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Background and Aim: Cyanobacterial blooms, driven by anthropogenic and climatic changes, pose significant ecological and health threats. This study investigates the long-term effects of microcystins (MCs), potent cyanotoxins, on cattle at Lake des Oiseaux, a Ramsar-listed wetland in Algeria. Aligning with the “One Health” framework, the research evaluates the biochemical, histological, and oxidative stress impacts of MCs on livestock as environmental sentinels. Materials and Methods: A herd of 40 cattle (20 exposed and 20 non-exposed) was studied during the summer bloom period of 2019. Blood and liver samples were analyzed to assess biochemical markers (ALT, AST, ALP, GGT, etc.), histopathological changes, and oxidative stress parameters (GPx, CAT, SOD, LPO and GSH). Results: Exposed cattle exhibited significant elevations in liver enzymes and oxidative stress markers, indicating hepatic inflammation and redox imbalance. Histological analysis revealed macrovacuolar steatosis, fibrosis, and bile duct dilatation. Antioxidant enzyme activities (GPx, CAT and SOD) were reduced, with notable depletion of GSH levels and increased lipid peroxidation. These findings reflect the cumulative cytotoxic effects of MC exposure. Non-exposed cattle showed no such changes. Conclusion: Long-term MC exposure disrupts liver function and induces oxidative stress in cattle, implicating significant risks for both animal and human health. The bioaccumulation of cyanotoxins in livestock emphasizes the urgent need for preventive measures, including water monitoring, restricted livestock access to contaminated sites, and farmer education. These strategies are vital to mitigate risks under the “One Health” approach, ensuring sustainable livestock and public health.

Abstract Background Occupational noise has been associated with numerous adverse health outcomes. However, limited evidence exists regarding its association with obesity. We aim to investigate the effect of occupational noise exposure on the risk of overweight/obesity among workers, providing scientific evidence for the prevention and management of overweight/obesity in the occupational population. Methods This study included 3427 participants from two factories in Guangzhou, China. Individual occupational noise exposure levels were assessed using cumulative noise exposure (CNE). Body mass index (BMI) data were obtained from physical examinations. Linear and logistic regression models, restricted cubic spline, as well as subgroup analyses, were used to explore the association. Results In continuous models, each 1 dB-year increase in CNE was significantly associated with a 0.03 (95% confidence interval (CI): 0.00, 0.05) kg/m² increase in BMI. In categorical models, higher CNE levels were significantly associated with BMI (β = 0.54, 95% CI: 0.16, 0.92) and overweight/obesity (odd ratio (OR) = 1.57, 95%CI: 1.21, 2.04). Restricted cubic splines (RCS) analysis demonstrated a linear dose-response relationship between CNE and overweight/obesity (P for overall=0.013, P for non-linear=0.175). Additionally, shift and night work were identified as critical moderating factors, with a stronger association observed among workers engaged in shift and night work. Conclusion Occupational noise exposure is positively associated with overweight/obesity, particularly among those engaged in shift and night work. Thus, enhancing noise source management and promoting awareness among workers for prevention are imperative.

Abstract Short-stem total hip arthroplasty (SHA) has become popular because it preserves femoral bone stock and enables the use of short femoral stems in revision total hip arthroplasty (THA). However, no study has evaluated whether a short stem in revision THA, replacing a standard stem, can provide adequate primary stability to facilitate osseous integration. In this biomechanical study, a metaphyseal anchoring SHA (Tri-Lock BPS) stem and a standard THA (Corail) stem were implanted into ten composite femurs and loaded dynamically from 300 to 1700 N with 1 Hz. Primary stability was estimated using three-dimensional (3D) micromotions at five points around the bone–implant interface. A revision scenario was then established by removing the standard stem and implanting the same Tri-Lock BPS stem, with subsequent measurements of 3D micromotions. In the primary scenario, no significant differences in 3D micromotions were noted between the short and standard stems at most of the test points. Compared with the Corail group, the Tri-Lock BPS group presented significantly greater 3D micromotions only at the lateral point of the distal femur (P5: Tri-Lock BPS 32.9 ± 7.54 μm vs. Corail 25.1 ± 4.32 μm; p = 0.011). In the revision scenario, no significant differences in the 3D micromotions were noted between the primary and revision Tri-Lock BPS stems at all test points. Our results show that the SHA (Tri-Lock BPS) offers good primary stability, which is similar to that of the standard THA (Corail). The Tri-Lock BPS stem obtained comparable stability in this revision scenario as in the primary scenario; therefore, it can be assumed that the Corail standard stem can safely be revised with a Tri-Lock BPS short stem.

Abstract Epitranscriptomic modifications, particularly N6-methyladenosine (m6A), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting m6A from Nanopore direct RNA sequencing (DRS) data are constrained by their reliance on experimentally validated labels, often resulting in the underestimation of modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive and unlabeled multi-instance learning (MIL) to address the challenges of incomplete labeling and missing read-level annotations. By combining electrical signal features with base alignment data and employing a weighted Noisy-OR probability mechanism, pum6a achieves enhanced sensitivity and accuracy in m6A detection, particularly in low-coverage loci. Pum6a outperforms existing methods in identifying m6A sites across various cell lines and species, without requiring extensive parameter tuning. We further apply pum6a to study the dynamic regulation of m6A demethylases in gastric cancer under hypoxia, revealing distinct roles for FTO and ALKBH5 in modulating m6A modifications and uncovering key insights into m6A -mediated transcript stability. Our findings highlight the potential of pum6a as a powerful tool for advancing the understanding of epitranscriptomic regulation in health and disease, paving the way for biotechnological and therapeutic applications.

Abstract Background Astrocytes, the most abundant glial cell type in the brain, will convert into the reactive state in response to proteotoxic stress such as tau accumulation, a characteristic feature of Alzheimer's disease (AD) and other tauopathies. The formation of reactive astrocytes is partially attributed to the disruption of autophagy lysosomal signaling, and inhibiting of some histone deacetylases (HDACs) has been demonstrated to reduce the molecular and functional characteristics of reactive astrocytes. However, the precise role of autophagy lysosomal signaling in astrocytes that regulates tau pathology remains unclear. Methods We investigated the expression of class IIa HDAC7 in astrocytes from AD patients and PS19 mice. PS19 mice were treated with AAVs expressing shRNA for HDAC7 with astrocyte-specific promoter and with a selective class IIa HDAC inhibitor, TMP195, and the effects on tau pathology, gliosis, synaptic plasticity and cognition-related behavioral performance were measured. Tau uptake and degradation assays in cultured astrocytes were utilized to investigate the role of HDAC7 on astrocyte-mediated tau clearance. Immunoprecipitation, immunofluorescence, western blotting, RT-qPCR, mass spectrometric, and luciferase reporter assay were used to identify HDAC7 substrates, modification site and related signaling pathways in astrocyte-tau clearance. We generated a new antibody to clarify the role of HDAC7-mediated signaling in AD patients and PS19 mice. Results Here, we found that the level of histone deacetylase 7 (HDAC7) was remarkably increased in the astrocytes of AD patients and P301S tau transgenic (PS19) mice. Genetic or pharmacological inhibition of HDAC7 effectively enhanced astrocytic clearance of tau with improved cognitive functions in PS19 mice. HDAC7 could modulate astrocytic uptake and lysosomal degradation of tau proteins through a transcriptional factor EB (TFEB) acetylation-dependent manner. Specifically, deacetylation of TFEB at K310 site by HDAC7 prevented TFEB nuclear translocation with reduced lysosomal biogenesis and tau clearance in astrocytes, whereas inhibiting HDAC7 restored astrocytic TFEB acetylation level at K310 with improved tau pathology and cognitive functions in PS19 mice. Conclusions Our findings suggest that upregulation of HDAC7 induces AD-like tau pathologies via deacetylating TFEB and inhibiting lysosomal biogenesis in astrocytes, and downregulating HDAC7-TFEB signaling is promising for arresting AD and other tauopathies.

ABSTRACT Objective Modic changes (MCs) classification system is the most widely used method in magnetic resonance imaging (MRI) for characterizing subchondral vertebral marrow changes. However, it shows a high degree of sensitivity to variations in MRI because of its semiquantitative nature. In 2021, the authors of this classification system further proposed a quantitative and reliable MC grading method. However, automated tools to grade MCs are lacking. This study developed and investigated the performance of convolutional neural network (CNN) in detecting and grading MCs based on their maximum vertical extent. In order to verify performance, we tested CNNs' generalization performance, the performance of CNN with that of junior doctors, and the consistency of junior doctors after AI assistance. Methods A retrospective analysis of 139 patients' MRIs with MCs was conducted and annotated by a spine surgeon. Of the 139 patients, MRIs from 109 patients were acquired using Philips scanners from June 2020 to June 2021, constituting Dataset 1. The remaining 30 patients had MRIs obtained from both Philips and United Imaging scanners from June 2022 to March 2023, forming Dataset 2. YOLOv8 and YOLOv5 were developed in PyCharm using the Python language and based on the PyTorch deep learning framework, data enhancement and transfer learning were applied to enhance model generalization. The model's performance was compared with precision, recall, F1 score, and mAP50. It also tested generalizability and compared it with the junior doctor's performance on the second data set (Dataset 2). Post hoc, the junior doctor graded Dataset 2 with CNN assistance. In addition, the region of interest was displayed using the class activation mapping heat map. Results On the unseen test set, the YOLOv8 and YOLOv5 models achieved precision of 81.60% and 61.59%, recall of 80.90% and 67.16%, mAP50 of 84.40% and 68.88%, and F1 of 0.81 and 0.60 respectively. On Dataset 2, YOLOv8 and junior doctor achieved precision of 95.1% and 72.5%, recall of 68.3% and 60.6%. In the AI‐assisted experiment, agreement between the junior doctor and the senior spine surgeon significantly improved from Cohen's kappa of 0.368–0.681. Conclusions YOLOv8 in detecting and grading MCs was significantly superior to that of YOLOv5. The performance of YOLOv8 is superior to that of junior doctors, and it can enhance the capabilities of junior doctors and improve the reliability of diagnoses.

Abstract We propose a holographic dual of boundary conformal field theory (BCFT) with T T ¯ $$ T\overline{T} $$ deformation, i.e. of T T ¯ $$ T\overline{T} $$ BCFT. Our holographic proposal distinguishes two types of T T ¯ $$ T\overline{T} $$ BCFTs, depending on whether the T T ¯ $$ T\overline{T} $$ deformation deforms the boundary. For the boundary-deformed case, we find that boundary entropy serves as an effective measure to quantify the impact of boundary deformation. In this scenario, we calculate the energy spectrum for the T T ¯ $$ T\overline{T} $$ BCFT within a finite interval to support the proposed dual. For the boundary-undeformed case, we calculate the entanglement entropy and Rényi entropy from both the field theory side and the gravity side, and find that they match.

Abstract The insulator-to-metal transition in VO2 has garnered extensive attention for its potential applications in ultrafast switches, neuronal network architectures, and storage technologies. However, the photoinduced insulator-to-metal transition remains controversial, especially whether a complete structural transformation from the monoclinic to rutile phase is necessary. Here we employ the real-time time-dependent density functional theory to track the dynamic evolution of atomic and electronic structures in photoexcited VO2, revealing the emergence of a long-lived monoclinic metal phase under low electronic excitation. The emergence of the metal phase in the monoclinic structure originates from the dissociation of the local V-V dimer, driven by the self-trapped and self-amplified dynamics of photoexcited holes, rather than by an electron-electron correction. On the other hand, the monoclinic-to-rutile phase transition does appear at higher electronic excitation. Our findings validate the existence of monoclinic metal phase and provide a comprehensive picture of the insulator-to-metal transition in photoexcited VO2.

Abstract Background This research aims to explore the anti-obesity potential of Wu-Mei-Wan (WMW), particularly its effects on adipose tissue regulation in obese mice induced by a high-fat diet (HFD). The study focuses on understanding the role of heat shock factor 1 (HSF1) in mediating these effects. Methods HFD-induced obese mice were treated with WMW. Body weight, food intake, and histopathological analysis of adipose tissue were conducted. Brown adipose tissue (BAT) activity was evaluated using Positron Emission Tomography, and ultrastructural changes were examined via transmission electron microscopy. Proteomic analysis identified targets of WMW in obesity treatment. HSF1 expression was inhibited to confirm its role. Molecular docking studied interactions between WMW and HSF1. Short-chain fatty acids (SCFAs) in the intestines were measured to determine if WMW’s effects on HSF1 are mediated through SCFAs. Protein expression was assessed using western blot, immunohistochemistry, immunofluorescence and RT-qPCR were employed to detect the mRNA levels. Statistical analyses included t-tests, ANOVA, and non-parametric tests like the Mann–Whitney U test or Kruskal–Wallis test. Results WMW significantly mitigates the adverse effects of a HFD on body weight and glucose metabolism in obese mice. Both low-dose WMW and high-dose WMW treatments led to reduced weight gain and improved glucose tolerance, with low-dose WMW showing more pronounced effects. WMW also reversed structural damage in BAT, enhancing mitochondrial integrity and thermogenic function, particularly at the low dose. Additionally, WMW treatment promoted the browning of WAT, evidenced by increased expression of key thermogenic proteins such as UCP1 and PGC-1α. The increase in HSF1 expression in both BAT and WAT, observed with WMW treatment, was crucial for these beneficial effects, as inhibition of HSF1 negated the positive outcomes. Furthermore, WMW treatment led to elevated levels of short-chain fatty acids SCFAs in the intestines, which are associated with increased HSF1 expression. Conclusions WMW represents a potent therapeutic strategy for obesity, promoting metabolic health and beneficial modulation of adipose tissue through an HSF1-dependent pathway.

Abstract Background: Metabolic syndrome (MetS) presents substantial health risks, and the supplementation of probiotics and prebiotics is regarded as a promising management approach. This study aims to explore the relationship between dietary intake of live microbes and non-dietary prebiotic/probiotic intake and MetS among US adults. Methods: Data from the National Health and Nutrition Examination Survey 1999–2016 was used in this study. MetS is defined according to the criteria set by the National Cholesterol Education Program-Adult Treatment Panel III-2005. Dietary intake information and probiotic/prebiotic intake data were collected through self-reported questionnaires. Multiple logistic models were applied to explore the relationships between dietary live microbes, and probiotic or prebiotic intake with MetS. Results: A significantly lower prevalence of MetS was observed in individuals with a high intake of dietary live microbes compared to those with a low intake (OR: 0.79, 95% CI: 0.69–0.91). This association was particularly strong among participants with higher economic status and advanced educational attainment (interaction P

Lignocellulosic biomass, including agricultural, forestry, and energy crop waste, is one of Earth’s most abundant renewable resources, accounting for approximately 50% of global renewable resources. It contains cellulose, hemicellulose, and lignin, making it crucial for biofuels and bio-based chemicals. Due to its complex structure, single-pretreatment methods are inefficient, leading to the development of combined pretreatment technologies. These methods enhance cellulose accessibility and conversion efficiency. This paper analyzes the principles, advantages, and disadvantages of various combined pretreatment methods and their practical benefits. It highlights recent research achievements and applications in biofuel, biochemical production, and feed. By integrating multiple pretreatment methods, biomass degradation efficiency can be significantly improved, energy consumption reduced, and chemical reagent use minimized. Future advancements in combined physical, chemical, and biological pretreatment technologies will further enhance biomass utilization efficiency, reduce energy consumption, and protect the environment, providing robust support for sustainable renewable energy development and ecological protection.

Abstract α-Functionalized Si-, Ge-, B-, Se-, and S-amide moieties are present in many medicinally active molecules, but their synthesis remains challenging. Here, we demonstrate a high-throughput synthesis using amide-sulfoxonium ylides as carbene precursors in a Si–H, Ge–H, B–H, Se–H, and S–H insertion reactions to target a wide range of α-silyl, α-geryl, α-boryl, α-selenyl, and α-sulfur (hetero)amides. The process is featured as simple operation, mild conditions, broad substrate scope, high functional group compatibility, and excellent chemoselectivity. Both experimental and computational studies are conducted to explore the mechanisms underlying the formation of C–Si/Ge/B/Se/S bond. This research highlights the use of highly selective X–H insertion reactions with amide-sulfoxonium ylide-derived carbenes, paving the way for the preparation of diverse functional organosilane, organogermane, organoboron, organoselenium, and organosulfur compounds from accessible and bench-stable precursors.

Abstract Background There is a lack of diagnostic non-invasive imaging technology for assessing the early structural and functional changes of the kidney in type 2 cardiorenal (CRS) patients. This study aims to explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for clinical application in type 2 CRS patients, to provide imaging markers for the assessment of kidney damage. Methods This is a retrospective observational clinical study conducted in Nanjing, China. The clinical characteristics, including age, gender, medical history, laboratory results, and ultrasound and magnetic resonance imaging results were collected from the electronic medical record. Thirty-one patients with type 2 CRS, 20 patients with chronic heart failure (HF) and 20 healthy controls were enrolled and divided into type 2 CRS, HF and control groups. All the participants underwent magnetic resonance imaging (MRI) scanning. The apparent diffusion coefficient (ADC) value and IVIM-DWI parameters including true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were obtained. The correlation between estimated glomerular filtration rate (eGFR), renal size and imaging parameters was evaluated by Spearman correlation analysis. Results ADC and D of the renal cortex in patients with type 2 CRS were lower than those in the healthy control group. ADC and f in the HF group were lower than those in the control group. D was positively correlated with the length (r = 0.3752, P = 0.0013) and transverse diameter (r = 0.3258, P = 0.0056) of the kidney. ADC (r = 0.2964, P = 0.0121) and D (r = 0.3051, P = 0.0097) were positively correlated with eGFR. Renal cortical ADC and D values could distinguish type 2 CRS patients from the healthy controls with area under the curve (AUC) of 0.723 and 0.706, respectively. Conclusion The ADC and D values were not only correlated with renal function, but also had lower levels in type 2 CRS. The IVIM-DWI parameter D was also related to kidney size, but further research is needed to determine whether it can be used as a novel imaging marker for type 2 CRS.

Abstract Background With existing researches identifying an increased rate of long-term conditions (LTCs) among Inflammatory Bowel Disease (IBD) patients, yet there is a lack of exploration into the patterns of comorbidity and prognostic rates for IBD patients with multiple morbidities. Methods The study included 8,305 participants who self-reported having IBD, comprising ulcerative colitis (UC) and Crohn’s disease (CD). Latent class analysis (LCA) was utilized to create optimal categories of LTC combinations for UC and CD patients with additional long-term conditions. Using Cox proportional hazards models, we compared the all-cause mortality rates over a 16-year follow-up among UC and CD patients within different LTC categories, both without LTCs and with the addition of one LTC, the probability of major adverse cardiovascular events (MACE), and the rates of IBD-related surgeries. Results A total of 5,617 participants reported having two or more LTCs, with the LCA method identifying three prevalence categories among CD patients, and four prevalence categories among UC patients. The highest mortality rate among CD patients was found in category 3: (HR 1.789, 95% CI (1.439–2.224)), and the highest rates of MACE were also in category 3: (HR 11.432, 95% CI (9.332–14.005)), with hypertension being the distinguishing characteristic of this category, and the highest rates of IBD-related surgeries being associated with pain in category 1: (HR 1.217, 95% CI (0.983–1.506)). Among UC patients, the highest mortality rate was in category 3: (HR 2.221, 95% CI (1.837–2.684)), with the highest MACE rates found in category 3: (HR 6.422, 95% CI (5.659–7.288)), and the highest rates of IBD-related surgeries being associated with pain, also in category 3: (HR 1.218, 95% CI (1.041–1.425)). Conclusion The rates of adverse health outcomes in IBD patients is closely associated with multimorbidity patterns, underscoring the need to fully consider multimorbidity patterns in the assessment, management, and treatment strategies for IBD.

Background Hepatocellular carcinoma (HCC) is the third leading cause of common cancer-related mortality globally, accounting for approximately 90% of all primary liver cancer cases. Its recurrence and mortality rates are high, with the underlying molecular mechanisms remaining unclear. Objective To explore potential molecular mechanisms of HCC and explore novel biomarkers. Methods RNA-seq expression data and clinical information were retrieved from TCGA database, differential gene expression analysis was conducted between normal liver tissue and HCC tissue. Enrichment analysis on the differentially expressed genes was performed. Based on the gene expression data profiles of HCC in TCGA, a co-expression network was established using the WGCNA R package, and weighted gene co-expression network analysis (WGCNA) was performed to select clinically significant modules and screen candidate Hub genes; the candidate Hub genes were further analyzed for significant differential expression in HCC tissues and normal liver tissues, and whether they were significantly correlated with the overall survival and disease-free survival of HCC patients. The Hub genes were conclusively identified, and their protein expression was validated through the Human Protein Atlas database. Results The genetic expression data in this study were obtained from 50 normal liver tissue samples and 373 HCC tissue samples. Through differential gene expression analysis, a total of 7 230 genes differential expression between HCC and normal hepatic tissue, comprising 3 691 up-regulated genes and 3 539 down-regulated genes in HCC were identified. Enrichment analysis showed that the up-regulated differentially expressed genes were mainly involved in cell cycle regulation and mitotic processes; the down-regulated differentially expressed genes were mainly involved in processes such as small molecule metabolism and organic acid metabolism. WGCNA identified 19 gene modules related to the clinical features of HCC patients, the cyan and purple modules were screened by analyzing the relationship between the modules and the clinical features. The first two genes in the cyan module genes that were strongly associated with both overall survival and disease-free survival of patients were VPS45 and FAM189B. In the purple module genes, first two genes that were strongly associated with both overall survival and disease-free survival of patients were CLEC1B and FCN3, respectively; therefore, VPS45, FAM189B, CLEC1B and FCN3 were identified as the final Hub genes. Immunohistochemical staining in the Human Protein Atlas database showed that VPS45 and FAM189B were expressed higher in HCC tissues than in normal liver tissues. FCN3 was expressed in HCC tissues lower than in normal liver tissues, the difference in the expression of CLEC1B between HCC tissues and normal liver tissues was not obvious. Conclusion VPS45, FAM189B, CLEC1B and FCN3 have been preliminary identified as possible novel potential biomarkers for HCC, which may provide a theoretical basis for targeted therapy of HCC.

Abstract Objectives This study aims to describe a novel dorsal venous complex (DVC) ligation‐free and parietal endopelvic fascia preserving technique for laparoscopic radical prostatectomy and to evaluate its post‐operative outcomes. Methods From April 2020 to May 2021, a total of 125 patients with localized prostate cancer received laparoscopic radical prostatectomy by a single surgeon. In the procedure, a novel technique of DVC ligation‐free and parietal endopelvic fascia preserving was used. Preoperative characteristics of patients and perioperative results were recorded. In this study, continence was defined as zero to one pad per day. Oncological outcomes were evaluated based on positive surgical margin. Results Five patients required a blood transfusion. Mean post‐operative hospital stay was 3.9 days (2–5), and the catheter could be removed on post‐operative day 7 to 9. Final pathologic evaluations were 87 stage pT2, 22 stage pT3a, and 7 pT3b, 9 stage pT4, respectively. The positive surgical margin rate was 10.4% in total. Ninety‐three patients (74.4%) returned to urinary continence 2 months post‐operatively, and 11 patients (11/125) developed biochemical recurrence 6 months post‐operatively. Conclusions The DVC ligation‐free and parietal endopelvic fascia preserving technique provides early recovery from incontinence without adversely affecting the oncological outcome.

Abstract Background Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a rare hereditary disorder caused by variants in PKHD1. Currently, aberrant splicing has been reported to play important roles in genetic disease. Our goal is to analyze intronic variants in PKHD1 at the mRNA level. Results The 12 candidate variants were introduced into the corresponding minigene and functionally assayed in HEK 293T and Hela cells. We identified 11 variants that induce splicing alterations, resulting in various consequences such as skipping of exons, intron retention and protein truncation. Conclusions This underlined the importance of mRNA-level assessment for genetic diagnostics in related genetic disorders.

The germination process of seeds is influenced by the interplay between two opposing factors, pectin methylesterase (PME) and pectin methylesterase inhibitor (PMEI), which collectively regulate patterns of pectin methylesterification. Despite the recognized importance of pectin methylesterification in seed germination, the specific mechanisms that govern this process remain unclear. In this study, we demonstrated that the overexpression of GhPMEI53 is associated with a decrease in PME activity and an increase in pectin methylesterification. This leads to seed cell wall softening, which positively regulates cotton seed germination. AtPMEI19, the homologue in Arabidopsis thaliana, plays a similar role in seed germination to GhPMEI53, indicating a conserved function and mechanism of PMEI in seed germination regulation. Further studies revealed that GhPMEI53 and AtPMEI19 directly contribute to promoting radicle protrusion and seed germination by inducing cell wall softening and reducing mechanical strength. Additionally, the pathways of abscicic acid (ABA) and gibberellin (GA) in the transgenic materials showed significant changes, suggesting that GhPMEI53/AtPMEI19-mediated pectin methylesterification serves as a regulatory signal for the related phytohormones involved in seed germination. In summary, GhPMEI53 and its homologs alter the mechanical properties of cell walls, which influence the mechanical resistance of the endosperm or testa. Moreover, they impact cellular phytohormone pathways (e.g., ABA and GA) to regulate seed germination. These findings enhance our understanding of pectin methylesterification in cellular morphological dynamics and signaling transduction, and contribute to a more comprehensive understanding of the PME/PMEI gene superfamily in plants.

Brachytherapy can kill cancer cells more effectively and make the normal tissues around the tumor free or less irradiated. It has become an effective means for the treatment of malignant tumors. 103Pd has a half-life of 16.96 days and a significant advantage in the field of brachytherapy due to its unique decay properties. In order to achieve the large-scale production of 103Pd, the preparation process based on Cyclone-30(C30) cyclotron was studied. The rhodium metal was electroplated on the copper target base by pulse electroplating method. The rhodium-plated target was transferred to C30 solid target station for irradiation with beam energy of 16-18 MeV, and the beam current was 200 μA. In order to obtain Curie-level 103Pd, the beam integral should be more than 10000 μA•h. After irradiation, the target was transferred to the separation and purification hot cell, the rhodium plating was separated from the target base first, then was ground into powder, and dissolved by high temperature melting of potassium bisulfate. The rhodium was converted into soluble rhodium sulfate, and the 103Pd nuclide was separated and purified by AG1-X8 resin. The impurities of Rh, Fe, Cu and Zn were rinsed with 6 mol/L hydrochloric acid and 0.03 mol/L hydrochloric acid, respectively. At last, 103Pd was desorbed with a mixed solution of ammonium chloride-ammonia mixed solution(volume ratio 1∶1). The radioactive activity, radionuclide purity and specific activity of 103Pd were measured respectively. The preparation of sealed seed core was studied by using the prepared 103Pd feed solution. The results show that the rhodium plating layer is smooth and dense, and firmly bonded with the copper plate, the rhodium layers mass thickness is greater than 150 mg/cm2. The production capacity of 103Pd is greater than 37 GBq, the radionuclide purity is greater than 99.9%, and the specific activity is greater than 875 GBq/mg, and activity concentrations greater than 6.2 GBq/mL. The preparation field of 103Pd brachytherapy sources is more than 90%, it can meet the requirements. The 103Pd preparation process is stable, and the quality is controllable. The large-scale production capacity has been reached, and it provides a stable source for the research of 103Pd brachytherapy sources.

Abstract Purpose This study aimed to investigate the real-world use and clinical outcomes of tixagevimab/cilgavimab in China during the Omicron outbreak in late 2022. Methods This observational, real-world study included patients who received tixagevimab/cilgavimab from July 9 to December 30, 2022, in Hainan, China. Here, we report the baseline and characteristics and interim analysis results of the clinical outcomes in those receiving at least one dose of tixagevimab/cilgavimab (300 mg) for pre-exposure prophylaxis. Results Among 248 subjects who received tixagevimab/cilgavimab, 229 subjects were included in this analysis. Until March 28, 2023, the median follow-up was 95 days. The mean age of the subjects was 44.4 ± 15.9 years, 11.8% were ≥ 65 years, and 41.5% were male. Fifty-eight (25.3%) subjects had comorbidities, 16.2% subjects had key immune compromised conditions. Seventy-two (32.6%) patients had laboratory-confirmed SARS-CoV-2 infection and/or received healthcare within three months; 71/72 (98.6%) had mild disease, and one (1.4%) was moderate. No COVID-19-related intensive care unit (ICU) admissions, extracorporeal membrane oxygenation utilizations, or death occurred. Two (0.9%) patients required hospitalization. One (0.4%) serious adverse event occurred, which was considered unrelated to tixagevimab/cilgavimab. Conclusion Among Chinese patients receiving prophylactic tixagevimab/cilgavimab, the incidence of COVID-19-related hospitalization, ICU admission, or death was low during the Omicron surge. Further randomized controlled trials with larger sample sizes are needed to determine the effectiveness of tixagevimab/cilgavimab in preventing severe COVID-19 outcomes. Trial registration The study was registered with clinicaltrial.gov (NCT05917951).

Abstract Background This study aimed to analyze the epidemic characteristics and influencing factors of school influenza outbreaks in Jiangsu Province, China from 2020 to 2023,following the COVID-19 pandemic, to inform prevention and control strategies. Methods Data on influenza-like illness(ILI) outbreaks from the Chinese Influenza Surveillance Information System and national-level influenza surveillance sentinel hospitals were analyzed. The temporal distribution, school type, virus strains, and outbreak scales were examined using descriptive statistics. Results From 2020 to 2023, 1142 influenza outbreaks occurred in schools, with primary schools(ages 6 to 12) accounting for 71.80%. Most large outbreaks were caused by A(H1N1) and A(H3N2), responsible for 8.99% of total outbreaks. Outbreaks were predominantly reported in the pre-peak periods of B(Victoria) and A(H1N1) circulation, accounting for 86.31% and 92.32% of their respective total outbreaks. No concurrent influenza and COVID-19 outbreaks were observed during the study period. Conclusion Primary and secondary schools are high-risk settings for influenza outbreaks. A(H3N2) shows higher adaptability and is more likely to co-circulate with other subtypes/lineages, especially A(H1N1), leading to larger outbreaks. B(Victoria)-caused outbreaks are more frequent but smaller in scale. School influenza outbreaks are more likely to occur during the early stages of seasonal peaks, particularly for B(Victoria) and A(H1N1). This suggests that influenza outbreaks in schools may play a crucial role in seeding and accelerating the spread of the virus within the broader community.

Abstract Multistage plate subduction plays a crucial role in magmatism; however, the mechanisms by which deep geodynamic processes govern volcanism in the Alaska subduction zone remain controversial. Using numerous travel-time data from several seismic arrays, we constructed high-resolution tomographic models to investigate the velocity structure of the Pacific Plate and Yakutat slab. Our tomographic results revealed high-velocity anomalies in the Pacific Plate and Yakutat slab, while the low-velocity areas within the Pacific Plate were identified as slab tears. We suggest that the Pacific Plate transitioned from oblique subduction along the Aleutian volcano chain to lower-angle subduction beneath the Pacific-Yakutat Plate interaction zone, forming two slab tears that enhance hot asthenosphere materials upwelling. The partial melting of the mantle wedge induced by Pacific slab dehydration and the concurrent upwelling of mantle materials jointly drove volcanism in the transition zone. Conversely, the flat subduction of the Yakutat slab into the mantle wedge overlying the Pacific slab effectively hindered the upwelling of hot hybrid materials, cooling the Pacific mantle wedge. These results offer a new perspective on the influence of slab dynamics on volcanic and magmatic processes in the region and represent an advancement in our understanding compared to previous studies, which did not resolve the tears within the slab or their geodynamic implications at this level of detail.

The paper concerns a room-temperature cross-bar H-mode (CH) drift tube linac (DTL) with KONUS (Kombinierte Null Grad Struktur) [1,2] beam dynamics. To make the acceleration in DTL cell more efficient, we studied the correlation between transit time factor (TTF) and structural coefficients, first. Furthermore, we developed a new code with Python to demonstrate the longitudinal dynamics more clearly. The code computationally generates clusters, bunch centers, and emittance growth in a single figure. Thus, the stabilization region and cluster evolution at various negative phases can be studied. Based on the above studies, we designed a 162.5 MHz CH-DTL to accelerate 10 mA D+ from 2.11 MeV to 3.25 MeV in continuous-wave (CW) mode. The proposed CH-DTL is a part of the Middle Energy Neutron Source (MENS). The dynamics and RF design were iterated to make the gap voltage error lower than 1 %. The initial beam is assumed to come from a Radio Frequency Quadrupole accelerator (RFQ). The geometries of the CH-DTL are optimized by using CST. Multiparticle tracking from LEBT to RFQ is performed with TraceWin and the transmission efficiency in the CH-DTL is 100 %.

Abstract Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized pathologically by extracellular deposition of β-amyloid (Aβ) into senile plaques and intracellular accumulation of hyperphosphorylated tau (pTau) as neurofibrillary tangles. Clinically, AD patients show memory deterioration with varying cognitive dysfunctions. The exact molecular mechanisms underlying AD are still not fully understood, and there are no efficient drugs to stop or reverse the disease progression. In this review, we first provide an update on how the risk factors, including APOE variants, infections and inflammation, contribute to AD; how Aβ and tau become abnormally accumulated and how this accumulation plays a role in AD neurodegeneration. Then we summarize the commonly used experimental models, diagnostic and prediction strategies, and advances in periphery biomarkers from high-risk populations for AD. Finally, we introduce current status of development of disease-modifying drugs, including the newly officially approved Aβ vaccines, as well as novel and promising strategies to target the abnormal pTau. Together, this paper was aimed to update AD research progress from fundamental mechanisms to the clinical diagnosis and therapies.

Abstract Background Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. Methods The keywords “lipid droplets” and “metabolic diseases” were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like “lipid droplets”, “lipid droplet-associated proteins”, “fatty liver disease”, “diabetes”, “diabetic kidney disease”, “obesity”, “atherosclerosis”, “hyperlipidemia”, “natural drug monomers” and “natural compounds”, the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. Results The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. Conclusion Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications. Graphical Abstract

In this study, we conducted morphological and molecular analyses of Perinereis wilsoni, a species being considered for aquaculture in China. We found this species difficult to identify because of its close morphological similarity to the sympatric P. mictodonta and thus sought genetic markers to more easily distinguish it and to investigate its phylogenetic relationship to P. mictodonta and other nereidids. For the first time, we sequenced, assembled, and annotated the complete mitochondrial genome, nuclear ribosomal sequences (18S-ITS1-5.8S-ITS2-28S), and four nuclear histone genes (H3-H2A-H2B-H4) of P. wilsoni. Comprehensive bioinformatics methods were employed to assemble the genome-skimming data of P. wilsoni to ensure assembly quality. Phylogenetic analyses based on five datasets of the available mitochondrial genomes (32 taxa in Nereididae, including 8 taxa in Perinereis), using maximum likelihood and Bayesian analyses, provide support for the monophyly of the genus Perinereis. In contrast, the P. nuntia species group, a subgroup within Perinereis, is nonmonophyletic. Perinereis wilsoni has a closer phylogenetic relationship with P. vancaurica and P. nuntia. Our study serves as a baseline for future work on the cultivation, reproductive biology, and phylogeny of P. wilsoni.

Abstract De novo purine synthesis metabolism plays a crucial role in tumor cell survival and malignant progression. However, the specific impact of this metabolic pathway on chemoresistance in ovarian cancer remains unclear. This study aims to elucidate the influence of de novo purine synthesis on chemoresistance in ovarian cancer and its underlying regulatory mechanisms. We analyzed metabolic differences between chemosensitive and chemoresistant ovarian cancer tissues using mass spectrometry-based metabolomics. Cell growth, metabolism, chemoresistance, and DNA damage repair characteristics were assessed in vitro using cell line models. Tumor growth and chemoresistance were assessed in vivo using ovarian cancer xenograft tumors. Intervention of purines and NEK6-mediated purine metabolism on chemoresistance was investigated at multiple levels. Chemoresistant ovarian cancers exhibited higher purine abundance and NEK6 expression. Inhibiting NEK6 led to decreased de novo purine synthesis, resulting in diminished chemoresistance in ovarian cancer cells. Mechanistically, NEK6 directly interacted with FOXO3, contributing to the phosphorylation of FOXO3 at S7 through its kinase activity, thereby inhibiting its nuclear translocation. Nuclear FOXO3 promoted FBXW7 transcription, leading to c-MYC ubiquitination and suppression of de novo purine synthesis. Paeonol, by inhibiting NEK6, suppressed de novo purine synthesis and enhanced chemosensitivity. The NEK6-mediated reprogramming of de novo purine synthesis emerges as a critical pathway influencing chemoresistance in ovarian cancer. Paeonol exhibits the potential to interfere with NEK6, thereby inhibiting chemoresistance.

Abstract Social isolation (SI) is a common phenomenon in the modern world, especially during the coronavirus disease 2019 pandemic, and causes lasting cognitive impairments and mental disorders. However, it is still unclear how SI alters molecules in the brain and induces behavioural dysfunctions. Here, we report that SI impairs cognitive function and induces depressive-like behaviours in C57BL/6 J mice, in addition to impairing synaptic plasticity and increasing the levels of APP cleavage-related enzymes, thereby promoting Aβ production. Moreover, we show that in APP/PS1 transgenic mice, SI accelerates pathological changes and behavioural deficits. Interestingly, downregulation of the expression of the BACE1 attenuates SI-induced Aβ toxicity and synaptic dysfunction. Furthermore, early intervention with BACE1 shRNA blocks SI-induced cognitive impairments. Together, our data strongly suggest that SI-induced upregulation of BACE1 expression mediates Aβ toxicity and induces behavioural deficits. Down-regulation of BACE1 may be a promising strategy for preventing SI-induced cognitive impairments.

Abstract Background Hygienic behavior, a specialized form of immune response evolved in social insects, plays a crucial role in safeguarding colonies from disease spread. In honeybee colonies, such behavior typically entails the dual steps of uncapping and removal of unhealthy and deceased brood. Although in recent years, numerous studies have examined the development of hygienic behavior, the mechanisms underlying the division in the performance of uncapping and removal have yet to be sufficiently elucidated. In this regard, long non-coding RNAs (lncRNAs) have been evidenced to be engaged in regulating the physiological activities of honeybees; however, whether lncRNAs are likewise involved in the uncapping and removal tasks has not been clarified. Results In this study, the strong hygienic Apis cerana worker bees were used and the processes of uncapping and removal behaviors in three colonies were assayed with freeze-killed brood in the field. We then sequenced the antennal RNAs of honeybees to identify differentially expressed lncRNAs and performed lncRNA-mRNA association analysis to establish the differences between uncapping and removal. We detected 1,323 differentially expressed lncRNAs in the antennae, and the findings of lncRNA-mRNA association analyses revealed that the target genes of differentially expressed lncRNAs between uncapping and removal worker bees were predominantly linked to response to stimulus, receptor activity, and synapse. Notably, among the lncRNAs enriched in cellular response to stimulus, XR_001766094.2 was exclusively expressed in the uncapping worker bees. Based on these findings, we hypothesize that XR_001766094.2 plays a key role in distinguishing uncapping from removal behaviors by responding to external stimulus, thereby suggesting that the division of hygienic behaviors is governed by differential thresholds of responsiveness to environmental cues. Conclusion We characterized differences in the uncapping and removal behaviors of worker bees from a perspective of lncRNAs. Uncapping bees may be equipped with a more rapid stimulatory response and more acute olfactory sensitivity, contributing to the rapid hygienic behavior in honeybee colonies. Our results thus establish a foundation for potential lncRNA-mediated gene expression regulation in hygienic behavior.

Abstract Since these large‐scale renewable power generation (RPGs) stations are always located far away from load centres, voltage source converters (VSCs) always operate in weak‐grid connected conditions, due to the long distance of transmission line and increasing capacity of RPGs. Large power disturbance of RPGs easily causes weak‐grid connected VSCs (WG‐VSCs) suffering from transient synchronization instability issue, which is lack of theoretical and quantitative analysis. This paper is motivated to fill this gap. By considering the dynamic interaction of outer DC voltage control, reactive power loop, and phase‐locked loop (PLL), an equivalent synchronization model of a WG‐VSC system is established first. Then, the mechanism of transient synchronization instability is revealed by the combination of equal area criterion and numerical integration method. Furthermore, the concept of feasible region of active power disturbance (FR‐APD) is introduced for the first time. With the constructed FR‐APD, the transient stability of the WG‐VSC system can be confirmed. Finally, experimental results based on the RT‐BOX hardware‐in‐the‐loop platform are presented to verify the theoretical analysis.

ObjectiveTo explore latent profiles of self-management behaviors in older adult patients with chronic diseases and identify the factors that influence different profiles, guiding targeted interventions.MethodsThis study used convenience sampling to recruit 536 older adult patients with chronic diseases from three tertiary hospitals in Anhui Province between October 2023 and May 2024. Data were collected using a general information questionnaire, the age-adjusted Charlson Comorbidity Index (aCCI), the Chronic Disease Self-Management Behavior Scale, the Chronic Disease Management Self-Efficacy Scale, the Psychological Status Scale, the Digital Health Literacy Scale, and the Social Support Scale. Latent profile analysis was conducted using Mplus 8.3, and univariate and multivariate logistic regression analyses were performed using SPSS 26.0.ResultsThree profiles of self-management behaviors emerged: “Low Self-Management” (50.2%), “High Exercise and Cognitive Management” (8.6%), and “Moderate Management with Enhanced Communication” (41.2%). Multivariate logistic regression revealed that residence, aCCI, number of digital devices used, perceived usefulness of digital health information, digital health literacy, social support, chronic disease management self-efficacy, and psychological status were significant factors affecting self-management profiles (all p < 0.05).ConclusionSelf-management behaviors in older adult patients with chronic diseases were generally low, with substantial heterogeneity across profiles. Healthcare providers should tailor interventions based on the characteristics of each group to enhance self-management in digital health contexts.

BackgroundPersonalized precision medicine (PPPM) in cancer immunology and oncology is a rapidly advancing field with significant potential. Gliomas, known for their poor prognosis, rank among the most lethal brain tumors. Despite advancements, there remains a critical need for precise, individualized treatment strategies.MethodsWe conducted a comprehensive analysis of RNA-seq and microarray data from the TCGA and GEO databases, supplemented by single-cell RNA sequencing (scRNA-seq) data from glioma patients. By integrating single-cell sequencing analysis with foundational experiments, we investigated the molecular variations and cellular interactions within neural glioma cell subpopulations during tumor progression.ResultsOur single-cell sequencing analysis revealed distinct gene expression patterns across glioma cell subpopulations. Notably, differentiation trajectory analysis identified NUSAP1 as a key marker for the terminal subpopulation. We found that elevated NUSAP1 expression correlated with poor prognosis, prompting further investigation of its functional role through both cellular and animal studies.ConclusionsNUSAP1-based risk models hold potential as predictive and therapeutic tools for personalized glioma treatment. In-depth exploration of NUSAP1’s mechanisms in glioblastoma could enhance our understanding of its response to immunotherapy, suggesting that targeting NUSAP1 may offer therapeutic benefits for glioma patients.

Porous organic cages (POCs) represent a novel class of low-density crystalline materials that exhibit distinctive pores comparable to those observed in three-dimensional extended network materials, including metal organic frameworks (MOFs), covalent organic frameworks (COFs), and porous organic polymers (POPs). Owing to their adjustable pore sizes, high specific surface areas, and discrete molecular structures, POCs exhibit excellent solution dispersibility and processability, thereby providing a broad spectrum of potential strategies for the design and fabrication of POC separation membranes. This review presents a comprehensive and systematic summary of the recent research progress in the preparation techniques and applications of POC separation membranes. We summarize a comprehensive overview of preparation strategies for POC separation membranes, including physical blending, spin coating, and interfacial polymerization, and analyze their advantages and limitations. Recent developments in the separation applications of POC separation membranes are highlighted, such as gas separation, ion separation and molecular separation, as well as current challenges and future development trends in this field, are briefly discussed. We anticipate that this review will offer a pertinent perspective to promote advancements in the development of advanced POC separation membranes, and be useful to researchers in related fields.

Gliomas are the most common primary tumors of the nervous system, which is generally treated using adjuvant chemotherapy following surgical resection. However, patient survival time is still short, and there is currently no successful treatment for highly malignant gliomas. Bullatine A (BLA) is a diterpenoid alkaloid of the genus Aconitum which antirheumatic and anti-inflammatory pharmacological properties. The effects of BLA on gliomas have not yet been elucidated. In this study, we investigated the effects of BLA on human brain malignant glioblastoma cells. Our results showed that BLA inhibited the proliferation of U87MG and U251 cells in a dose-dependent manner and decreased their survival rate. BLA dose-dependently induced apoptosis in U87MG cells, upregulated the expression of cleaved caspase-9, cleaved caspase-3 pro-apoptotic protein, and Bax protein, and downregulated the expression of Bcl-2 anti-apoptotic protein. Moreover, BLA dose-dependently induced U87MG and U251 cell cycle arrest in the G2/M phase, and downregulated the expression of p-ERK and Myc proteins. Further, BLA significantly inhibited the acetylation of histones H3K9 and H3K56, and upregulated the expression of the protein deacetylase SIRT6. Mechanistic studies revealed that the effect of BLA on inducing apoptosis and inhibiting the proliferation of glioma cells was blocked by SIRT6 knockout. In summary, our study indicated that BLA is a potential therapeutic agent for glioma that targets SIRT6 to inhibit glioma cell proliferation and induce apoptosis.

Obesity is a major contributor to metabolic and cardiovascular disease. Although senescent cells have been shown to accumulate in adipose tissue, the role of senescence in obesity-induced metabolic disorders and in cardiac dysfunction is not yet clear; therefore, the therapeutic potential of managing senescence in obesity-related metabolic and cardiac disorders remains to be fully defined. Objective: We investigated the beneficial effects of a senolytic cocktail (dasatinib and quercetin) on senescence and its influence on obesity-related parameters. Methods and Results: We found that the increase in body weight and adiposity, glucose intolerance, insulin resistance, dyslipidemia, hyperleptinemia, and hepatic disorders which were induced by an obesogenic diet were alleviated by senolytic cocktail treatment in mice. Treatment with senolytic compounds eliminated senescent cells, counteracting the activation of the senescence program and DNA damage in white adipose tissue (WAT) observed with an obesogenic diet. Moreover, the senolytic cocktail prevented the brown adipose tissue (BAT) whitening and increased the expression of the thermogenic gene profile in BAT and pWAT. In the hearts of obese mice, senolytic combination abolished myocardial maladaptation, reducing the senescence-associated secretory phenotype (SASP) and DNA damage, repressing cardiac hypertrophy, and improving diastolic dysfunction. Additionally, we showed that treatment with the senolytic cocktail corrected gene expression programs associated with fatty acid metabolism, oxidative phosphorylation, the P53 pathway, and DNA repair, which were all downregulated in obese mice. Conclusions: Collectively, these data suggest that a senolytic cocktail can prevent the activation of the senescence program in the heart and WAT and activate the thermogenic program in BAT. Our results suggest that targeting senescent cells may be a novel therapeutic strategy for alleviating obesity-related metabolic and cardiac disorders.

BackgroundHJIG is a potential treatment for erectile dysfunction (ED) that has been used in China for over 20 years. We conducted a multi-center, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness and safety of the Chinese Herbal Medicine, Hongjing I granule (HJIG), in patients with mild to moderate erectile dysfunction (ED).MethodsThis study is structured as a randomized, double-blind, placebo-controlled trial, executed across multiple centers. The recruitment strategy is primarily oriented towards patients demonstrating a pronounced preference for solely leveraging traditional Chinese medicine (TCM) interventions, a preference that is widely observed within TCM healthcare settings. A total of 100 patients, presenting with mild to moderate ED, specifically linked to the traditional diagnostic criteria of qi deficiency and blood stasis, will be enrolled. These participants will be randomly distributed between the HJIG (N = 50) and placebo (N = 50) arms. The designated treatment period is set at 8 weeks. Primary outcome measures encompass the International Index of Erectile Function-Erectile Function domain (IIEF-EF) score, the Sexual Encounter Profile (SEP), and scores derived from the traditional Chinese medicine symptom evaluation.ResultsOf the 122 men enrolled, the baseline IIEF-EF score averaged 16.00 [IQR: 13.00, 18.00]. Eight weeks post-randomization, the HJIG group demonstrated a mean change in IIEF-EF scores of 7.80 (±3.25), compared to 3.33 (±3.90) in the placebo group, signifying a marked difference (P < 0.001). The median alterations in SEP3 scores were 0.50 [IQR: 0.36, 0.75] for the HJIG group and 0.50 [0.20, 0.67] for the placebo group, revealing a statistically relevant distinction (P = 0.05). In both primary outcomes, HJIG proved superior to the placebo. Additionally, improvements in TCM symptom scores were notably greater in the HJIG group relative to the placebo, with no adverse events reported across both groups.ConclusionThe Hongjing I granule significantly improved symptoms in patients with mild to moderate ED. However, to validate these findings, further extended randomized trials are warranted.Clinical Trial RegistrationThe study has been registered in the Chinese Clinical Trial Registry (ChiCTR) and the registration number was ChiCTR2000041127.

Satellite navigation interference monitoring is an important means to effectively evaluate interference and ensure the normal operation of global navigation satellite system (GNSS). Once interference is detected, this monitoring can identify the type of it, perform direction-finding and localization, evaluate its impact on GNSS, and guide the implementation of effective countermeasures. With the continuous progress of interference technology, the power required to cause the same jamming effect to the navigation system is getting smaller and smaller. Traditional radio monitoring system has been unable to meet the needs of the current satellite navigation monitoring in terms of sensitivity and accuracy. It is of great significance to develop and improve the dedicated satellite navigation monitoring system. This paper introduces the basic concept of satellite navigation interference monitoring and the composition of the system, analyzes the key technologies and finally gives an outlook on the development trends in this field.

At present, in order to reduce the environmental pollution caused by the use of petrochemical products, the preparation of flame-retardant polyurethane foam (PUF) using green raw materials is increasingly attracting widespread attention. A biomass protein-based green flame-retardant rigid PUF (RPUF) with expandable graphite (EG) and silk fibroin (SF) was prepared in a one-step process. Thermal stability, combustion characteristics and compression properties of modified RPUFs were investigated by thermogravimetric analysis, cone test, limiting oxygen index (LOI) test, UL-94 vertical burning test and mechanical compression test. The RPUF with 10 wt% EG (RPUF-SF/EG10) exhibited superior heat resistance, with the highest initial decomposition temperature (Ti), integral programmed decomposition temperatures (IPDT) and activation energy (E). And RPUF-SF/EG10 had the lowest peak heat release rate (PHRR) and total heat release (THR), and it also showed the highest LOI and had a flammability rating of V-0. In Addition, the apparent density and compressive strength of RPUF-SF/EG10 were the largest among the four EG-added materials. The results indicated that RPUF-SF/EG10 had excellent thermal stability, flame retardancy and compression resistance, which was attributed to the synergistic effect of SF and EG in the system. This provided a valuable reference for the development of new, environmentally friendly and high-performance RPUFs.

Light is an important factor for plant growth, and native plant communities are frequently invaded by alien plants to varying degrees. However, little is known about the effect of lighting on the resistance of native plant communities to alien plants with different degrees of invasion. We assessed the interactive effects of light condition and invasion degree on the growth of the invasive plant Solidago canadensis, the characteristics of the native plant communities and the invasion success of S. canadensis through both a field survey and greenhouse experiment. The field survey data showed that shading decreased the biomass of both S. canadensis and the native plant communities. However, it improved the relative dominance and thus, the invasion success of S. canadensis under the low and moderate invasion degrees but not at the high invasion degree. The data of the greenhouse experiment also showed that the native plant communities under shade were more susceptible to invasion by S. canadensis than the unshaded communities, particularly under the low and moderate invasion degree. In summary, we found that shading can weaken the resistance of native plant communities to alien plant invasions when there is a minimal invasion degree. These results underscore that managers need to be more attentive to the invasion of S. canadensis in sheltered environments. These findings provide a scientific reference to manage and control invasion by S. canadensis.

Objective: This study aims to develop a deep learning model using the 3DResUNet architecture to predict vertebral volumetric bone mineral density (vBMD) from Quantitative Computed Tomography (QCT) scans in patients with spinal metastatic tumors, enhancing osteoporosis screening capabilities. Methods: 749 patients with spinal metastatic tumors underwent QCT vertebral vBMD measurements. The dataset was randomly split into training (599 cases) and test sets (150 cases). The 3DResUNet model was trained for vBMD classification and prediction using QCT images processed with automated bone segmentation and ROI extraction. Results: The deep learning model demonstrated strong performance with Spearman correlation coefficients of 0.923 (training set) and 0.918 (test set) between predicted and QCT-measured vBMD values. Bland-Altman analysis showed a slight bias of −1.42 mg/cm3 (training set) and −1.14 mg/cm3 (test set) between the model predictions and QCT measurements. The model achieved an area under the curve (AUC) of 0.977 (training set) and 0.966 (test set) for diagnosing Osteoporosis based on vBMD. Conclusion: The developed deep learning model using 3DResUNet effectively predicts vertebral vBMD from QCT scans in patients with spinal metastatic tumors. It provides accurate and automated vBMD measurements, potentially facilitating widespread osteoporosis screening in clinical practice, mainly where DXA availability is limited.

Mesenchymal stem cells (MSCs) with multipotential differentiation ability are main cell source for cartilage tissue engineering, but its application is restricted by the difficulty in regulating committed chondrogenic differentiation. Study revealed that certain substrate topographic structure can enhance the chondrogenic differentiation of MSCs. This study prepared silk fibroin (SF) films with gradient microscopic surface patterns based on P280-P7000 type specification sandpapers, and investigated the adhesion, proliferation and chondrogenic differentiation of human adipose-derived stem cells (hADSCs) on the SF films. The results showed that the SF films surface had convex dots with diameter of 3–50 μm, and hADSCs could adhere and proliferate well on the film. Transcriptomics analysis indicated that hADSCs tend to differentiate differently on the SF films, among which hADSCs on P1000 SF films had higher expression of chondrogenic markers Sox-9 and Col-II, with activated yes associated protein (YAP) and restricted F-actin. In vitro co-culture of human OA knee cartilage with hADSCs seeded SF films found satisfactory cartilage protection effect in P1000 group. Overall, this study preliminarily revealed the microscopic surface pattern of SF films may induce chondrogenic differentiation of hADSCs through extracellular matrix mediated Hippo/Yap pathway, and provided a new strategy for cartilage repair.

A 66-year-old female patient presenting with dysphagia was diagnosed with stage IV unresectable gastric cancer (cTxN+M1). Multiple liver metastases were identified. The patient subsequently underwent five courses of chemotherapy and immunotherapy, including the capecitabine plus oxaliplatin (XELOX) regimen combined with tislelizumab. After fifth course treatment, it was confirmed that the liver metastases had completely disappeared and the primary tumor had significantly reduced in size. Consequently, a laparoscopy was performed, revealing a retraction-like response in the primary tumor and no obvious metastases in the abdominal cavity. Subsequently, a radical total gastrectomy was carried out through open abdominal surgery. Pathological analysis showed no remaining cancer or lymph node metastases, and the tumor regression was classified as grade 0. The patient has been now receiving additional chemotherapy and immunotherapy to manage any potential residual metastases. This case illustrated the rare and significant impact of combining chemotherapy with tislelizumab, transitioning the treatment approach from palliative to curative. It highlighted the critical role of immunotherapy in managing advanced gastric cancer with liver metastases.

Abstract Background Work-related musculoskeletal disorders (WMSDs) show a rapid growth trend. It has brought a huge economic burden to the society and become a serious occupational health problem that needs to be solved urgently. This study aimed to analyze the local muscle response under continuous ergonomic load, screen sensitive fatigue-related biomarkers and provide data support for the early prevention of local muscle damage and the exploration of early warning indicators. Methods Thirteen male college student volunteers were recruited to perform simulated repetitive manual lifting tasks in the laboratory. The lifting task was designed for 4 periods which lasted for 12 min in each, and then paused for 3 min for sampling. Local muscle fatigue is assesed by the Rating of perceived exertion (RPE) and the Joint analysis of sEMG spectrum and amplitude (JASA). Elbow venous blood was collected and 14 kinds of biomarkers were analyzed, which included Metabolic markers Ammonia (AMM), Lactic acid (LAC), Creatine kinase (CK), Lactate dehydrogenase (LDH), Cartilage oligomeric matrix protein (COMP), C-telopeptide of collagen I and II (CTX-I, CTX-II) and Calcium ion (Ca2+); Oxidative stress marker Glutathione (GSH); Inflammatory markers C-reaction protein (CRP), Prostaglandin E2 (PG-E2), Interleukin-6 (IL-6) and Tumor necrosis factor α (TNF-α); Pain marker Neuropeptide Y (NPY). Repeated measures analysis of variance (Repeated ANOVA), linear regression analysis, t-test and spearman correlation analysis were used to analyze the data. Results Both subjective and objective fatigue appeared at the same period. Serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+ and NPY after fatigue were significantly higher than those before fatigue (p

Abstract Over recent years, as digitalization and intelligence in oil wellbore have increased, so have the stricter requirements for wireless communication technology in terms of distance, accuracy, and portability. As a result, it’s necessary to rely on more advanced and efficient wireless communication technologies to meet the industry’s needs. However, traditional communication technologies such as cables and optical fibers have inherent shortcomings in construction, data interpretation, and cost. ELF electromagnetic waves are an ideal solution for communication in complex wellbore conditions due to long-distance communication and strong penetration capabilities, making it a highly effective option. Based on the theory of network splitting, this paper establishes a polygonal multiple-delays uncertainty coupled complex network model of ELF electromagnetic waves propagating through the casing in layered media and designs a controller, including expressions for the intensity of the magnetic and electric fields in different directions, and the propagation and distribution characteristics in different media. We determined that the optimal transmitting frequency of ELF electromagnetic waves under general conditions is 12.7 Hz. Based on field experiments, we verified that ELF electromagnetic waves can enable wireless wellbore communication within 1500 m without relays. We also analyzed the impact of casing thread deformation on ELF electromagnetic wave propagation due to high-temperature and high-pressure environments. We used simulation experiments to solve the distribution relationship between the electric and magnetic fields of the solenoids through casing and strata, as well as the coupling coefficients between the transmitting and receiving solenoids, and explore how different transmitting frequencies affect the efficiency of signal propagation. Both theories and experiments have verified the correctness of the model, and have also demonstrated the reliability and continuity of using ELF electromagnetic waves to achieve wireless wellbore communication, which provides a theoretical basis and feasibility for subsequent engineering applications.