PFS of EGFR-mutated advanced NSCLC treated with allogenic CD8+ NKT cells combined with gefitinib was longer than that of gefitinib alone. No obvious serious adverse reactions occurred, and the patients compliance and survival status were good.

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome (SSNS) using genome-wide association studies (GWAS) strategy is important for understanding the disease. We conducted a multicenter cohort study (360 patients and 1835 controls) combined with a GWAS strategy to identify susceptibility variants associated with the following two subphenotypes of SSNS: steroid-sensitive nephrotic syndrome without relapse (SSNSWR, 181 patients) and steroid-dependent/frequent relapse nephrotic syndrome (SDNS/FRNS, 179 patients). The distribution of two single-nucleotide polymorphisms (SNPs) in ANKRD36 and ALPG was significant between SSNSWR and healthy controls, and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls. Interestingly, rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR. No significant SNPs were observed between SSNSWR and SDNS/FRNS. Meanwhile, chromosome 2:171713702 in GAD1 was associated with a greater steroid dose (>0.75 mg/kg/d) upon relapse to first remission in patients with SDNS/FRNS (odds ratio = 3.14; 95% confidence interval, 0.97–9.87; P = 0.034). rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20% compared with the baseline in SDNS/FRNS patients (P = 0.0001). Protein–protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA. Thus, SSNSWR belongs to non-HLA region-dependent nephropathy, and the HLA-DQA/DQB region is likely strongly associated with disease relapse, especially in SDNS/FRNS. The study provides a novel approach for the GWAS strategy of SSNS and contributes to our understanding of the pathological mechanisms of SSNSWR and SDNS/FRNS.

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancer types, with a low 5-year survival rate of ~20%. Our prior research has suggested that DNA Polymerase iota (Pol ι), a member of Y-family DNA polymerase, plays a crucial role in the invasion and metastasis of ESCC. However, the underlying mechanism is not well understood. In this study, we utilized ChIP-PCR and luciferase reporter assays to investigate the binding of HIF-1α to the promoter of the Pol ι gene. Transwell, wound healing, and mouse models were employed to assess the impact of Pol ι and HIF-1α on the motility of ESCC cells. Co-immunoprecipitation and Western blot were carried out to explore the interaction between Pol ι and HIF-1α, while qRT-PCR and Western blot were conducted to confirm the regulation of Pol ι and HIF-1α on their downstream targets. Our results demonstrate that HIF-1α activates the transcription of the Pol ι gene in ESCC cells under hypoxic conditions. Furthermore, the knockdown of Pol ι impeded HIF-1α-induced invasion and metastasis. Additionally, we found that Pol ι regulates the expression of genes involved in epithelial-mesenchymal transition (EMT) and initiates EMT through the stabilization of HIF-1α. Mechanistically, Pol ι maintains the protein stability of HIF-1α by recruiting USP7 to mediate the deubiquitination of HIF-1α, with the residues 446–578 of Pol being crucial for the interaction between Pol ι and USP7. Collectively, our findings unveil a novel feedforward molecular axis of HIF-1α- Pol ι -USP7 in ESCC that contributes to ESCC metastasis. Hence, our results present an attractive target for intervention in ESCC.

Abstract Background Novel biomarkers are required in gastric cancer (GC) treated by immunotherapy. Epstein-Barr virus (EBV) infection induces an immune-active tumor microenvironment, while its association with immunotherapy response is still controversial. Genes underlying EBV infection may determine the response heterogeneity of EBV + GC. Thus, we screened hub genes associated with EBV infection to predict the response to immunotherapy in GC. Methods Prognostic hub genes associated with EBV infection were screened using multi-omic data of GC. EBV + GC cells were established and confirmed by EBV-encoded small RNA in situ hybridization (EBER-ISH). Immunohistochemistry (IHC) staining of the hub genes was conducted in GC samples with EBER-ISH assay. Infiltrating immune cells were stained using immunofluorescence. Results CHAF1A was identified as a hub gene in EBV + GC, and its expression was an independent predictor of overall survival (OS). EBV infection up-regulated CHAF1A expression which also predicted EBV infection well. CHAF1A expression also predicted microsatellite instability (MSI) and a high tumor mutation burden (TMB). The combined score (CS) of CHAF1A expression with MSI or TMB further improved prognostic stratification. CHAF1A IHC score positively correlated with the infiltration of NK cells and macrophages M1. CHAF1A expression alone could predict the immunotherapy response, but its CS with EBV infection, MSI, TMB, or PD-L1 expression showed better effects and improved response stratification based on current biomarkers. Conclusions CHAF1A could be a novel biomarker for immunotherapy of GC, with the potential to improve the efficacy of existing biomarkers.

Abstract Isolated anti-HBc (IAHBc) is defined by the presence of anti-HBc in the absence of HBsAg and hepatitis B surface antibody (anti-HBs). IAHBc is of great clinical significance as a specific pattern of HBV infection, but IAHBc has not been fully clarified. This study aimed to explore the prevalence and influential factors of IAHBc from routine examination results of inpatients.A total of 61,247 individuals were included in the study, with a median age of 55 years (range: 43–68), and a male-to-female ratio of 0.90:1. The prevalence of current HBV infection (HBsAg positive) was 6.82%, while the prevalence of previous HBV infection (HBsAg negative but anti-HBc positive) was 48.63%. The prevalence of IAHBc was 12.31%. Among them, the rates for males were 7.10%, 52.16%, and 13.70%, respectively, which were significantly higher than the rates for females at 6.56%, 45.45%, and 11.06% (P 0.05). Among IAHBc individuals, approximately 33.83% tested positive for anti-HBe, and their anti-HBc absorbance values were significantly higher compared to anti-HBe negative individuals (7.08 and 5.31, P 0.05).

Abstract It is difficult to distinguish other pathologies mimicking Ménière’s disease (MD) clinically. This study aims to investigate the differences of imaging findings and features between MD and other menieriform diseases via intravenous gadolinium-enhanced magnetic resonance imaging (MRI). 426 patients with menieriform symptoms, including MD, vestibular migraine (VM), and vestibular schwannoma (VS), underwent 3D-FLAIR and 3D-T2WI MRI 6 h after the intravenous gadolinium injection. MR images were analyzed for inner ear morphology, perilymphatic enhancement (PE), EH and other abnormalities. EH was observed at a higher rate in MD patients (85.71%) than patients with other menieriform diseases (VM group = 14.75%, VS group = 37.50%). The prevalence of unilateral EH as well as both cochlear and vestibular EH showed significant differences between MD and VM groups. The prevalence of cochlear EH (I and II) and vestibular EH (II and III) was different between MD and VM groups. The prevalence of PE was higher in MD than VM group. The degrees of cochlear and vestibular hydrops were higher in the definite than probable MD group (P

Abstract Background Although aspirin is increasingly utilized to reduce the event of severe perioperative complications, the effect of long-term aspirin use (L-AU) on perioperative complications in patients undergoing shoulder arthroplasty (SA) has not been well studied. The goal of the present study is to identify the influence of L-AU on perioperative complications in individuals undergoing SA. Methods We selected data from the National Inpatient Sample database between 2010 and 2019, to identify adult patients with SA. Patients were subsequently categorized into L-AU and whole non-L-AU cohorts according to the presence of aspirin use. The demographic and comorbidity characteristics were matched using propensity score matching (PSM). The Pearson chi-square test, Wilcoxon rank test and logistic regression were utilized to assess the association of L-AU with perioperative complications. Results From 2010 to 2019, a total of 162,418 SA patients satisfied the inclusion criteria, with 22,659 (13.95%) using aspirin on a long-term basis. The vast majority of the patients with pre-existing L-AU were aged 65–74 years, female, White and had Medicare insurance. L-AU before surgery was linked to increased risks of perioperative complications, such as blood transfusion (adjusted odds ratio [aOR]: 1.339), genitourinary disease (aOR: 1.349), acute renal failure (aOR: 1.292), acute myocardial infarction (aOR: 1.494), higher total charge (L-AU vs. the whole non-L-AU vs. matched non-L-AU: $66,727.15 vs. $59,697.08 vs. $59,926.32), and prolonged hospitalization stay (LOS) (aOR: 0.837). However, L-AU was considered a protective factor of acute cerebrovascular disease (aOR: 0.722) and stroke (aOR: 0.725). Conclusions Our study is based on the largest open-access all-payer inpatient database, revealing a noteworthy finding of aspirin's protective and adverse impact on different postoperative complications in the US population, such as acute cardiovascular disease, and stroke, etc. Further studies assessing the optimum preoperative aspirin duration and dosage to meet the best benefit quantity for patients with planned joint arthroplasties are suggested.

This study aims to explore the impact of metabolites from three vaginal bacteria on the expression of Syndecan 1 (SDC-1). Human cervical epithelial cells (HcerEpic) were separately incubated with the cell-free supernatants of Lactobacillus crispatus (LCS group), Gardnerella vaginalis (GVS group), and Atopobium vaginalis (AVS group). LCS showed a proliferative effect on HcerEpic, with the most significant effect observed at a concentration of 30 % (P 0.05). LCS promotes HcerEpic proliferation, without significant impact on SDC-1 expression and shedding. This provides molecular evidence for LCS as a protective factor against human papillomavirus infection in the cervix. Metabolites of GV and AV inhibit HcerEpic proliferation, induce cytokine secretion, suppress SDC-1 transcription and expression, and promote SDC-1 shedding.

The heterogeneity of Hepatocellular Carcinoma (HCC) poses a barrier to effective treatment. Stratifying highly heterogeneous HCC into molecular subtypes with similar features is crucial for personalized anti-tumor therapies. Although driver genes play pivotal roles in cancer progression, their potential in HCC subtyping has been largely overlooked. This study aims to utilize driver genes to construct HCC subtype models and unravel their molecular mechanisms. Utilizing a novel computational framework, we expanded the initially identified 96 driver genes to 1192 based on mutational aspects and an additional 233 considering driver dysregulation. These genes were subsequently employed as stratification markers for further analyses. A novel multi-omics subtype classification algorithm was developed, leveraging mutation and expression data of the identified stratification genes. This algorithm successfully categorized HCC into two distinct subtypes, CLASS A and CLASS B, demonstrating significant differences in survival outcomes. Integrating multi-omics and single-cell data unveiled substantial distinctions between these subtypes regarding transcriptomics, mutations, copy number variations, and epigenomics. Moreover, our prognostic model exhibited excellent predictive performance in training and external validation cohorts. Finally, a 10-gene classification model for these subtypes identified TTK as a promising therapeutic target with robust classification capabilities. This comprehensive study provides a novel perspective on HCC stratification, offering crucial insights for a deeper understanding of its pathogenesis and the development of promising treatment strategies.

Abstract Dry eye syndrome (DES) is a chronic ocular disease that induces epithelial damage to the cornea by decreasing tear production and quality. Adequate treatment options have not been established for severe DES such as Sjogren’s syndrome due to complicated pathological conditions. To solve this problem, we focused on the conditioned medium of human adipose-derived mesenchymal stem cells (hAdMSC-CM), which have multiple therapeutic properties. Here, we showed that hAdMSC-CM suppressed Benzalkonium Chloride (BAC)-induced cytotoxicity and inflammation in human corneal epithelial cells (hCECs). In addition, hAdMSC-CM increased the expression level and regulated the localisation of barrier function-related components, and improved the BAC-induced barrier dysfunction in hCECs. RNA-seq analysis and pharmacological inhibition experiments revealed that the effects of hAdMSC-CM were associated with the TGFβ and JAK-STAT signalling pathways. Moreover, in DES model rats with exorbital and intraorbital lacrimal gland excision, ocular instillation of hAdMSC-CM suppressed corneal epithelial damage by improving barrier dysfunction of the cornea. Thus, we demonstrated that hAdMSC-CM has multiple therapeutic properties associated with TGFβ and JAK-STAT signalling pathways, and ocular instillation of hAdMSC-CM may serve as an innovative therapeutic agent for DES by improving corneal barrier function.

Abstract Background Ovarian-Adnexal Reporting and Data System (O-RADS) for ultrasound is a lexicon and risk stratification system that includes all risk categories and relevant management recommendation. It has high sensitivity in diagnosing malignant adnexal tumors, but the specificity is lower. Objective To explore the value of O-RADS combined with contrast-enhanced ultrasound (CEUS) in risk stratification of adnexal masses. Methods A retrospective study was performed on 85 patients with 100 adnexal masses that preoperatively underwent conventional ultrasound as well as CEUS examination and obtained the postoperative pathological results. The masses were classified into O-RADS2, 3, 4, and 5 by conventional ultrasound. After contrast enhancement, the classification of O-RADS was adjusted according to CEUS imaging features. The O-RADS 2 and 3 lesions with suspected malignant features like irregular blood vessels or internal inhomogeneous hyperenhancement were upgraded to O-RADS 4, and the O-RADS 4 lesions with the above features were upgraded to O-RADS 5. The O-RADS 4 lesions with suspicious benign angiographic features like a regular vessel, interior hypoenhancement or non-enhancement were downgraded to O-RADS 3; the O-RADS 5 lesions with rim ring-enhancement and interior non-enhancement were downgraded to O-RADS 3. The sensitivity, specificity, accuracy, PPV, NPV, and AUC of the two methods were compared, taking pathological results as the gold standard. Results The sensitivity, specificity, accuracy, PPV, NPV, and AUC of O-RADS and O-RADS combined with CEUS in the diagnosis of malignant adnexal tumors were 96.6%, 66.2%, 75.0%, 53.8%, 97.9%, 0.910 and 96.6%, 91.5%, 93.0%, 82.4%, 98.5%, 0.962, respectively. The specificity, accuracy, PPV, and AUC of O-RADS combined with CEUS were considerably higher than those of O-RADS (P 0.05). Conclusion Combination of O-RADS and CEUS can significantly improve the specificity and PPV in diagnosing malignant adnexal tumors. It seems promising in the clinical application of risk stratification of adnexal masses.

Antimony (Sb) is a toxic trace element for plants and animals. With the development of industrial applications and mining, Sb pollution is becoming more serious. Phytoremediation is regarded as an eco-friendly technique to reduce the threat of Sb to the environment and human health, and tall fescue that is highly adaptable to heavy metal stress can be a candidate species for Sb-contaminated soil phytoremediation. However, the mechanism of the Sb stress response in tall fescue is not clear. Therefore, transcriptomic analysis was used in this study to reveal the molecular mechanisms of Sb stress response regulation in tall fescue. The results suggested that the roots and leaves of tall fescue responded to Sb stress in different ways. In roots, the lignin and flavonoids might reduce the toxicity of Sb by anti-oxidation and Sb chelation. At the same time, the DEGs in leaves were mainly enriched in the pathways of glutathione metabolism, β-alanine metabolism, and glycine, serine, and threonine metabolism. Additionally, genes related to the pathways, such as 4CL, GST, AGXT2, and ALDH7A1, especially cytochrome P450 family genes (e.g., CYP73A, CYP75A, and CYP98A), might play key roles in the regulation of the Sb stress response in tall fescue. These findings provided a theoretical reference for the efficient use of tall fescue to control Sb-contaminated soil in the future.

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent endocrine disease in women, intricately linked to hormonal imbalances. The microbiota composition plays a pivotal role in influencing hormonal levels within the body. In this study, we utilized a murine model to investigate how intestinal and vaginal microbiota interact with hormones in the development of PCOS.MethodsTwenty female mice were randomly assigned to the normal group (N) and the model group (P), where the latter received daily subcutaneous injections of 0.1 mL DHEA (6 mg/100 g). Throughout the experiment, we evaluated the PCOS mouse model by estrus cycle, serum total testosterone (T), prolactin (PRL) and luteinizing hormone (LH) levels, and ovarian pathological morphology. The microbial composition in both intestinal content and vaginal microbiota were studied by 16S rRNA gene high-throughput sequencing.ResultsCompared with the N group, the P group showed significant increases in body weight, T, and PRL, with significant decrease in LH. Ovaries exhibited polycystic changes, and the estrous cycle was disrupted. The intestinal microbiota result shows that Chao1, ACE, Shannon and Simpson indexes were decreased, Desulfobacterota and Acidobacteriota were increased, and Muribaculaceae, Limosilactobacillus and Lactobacillus were decreased in the P group. T was significantly positively correlated with Enterorhabdus, and LH was significantly positively correlated with Lactobacillus. The analysis of vaginal microbiota revealed no significant changes in Chao1, ACE, Shannon, and Simpson indices. However, there were increased in Firmicutes, Bacteroidota, Actinobacteriota, Streptococcus, and Muribaculaceae. Particularly, Rodentibacter displayed a robust negative correlation with other components of the vaginal microbiota.ConclusionTherefore, the response of the intestinal microbiota to PCOS is more significant than that of the vaginal microbiota. The intestinal microbiota is likely involved in the development of PCOS through its participation in hormonal regulation.

Defective erythropoiesis is one of the causes of anemia and leukemia. However, the mechanisms underlying defective erythropoiesis under a low-dose environment of benzene are poorly understood. In the present study, multiple omics (transcriptomics and metabolomics) and methods from epidemiology to experimental biology (e.g., benzene-induced (WT and HIF-1α + ) mouse, hiPSC-derived HSPCs) were used. Here, we showed that erythropoiesis is more easily impacted than other blood cells, and the process is reversible, which involves HIF-1 and NF-kB signaling pathways in low-level benzene exposure workers. Decreased HIF-1α expression in benzene-induced mouse bone marrow resulted in DNA damage, senescence, and apoptosis in BMCs and HSCs, causing disturbances in iron homeostasis and erythropoiesis. We further revealed that HIF-1α mediates CCL3/macrophage-related immunosurveillance against benzene-induced senescent and damaged cells and contributes to iron homeostasis. Mechanistically, we showed that m6A modification is essential in this process. Benzene-induced depletion of m6A promotes the mRNA stability of gene NFKBIA and regulates the NF-κB/CCL3 pathway, which is regulated by HIF-1α/METTL3/YTHDF2. Overall, our results identified an unidentified role for HIF-1α, m6A, and the NF-kB signaling machinery in erythroid progenitor cells, suggesting that HIF-1α/METTL3/YTHDF2-m6A/NF-κB/CCL3 axis may be a potential prevention and therapeutic target for chronic exposure of humans to benzene-associated anemia and leukemia.

This study investigated the effects of substituting fish meal (FM) in practical diet by chlorella meal on the growth, feed utilization, and flesh quality of Pacific white shrimp (Penaeus vannamei). First, a basal diet was prepared with 200 g/kg FM inclusion (FM-20), and then chlorella meal was used to reduce FM inclusion to 150 g/kg (FM-15), 100 g/kg (FM-10), 50 g/kg (FM-5), and 0 g/kg (FM-0), corresponding to the replacement levels of 25%, 50%, 75%, and 100% of dietary FM, respectively. Shrimp (1.37 ± 0.10 g) were fed with the five isonitrogenous and isolipidic diets for 56 days. No significant difference was observed in feed conversion ratio (FCR) and weight gain (WG) between FM-20 and FM-15 group (P>0.05), but when chlorella meal substituted 50% of dietary FM, WG, protein and lipid retention, and n-3/n-6 PUFAs in flesh were significantly reduced with significant increase in FCR (P0.05). When dietary FM was totally substituted by chlorella meal, the body yellowness and redness and essential amino acid content in flesh, including Lys and Met, were significantly reduced (P0.05). To sum up, in a practical diet with 200 g/kg FM inclusion, chlorella meal successfully replaced 25% of dietary FM without adverse impacts on the growth and feed utilization, and the substitution of 75% of dietary FM did not negatively affect the flesh quality of Pacific white shrimp.

Abstract Background The fat deposition has a crucial role in animal meat flavor, and fat deposition-related traits are vital for breeding in the commercial duck industry. Avian fat-related traits are typical complex phenotypes, which need a large amount of data to analyze the genetic loci. Results In this study, we performed a new phenotypic analysis of fat traits and genotyped whole-genome variations for 1,246 ducks, and combed with previous GWAS data to reach 1,880 ducks for following analysis. The carcass composition traits, subcutaneous fat weight (SFW), subcutaneous fat percentage (SFP), abdominal fat weight (AFW), abdominal fat percentage (AFP) and the body weight of day 42 (BW42) for each duck were collected. We identified a set of new loci that affect the traits related to fat deposition in avian. Among these loci, ceroid-lipofuscinosis, neuronal 8 (CLN8) is a novel candidate gene controlling fat deposition. We investigated its novel function and regulation in avian adipogenesis. Five significant SNPs (the most significant SNP, P-value = 21.37E−12) and a single haplotype were detected in the upstream of CLN8 for subcutaneous fat percentage. Subsequently, luciferase assay demonstrated that 5 linked SNPs in the upstream of the CLN8 gene significantly decreased the transcriptional activity of CLN8. Further, ATAC-seq analysis showed that transcription factor binding sites were identified in a region close to the haplotype. A set of luciferase reporter gene vectors that contained different deletion fragments of the CLN8 promoter were constructed, and the core promoter area of CLN8 was finally identified in the −1,884/−1,207 bp region of the 5′ flanking sequences, which contains adipogenesis-related transcription factors binding sites. Moreover, the over-expression of CLN8 can remarkably facilitate adipocyte differentiation in ICPs. Consistent with these, the global transcriptome profiling and functional analysis of the over-expressed CLN8 in the cell line further revealed that the lipid biosynthetic process during the adipogenesis was significantly enriched. Conclusions Our results demonstrated that CLN8 is a positive regulator of avian adipocyte differentiation. These findings identify a novel function of CLN8 in adipocyte differentiation, which provides important clues for the further study of the mechanism of avian fat deposition.

According to some hot spots such as exploration before excavation，difficulties like drainage mining under special conditions and contradictory while operating procedures in recent coal mining water prevention projects, confusions brought to production practice and safety supervision are analyzed, some opinions are also put forward. Firstly, the connation of “doubt will be prospected” is discussed in this paper. It is assured that “doubt will be explored” comes after “prediction and forecast”. The “prediction and forecast” are key factors to problems like types of water hazards, water pressure and positions of water, based on what water exploration and release can be designed. From the historical background and realistic conditions, the analysis shows that the exploration before excavation proposed in [2011] No.70 document formulated by Shanxi Province is implemented under specific conditions, with strong pertinence (ancient wells and cellar water). The type of water damage is clear, the space position of water pressure source is roughly known, and the design conditions of drilling hole are available. Therefore, design conditions of water exploration drillings are acquired and “exploration before excavation” is reasonable. However, the scope of “exploration before excavation” cannot be extended infinitely to other fields, otherwise it will be aimless, causing bumps in design, execution and supervision. Secondly, degradation of water on soft rocks is analyzed. Degradations like crumble, rock mud, expansion and floor heave can happen on complicated soft rocks which possess weak cementation, low altitude, high expansion and strong watery, limiting production efficiency. The purpose of pre-dredging weak aquifer under soft rock condition is to improve the production conditions and to increase production efficiency. It is suggested that the regulations should make principles constraints on such drainage holes, so as to facilitate enterprises to formulate construction technical measures in combination with the actual situations. Otherwise, there will be a difference in understanding between government regulators and enterprises. Finally, according to the definition in the procedure, the water-conducting fracture zone does not include the caving zone (above the caving zone); nevertheless, the empirical formula in the procedure and the attached drawings show that the water-conducting fracture zone includes the caving zone, which has inconsistency between the front and the back. For this case, two alternative revision suggestions are advanced. Through the analysis of this paper, some fuzzy concepts are clarified, which is convenient for the production unit to accurately implement the rules and regulations, conducive to the precise supervision of safety supervision department. Besides, dilemma between the supervision department and the enterprise can be avoided.

Abstract The tumormicroenvironment (TME) plays a key role in tumor progression. Tumor-associated macrophages (TAMs), which are natural immune cells abundantin the TME, are mainly divided into the anti-tumor M1 subtype and pro-tumor M2 subtype. Due to the high plasticity of TAMs, the conversion of the M1 to M2 phenotype in hypoxic and hypoglycemic TME promotes cancer progression, which is closely related to lipid metabolism. Key factors of lipid metabolism in TAMs, including peroxisome proliferator-activated receptor and lipoxygenase, promote the formation of a tumor immunosuppressive microenvironment and facilitate immune escape. In addition, tumor cells promote lipid accumulation in TAMs, causing TAMs to polarize to the M2 phenotype. Moreover, other factors of lipid metabolism, such as abhydrolase domain containing 5 and fatty acid binding protein, have both promoting and inhibiting effects on tumor cells. Therefore, further research on lipid metabolism in tumors is still required. In addition, statins, as core drugs regulating cholesterol metabolism, can inhibit lipid rafts and adhesion of tumor cells, which can sensitize them to chemotherapeutic drugs. Clinical studies on simvastatin and lovastatin in a variety of tumors are underway. This article provides a comprehensive review of the role of lipid metabolism in TAMs in tumor progression, and provides new ideas for targeting lipid metabolism in tumor therapy.

In recent years, there have been several outbreaks of extensive flooding in northern provinces. Asparagus stem blight disease and brown spot diseases have become increasingly serious, significantly reducing the yield of asparagus grown in large fields, and asparagus production has developed toward facility agriculture. To solve the problems of high labor costs, labor shortages, and low production efficiency faced by facility agriculture, the adoption of mechanized harvesting for asparagus is an inevitable trend. A prerequisite for mechanized harvesting is target detection. Compared with algorithms such as Faster R-CNN, which require the use features of candidate regions for classification and recognition and cannot meet the real-time requirements of mechanized harvesting, this paper proposes a YOLO-based asparagus recognition scheme that can quickly perform target detection with a detection accuracy of 85.45% and significantly enhanced interference resistance, which can greatly improve the production efficiency of facility agriculture and accelerate the mechanization process of facility agriculture.

OBJECTIVE: May–Thurner syndrome (MTS) is a common cause of lower-extremity deep venous thrombosis (DVT). Stenting is effective in the treatment of MTS; however, there are still complications that may affect the patency of the stent. In addition, the long-term efficacy of stenting remains uncertain. This retrospective study investigated the efficacy and prognosis of endovascular treatment of acute proximal DVT with MTS. MATERIALS AND METHODS: Between June 2014 and December 2017, 122 patients with acute symptomatic proximal DVT at our hospital underwent endovascular surgery. The clinical data of the patients were retrospectively collected including follow-up information. The analysis used the generalized additive mixed model and Kaplan–Meier curves (log-rank test). RESULTS: Of the 122 patients, 75 underwent only catheter-directed thrombolysis (CDT), and 47 underwent CDT with stent placement. Characteristics such as age (P = 0.630 ) and gender (P = 0.842) did not show significant differences between the two groups. The freedom from target lesion revascularization did not show significant differences between the two groups (P = 0.82). There were no significant differences between the two groups in the Venous Clinical Severity Score and Villalta Score. CONCLUSIONS: Endovascular treatment of acute lower limb DVT with MTS has good overall efficacy. In young patients with DVT caused by multiple factors besides MTS, prolonged anticoagulation and close follow-up may be more appropriate than primary stenting after thrombus clearance and significant relief of lower limb symptoms.

N6-methyladenosine (m6A) methylation modification is a ubiquitous RNA modification involved in the regulation of various cellular processes, including regulation of RNA stability, metabolism, splicing and translation. Gastrointestinal (GI) cancers are some of the world’s most common and fatal cancers. Emerging evidence has shown that m6A modification is dynamically regulated by a complex network of enzymes and that the catalytic subunit m6A-METTL complex (MAC)-METTL3/14, a core component of m6A methyltransferases, participates in the development and progression of GI cancers. Furthermore, it has been shown that METTL3/14 modulates immune cell infiltration in an m6A-dependent manner in TIME (Tumor immune microenvironment), thereby altering the response of cancer cells to ICIs (Immune checkpoint inhibitors). Immunotherapy has emerged as a promising approach for treating GI cancers. Moreover, targeting the expression of METTL3/14 and its downstream genes may improve patient response to immunotherapy. Therefore, understanding the role of MAC in the pathogenesis of GI cancers and its impact on immune cell infiltration may provide new insights into the development of effective therapeutic strategies for GI cancers.

The present study aimed to evaluate the dietary effects of Clostridium butyricum culture (CC) or sodium butyrate (SB) on the growth, feed utilization, serum indicators, intestinal histology and microbiota of largemouth bass (Micropterus salmoides). CC and coated SB (50%) were supplemented to a low fish meal diet (245 g/kg) (control diet) at the inclusion levels of 1 g/kg and 2 g/kg, to form five iso-nitrogenous and iso-lipidic diets (control, CC-1, CC-2, SB-1, and SB-2). Then, the five diets were fed to largemouth bass with initial body weight of 70.2 ± 0.1 g. After 8 weeks of feeding, dietary supplementation of 1 g/kg CC increased the weight gain (WG) by 7.4% (P 0.05), when compared to the control. The muscle composition was not significantly affected by the inclusion of CC or SB (P > 0.05). Dietary inclusion of CC or SB significantly reduced serum diamine oxidase activity and increased lysozyme activity (P

The aim of this trial was to investigate the effects of dietary protein and lipid levels on growth performance and flesh quality of largemouth bass (Micropterus salmoides). A 3 × 3 two-factor design was used, including three crude protein levels of 46%, 50%, 54% (P46, P50, P54) and three crude lipid levels of 8%, 12%, 16% (L8, L12, L16). Thus, a total of nine diets (P46/L8, P46/L12, P46/L16, P50/L8, P50/L12, P50/L16, P54/L8, P54/L12 and P54/L16) were prepared and fed to large-size largemouth bass with initial body weight of 109.7 g for 84 days. At the same dietary protein level, weight gain rate (WGR), protein efficiency rate (PER), viscerosomatic index and polyunsaturated fatty acids (PUFAs) percent in flesh showed an increasing trend with increasing the dietary lipid level, while feed conversion ratio (FCR) showed a decreasing trend. At P46 and P50, whole fish crude protein, muscle crude protein, total collagen content, hardness, springiness, chewiness and shear force increased, and steaming loss and freezing loss decreased with increasing the dietary lipid level, while the above indicators showed an opposite trend at P54. At P50, the protein retention (PR) of 16% crude lipid group was significantly higher than that in the 8% and 12% crude lipid groups (P 0.05). The P50/L16 group showed the highest PER, PR, whole fish protein, muscle protein, total collagen, PUFAs, muscle hardness, springiness, chewiness, shear force and the lowest steaming loss. In conclusion, based on growth performance and flesh quality, the appropriate dietary protein and lipid requirements for large-size largemouth bass were 50% and 16%, respectively.

To investigate the impact of dietary inclusion of ferulic acid (FA) on growth performance, physiological and biochemical functions and hepato-intestinal health, three iso-nitrogenous and iso-lipidic diets supplemented with 0 mg/kg, 100 mg/kg, and 200 mg/kg FA were fed to Megalobrama amblycephala (9.75 ± 0.04 g) for 8 weeks. The growth performance, physiological and biochemical parameters, antioxidant capacity and the expression of genes were assessed on 4th and 8th week. The results indicated that 100 mg/kg FA inclusion significantly enhanced the weight gain rate (on week 4 and 8), feed intake (on 4th week), protein efficiency ratio (on week 8) and condition factor (on week 4) (P

ABSTRACTSynbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.

BackgroundAberrant metabolism is a major hallmark of cancers and hereditary diseases. Genes associated with inborn metabolic errors may also play roles in cancer development. This study evaluated the overall impact of these genes on gastric cancer (GC).MethodsIn total, 162 genes involved in 203 hereditary metabolic diseases were identified in the Human Phenotype Ontology database. Clinical and multi-omic data were acquired from the GC cohort of the Affiliated Hospital of Jiangsu University and other published cohorts. A 4-gene and 32-gene signature was established for diagnosis and prognosis or therapeutic prediction, respectively, and corresponding abnormal metabolism scores (AMscores) were calculated.ResultsThe diagnostic AMscore showed high sensitivity (0.88-1.00) and specificity (0.89-1.00) to distinguish between GC and paired normal tissues, with area under the receiver operating characteristic curve (AUC) ranging from 0.911 to 1.000 in four GC cohorts. The prognostic or predictive AMscore was an independent predictor of overall survival (OS) in five GC cohorts and a predictor of the OS and disease-free survival benefit of postoperative chemotherapy or chemoradiotherapy in one GC cohort with such data. The AMscore adversely impacts immune biomarkers, including tumor mutation burden, tumor neoantigen burden, microsatellite instability, programmed death-ligand 1 protein expression, tumor microenvironment score, T cell receptor clonality, and immune cell infiltration detected by multiplex immunofluorescence staining. The AUC of the AMscore for predicting immunotherapy response ranging from 0.780 to 0.964 in four cohorts involving GC, urothelial cancer, melanoma, and lung cancer. The objective response rates in the low and high AMscore subgroups were 78.6% and 3.2%, 40.4% and 7%, 52.6% and 0%, and 72.7% and 0%, respectively (all p

Yeast culture (YC) is a yeast-fermented product of enzymolysis soybean protein with plenty of small peptide and nucleotide. This study aimed to investigate the effects of YC as a substitute for fish meal (FM) on the growth, serum biochemical parameters, intestinal histology and microorganisms of hybrid snakehead (Channa argus ♂ × C. maculate ♀). In a basal diet containing 250 g/kg FM, YC was included at the levels of 0, 40, 80, 120 g/kg to replace 0, 29.5, 59.0 and 88.5 g/kg FM to form four isonitrogenous diets (CON, YC-40, YC-80 and YC-120). The four diets were fed to hybrid snakehead with initial body weight (9.2 ± 0.1 g) for 70 days. The results showed that there were no significant differences in weight gain (WG), feed conversion ratio, protein efficiency ratio (PER), protein retention (PR) and lipid retention (LR) among the three groups of CON, YC-40 and YC-80 groups (P > 0.05). However, the WG, PER, PR and LR in YC-120 group were significantly lower than those in the CON group (P 0.05). In serum biochemical parameters, superoxide dismutase activity and total antioxidant capacity in YC-40 and YC-80 groups were significantly increased, and total cholesterol content in YC-120 group was significantly decreased when compared to the control (P 0.05). Intestinal microbial analysis showed that the major intestinal microorganisms in all groups were Firmicutes, Spirochaetota, Proteobacteria and Actinobacteria. The relative abundance of Brevinema in YC-120 group was significantly higher than that in CON group (P

Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7high, TCF7high, and HLA-DRlow) and Treg2 (CCR7low, TCF7low, and HLA-DRhigh). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.

The steel plate reinforcement method is widely used for strengthening damaged linings. Nevertheless, low durability is one of the disadvantages of the steel plate reinforcement method, which uses epoxy resin as the interface binder. To enhance the load-bearing performance and strengthening effect of steel-plate-reinforced structures, this study introduced ultra-high performance concrete (UHPC) as the reinforcing bonding layer and proposed a novel method for steel plate–UHPC reinforcement of cracked linings. A mechanical performance model test was conducted on a 1/5 scale lining model using a loading test device to evaluate the load-bearing performance and stress deformation of both conventional steel plate and steel plate–UHPC reinforced cracked linings. The characteristics, mechanisms of failure, and impacts of strengthening of the steel plate reinforcement method and steel plate–UHPC reinforcement method for cracked linings were compared. A numerical simulation model was developed to investigate the reinforcement effect of cracked linings using steel plate–UHPC reinforcement. The analysis included examining the influence of steel plate thickness, UHPC bonding layer thickness, and reinforcement timing. Model test results show that the overall damage mode of the steel plate–UHPC-reinforced structure had good elastic–plastic behaviour, and the deformation and damage process under the vertical concentrated load can be divided into four typical phases. Compared with the traditional steel plate reinforcement, the ultimate load-carrying capacity and ductility of the steel plate–UHPC-reinforced structure were increased by 53% and 366%, respectively, showing significantly better load-carrying capacity and deformation performance. Numerical simulation results show that the reinforced structure’s load-carrying capacity and stiffness enhancement rate increased non-linearly with the increase in UHPC layer thickness and steel plate thickness. However, reasonable reinforcement timing exists for steel plate-UHPC reinforcement, and too late reinforcement timing leads to a decrease in structural load-carrying capacity and stiffness enhancement rate.

Ischemic stroke (IS) remains a serious threat to human health. Neuroinflammatory response is an important pathophysiological process after IS. Circular RNAs (circRNAs), a member of the non-coding RNA family, are highly expressed in the central nervous system and widely involved in regulating physiological and pathophysiological processes. This study reviews the current evidence on neuroinflammatory responses, the role of circRNAs in IS and their potential mechanisms in regulating inflammatory cells, and inflammatory factors affecting IS damage. This review lays a foundation for future clinical application of circRNAs as novel biomarkers and therapeutic targets.

Located in the central part of the arid regions of Northwest China, the Heihe River Basin (HRB) plays an important role in wind prevention, sand fixation, and soil and water conservation as the second largest inland river basin. In the context of the warming and wetting climate observed in Northwest China, the situation of the ecological environment in the HRB is of significant concern. Using the data from meteorological observation stations, grid fusion and hydrological monitoring, this study analyzes the multi-scale climate changes in the HRB and their impacts on runoff. In addition, predictive models for runoff in the upper and middle reaches were developed using machine learning methods. The results indicate that the climate in the HRB has experienced an overall warming and wetting trend over the past 60 years. At the same time, there are clear regional variabilities in the climate changes. Precipitation shows decreasing trends in the northwestern part of the HRB, while it shows increases at rates higher than the regional average in the southeastern part. Moreover, the temperature increases are generally smaller in the upper reaches than those in the middle and lower reaches. Over the past 60 years, there has been a remarkable increase in runoff at the Yingluo Gorge (YL) hydrological station, which exhibits a distinct “single-peak” pattern in the variation of monthly runoff. The annual runoff volume at the YL (ZY) hydrological station is significantly correlated with the precipitation in the upper (middle) reaches, indicating the precipitation is the primary influencing factor determining the annual runoff. Temperature has a significant impact only on the runoff in the upper reaches, while its impact is not significant in the middle reaches. The models trained by the support vector machines and random forest models perform best in predicting the annual runoff and monthly runoff, respectively. This study can provide a scientific basis for environmental protection and sustainable development in the HRB.

Abstract For social insects such as ants, the internal organs are likely important in understanding their eusocial behavior and evolution. Such organs, however, are rarely preserved on fossils. In each of the few cases reporting exceptionally fossilized soft tissues in arthropods, the nervous, muscular and cardiovascular systems have been described individually, but never in combination. Here, we report a female specimen (gyne) of the extinct ant group—† Zigrasimecia—included in a Cretaceous amber piece from Kachin, Myanmar, with an almost complete system formed by various internal organs. These include the brain, the main exocrine system, part of the digestive tract, and several muscle clusters. This research expands our knowledge of internal anatomy in stem group ants. As the gyne bears a morphologically unique labrum, our specimen’s internal and external features support the notion that the early ant may have special ecological habits during the Cretaceous period.