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IntroductionNon-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with high morbidity and mortality. The rapidly increasing incidence of NAFLD is becoming an essential precursor of HCC globally. MicroRNAs (miRNAs) are involved in the progression of NAFLD and HCC.MethodPotential miRNAs associated with NAFLD in HCC tumorigenesis were identified through a systematic review, and their roles were evaluated by data mining analysis. The biological function of the potential miRNA and its target genes in NAFLD and HCC were evaluated by bioinformatic analysis.ResultMIR122 was identified as the potential miRNA associated with NAFLD and HCC. Then, MIR122 expression was significantly lower in HCC patients, and higher MIR122 levels were associated with significantly better overall survival. Next, the biological functions of MIR122 and target genes were predicted to be involved in inflammation, fibrosis, cell proliferation, invasion, metastasis, and apoptosis. In particular, the FOXO signaling pathway may regulate the above biological functions.ConclusionMIR122 was suggested to be involved in progressing from NAFLD to HCC through the PI3K/AKT/FOXO pathway.Systematic review registrationPROSPERO, identifier: CRD 42024517940.

Bone metastasis is a debilitating complication that frequently occurs in the advanced stages of breast cancer. However, the underlying molecular and cellular mechanisms of the bone metastasis remain unclear. Here, we elucidate how bone metastasis arises from tumor cells that detach from the primary lesions and infiltrate into the surrounding tissue, as well as how these cells disseminate to distant sites. Specifically, we elaborate how tumor cells preferentially grow within the bone micro-environment and interact with bone cells to facilitate bone destruction, characterized as osteoclastic bone metastasis, as well as new bone matrix deposition, characterized as osteoblastic bone metastasis. We also updated the current understanding of the molecular mechanisms underlying bone metastasis and reasons for relapse in breast cancer, and also opportunities of developing novel diagnostic approaches and treatment.

To accurately understand the moisture variation and drying characteristics of Lentinus edodes (L. edodes) during the drying process, the kinetics model of L. edodes with a wider application range was investigated. First, the heat pump drying kinetics model for L. edodes was fitted, verified and extended based on the orthogonal experimental data. Then, the expression of moisture ratio of L. edodes with respect to drying time, air supply temperature (AST), loading density (LD) and circulating air volume (CAV) was proposed, and interaction effects of the three key parameters on the drying time were studied based on the prediction model. The findings indicated a substantial agreement between the predicted and experimental values. The drying time could be shortened by increasing the air supply temperature and the circulating air volume or decreasing the loading density. Among these three factors, the AST had the greatest impact on drying time, followed by CAV and LD. For every 48 g/m2 reduction in LD and 11.3 m3/h increase in CAV, the drying time could be reduced by 10.5–29.9 min. Similarly, increasing the AST by 1 °C and the CAV by 11.3 m3/h could decrease the drying time by 13.7–100.6 min. The research results are helpful to optimize the drying process, improve the drying efficiency, and provide guidance and references for practical production of L. edodes HPD.

BackgroundHypoglycemic episodes cause varying degrees of damage in the functional system of elderly inpatients with type 2 diabetes mellitus (T2DM). The purpose of the study is to construct a nomogram prediction model for the risk of hypoglycemia in elderly inpatients with T2DM and to evaluate the predictive performance of the model.MethodsFrom August 2022 to April 2023, 546 elderly inpatients with T2DM were recruited in seven tertiary-level general hospitals in Beijing and Inner Mongolia province, China. Medical history and clinical data of the inpatients were collected with a self-designed questionnaire, with follow up on the occurrence of hypoglycemia within one week. Factors related to the occurrence of hypoglycemia were screened using regularized logistic analysis(r-LR), and a nomogram prediction visual model of hypoglycemia was constructed. AUROC, Hosmer-Lemeshow, and DCA were used to analyze the prediction performance of the model.ResultsThe incidence of hypoglycemia of elderly inpatients with T2DM was 41.21% (225/546). The risk prediction model included 8 predictors as follows(named ADOCHBIU): duration of diabetes (OR=2.276, 95%CI 2.097˜2.469), urinary microalbumin(OR=0.864, 95%CI 0.798˜0.935), oral hypoglycemic agents (OR=1.345, 95%CI 1.243˜1.452), cognitive impairment (OR=1.226, 95%CI 1.178˜1.276), insulin usage (OR=1.002, 95%CI 0.948˜1.060), hypertension (OR=1.113, 95%CI 1.103˜1.124), blood glucose monitoring (OR=1.909, 95%CI 1.791˜2.036), and abdominal circumference (OR=2.998, 95%CI 2.972˜3.024). The AUROC of the prediction model was 0.871, with sensitivity of 0.889 and specificity of 0.737, which indicated that the nomogram model has good discrimination. The Hosmer-Lemeshow was χ2 = 2.147 (P=0.75), which meant that the prediction model is well calibrated. DCA curve is consistently higher than all the positive line and all the negative line, which indicated that the nomogram prediction model has good clinical utility.ConclusionsThe nomogram hypoglycemia prediction model constructed in this study had good prediction effect. It is used for early detection of high-risk individuals with hypoglycemia in elderly inpatients with T2DM, so as to take targeted measures to prevent hypoglycemia.Trial registrationChiCTR2200062277. Registered on 31 July 2022.

BackgroundInterferon-alpha1b (IFN-α1b) has shown remarkable therapeutic potential as adjuvant therapy for melanoma. This study aimed to develop five machine learning models to evaluate the efficacy of postoperative IFN-α1b in patients with advanced melanoma.MethodsWe retrospectively analyzed 113 patients with the American Joint Committee on Cancer (AJCC) stage III-IV melanoma who received postoperative IFN-α1b therapy between July 2009 and February 2024. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Five machine learning models (Decision Tree, Cox Proportional Hazards, Random Forest, Support Vector Machine, and LASSO regression) were developed and compared for their capacity to predict the outcomes of patients. Model performance was evaluated using concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis.ResultsThe 1-year, 2-year, and 3-year RFS rates were 71.10%, 43.10%, and 31.10%, respectively. For OS, the 1-year, 2-year, and 3-year OS rates were 99.10%, 82.30%, and 75.00%, respectively. The Decision Tree (DT) model demonstrated superior predictive performance with the highest C-index of 0.792. Time-dependent ROC analysis for predicting 1-, 2-, and 3-year RFS based on the DT model is 0.77, 0.79 and 0.76, respectively. Serum albumin emerged as the important predictor of RFS.ConclusionsOur study demonstrates the considerable efficacy DT model for predicting the efficacy of adjuvant IFN-α1b in patients with advanced melanoma. Serum albumin was identified as a key predictive factor of the treatment efficacy.

BackgroundPonatinib, a third-generation tyrosine kinase inhibitor, is employed in the management of adult chronic myeloid leukemia. Nevertheless, the presence of process impurities and degradation impurities linked to ponatinib may potentially influence its effectiveness and safety. Therefore, the objective of this research was to establish a robust liquid chromatography method and systematically validate it for the detection of substances related to ponatinib.MethodsThe separation of ponatinib and its impurities was conducted using an Agilent 5HC-C18 chromatographic column (4.6 mm × 250 mm, 5 μm). The mobile phase A comprised a mixture of water and acetonitrile in a 9:1 ratio, with an aqueous solution of pH 2.4 containing 2 mM potassium dihydrogen phosphate and 0.4% triethylamine. Mobile phase B, consisting of acetonitrile, was eluted in a gradient fashion. The flow rate was set at 1.0 mL/min, detection wavelength at 250 nm, column temperature at 40°C, and injection volume at 10 μL.ResultsThe method demonstrated high specificity, sensitivity, solution stability, linearity, precision, accuracy, and robustness. Additionally, this research unveiled a novel compound, imp-B, generated via the oxidative degradation of ponatinib. The molecular structure of the newly discovered product was elucidated through the utilization of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS).ConclusionIn conclusion, the chromatographic method developed in this study has the potential to be utilized for the detection of ponatinib and its impurities, thereby offering significant insights for quality assessment in ponatinib research.

Pathogenic genes in most patients with cleidocranial dysplasia have been confirmed to be runt-related transcription factor 2 (RUNX2), which controls mutations in specific osteoblast transcription factors and affects skull ossification and suture adhesion. This study aimed to explore the role of RUNX2 mutations. Here, we report a rare case of a splice site mutation in a Chinese population with typical cleidocranial dysplasia symptoms, cranial suture insufficiency, clavicle dysplasia, and dental anomalies. Peripheral blood samples from the proband and her mother were subjected to Sanger sequencing. The expression levels of RUNX2 before and after mutation were verified using digital PCR (dPCR). The results revealed a classic mutation at the fifth base of the intron 5 initiation splicing sequence (NM001024630.4: C.685+5G > A). The mutation rate in the proband was 53 %, while the mother did not have any mutations. The secondary RNA structure of the RUNX2 gene in the progenitor was predicted to change, and the structural free energy was low in the wild-type, with the stem folded first and the structure being relatively stable. After the mutation, the free energy increased. This finding enriches the RUNX2 mutation library of CD-related genes in Chinese individuals.

Leaf area index (LAI) of alfalfa is a crucial indicator of its growth status and a predictor of yield. The LAI of alfalfa is influenced by environmental factors, and the limitations of non-linear models in integrating these factors affect the accuracy of LAI predictions. This study explores the potential of classical non-linear models and deep learning for predicting alfalfa LAI. Initially, Logistic, Gompertz, and Richards models were developed based on growth days to assess the applicability of nonlinear models for LAI prediction of alfalfa. In contrast, this study combines environmental factors such as temperature and soil moisture, and proposes a time series prediction model based on mutation point detection method and encoder-attention-decoder BiLSTM network (TMEAD-BiLSTM). The model’s performance was analyzed and evaluated against LAI data from different years and cuts. The results indicate that the TMEAD-BiLSTM model achieved the highest prediction accuracy (R² > 0.99), while the non-linear models exhibited lower accuracy (R² > 0.78). The TMEAD-BiLSTM model overcomes the limitations of nonlinear models in integrating environmental factors, enabling rapid and accurate predictions of alfalfa LAI, which can provide valuable references for alfalfa growth monitoring and the establishment of field management practices.

Abstract Despite the widespread adoption of emergency coronary reperfusion therapy, reperfusion‐induced myocardial injury remains a challenging issue in clinical practice. Following myocardial reperfusion, S100A8/A9 molecules are considered pivotal in initiating and regulating tissue inflammatory damage. Effectively reducing the S100A8/A9 level in ischemic myocardial tissue holds significant therapeutic value in salvaging damaged myocardium. In this study, HA (hemagglutinin)‐ and RAGE (receptor for advanced glycation end products)‐ comodified macrophage membrane‐coated siRNA nanoparticles (MMM/RNA NPs) with siRNA targeting S100A9 (S100A9‐siRNA) are successfully prepared. This nanocarrier system is able to target effectively the injured myocardium in an inflammatory environment while evading digestive damage by lysosomes. In vivo, migration of MMM/RNA NPs to myocardial injury lesions is confirmed in a myocardial ischemia‐reperfusion injury (MIRI) mouse model. Intravenous injection of MMM/RNA NPs significantly reduced S100A9 levels in serum and myocardial tissues, further decreasing myocardial infarction area and improving cardiac function. Targeted reduction of S100A8/A9 by genetically modified macrophage membrane‐coated nanoparticles may represent a new therapeutic intervention for MIRI.

The potential health risks posed by bioaerosols containing pathogens originating from wastewater treatment plants (WWTPs) have gaining intensive attention. This study designated sampling locations within a WWTP situated in Xi'an, a major city in northwest China. The airborne bacterial concentration, taxonomic composition, and the associated health risks were analyzed in the aeration tanks with bottom microporous aeration system. The Anaerobic-Anoxic-Oxic (AAO) tank emitted significantly higher culturable bacteria (1.58×104 CFU m−3 in spring, 6.69×103 CFU m−3 in winter) compared to Double-ditch (DE) oxidation ditch and aerated grit chamber (AGC) chamber, aligning with 16S rDNA quantification results. The bacterial concentrations are higher in spring than that in winter, with the AAO tank posing the highest exposure risk during the spring season. The dominant genera in the air samples include Cutibacterium, Lawsonella, Acinetobacter, Pseudomonas, and Aeromonas. Among the identified genus, 139 bacterial genera were identified as potential human pathogens like Neisseria, Moraxella, Haemophilus, Escherichia-Shigella and Streptococcus. These pathogens further elevate exposure risks from WWTP bioaerosols. This study provides relevant information on the seasonal health risk variations tied to bioaerosol emissions from diverse aeration tanks with bottom microporous aeration system in the mega city of northwest China, emphasizing the imperative to enhance the management and control measures for bioaerosols originating from the AAO tank.

Background: While gender differences in ball skills are widely recognized, the differences in locomotor skills remain unclear. This study aims to explore these gender differences among preschool children in Jinhua City, China, and to examine the influence of evolutionary factors and local cultural activities on these skills. Methods: A cluster random sampling method was employed to select 777 preschool children aged 5.1–6.7 years from seven kindergartens in Jinhua, Zhejiang Province, Eastern China. The Test of Gross Motor Development-Third Edition (TGMD-3) was used to assess GMS, including locomotor and ball skills. Results: Boys outperformed girls in ball skills, such as underhand throwing, catching, two-handed striking, and kicking. However, no significant overall gender differences were found in locomotor skills. A deeper analysis revealed that boys excelled in running-related tasks, whereas girls performed better in skipping-related tasks. These findings suggest that TGMD-3 locomotor skills should be divided into running-related and jumping-related categories. The results also show that not all ball skills are dominated by boys, indicating the impact of environmental factors. The findings highlight the role of both evolutionary factors and local cultural activities in shaping these specific gender differences. Conclusion: The study's cross-sectional design provides a snapshot of existing gender differences in motor skills among preschool children. The results suggest the need for gender-sensitive physical education programs to address these disparities early on. Future research should utilize longitudinal methods and objective measures to further understand the development of these skills over time and the underlying factors contributing to these differences.

BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking hormone receptors and HER2 expression, leading to limited treatment options and poor prognosis. Mitophagy, a selective autophagy process targeting damaged mitochondria, plays a complex role in cancer progression, yet its prognostic significance in TNBC is not well understood.MethodsThis study utilized single-cell RNA sequencing data from the TCGA and GEO databases to identify mitophagy-related genes (MRGs) associated with TNBC. A prognostic model was developed using univariate Cox analysis and LASSO regression. The model was validated across multiple independent cohorts, and correlations between MRG expression, immune infiltration, and drug sensitivity were explored.ResultsNine key MRGs were identified and used to stratify TNBC patients into high-risk and low-risk groups, with the high-risk group showing significantly worse survival outcomes. The model demonstrated strong predictive accuracy across various datasets. Additionally, the study revealed a correlation between higher MRG expression levels and increased immune cell infiltration, as well as potential responsiveness to specific chemotherapeutic agents.ConclusionThe mitophagy-related prognostic model offers a novel method for predicting outcomes in TNBC patients and highlights the role of mitophagy in influencing the tumor microenvironment, with potential applications in personalized treatment strategies.

BackgroundSeveral heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients.MethodsPatients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs.ResultsNinety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890–0.990) for predicting 1-year RRF decline.ConclusionThe nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients.

Meteorological disasters occur frequently, and Gansu Province is a sensitive area for food production. Potatoes are a major crop in this province. As a result, executing risk zoning and risk prediction for potato production is quite important. However, in existing risk assessment and prediction research, the dynamic nature of risks and improving the accuracy of risk prediction are urgent scientific issues that must be addressed. Weighting, spatial econometric analysis, climate diagnosis technology, and machine learning models were used to provide a refined spatiotemporal evolution of potato disaster risk in China's Gansu Province, as well as predict future potato production risk. The findings indicate that there are significant interdecadal fluctuations in the potato disaster loss, which has decreased considerably since 2000. The average yield decrease rate in the 1980s, 1990s, 2000s, and 2010s was -13.9%, -15.4%, -9.1%, and -7.3%, respectively, and the county percentage susceptible to severe yield loss was 26.1%, 39.1%, 22.9%, and 12.9%. Second, most counties' potato production falls within the medium–low or low risk region. Eastern and southern Gansu are particularly vulnerable to catastrophic calamities. High risk counties are primarily clustered in Qingyang and Longnan, whereas low risk counties are concentrated in Wuwei and Gannan. Third, high risk locations have altered, and the migration trajectory of the risk indicator’s barycenter shows significant differences in direction and distance. The comprehensive risk moves in a southeast-west-northern direction, but the distance is short. Overall, disaster losses in most counties are decreasing, and future trends will be similar with previous patterns. The Interpolation-EMD-SVM scheme greatly increases the accuracy of the disaster loss risk prediction. The technology and methods provide a scientific foundation for accurately assessing risk dynamic characteristics, managing regional disaster risks, and preventing and mitigating disasters.

In recent years, the Dataset for Object deTection in Aerial images (DOTA) dataset has played a pivotal role in advancing object detection in aerial images (ODAI). Despite its significance, there hasn’t been a comprehensive review summarizing its research developments. Addressing this gap, this paper offers the first comprehensive overview on the subject. Within this review, we begin by examining prevalent object detection datasets of natural scene images alongside object detection datasets of remote sensing images (RSIs). We then present an in-depth comparative analysis between these datasets and the DOTA dataset, supported by numerous charts and tables. We proceed to outline both traditional techniques for ODAI and methods rooted in deep learning. Subsequently, we provide a recap of the latest advancements in the field achieved using the DOTA dataset. Concluding our review, we delve into the current challenges facing ODAI and propose potential future research directions.

Traditional denitrification methods for coal-fired power boilers face challenges like reduced flue gas temperature at low loads, decreased efficiency of existing denitrification devices, and increased ammonia consumption. Biomass, a renewable energy source, has proven effective for denitrification in medium to high-temperature ranges. To improve denitrification efficiency at low loads, this study focuses on optimizing re-burning denitrification of biomass by nitrogen-impregnated of corncob at room temperature. Investigating the effects of nitrogen impregnation and washing on biomass re-burning denitrification reactivity within 550–950 °C, the study finds that denitrification efficiency improvement is not caused only by surface-covered urea or washing. Nitrogen impregnation enhances biomass pyrolysis, releasing more CO, HCN, and NH3 products, thereby enhancing NO reduction during denitrification. Additionally, nitrogen impregnation boosts nitrogen-containing functional groups such N-6 on biomass char surfaces during the re-burning process, improving denitrification efficiency. The maximum denitrification efficiency of the nitrogen impregnated sample reached 97.52 % at 950 °C, while it reached 76.51 % at 650 °C when the coated urea was washed. Furthermore, chlorine and alkali metal contents in biomass notably decrease after nitrogen-impregnation and washing, optimizing biomass combustion conditions for furnace protection. This study offers theoretical insights for promoting and applying biomass denitrification techniques.

Objective: Chronic inflammation and oxidative stress mediate the pathological progression of diabetic complications, like diabetic retinopathy (DR), peripheral neuropathy (DPN) and impaired wound healing. Studies have shown that treatment with a stable form of arginase 1 that reduces l-arginine levels and increases ornithine and urea limits retinal injury and improves visual function in DR. We tested the therapeutic efficacy of PEGylated arginine deiminase (ADI-PEG20) that depletes l-arginine and elevates l-citrulline on diabetic complications in the db/db mouse model of type 2 diabetes (T2D). Methods: Mice received intraperitoneal (IP), intramuscular (IM), or intravitreal (IVT) injections of ADI-PEG20 or PEG20 as control. Effects on body weight, fasting blood glucose levels, blood-retinal-barrier (BRB) function, visual acuity, contrast sensitivity, thermal sensitivity, and wound healing were determined. Studies using bone marrow-derived macrophages (BMDM) examined the underlying signaling pathway. Results: Systemic injections of ADI-PEG20 reduced body weight and blood glucose and decreased oxidative stress and inflammation in db/db retinas. These changes were associated with improved BRB and visual function along with thermal sensitivity and wound healing. IVT injections of either ADI-PEG20, anti-VEGF antibody or their combination also improved BRB and visual function. ADI-PEG20 treatment also prevented LPS/IFNℽ-induced activation of BMDM in vitro as did depletion of l-arginine and elevation of l-citrulline. Conclusions/interpretation: ADI-PEG20 treatment limited signs of DR and DPN and enhanced wound healing in db/db mice. Studies using BMDM suggest that the anti-inflammatory effects of ADI-PEG20 involve blockade of the JAK2-STAT1 signaling pathway via l-arginine depletion and l-citrulline production.

Adenoviral infections, particularly in children, remain a significant public health issue with no approved targeted treatments. Artemisinin and its derivatives, well-known for their use in malaria treatment, have shown antiviral activities in recent studies. However, their efficacy against human adenovirus (HAdV) remains unexplored. This study aimed to assess the activity of artemisinin and its derivatives against HAdV infection in vitro using cell lines and primary cells. Our data revealed that artemisinin exhibited dose-dependent anti-HAdV activity with no apparent cytotoxicity over a wide concentration range. Mechanistically, artemisinin did not affect viral attachment or entry into target cells, nor the viral genome entry into cell nucleus. Instead, it inhibited HAdV through suppression of viral DNA replication. Comparative analysis with its derivatives, artesunate and artemisone, showed distinct cytotoxicity and anti-adenoviral profiles, with artemisone showing superior efficacy and lower toxicity. Further validation using a primary airway epithelial cell model confirmed the anti-adenoviral activity of both artemisinin and artemisone against different virus strains. Together, our findings suggest that artemisinin and its derivatives may be promising candidates for anti-HAdV treatment.

Clay-based adsorbent materials are widely used to remove heavy metal ions from water. In this study, we have fabricated a novel composite material, consisting of rectorite and sludge-derived biochar (REC/SDBC), and characterized its effectiveness in removing lead from water. Our SEM images show that the REC is evenly dispersed on the surface of the SDBC. The composites have a mesoporous structure, and its BET surface is (16.5 m 2 /g) comparable with that of SDBC but larger than that of REC. We found that the maximum adsorption capacity for Pb(II) was 26.89 mg g −1 for REC/SDBC composites with a REC:SDBC ratio of 3:1, which was achieved within 120 min. This is higher than the adsorption capacities of REC (19.81 mg g −1 ) and SDBC (23.15 mg g −1 ) alone. Furthermore, we observed that the adsorption capacity was greater at pH 5.0 compared to other pH values. Our results also indicate that the pseudo-second-order model and the Langmuir isotherm model provide good fits for the rates and isotherms of Pb(II) adsorption onto REC/SDBC composites. The adsorption kinetic constant and the Langmuir adsorption constant were calculated to be 0.0065 g mg −1 min −1 and 0.319 L mg −1 , respectively. X-ray photoelectron spectroscopy analysis confirmed that the reaction mechanism is mainly dominated by chemisorption, involving cationic exchange, surface complexation, and surface precipitation. The high adsorption capacity, combined with the cost-effectiveness and environmental-friendly nature of REC/SDBC composites, make them promising candidates for removing heavy metallic elements from wastewater.

Objective In this study, we investigated the cause of the AngII dose elevation in aqueous humor of primary open-angle glaucoma (POAG) patients. Methods Enzyme-linked immunosorbent assay (ELISA), western blotting were used to detect concentration of Angiotensin Converting Enzyme 2 (ACE2) and Prolylcarboxypeptidase (PRCP). AngII and AngII + Recombinant PRCP were injected into anterior chamber of mouse eye. Mouse Intraocular pressure (IOP) was measured every week, mouse eye sections were conducted Hematoxylin-and-Eosin (H&E) staining, Masson’ staining and Immunofluorescence staining. Western blotting and Immunofluorescence staining assays to detected fibrosis of trabecular meshwork cells. Mass spectrometry was used to identify proteins of aqueous humor. Results PRCP dose are decreased in aqueous humor of POAG patients. There is a negative correlation between PRCP and AngII levels in aqueous humor and between PRCP levels and the IOP. PRCP treatment reverses fibrosis of trabecular meshwork (TM) and prevents IOP elevation induced by AngII. Exogenous PRCP rescues fibrosis induced by AngII in HTMCs. Proteome profiling detected 502 differentially expressed proteins. Conclusion Our study found PRCP dose was decreased in POAG patients’ aqueous humor, and it might cause high level of AngII. Restoration of PRCP rescued fibrosis of TM cells and ameliorated IOP in AngII treatment mouse.

Abstract Background The composition and function of gut microbiota, lipids, and metabolites in patients with type 1 diabetes (T1D) or its association with glycemic control remains unknown. We aimed to use multi‐omics sequencing technology and machine learning (ML) approaches to investigate potential function and relationships among the gut microbiota, lipids, and metabolites in T1D patients at varied glycemic levels. Methods We conducted a multi‐omics analysis of the gut microbiome from fecal samples, metabolites, and lipids obtained from serum samples, collected from a cohort of 72 T1D patients. The patients were divided into two groups based on their hemoglobin A1c (HbA1c) levels. 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in composition and function of gut microbiota, metabolites, and lipids. Results The linear discriminant analysis, Shapley additive explanations (SHAP) algorithm, and ML algorithms revealed the enrichment of Bacteroides_nordii, Bacteroides_cellulosilyticus in the glycemic control (GC) group, while Bacteroides_coprocola and Sutterella_wadsworthensis were enriched in the poor glycemic control (PGC) group. Several metabolic enrichment sets like fatty acid biosynthesis and glycerol phosphate shuttle metabolism were different between two groups. Bacteroides_nordii exhibited a negative association with D‐fructose, a component involved in the starch and sucrose metabolism pathway, as well as with monoglycerides (16:0) involved in the glycerolipid metabolism pathway. Conclusions We identified distinct characteristics of gut microbiota, metabolites, and lipids in T1D patients exhibiting different levels of glycemic control. Through comprehensive analysis, microbiota (Bacteroides_nordii, Bacteroides_coprocola), metabolites (D‐fructose), and lipids (Monoglycerides) may serve as potential mediators that communicated the interaction between the gut, circulatory systems, and glucose fluctuations in T1D patients.

Abstract Wound infection is a major factor affecting the speed and quality of wound healing. While hydrogen peroxide (H2O2) is recognized for its antibacterial capacity and facilitation of wound healing, its administration requires careful dosage differentiation. Inappropriately matched dosages can protract the healing of infected wounds. Herein, a calcium peroxide‐based hydrogel (CPO‐Alg hydrogel) is fabricated to enable a biphasic tapered release of H2O2, ensuring robust initial antimicrobial activity followed by sustained promotion of cellular proliferation of wound healing. The design of the hydrogel allowed for the calcium peroxide nanoparticles (CPO NPs) being in two spatial niches within the gel framework. When applied to infectious wounds, CPO NPs with weak constraints are promptly released out of the gel, penetrating into infected regions to serve as antibacterial agents that eliminate bacteria and biofilms at high concentrations. Conversely, the entrapped CPO NPs structurally integrated into the gel remain confined, thus gradually degrading and allowing a mild release of H2O2 through hydrolysis in a moist environment that contributes to the cell growth in the later stage. The CPO‐Alg hydrogel represents an innovative and practical solution for the antimicrobial protection of chronic wounds, offering promising prospects for advancing wound healing.

Methane (CH4) contributes an essential portion for global warming as a pivotal greenhouse gas. Microorganisms are identified as an effective way to mediate and control CH4 emission. Cable bacteria is a promising microorganism to mitigate CH4, however, the studies of distribution, abundance and function for CH4 reduction of cable bacteria in inland water still remain unclear. In this paper, we propose the probable CH4 mitigation metabolism within cable bacteria in anoxic condition, and present the future research directions about the application potential of cable bacteria in CH4 reduction. The viewpoint will help to understand the significant role of cable bacteria in CH4 mitigation and provide a potential way to control CH4 emissions in inland freshwater ecosystem.

Abstract The manipulation of hydrogen bonding within protic ionic liquids is conducive to conquering the robust hydrogen bonding interactions in cellulose for its effective dissolution, but it is a great challenge to establish the delicate balance of hydrogen bonding network between solvent and cellulose. Herein, we proposed the concept of “hydrogen bond producers” for urea molecules in 1,1,3,3‐tetramethylguanidinium methoxyacetate acid ([TMGH][MAA]) to enhance the dissolution of cellulose. The optimization of physicochemical properties for [TMGH][MAA] solvent as a function of urea concentration revealed a remarkable increase in cellulose solubility from 13% to 17% (w/w) by adding only 0.25 wt% urea, highlighting the efficiency of [TMGH][MAA] as a powerful solvent for the dissolution of cellulose. The experimental and simulation results verified that the significant improvement on dissolution of cellulose was attributed to the hydrogen bonding interaction of urea molecules with ion pairs and part of free ions, reducing the interference with the active ions bonded to cellulose. Furthermore, the considerable enhancement on comprehensive properties of regenerated cellulose films demonstrated the effectiveness of [TMGH][MAA]/urea solvent. The concept of “hydrogen bond producers” presented here opens a new avenue for significantly enhancing the dissolution of natural cellulose, promoting the sustainable development in large‐scale processing of cellulose.

Abstract Central and systemic inflammation play pivotal roles in epileptogenesis and proepileptogenesis in temporal lobe epilepsy (TLE). The interplay between peripheral CD4+ T cells and central microglia orchestrates the “systemic‐central” immune response in TLE. However, the precise molecular mechanisms linking central and systemic inflammation in TLE remain unknown. This preliminary findings revealed an imbalance in Th1/Th2 subsets in the periphery，accompanied by related cytokines release in TLE patients. they proposed that this peripheral Th1/Th2 imbalance may influence central inflammation by mediating microglial state dynamics within epileptic foci and distant brain regions. In Li‐pilocarpine‐induced TLE rats, a peripheral Th1/Th2 imbalance and observed corresponding central and systemic responses is confirmed. Notably, CD4+ T cells infiltrated through the compromised blood‐brain barrierand are spatially close to microglia around epileptic foci. Intravenous depletion and reinfusion of CD4+ T cells modulated microglia state dynamics and altered neuroinflammatory cytokines secretion. Moreover, mRNA sequencing of the human hippocampus identified Notch1 as a key regulator of Th1/Th2 differentiation, CD4+ T cell recruitment to brain infiltration sites, and the regulation of microglial responses, seizure frequency, and cognition. This study underscores the significance of Th1/Th2 imbalance in modulating the “systemic‐central” response in TLE, highlighting Notch1 as a potential therapeutic target.

BackgroundRecent studies have underscored the biological significance of RNA modifications in tumorigenicity and progression. However, the potential roles of RNA modifications in immune regulation and the formation of the tumor microenvironment (TME) in head and neck squamous carcinoma (HNSC) remain unclear.MethodsWe collected 199 untreated HNSC samples and clinicopathological data from Fujian Provincial Cancer Hospital. MeRIP-seq and RNA-seq were performed to generate methylation and gene expression profiles, respectively. Consensus molecular subtyping was employed to identify prognosis-related genes and RNA modification patterns in HNSC. Experiments confirmed the potential oncogenic behavior influenced by key genes. Molecular subtypes were identified through consensus clustering and validated using external cohort validation sets.ResultsAmong the RNA modification-related genes, IGF2BP1 emerged as the most prognostic. HNSC patients were categorized into high and low IGF2BP1 expression groups. High-expressing patients exhibited poorer survival and reduced chemosensitivity, coupled with increased tumor mutational burden, low PD-L1 expression, and limited immune cell infiltration, indicative of aggressive disease. Analysis revealed two distinct RNA modification patterns associated with IGF2BP1 expression: biosynthetically intense type (BIT) and oncogenically active type (OAT), each characterized by distinct clinical features, outcomes, and biological pathways. In an independent immunotherapy cohort, BIT patients displayed enhanced immune responses and sustained clinical benefits.ConclusionsThis study highlights the crucial link between RNA modification and TME diversity. Evaluating RNA modification in tumors improves our understanding of TME features and supports the development of effective immunotherapy strategies.

Cordyceps militaris is a filamentous fungus used for both medicinal and culinary purposes. It exhibits a wide range of pharmacological activities due to its valuable contents of cordycepin, polysaccharides, carotenoids, terpenoids and other metabolites. However, C. militaris strains are highly susceptible to irreversible degradation in agricultural production, which is often manifested as a prolonged color change period and a significant decrease in the production of secondary metabolites. UDP-glycosyltransferases are an important enzyme family that participates in the synthesis of terpenoids by performing the glycosylation of key residues of enzymes or molecules. However, few studies have focused on its effect on the regulation of metabolite production in C. militaris. Therefore, in this study, we performed transcriptome analysis across four different developmental stages of C. militaris to target the putative glycosyltransferase gene CmUGT1, which plays important roles in metabolite production. We further constructed and screened a CmUGT1-overexpressing strain by Agrobacterium tumefaciens-mediated infestation of C. militaris spores. The major metabolite production of the wild-type and CmUGT1-overexpressing C. militaris strains was determined after short-term shake-flask cultivation of mycelia. The results showed that the yields of carotenoids and polysaccharides in the mycelia of the CmUGT1-overexpressing strains were 3.8 and 3.4 times greater than those in the mycelia of the wild type, respectively (p

Abstract Light‐sheet fluorescence microscopy (LSFM) introduces fast scanning of biological phenomena with deep photon penetration and minimal phototoxicity. This advancement represents a significant shift in 3‐D imaging of large‐scale biological tissues and 4‐D (space + time) imaging of small live animals. The large data associated with LSFM require efficient imaging acquisition and analysis with the use of artificial intelligence (AI)/machine learning (ML) algorithms. To this end, AI/ML‐directed LSFM is an emerging area for multiorgan imaging and tumor diagnostics. This review will present the development of LSFM and highlight various LSFM configurations and designs for multiscale imaging. Optical clearance techniques will be compared for effective reduction in light scattering and optimal deep‐tissue imaging. This review will further depict a diverse range of research and translational applications, from small live organisms to multiorgan imaging to tumor diagnosis. In addition, this review will address AI/ML‐directed imaging reconstruction, including the application of convolutional neural networks (CNNs) and generative adversarial networks (GANs). In summary, the advancements of LSFM have enabled effective and efficient post‐imaging reconstruction and data analyses, underscoring LSFM's contribution to advancing fundamental and translational research.

This study investigated the effects of Enterococcus hirae (Eh) derived from Ningxiang pigs on growth performance, diarrhea incidence, and immune responses in ETEC-challenged piglets. The results showed that compared to the CON group, ETEC infection significantly reduced the average daily gain (ADG) and average daily feed intake (ADFI), increased rectal temperature, and resulted in a diarrhea rate of up to 24%. Additionally, ETEC infection significantly increased the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of piglets. Compared to the ETEC group, orally Eh significantly increased ADFI in ETEC-infected piglets, reduced the diarrhea rate to 11.53%, reduced the spleen index and the expression of inflammatory cytokines in the spleen, serum and intestine, with decreasing serum sIgA and colonic SCFAs of ETEC-infected piglets. Furthermore, correlation analysis revealed that the levels of SCFAs (particularly acetate) were significantly negatively correlated with the expression levels of inflammatory cytokines in colonic and splenic tissues, suggesting that acetate may be a key metabolite in the anti-inflammatory effects of Eh. These results indicate that Eh can enhance the protection of piglets against ETEC K88 via intestine-acetate-spleen axis, thereby alleviating diarrhea and improving growth performance in piglets.

IntroductionSoil contamination with copper (Cu) threatens ecological security and human health. Rapeseed demonstrates potential in remediating copper-contaminated soil, and biochar-assisted phytoremediation is increasingly being employed to improve remediation efficiency. However, the combined application of them has not been thoroughly studied in terms of the synergistic effects and the mechanisms of their interaction.MethodsIn this regard, this study conducted a pot experiment to evaluate biochar-assisted remediation under Cu-contaminated soil with varying biochar application rates; Furthermore, the plant physiological mechanism and soil physicochemical properties involved in the biocharrapeseed system was explored.ResultsOur results showed that the exchangeable pool of copper in soil decreased by 10.0% and 12.3% with adding 5% biochar (BC1) and 10% biochar (BC2) relative to control (BC0), respectively, prior to rapeseed cultivation. The rapeseed cultivation for one season further reclaimed 4.9%, 9.0%, and 13.6% of the available copper in this soil by root extraction under the BC0, BC1, and BC2 treatments, respectively. The overall copper concentration in plants decreased by 23.7% under BC2 and 13.3% under BC1 compared to BC0. However, the plant’s dry biomass at BC1 and BC2 treatments increased by 1.7-fold and 2.7-fold relative to BC0, which offset the negative impact of the decreased copper concentration on phytoremediation. Physiological analysis showed adding 10% biochar decreased the MDA content by 36% in the leaf and 49% in the root, compared to BC0. The transmission electron microscopy for cell wall ultrastructure in root tips showed that biochar addition in Cu-contaminated soil increased the mechanical strength of the celL wall, explicitly increasing the thickness of the secondary cell wall. Further cell wall components analysis revealed a remarkable increment of the pectin content in BC2 relative to BC0, increased by 56% in the leaf and 99% in the root, respectively. Additionally, 10% biochar application led to a roughly 2-fold increase in seed yield via ameliorating the soil physicochemical properties and increasing the rapeseed growth.DiscussionThese findings offer insights into synergistic rapeseed-biochar use for Cu-contaminated soil remediation.

Background: Plasma Epstein–Barr virus (EBV) DNA has been identified as a significant prognostic marker for nasopharyngeal carcinoma (NPC), yet there is limited research on the prognosis of NPC patients with negative EBV DNA. Objectives: We explore the prognostic value of comprehensive immune-inflammatory and nutritional indicators to offer personalized treatment recommendations and prognosis predictions for non-metastatic NPC patients with negative EBV DNA. Design: This was a retrospective study. Methods: This study retrospectively analyzed 257 non-metastatic NPC patients with negative EBV DNA between January 2015 and December 2019. The Kaplan–Meier survival curves evaluated survival endpoints, and group discrepancies were assessed with log-rank tests. Principal component analysis (PCA) reduced data dimensionality. Univariate and multivariate Cox regression analyses identified significant prognostic variables. Risk stratification was performed based on recursive partitioning analysis (RPA). A robust prognostic model was constructed by nomogram and evaluated by calibration curves, decision curves, and the time-dependent area under the curve analysis. Results: PCA was employed to compute the immune-inflammation index (III) and nutrition index (NI). Multivariate Cox regression analysis revealed lactate dehydrogenase, III, and NI as significant prognostic variables for overall survival (OS). Utilizing RPA, we stratified the risk into three categories: low-risk group (low III + high NI), middle-risk group (low III + low NI), and high-risk group (high III). Both the middle- ( p = 0.025) and high-risk groups ( p

The rice blast disease, caused by the fungus Magnaporthe oryzae, is a significant agricultural problem that adversely impacts rice production and food security. Understanding the precise molecular pathways involved in the interaction between the pathogen and its host is crucial for developing effective disease management strategies. This study examines the crucial function of the nucleolin MoNsr1 in regulating M. oryzae physiological functions. ΔMoNsr1 deletion mutants showed reduced fungal growth, asexual sporulation, and pathogenicity compared to the wild-type. Mutants exhibited impaired conidial germination and appressoria formation, reducing infection progression. Additionally, ΔMoNsr1 deletion mutant had less turgor pressure, confirming that MoNsr1 is essential for cell wall biogenesis and resistant to external stresses. Furthermore, ΔMoNsr1 deletion mutant showed enhanced sensitivity to oxidative stress, reactive oxygen species, and cold tolerance. Our results offer a thorough understanding of the function of MoNsr1 in the virulence and stress-resilient capability in M. oryzae. These findings provide insights into the novel targets and contribute to the emergence of innovative approaches for managing rice blast disease.

Summary: Background: The phase 2 PERMEATE study has shown the antitumor activity and safety of pyrotinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and brain metastases. In this report, survival results were updated with extended follow-up. Methods: Between January 29, 2019 and July 10, 2020, adult patients with HER2-positive metastatic breast cancer who had radiotherapy-naïve brain metastases (cohort A, n = 59) or progressive disease after radiotherapy (cohort B, n = 19) were enrolled and received pyrotinib (400 mg once daily) and capecitabine (1000 mg/m2 twice daily on days 1–14 of each 21-day cycle) until disease progression or unacceptable toxicity. Secondary endpoints progression-free survival (PFS) and overall survival (OS) were updated, and post-hoc central nervous system (CNS)-PFS was analyzed. This study is registered with ClinicalTrials.gov (NCT03691051). Findings: As of February 2, 2023, the median follow-up duration was 30.9 months (interquartile range, 16.1–39.8). Median PFS was 10.9 months (95% confidence interval [CI], 7.6–14.6) in cohort A and 5.7 months (95% CI, 3.4–11.5) in cohort B. Median OS was 35.9 months (95% CI, 24.4-not reached) in cohort A and 30.6 months (95% CI, 12.6–33.3) in cohort B. Median CNS-PFS was 13.6 months (95% CI, 9.0–15.8) in cohort A and 5.7 months (95% CI, 3.4–11.5) in cohort B. Median OS was 34.1 months (95% CI, 21.7-not reached) for 14 patients with intracranial progression only in cohort A who restarted pyrotinib plus capecitabine after local radiotherapy. Interpretation: These data support further validation in a randomized controlled trial for the assessment of pyrotinib in combination with capecitabine as systemic therapy for patients with HER2-positive breast cancer and brain metastases. Funding: National Cancer Center Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals.

Abstract Improving the utilization of thermal energy is crucial in the world nowadays due to the high levels of energy consumption. One way to achieve this is to use phase change materials (PCMs) as thermal energy storage media, which can be used to regulate temperature or provide heating/cooling in various applications. However, PCMs have limitations like low thermal conductivity, leakage, and corrosion. To overcome these challenges, PCMs are encapsulated into microencapsulated phase change materials (MEPCMs) capsules/fibers. This encapsulation prevents PCMs from leakage and corrosion issues, and the microcapsules/fibers act as conduits for heat transfer, enabling efficient exchange between the PCM and its surroundings. Microfluidics‐based MEPCMs have attracted intensive attention over the past decade due to the exquisite control over flow conditions and size of microcapsules. This review paper aims to provide an overview of the state‐of‐art progress in microfluidics‐based encapsulation of PCMs. The principle and method of preparing MEPCM capsules/fibers using microfluidic technology are elaborated, followed by the analysis of their thermal and microstructure characteristics. Meanwhile, the applications of MEPCM in the fields of building energy conservation, textiles, military aviation, solar energy utilization, and bioengineering are summarized. Finally, the perspectives on MEPCM capsules/fibers are discussed.

Camera relocalization determines the position and orientation of a camera in a 3D space. Althouh methods based on scene coordinate regression yield highly accurate results in indoor scenes, they exhibit poor performance in outdoor scenarios due to their large scale and increased complexity. A visual localization method, Py-Net, is therefore proposed herein. Py-Net is based on voting segmentation and comprises a main encoder containing Py-layer and two branch decoders. The Py-layer comprises pyramid convolution and 1 × 1 convolution kernels for feature extraction across multiple levels, with fewer parameters to enhance the model’s ability to extract scene information. Coordinate attention was added at the end of the encoder for feature correction, which improved the model robustness to interference. To prevent the feature loss caused by repetitive structures and low-texture images in the scene, deep over-parameterized convolution modules were incorporated into the seg and vote decoders. Landmark segmentation and voting maps were used to establish the relation between images and landmarks in 3D space, reducing anomalies and achieving high precision with a small number of landmarks. The experimental results show that, in multiple outdoor scenes, Py-Net achieves lower distance and angle errors compared to existing methods. Additionally, compared to VS-Net, which also uses a voting segmentation structure, Py-Net reduces the number of parameters by 31.85% and decreases the model size from 236MB to 170 MB.

BackgroundStudies have shown the positive impact of perceived social support on cognitive function among older adults in rural areas. However, existing studies often overlook the impact of different support sources. This study aimed to explore the relationship between the diverse sources of perceived social support and cognitive function.MethodsParticipants were drawn from the Guizhou Rural Older Adults’ Health Study (HSRO) in China. We included 791 participants who participated in a baseline survey in 2019 and a 3-year follow-up survey. Perceived social support was investigated from the six main sources (friend, relative, children, spouse, sibling, and neighbor). Hierarchical linear regression models were used to observe the effects of diverse sources of perceived social support and their combinations on cognitive function.ResultsCognitive function was positively associated with perceived support from children, friends, and neighbors. A positive association was found between cognitive function and increases in each additional source [β = 0.75 (95%CI: 0.51, 0.98), p

BackgroundDry age-related macular degeneration (AMD) is a retinal disease, which has been the third leading cause of vision loss. But current AMD classification technologies did not focus on the classification of early stage. This study aimed to develop a deep learning architecture to improve the classification accuracy of dry AMD, through the analysis of optical coherence tomography (OCT) images.MethodsWe put forward an ensemble deep learning architecture which integrated four different convolution neural networks including ResNet50, EfficientNetB4, MobileNetV3 and Xception. All networks were pre-trained and fine-tuned. Then diverse convolution neural networks were combined. To classify OCT images, the proposed architecture was trained on the dataset from Shenyang Aier Excellence Hospital. The number of original images was 4,096 from 1,310 patients. After rotation and flipping operations, the dataset consisting of 16,384 retinal OCT images could be established.ResultsEvaluation and comparison obtained from three-fold cross-validation were used to show the advantage of the proposed architecture. Four metrics were applied to compare the performance of each base model. Moreover, different combination strategies were also compared to validate the merit of the proposed architecture. The results demonstrated that the proposed architecture could categorize various stages of AMD. Moreover, the proposed network could improve the classification performance of nascent geographic atrophy (nGA).ConclusionIn this article, an ensemble deep learning was proposed to classify dry AMD progression stages. The performance of the proposed architecture produced promising classification results which showed its advantage to provide global diagnosis for early AMD screening. The classification performance demonstrated its potential for individualized treatment plans for patients with AMD.

IntroductionPike perch (Sander Lucioperca) is a predatory freshwater fish, which is highly popular amongst consumers, owing to its white flesh with a delicate structure and mild flavor. Compared to wild pike perch, the diet of farmed ones has shifted from natural food to artificial feeds. These changes would affect the gut flora of the pike perch. Endogenous metabolites of the intestinal flora are transferred through the gut-liver axis, which affects the physiological functions of the host. By studying wild and farmed individuals of the pike perch, novel insights into the stability of the intestinal flora can be provided.Methods and resultsIn this study, we measured various immune parameters in the blood, liver and intestine of wild and farmed pike perch using enzyme activity assays and real-time fluorescence quantitative PCR. Gut microbes were also collected for 16S rRNA gene sequencing. Our results showed that the serum low-density lipoprotein cholesterol (LDL-C) levels were twice as high in the wild group as in the farmed group. Furthermore, the activities of glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) in the intestinal tissues of the wild group were 733.91 U/g and 375.35 U/g, which were significantly higher than those of the farmed group. Expression of IL10 in the liver of farmed pike perch was also 4-fold higher than that of wild pike perch. The expression of genes related to the p53-BAX/Bcl2 signaling pathway was higher in both intestinal and liver tissues of wild pike perch compared with farmed. 16S rRNA gene analysis of the gut microflora showed a high relative abundance of Cetobacterium in the gut of farmed pike perch.ConclusionAs a result, our study indicates that dietary differences affect the diversity, composition and relative abundance of the gut flora of the pike perch. Meanwhile, it affects the glycolipid metabolism and immunomodulation of pike perch.

IntroductionIn maize and peanut intercropping, shading emerges as a critical factor for restricting peanut growth, yield, and quality.MethodsThis study investigated the impact of 30% shade on shade-tolerant [Huayu 22 (HY22) and Fuhua 12 (FH12)] and shade-sensitive [Nonghua 11 (NH11) and Nonghua 5(NH5)] peanut varieties, with non-shaded condition as the control (CK). The effects of shade stress on plant morphology, photosynthetic characteristics, dry-matter accumulation, chloroplast ultra-microstructure, yield, and quality of different shade-tolerant peanut varieties were examined.ResultsCompared to that in the control, shade stress led to an elongation of the main stem, shortening of the lateral branches, and reduction in the leaf area. However, these changes were less significant in the shade-tolerant than in the shade-sensitive peanut varieties, with minimal effect on the elongation of the main stem height and shortening of the lateral branches. Differences in leaf area became significant during the later stages of shade stress, particularly pronounced in the shade-sensitive peanut varieties. To enhance light capture by leaves, the shade-tolerant peanut varieties exhibited increased chlorophyll content and chloroplast grain-layer numbers. The decrease in the chlorophyll a/b ratio was more pronounced in the shade-tolerant than in the shade-sensitive peanut varieties, with significant differences. However, reduced activities of ribulose 1,5-biphosphate (RuBP) carboxylase/oxygenase and fructose 1,6-biphosphate aldolase (FBA) resulted in decreased net photosynthetic rates, particularly evident in the shade-sensitive peanut varieties during the late shade period. Shade stress led to decreased dry-matter accumulation, reduced weight of 100 fruits and kernels, and a significant decline in yield in the shade-sensitive cultivars. Shading also affected peanut-kernel quality. Compared with that in the control, the protein content increased and amino-acid (except cysteine) content decreased in the shade-tolerant cultivars.DiscussionUnder shade stress, shade tolerant peanut varieties have increased the yield by improving the photosynthetic efficiency, which provided a reference for rational selection of shade tolerant peanut varieties in maize and peanut intercropping system.

ObjectiveMVN GABAergic neurons is involved in the rebalance of commissural system contributing to alleviating acute peripheral vestibular dysfunction syndrome. This study aims to depict monosynaptic inputs to MVN GABAergic neurons.MethodsThe modified rabies virus-based retrogradation method combined with the VGAT-IRES-Cre mice was used in this study. Moreover, the commissural connections with MVN GABAergic neurons were analyzed.ResultsWe identified 60 nuclei projecting to MVN GABAergic neurons primarily distributed in the cerebellum and the medulla. The uvula-nodulus, gigantocellular reticular nucleus, prepositus nucleus, intermediate reticular nucleus, and three other nuclei sent dense inputs to MVN GABAergic neurons. The medial (fastigial) cerebellar nucleus, dorsal paragigantocellular nucleus, lateral paragigantocellular nucleus and 10 other nuclei sent moderate inputs to MVN GABAergic neurons. Sparse inputs to MVN GABAergic neurons originated from the nucleus of the solitary tract, lateral reticular nucleus, pedunculopontine tegmental nucleus and 37 other nuclei. The MVN GABAergic neurons were regulated by the contralateral MVN, lateral vestibular nucleus, superior vestibular nucleus, and inferior vestibular nucleus.ConclusionOur study contributes to further understanding of the vestibular dysfunction in terms of neural circuits and search for new strategies to facilitate vestibular compensation.

The O-GlcNAc transferase (OGT) is an essential enzyme that mediates protein O-GlcNAcylation, a unique form of posttranslational modification of many nuclear and cytosolic proteins. Recent studies observed increased OGT and O-GlcNAcylation levels in a broad range of human cancer tissues compared to adjacent normal tissues, indicating a universal effect of OGT in promoting tumorigenesis. Here, we show that OGT is essential for tumor growth in immunocompetent mice by repressing the cyclic GMP-AMP synthase (cGAS)-dependent DNA sensing pathway. We found that deletion of OGT (Ogt−/−) caused a marked reduction in tumor growth in both syngeneic mice tumor models and a genetic mice colorectal cancer (CRC) model induced by mutation of the Apc gene (Apcmin). Pharmacological inhibition or genetic deletion of OGT induced a robust genomic instability (GIN), leading to cGAS-dependent production of the type I interferon (IFN-I) and IFN-stimulated genes (ISGs). As a result, deletion of Cgas or Sting from Ogt−/− cancer cells restored tumor growth, and this correlated with impaired CD8+ T-cell-mediated antitumor immunity. Mechanistically, we found that OGT-dependent cleavage of host cell factor C1 (HCF-1) is required for the avoidance of GIN and IFN-I production in tumors. In summary, our results identify OGT-mediated genomic stability and activate cGAS-STING pathway as an important tumor-cell-intrinsic mechanism to repress antitumor immunity.

This work aimed to investigate the corrosion behavior of Si-18at%Y alloys in air oxidation and water-oxygen corrosion environments. The objective was to understand how different times, temperatures, and the presence or absence of water vapor affected the distribution and transformation of the alloy’s phases. The results revealed that extended duration facilitates growth of yttrium silicate, while higher temperature promotes stable phase transformation. The distribution and type of yttrium silicate are influenced by the presence of SiO2. At lower temperatures, water vapor facilitated the formation of SiO2, whereas at higher temperatures, it depleted SiO2 and inhibited the generation of yttrium silicate.

In diabetic patients, compromised angiogenesis due to endothelial dysfunction leads to delayed intraoral wound healing. However, the moist and dynamic environment of the oral cavity impedes the use of normal wound dressings. Sulfated chitosan (SCS) is a promising biomaterial that promoting angiogenesis. Here, a light-responsive hydrogel combined with SCS explored intraoral wound healing. We designed a SCS-modified hydrogel combined with alginate Methacryloyl (AlgMA) and acrylamide (AM) and demonstrated efficient wet adhesion and mechanical properties suitable for the wet and dynamic oral environment. In vitro, the SAA hydrogel improved the tube formation of human umbilical vein endothelial cells (HUVECs) under high-glucose conditions. Further investigations revealed that the SAA hydrogel can regulate HUVEC-macrophage interactions, leading to a shift in macrophage polarization from M1 to M2, thereby fostering an environment conducive to angiogenesis under high-glucose condition. The results demonstrated the substantial therapeutic impact of the SAA hydrogel on diabetic oral defect repair by effectively enhancing the local blood supply and angiogenesis.

ABSTRACT Ningxiang pigs (NXPs) have a strong ability to deposit fat and intramuscular fat (IMF). However, microbiota-metabolite development and the role in IMF deposition have been rarely reported. Here, we compared the gut microbiota and metabolite profiles and IMF content at 30, 70, 150, 200, and 250 days of age of NXPs. The results revealed that the IMF content in NXPs increased significantly (P < 0.05) as the pigs’ age extended. Additionally, the C14:0 content in the longissimus dorsi muscle at 30 and 70 days of age was significantly lower (P < 0.05) than that at 150 and 200 days of age. The Shannon index and ACE index showed a pattern of initially increasing and then decreasing. LEfSe analysis revealed that 41 differential bacteria at the genus level were specific to different growth stages, indicating the dominant bacteria’s dynamic changes in the NXPs during different stages of age. Furthermore, we found that there were significant differences in cecal metabolism, the classification of differential metabolites revealed that 15.61% of compounds were fatty acyls, 13.98% were prenol lipids, and 10.57% were steroids and steroid derivatives. Next, the network analysis showed that Lachnospiraceae-XPB1014-group was positively related to 4-2-Aminophenyl-2-4-dioxobutanoic-acid, (Z)-3-Octene, 5-Methyl-furaldehyde, Propyl-2-4-decadienoate, which were also positively correlated with the IMF content. Our findings illustrated the dynamic distribution of cecal microbiota and metabolite composition at different growth stages in NXPs and their correlation with IMF deposition. These results provide a valuable insight into optimizing meat quality and overall health in post-weaning NXPs, providing a foundation for enhancement in pork product.IMPORTANCEUnderstanding the dynamic interplay between gut microbiota, metabolites, and intramuscular fat (IMF) deposition in pigs at various growth stages holds significant importance for the pork industry. This research sheds light on how the composition of gut microbiota and metabolites changes throughout the developmental stages of pigs, impacting IMF content in meat. By identifying specific bacterial genera and metabolites associated with IMF deposition, this study offers valuable insights for optimizing meat quality and health in post-weaning pigs. Such knowledge could lead to targeted interventions or management strategies aimed at enhancing pork product quality and overall profitability for producers. Ultimately, this research contributes to advancing our understanding of the complex relationship between gut microbiota, metabolites, and meat quality, offering practical implications for the swine industry.

Background Sympathetic hyperactivity plays an important role in the initiation and maintenance of pulmonary hypertension. Carotid baroreceptor stimulation (CBS) is an effective autonomic neuromodulation therapy. We aim to investigate the effects of CBS on hypoxia‐induced pulmonary hypertension and its underlying mechanisms. Methods and Results Rats were randomly assigned into 4 groups, including a Control‐sham group (n=7), a Control‐CBS group (n=7), a Hypoxia‐sham group (n=10) and a Hypoxia‐CBS group (n=10). Echocardiography, ECG, and hemodynamics examination were performed. Samples of blood, lung tissue, pulmonary arteries, and right ventricle were collected for the further analysis. In the in vivo study, CBS reduced wall thickness and muscularization degree in pulmonary arterioles, thereby improving pulmonary hemodynamics. Right ventricle hypertrophy, fibrosis and dysfunction were all improved. CBS rebalanced autonomic tone and reduced the density of sympathetic nerves around pulmonary artery trunks and bifurcations. RNA‐seq analysis identified BDNF and periostin (POSTN) as key genes involved in hypoxia‐induced pulmonary hypertension, and CBS downregulated the mRNA expression of BDNF and POSTN in rat pulmonary arteries. In the in vitro study, norepinephrine was found to promote pulmonary artery smooth muscle cell proliferation while upregulating BDNF and POSTN expression. The proliferative effect was alleviated by silence BDNF or POSTN. Conclusions Our results showed that CBS could rebalance autonomic tone, inhibit pulmonary arterial remodeling, and improve pulmonary hemodynamics and right ventricle function, thus delaying hypoxia‐induced pulmonary hypertension progression. There may be a reciprocal interaction between POSTN and BDNF that is responsible for the underlying mechanism.

Physiologically Based Pharmacokinetic (PBPK) models can provide forecasts of the drug residues within the organism. Ractopamine (RAC) is a typical β-agonist. In this study, we developed a PBPK model for RAC in goats. The goal was to predict the distribution of the drug after multiple oral administrations. The preliminary PBPK model for RAC in goats performed well in predicting the drug’s distribution in most tissues. In our sensitivity analysis, we found that the parameter of Qclu (Blood Flow Volume through Lungs) had the greatest impact on the RAC concentrations in plasma, liver, and kidney and was the most sensitive parameter. Furthermore, our study aimed to assess the withdrawal time (WT) of RAC in different tissues after RAC long-term exposure in goats. We found that the WT of RAC in the kidney was the longest, lasting for 13 days. Overall, the insights gained from this study have important implications for optimizing drug administration in goats and ensuring appropriate withdrawal times to prevent any potential risks.

Astragali Radix (AS) is a widely used herb in traditional Chinese medicine, with calycosin as its main isoflavonoid. Our previous study discovered that calycosin triggers host defense peptide (HDP) production in IPEC-J2 cells. The aim of this study is to investigate the alleviation effects of AS total flavone and AS calycosin on growth performance, intestinal immunity, and microflora in weaned piglets. Sixty-four piglets were assigned randomly to 4 treatment groups, (1) CON: the basal diet, (2) P-CON: the basal diet plus antibiotics (1 g/kg), (3) AS-TF: the basal diet plus AS total flavone at 60 mg/day per piglet, (4) AS-CA: the basal diet plus AS calycosin at 30 mg/day per piglet. Each treatment consists of 4 replicates with 4 piglets per replicate. Results showed that treatment with AS-TF and AS-CA enhanced average daily growth and average daily feed intake compared to the CON group (P < 0.01), while AS-CA significantly reduced the diarrhea rate (P < 0.05). Both AS-TF and AS-CA significantly increased serum immunoglobulin (Ig) A and IgG levels, with AS-CA further boosting intestinal mucosal secretory IgA levels (P < 0.05). Histological analysis revealed improvements in the morphology of the jejunum and ileum and goblet cell count by AS-TF and AS-CA (P < 0.05). Supplementation of AS-TF and AS-CA promoted the expression of several intestinal HDPs (P < 0.05), and the effect of AS-CA was better than that of AS-TF. In addition, the AS-TF and AS-CA regulated jejunal microbial diversity and composition, with certain differential bacteria genera were showing high correlation with serum cytokines and immunoglobulin levels, suggesting that the intestinal flora affected by AS-TF and AS-CA may contribute to host immunity. Overall, AS CA and AS TF all improved growth performance and health, likely by enhancing nutrition digestibility, serum and intestinal immunity, and intestinal microbial composition. They showed the similar beneficial effect, indicating AS CA appears to be a major compound contributing to the effects of AS TF. This study demonstrated the positive effect of AS flavonoids on weaned piglets and provided a scientific reference for the efficient use of AS products.

Objective: Emerging evidence highlights the pivotal roles of long non-coding RNAs (lncRNAs) in lipid metabolism. Apoprotein C3 (ApoC3) is a well-established therapeutic target for hypertriglyceridemia and exhibits a strong association with cardiovascular disease. However, the exact mechanisms via which the lncRNAs control ApoC3 expression remain unclear. Methods: We identified a novel long noncoding RNA (lncRNA), GM47544, within the ApoA1/C3/A4/A5 gene cluster. Subsequently, the effect of GM47544 on intracellular triglyceride metabolism was analyzed. The diet-induced mouse models of hyperlipidemia and atherosclerosis were established to explore the effect of GM47544 on dyslipidemia and plaque formation in vivo. The molecular mechanism was explored through RNA sequencing, immunoprecipitation, RNA pull-down assay, and RNA immunoprecipitation. Results: GM47544 was overexpressed under high-fat stimulation. GM47544 effectively improved hepatic steatosis, reduced blood lipid levels, and alleviated atherosclerosis in vitro and in vivo. Mechanistically, GM47544 directly bound to ApoC3 and facilitated the ubiquitination at lysine 79 in ApoC3, thereby facilitating ApoC3 degradation via the ubiquitin-proteasome pathway. Moreover, we identified AP006216.5 as the human GM47544 transcript, which fulfills a comparable function in human hepatocytes. Conclusions: The identification of GM47544 as a lncRNA modulator of ApoC3 reveals a novel mechanism of post-translational modification, with significant clinical implications for the treatment of hypertriglyceridemia and atherosclerosis.