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Abstract The ClC-3 chloride/proton exchanger is both physiologically and pathologically critical, as it is potentiated by ATP to detect metabolic energy level and point mutations in ClC-3 lead to severe neurodegenerative diseases in human. However, why this exchanger is differentially modulated by ATP, ADP or AMP and how mutations caused gain-of-function remains largely unknow. Here we determine the high-resolution structures of dimeric wildtype ClC-3 in the apo state and in complex with ATP, ADP and AMP, and the disease-causing I607T mutant in the apo and ATP-bounded state by cryo-electron microscopy. In combination with patch-clamp recordings and molecular dynamic simulations, we reveal how the adenine nucleotides binds to ClC-3 and changes in ion occupancy between apo and ATP-bounded state. We further observe I607T mutation induced conformational changes and augments in current. Therefore, our study not only lays the structural basis of adenine nucleotides regulation in ClC-3, but also clearly indicates the target region for drug discovery against ClC-3 mediated neurodegenerative diseases.

Abstract Background This study investigated the effect of carbodiimide (EDC) combined with Clearfil SE self-etch adhesive on the shear bond strength (SBS), crosslinking degree, denaturation temperature, and enzyme activity of dentin in vitro. Materials and methods Collected human sound third molars were randomly divided into different groups with or without EDC treatment (0.01–1 M). The specimens (n = 16)were stored for 24 h (immediate) or 12 months (aging) before testing the SBS. Fine dentin powder was obtained and treated with the same solutions. Then the crosslinking degree, denaturation temperature (Td), and enzyme activity were tested. Statistical analysis was performed using a one-way analysis of variance (ANOVA) to compare the differences of data between groups (α = 0.05). Results There was a significant drop in immediate SBS and more adhesive fracture of 1.0 M EDC group, while there were no significant differences among the other groups. SEM showed a homogeneous interface under all treatments. After 12 months of aging, the SBS significantly decreased. Less decreases of SBS in the 0.3 and 0.5 M groups were found. Due to thermal and enzymatical properties consideration, the 0.3 and 0.5 M treatments also showed higher cross-link degree and Td with lower enzyme activity. Conclusion 0.3 and 0.5 M EDC may be favorable for delaying the aging of self-etch bond strength for 12 months. But it is still needed thoroughly study.

Abstract Objective To explore the risk factors for maternal near-miss (MNM) using the WHO near-miss approach. Methods Data were obtained from the Maternal Near-Miss Surveillance System in Hunan Province, China, 2012–2022. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (aORs) were used to identify risk factors for MNM. Results Our study included 780,359 women with 731,185 live births, a total of 2461 (0.32%) MNMs, 777,846 (99.68%) non-MNMs, and 52 (0.006%) maternal deaths were identified. The MNM ratio was 3.37‰ (95%CI: 3.23–3.50). Coagulation/hematological dysfunction was the most common cause of MNM (75.66%). Results of multivariate logistic regression analysis showed risk factors for MNM: maternal age > = 30 years old (aOR > 1, P = 2 (aOR > 1, P = 3 (aOR = 1.95, 95%CI: 1.50–2.55), prenatal examinations = 2 (aOR = 2.48, 95%CI: 1.99–3.09). Conclusion The MNM ratio was relatively low in Hunan Province. Advanced maternal age, unmarried status, a high number of pregnancies, nulliparity or high parity, a low number of prenatal examinations, and cesarean sections were risk factors for MNM. Our study is essential for improving the quality of maternal health care and preventing MNM.

Background Clinical trials are fundamental to healthcare, however, they also contribute to anthropogenic climate change. Following previous work to develop and test a method and guidance to calculate the carbon footprint of clinical trials, we have now applied the guidance to 10 further UK and international, academically sponsored clinical trials to continue the identification of hotspots and opportunities for lower carbon trial design.Methods 10 collaborating clinical trial units (CTUs) self-identified and a trial was selected from their portfolio to represent a variety of designs, health areas and interventions. Trial activity data was collated by trial teams across 10 modules spanning trial setup through to closure, then multiplied by emission factors provided in the guidance to calculate the carbon footprint. Feedback was collected from trial teams on the process, experience and ease of use of the guidance.Results We footprinted 10 trials: 6 investigational medicinal product trials, 1 nutritional, 1 surgical, 1 health surveillance and one complex intervention trial. Six of these were completed and four ongoing (two in follow-up and two recruiting). The carbon footprint of the 10 trials ranged from 16 to 765 tonnes CO2e. Common hotspots were identified as CTU emissions, trial-specific patient assessments and trial team meetings and travel. Hotspots for specific trial designs were also identified. The time taken to collate activity data and complete carbon calculations ranged from 5 to 60 hours. The draft guidance was updated to include new activities identified from the 10 trials and in response to user feedback.Discussion There are opportunities to reduce the impact of trials across all modules, particularly trial-specific meetings and travel, patient assessments and laboratory practice. A trial’s carbon footprint should be considered at the design stage, but work is required to make this common place.

Background This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods and Results ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low‐dose versus standard‐dose intravenous alteplase and intensive versus guideline‐recommended blood pressure lowering in thrombolysis‐eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90‐day favorable functional recovery (modified Rankin Scale [mRS] score 0–2) and excellent functional recovery (mRS score 0–1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24‐hour NIHSS score had the highest discriminative ability for predicting favorable 90‐day functional recovery (mRS score 0–2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P

Abstract T cell immunity is central to contemporary cancer and autoimmune therapies, encompassing immune checkpoint blockade and adoptive T cell therapies. Their diverse characteristics can be reprogrammed by different immune challenges dependent on antigen stimulation levels, metabolic conditions, and the degree of inflammation. T cell-based therapeutic strategies are gaining widespread adoption in oncology and treating inflammatory conditions. Emerging researches reveal that clustered regularly interspaced palindromic repeats–associated protein 9 (CRISPR–Cas9) genome editing has enabled T cells to be more adaptable to specific microenvironments, opening the door to advanced T cell therapies in preclinical and clinical trials. CRISPR–Cas9 can edit both primary T cells and engineered T cells, including CAR-T and TCR-T, in vivo and in vitro to regulate T cell differentiation and activation states. This review first provides a comprehensive summary of the role of CRISPR–Cas9 in T cells and its applications in preclinical and clinical studies for T cell-based therapies. We also explore the application of CRISPR screen high-throughput technology in editing T cells and anticipate the current limitations of CRISPR–Cas9, including off-target effects and delivery challenges, and envisioned improvements in related technologies for disease screening, diagnosis, and treatment.

Abstract DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It is yet unclear if UHRF1 functions solely by stimulating DNA methylation maintenance by DNMT1, or if it has important additional functions. Using degron alleles, we show that UHRF1 depletion causes a much greater loss of DNA methylation than DNMT1 depletion. This is not caused by passive demethylation as UHRF1-depleted cells proliferate more slowly than DNMT1-depleted cells. Instead, bioinformatics, proteomics and genetics experiments establish that UHRF1, besides activating DNMT1, interacts with DNMT3A and DNMT3B and promotes their activity. In addition, we show that UHRF1 antagonizes active DNA demethylation by TET2. Therefore, UHRF1 has non-canonical roles that contribute importantly to DNA methylation homeostasis; these findings have practical implications for epigenetics in health and disease.

The intestinal tract plays an important role in digestion and absorption, nutrient metabolism, and immune anti-stress. At the same time, the intestine is also the major site for pathogens and various harmful substances to invade. Probiotics, as living microbial agents, improve animal health by maintaining the microecological balance of the host's intestinal flora. To explore the protective effect of Clostridium butyricum (CB) on the gut, we investigated the changes in digestion, antioxidant, and gut microbiota in juvenile largemouth bass. The fish were fed with diets containing 0 (control, CB0), 4.3×108 (CB1), 7.5×108 (CB2), 1.5×109 (CB3), and 3.2×109 (CB4) CFU/kg Clostridium butyricum for 56 days. After 56 days of dietary supplementation with 4.3×108 and 3.2×109 CFU/kg of CB, significant growth promotion and feed utilization improvement were observed in largemouth bass (P < 0.05). The activities of digestive enzymes (trypsin, protease and amylase) and intestinal functional indicators (sodium-potassium ATP, γ-GT and CK) were significantly increased in the intestine of largemouth bass (P < 0.05). The contents of intestinal short-chain fatty acids (acetic acid, propionic acid, isobutyric acid, N-butyric acid and isovaleric acid) in largemouth bass were significantly increased (P < 0.05). CB significantly increased the activities of antioxidant enzymes (T-AOC, CAT, POD, GSH-Px and SOD) and decreased the content of MDA in the intestine of largemouth bass (P < 0.05). It was also observed that CB significantly increased the activities of immune-related markers lysozyme and alkaline phosphatase (P < 0.05). High-throughput sequencing of the 16 S rRNA gene in largemouth bass revealed a significant increase in gut microbial richness. KEGG pathway analysis showed that CB had significant effects on intestinal microbiota functions, such as nutrient metabolism and energy conversion. The results showed that CB could stimulate intestine to produce the organic product butyric acid, which was customized in the gut to enhance digestive performance, promote nutrient metabolism, and protect microbial homeostasis in the intestinal tract of largemouth bass. These results provide new insights into the protective effects of CB on the intestinal tract of aquatic animals.

Liver fibrosis, a common characteristic in various chronic liver diseases, is largely influenced by glycolysis. Quercetin (QE), a natural flavonoid known to regulate glycolysis, was studied for its effects on liver fibrosis and its underlying mechanism. Results showed that QE effectively improved liver injury and fibrosis caused by carbon tetrachloride (CCl4). This was supported by evidence of improved pathological features and reduced levels of serum markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), hyaluronic acid (HA), laminin (LN), and procollagen type III. QE also decreased lactate production and downregulated the expression of glycolysis-related enzymes – pyruvate kinase M2 (PKM2), phosphofructokinase platelet (PFKP), and hexokinase 2 (HK2) – at both the mRNA and protein levels. In liver sinusoidal endothelial cells (LSECs), QE reduced the expression and activity of these enzymes, resulting in reduced glucose consumption, ATP production, and lactate generation. Further analysis revealed that QE inhibited the production of chemokine (C-X-C motif) ligand 1 (CXCL1) and suppressed neutrophil recruitment. Overall, QE showed promising therapeutic potential for liver fibrosis by targeting LSEC glycolysis and reducing neutrophil infiltration.

Background: Although total joint arthroplasty is the most effective procedures for end-stage arthritis, the incidence of postoperative death and complications remains high. The association of additional peripheral nerve blocks (PNBs) to routine spinal or general anesthesia with major adverse events (including mortality and complication rates) in elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) has been subject to inconclusive findings. Methods: This retrospective observational single institution study included all patients ≧ 18 years undergoing their first elective THA or TKA from January 1, 2012 to December 31, 2021. A 1:2 propensity score matching (PSM) was performed to account for the baseline differences between two groups that were accepted to PNB or not. Kaplan–Meier curves were employed to estimate the effects of PNB on mortality. The associations of PNB and the complications were assessed by logistic regression models. Results: We identified 1328 patients, among whom 197 had PNB and 1131 had not. The 90-day all-cause mortality was significantly reduced in patients with PNBs (0 % vs 2.79 %, P = 0.041) after THA or TKA, when compared to the non-PNB group. PNB was also associated with a lower risk of pulmonary complications (odds ratio [OR], 0.430; 95%confidence interval [CI],0.216–0.857) and deep vein thrombosis (OR, 0.103; 95%CI, 0.011–0.954). Interpretation: The results of this observational, propensity score–matched cohort study suggested a strong association between the addition of PNBs to routine spinal or general anesthesia and decreased risks of major adverse events.

Atherosclerosis is a cardiovascular disease that seriously endangers human health. Low shear stress (LSS) is recognized as a vital factor in causing chronic inflammatory and further inducing the occurrence and development of atherosclerosis. Targeting imaging and treatment are of substantial significance for the diagnosis and therapy of atherosclerosis. On this ground, a kind of ultrasound (US) imaging-guided therapeutic polymer nanobubbles (NBs) with dual targeting of magnetism and antibody was rationally designed and constructed for the efficiently treating LSS-mediated atherosclerosis. Under the combined targeting effect of an external magnetic field and antibodies, the drug-loaded therapeutic NBs can be effectively accumulated in the inflammatory area caused by LSS. Upon US irradiation, the NBs can be selectively disrupted, leading to the rapid release of the loaded drugs at the targeted site. Notably, the US irradiation generates a cavitation effect that induces repairable micro gaps in nearby cells, thereby enhancing the uptake of released drugs and further improving the therapeutic effect. The prominent US imaging, efficient anti-inflammatory effect and treatment outcome of LSS-mediated atherosclerosis had been verified in vivo on a surgically constructed LSS-atherosclerosis animal model. This work showcased the potential of the designed NBs with multifunctionality for in vivo imaging, dual-targeting, and drug delivery in the treatment of atherosclerosis.

Inductive power transfer (IPT), as a method of wireless power transfer (WPT) via magnetic induction, can be applied to electric vehicles (EVs) due to its convenience and automation. Interoperability and misalignment tolerance are both major research difficulties for WPT of EVs. This paper proposes a two-channel topology and a coil optimization method, which can improve misalignment tolerance for the unipolar coil (Q) and interoperate with the bipolar coil (DD). Firstly, a topology with phase shift strategy is constructed to increase output ability with Y misalignments and the mathematical model of the proposed topology is established. Secondly, a coil density optimization method is presented to smooth the transmitting mutual inductances fluctuation. Finally, a 1-kW prototype is built to verify the proposed system which can achieve load-independent constant-current charging. With the Y misalignment of 150 mm, the experimental results agree well with the theoretical analysis. The proposed system is able to interoperate with two types of coils and can achieve misalignment tolerance.

Abstract Teacher innovative behavior is one of the vital factors, affecting student engagement, addresses diverse needs, promotes critical thinking, fosters lifelong learning, and contributes to educational research and development. By encouraging and supporting teacher innovation, we may can ensure that education remains relevant, effective, and impactful in preparing students for the future. Teacher innovative behavior is also needed to improve the mathematics skills of elementary school students, and it is important to determine the predictors that significantly affecting Teacher innovative behavior. Therefore, this study aimed to develop a model that predicted possible factors affecting mathematics teachers' innovative behavior based on Social Cognitive Theory (SCT). Data were collected from 132 elementary school teachers in China to verify the model, and the analysis was conducted using a structural equation modelling approach. Theoretically, 10 of the 15 hypotheses were found to be significant. The results showed that facilitating conditions and self-efficacy significantly affect mathematics teachers' innovative behavior. Meanwhile, Technological, Pedagogical and Content Knowledge (TPACK) knowledge, Social Influences, Rewards, Work engagement and anxiety did not show any effect. The contribution developed a model and provided new knowledge about the factors affecting elementary school teachers' innovative behavior. Practically, this could be used to improve teachers' innovative behavior.

Castration is a prevalent and indispensable practice in sheep husbandry, aiding in enhancing meat quality, mitigating aggressive behavior, and managing unwanted reproduction. Nevertheless, the conventional surgical castration procedure poses several challenges, including heightened stress and pain, detrimental impacts on animal welfare, and diminished economic efficacy in farming operations. Consequently, immunocastration methods, serving as substitutes for surgical castration, are progressively finding application in livestock. The rumen, an essential and distinctive digestive and absorptive organ in ruminants, has been associated with enhanced meat quality and productive performance following castration in previous research studies, albeit fewer investigations have explored the potential impacts of GnRH immunization on the rumen’s internal milieu in sheep post-de-escalation. Hence, the present study delved into evaluating the impact of GnRH immunocastration on the rumen microbiome and metabolomics in male Xizang sheep. This was achieved through the establishment of a GnRH immunocastration animal model and the collection of rumen fluid for microbiological and comprehensive metabolomics investigations. The outcomes of this investigation unveiled that the impact of GnRH immunocastration on body weight gain was more pronounced during the achievement of the castration objective. In addition, the Firmicutes-to-Bacteroidota ratio in the immune male (IM) group exceeded that of the control group (EM), suggesting that GnRH immunodeficiency may enhance the digestion and absorption of feed in male Xizang sheep. At the taxonomic level, the elevated presence of Prevotella and Quinella bacteria in the IM group compared to the EM group indicated that castration influenced a segment of the rumen microbiota in male Xizang sheep, thereby bolstering the digestive and metabolic efficacy of the rumen concerning nutrient utilization, particularly in the breakdown and absorption of proteins, carbohydrates, and lipids, ultimately expediting the fattening process and weight gain in male Xizang sheep following castration. Moreover, analysis of ruminal fluid metabolomics revealed that GnRH immunization had notable impacts on certain metabolites in the ruminal fluid of male Xizang sheep, with metabolites like 5-hydroxyindole acetic acid and 3-hydroxyindole acetic acid showing significant downregulation in the IM group compared to the EM group, while niacin and tyramine exhibited significant upregulation. These findings indicate a profound influence of GnRH immunization on the maintenance of ruminal equilibrium and ruminal health (including the health of ruminal epithelial cells). This study validates that GnRH immunocastration not only achieves the objectives of castration but also enhances ruminal health in male Xizang sheep, thus laying a foundational theoretical basis for the application and dissemination of GnRH immunocastration technology.

Human skeletal muscle contains different types of tissues with skeletal muscle fibers (SMFs) and intermuscular adipose tissues (IMATs) as the main components. We maintained human skeletal muscle tissues from 12 study participants under native conditions in vitro for 11 days to investigate the dynamics of macrophages that reside in adjacent IMATs and SMFs simultaneously. The samples were subjected to immunohistochemical analysis for macrophage phenotyping and mitochondrial mass assessment before and after maintenance in vitro. Multiplex protein analysis was used to determine cytokine/chemokine expression in tissue extracts. The results revealed significant correlations between donor age or body mass index (BMI) and distinct phenotypes of resident macrophages in SMFs and IMATs. The dynamics of SMF- and IMAT-resident macrophages differed significantly in vitro and exhibited inverse correlations with chemokine/cytokine expression levels and mitochondrial activity. Moreover, the responses of macrophages to saturated and unsaturated fatty acids (FAs) differed substantially between SMFs and IMATs. These findings showed the functional diversity of phenotypically identical macrophages in adjacent niches. Thus, the currently available macrophage markers cannot capture the functional diversity of human tissue-resident macrophages. The model used in the present study may help elucidate how macrophages affect muscle homeostasis and disease in humans.

Objectives: The substitution of chemical fertilizers with organic alternatives presents a viable strategy for enhancing soil quality and boosting agricultural productivity. However, the question remains whether organic–inorganic compound fertilizers (COIFs) can sustain improved soil quality and crop yields while reducing chemical fertilizer use. The underlying mechanisms of COIF’s impact still warrant further exploration. Methods: In this study, a long-term fertilization trial was conducted from 2020 to 2023 at two sites with different soil textures and types in the Huang-Huai-Hai Plain, China. The experiment involved three fertilization treatments, each replicated three times: (1) LCF (conventional fertilizer treatment); (2) COIF1 (COIF applied at 90% of the recommended rate); and (3) COIF2 (COIF applied at 80% of the recommended rate). The objective was to assess the effects of COIF on summer maize growth, grain yield, nutrient uptake and utilization, and soil quality. Results: Compared to LCF, COIF1 in Yantai and Dezhou increased biomass by 6.4% and 8.1%, grain yield by 5.9% and 4.12%, PFP (N, P, and K) by 17.6% and 15.7%, and soil quality by 563.6% and 462.5%, respectively. No significant differences in biomass and grain yield were observed between COIF2 and LCF, yet COIF1 in Yantai and Dezhou enhanced PFP (N, P, and K) by 19.7% and 18.6%, and soil quality by 109.1% and 175.0%, respectively. In conclusion, COIF improved soil quality by enhancing soil organic matter (SOM), available nutrients, pH, and other soil indices. It promoted summer maize growth, increased grain yield, and improved nutrient utilization. COIF was a practical and effective measure to reduce chemical fertilizer use, enhance field soil quality, and ultimately increase maize yield and nutrient utilization.

There have been many research reports on the reinforcement of small-sized square columns with a cross-section of 200mm–300mm using prestressed carbon fiber-reinforced polymer (CFRP) materials, while there are few studies on piers in bridge and tower columns in cable-stayed bridges with a cross-section of several meters or even tens of meters. The horizontal prestressed steel tendons in the anchorage zone of tower columns in cable-stayed bridge replaced by prestressed CFRP sheets can not only facilitate construction and maintenance, but also have good fatigue resistance. The prestressed CFRP plate is used to reinforce the large-sized tower columns by using a specific device to tension the CFRP plate wrapped around the surface of the members. The tensioning device and test pedestal based on WSGG (wave-shaped-gear-grip) anchor clamping of CFRP plate have been developed in this paper, and the CFRP plate circumferential tensioning tests on the pedestal have been conducted. The test results are as follows: (1) the developed device can achieve circumferential tensioning of single-layer CFRP plate to 0.5ftk of the material, reaching a tensile force of 60kN, and generate effective restraint pressure on a 2-m long composite compression component; (2)The calculation formula for the constraint pressure generated by the circumferential prestressed CFRP sheet on the component has been derived and verified, and the maximum error between the calculated value and the experimental value is within 5%; (3) When iron sheet serves as the interface medium between CFRP plate and compression components, the prestress loss of the CFRP plate tensioned at one end is about 84% and 58%–60% when tensioned at both ends. It can be seen that the effective prestress of the CFRP plate with iron sheet as the interface medium is relatively small. Meanwhile, based on the distribution of compressive stress in the components and the effective pre tension value of CFRP plate, it can be seen that two end tensioning is better than one end tensioning; (4) The tensile stress of CFRP plate along the member is a cubic function when the tension force is 60kN, so it is deduced that the constrained compressive stress generated by CFRP plate on the member is a quadratic function distribution.

The medicinal plant Spatholobus suberectus Dunn is easily exposed to shade stress during growth, but its shade responses and shade stress resistant mechanisms have not been clarified. In this study, shade treatments including four attenuated sunlight intensities (100%, 60%, 40%, and 10%) and three shade durations (30 d, 45 d, and 60 d) were applied to S. suberectus. The shade-induced morphological indicators, phytohormonal regulations, metabolic flavonoids contents, transcriptomic flavonoid pathway gene expressions, and stress physiological changes of S. suberectus were analyzed. The putative promoter cis-regulatory elements (CREs) of 18 flavonoid biosynthetic pathway genes were identified. Results showed the stem growth indicators of S. suberectus were better at 40% light intensity. Phytohormones were involved in the shade-induced responses. Short-term shade (30 d) increased total flavonoids, gallated catechins and especially epigallocatechin gallate contents and favored for boosting medicinal value. Long-term shade (45 d, 60 d) tended to decrease flavonoids. The shade-induced flavonoids changes were attributed to their corresponding biosynthesizing genes expression variations. The high antioxidant capacity and the presence of phytohormone-, stress-, and development-related CREs provided the basis for stress resistance. In conclusion, the multiple responses under shade and the CREs analysis elucidated S. suberectus’ shade tolerance.

The close connection between community residents and tourists in heritage tourism sites strengthens the relationship between people and places. To explore the mechanisms of host–guest interaction and the driving factors of residents’ willingness to participate in tourism in heritage tourism destinations, this study adopts a mixed-method approach combining qualitative research and quantitative analysis. The results of the study show that host–guest symbiosis in heritage tourism destinations goes through four stages: identity qualification, bodily co-presence, common focus, and emotional solidarity. Quantitative research (SEM) reveals the impact of residents’ welcoming nature, emotional closeness, and sympathetic understanding towards tourists on the sense of community belonging, as well as the subsequent response of willingness to participate in tourism. Through the analysis of the host–guest interaction mechanisms and symbiotic relationships in heritage tourism sites, the key emotional factors influencing residents’ participation in tourism are revealed.

This study aims to examine the effects of the mixture of Bacillus cereus G1–11 and Exiguobacterium acetylicum G1–33, isolated from the gut of hybrid groupers (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂), on the host. The hybrid groupers were divided into a control (C, without any probiotics), B. cereus (BC, 1010 cfu/g), E. acetylicum (EA, 108 cfu/g), compound (mix, a 1:1 mixture of B. cereus and E. acetylicum), and positive reference group (P, Lactobacillus acidophilus, 5 × 108 cfu/L). Each group had four replicates, with 30 fish per replicate (53.30 ± 0.50 g), and were fed for 60 days. The results showed that adding probiotics to the feed significantly improved the weight gain, weight growth rate, specific growth rate, and digestive enzyme activities of hybrid groupers compared to the C group. The compound group was the most significant. In addition, composite probiotics added to feed significantly upregulated the expression levels of several growth-related genes in the liver and muscles. The activities of alkaline phosphatase, catalase, glutathione peroxidase, glutathione transferase, lysozyme, and total antioxidant capacity in the serum and liver were significantly influenced through mixed probiotic feeding. Moreover, the expression levels of several immune-related genes in the liver, spleen, and head kidney were significantly enhanced by adding single and mixed probiotics to feed, with the synergy of mixed probiotics being the best. An analysis of the gut microbiota showed that adding composite bacteria enhanced the richness and diversity of the gut microbiota, significantly increasing the relative abundance of potential probiotics (Cetobacterium and Microbacterium) while decreasing the presence of potential pathogens (Mycoplasma). Overall, our findings highlighted the efficacy of mixed probiotics (B. cereus and E. acetylicum) in enhancing growth performance, nutritional value of hybrid grouper feed, antioxidant capacity, immune response, and intestinal health, in finding the best combination of functional feed additives.

In magnetically coupled wireless charging systems for electric vehicles, it is common for metal objects to enter the charging system. In this case, the strong magnetic field of wireless charging causes an eddy current effect in the metal object, which generates a large amount of heat. This heat accumulation poses a risk of fire. In this paper, a novel metal object detection system designed for wireless charging of electric vehicles is proposed. The system utilizes the principle that the coil impedance and coupling coefficient change with the presence of metal objects, and a set of composite coils is designed to improve the sensitivity of detection. The detection coil and feedback coil in the composite coil are decoupled by reverse series connection. An LC oscillating circuit based on transformer feedback is used to detect metal objects, and the circuit can make good use of the parameter changes of the composite coil. Finally, an experimental platform for wireless charging metal detection in electric vehicles has been built to validate the proposed system. Through testing, it has been demonstrated that the system can detect the presence of metal objects in a timely and accurate manner.

Background The urgency of the climate crisis requires attention from biomedical research, not least clinical trials which can involve significant greenhouse gas emissions. The Low Carbon Clinical Trials Working Group set out a strategy to reduce the emissions of clinical trials, starting with the development of a method to measure their carbon footprint (CO2e).Methods As a first step, we developed a process map defining clinical trial core activities. Corresponding emission factors were sourced to convert activity data into greenhouse gas emissions. The subsequent method was applied to two Cancer Research UK (CRUK)-funded trials (the international randomised sarcoma trial CASPS (ISRCTN63733470) and the UK cohort-based breast cancer trial PRIMETIME (ISRCTN41579286)). A guidance document defining the scope, method and assumptions was written to allow application to any publicly funded/investigator initiated clinical trial.Results Trial specific activities over and above routine care were grouped into 10 modules covering trial set up, conduct and closure. We identified emission factors for all trial activities within both trials and used them to estimate their total carbon footprint. The carbon footprint of CASPS, an international phase 2 trial of an investigational medicinal product with 47 participants, was 72 tonnes CO2e, largely attributable to clinical trials unit emissions and staff travel. PRIMETIME, a UK-based phase 3 non-investigational medicinal product trial with 1962 patients, produced 89 tonnes CO2e, largely attributable to trial-specific in-person participant assessments.Conclusion We have developed a method and guidance that trialists can use to determine the carbon footprint of clinical trials. The guidance can be used to identify carbon hotspots where alternative approaches to trial design and conduct could reduce a trial footprint, and where methodology research is required to investigate the potential impact of interventions taken to reduce carbon emissions. We will continue to refine the guidance to increase the potential application and improve usability.

In order to compare the influence of different soil types and stratification on water infiltration capacity, two main types of soil in the desert steppe, sierozem (S) and aeolian sandy soil (A), were selected, and infiltration simulation tests were conducted on homogeneous soil and layered soil (layer thickness 5, 10, and 20 cm), respectively. The results show that during the whole experiment, there was a small difference between S5A95 (aeolian sandy soil 95 cm thick was covered with sierozem 5 cm thick) and S10A90 (aeolian sandy soil 90 cm thick was covered with sierozem 10 cm thick) in the wetting front process, infiltration rate and cumulative infiltration, but there was a significant difference between S5A95 and S20A80 (aeolian sandy soil 80 cm thick was covered with sierozem 20 cm thick). In the initial infiltration stage, there was no significant difference between A5S95 (sierozem 95 cm thick was covered with aeolian sandy soil 5 cm thick) and A10S90 (sierozem 90 cm thick was covered with aeolian sandy soil 10 cm thick). However, with the increase of infiltration time, the wetting front process, A5S95, A10S90 and A20S80 had significant differences in terms of wetting front process, infiltration rate and cumulative infiltration. The infiltration capacity of A was significantly higher than that of S. Combined with linear Ä2 value and model parameters, the three infiltration models were comprehensively compared, and the fitting process and results of the general empirical model for the infiltration process of homogeneous soil and layered soil showed good results. Three models were used to simulate the water infiltration process of layered soil with different textures, and the order of the effect is as follows; general empirical model > Kostiakov model > Philip model. Soil type and layer thickness had a great influence on water infiltration process. When sierozem was covered with aeolian sandy soil 20 cm thick, the infiltration capacity was the best. As aeolian sandy soil was covered with sierozem 10 cm thick, the infiltration effect was the worst. Therefore, once coarse graying occurs on the surface of sierozem (the thickness of sand is more than 20 cm) or when the content of fine particles overlying aeolian sandy soil (the thickness of silt and clay soil is more than 10 cm) during ecological restoration is high, the soil hydrological characteristics will change significantly, which may lead to changes in vegetation types and even ecosystem structure. [ABSTRACT FROM AUTHOR]

Introduction: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. This study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. Methods: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20–30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day × 28 d, oral) or matching placebo. A sample size of 1,504 patients is estimated to provide 90% power (α 0.05) to detect a ≥20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-5L scale at different time points over 6 months of follow-up. The key safety measure is serious adverse events. Conclusion: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH. [ABSTRACT FROM AUTHOR]

Background: Dupilumab has been shown to be effective in clinical trials for moderate-to-severe uncontrolled asthma. However, the efficacy of dupilumab in the real world and the prediction of treatment response have not been well studied in patients with asthma. Objective: To investigate the efficacy of dupilumab and explore predictors of super-responders in a Chinese retrospective cohort. Methods: From January 2021 through December 2022, the patients with uncontrolled asthma who were treated with dupilumab for 4 months were included. Symptom control, type 2 inflammatory biomarkers, and lung function were collected at baseline and follow-up for efficacy assessment. Super-responders were defined as exacerbation-free, off maintenance of oral corticosteroids (mOCS), and with a score of the five-item Asthma Control Questionnaire (ACQ-5) of <0.5. The uni- and multi-variable logistic regressions were used to construct predictive models for super-responders based on baseline features. Results: A total of 53 patients were included. After 4 months treatment, the median (interquartile range [IQR]) ACQ-5 score decreased from 1.8 (1.6-2.4) to 0.4 (0.2-0.8) (p < 0.001), the median (IQR) number of exacerbations, from 0.0 (0.0-1.0) to 0.0 (0.0-0.0) (p = 0.005). The median (IQR) dose of mOCS (prednisone equivalent) decreased from 15.0 mg/day (8.8-22.5 mg/day) to 2.5 mg/day (0.0-10.0 mg/day) (p = 0.008) in nine patients who were receiving mOCS. All efficacy assessment parameters, including sputum eosinophil were significantly improved, while blood eosinophil count did not decline (530 cells/mm³ [300-815 cells/mm³] versus 560 cells/mm³ [220-938 cells/mm³], p = 0.710). After taking dupilumab, 25 of 53 patients (47.2%) achieved a super-response. The age of onset < 42 years (odds ratio [OR] 7.471 [95% confidence interval {CI}, 1.286-43.394) and the baseline fractional exhaled nitric oxide (FeNO) of 25-50 ppb (OR 35.038 [95% CI, 3.104-395.553]) predicted super-responders, which showed a C-index of 0.822 (95% CI, 0.697-0.947). Conclusion: Dupilumab significantly improved symptom control, type 2 inflammatory markers, and lung function in Chinese patients with uncontrolled asthma. Airway eosinophils, rather than blood eosinophils, can be a reliable indicator of therapeutic efficacy. The early-onset asthma as well as the medium-high level of baseline FeNO contributed to the prediction of super-responders. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect of lacidophilin on inflammation and intestinal microflora in H. pylori-induced gastritis mice. Methods: Established an H. pylori-infected mice model by orally administering an H. pylori suspension. The mice were randomly divided into a model group and a lacidophilin treatment group, which received treatment for four weeks. Gram staining, Warthin-Starry silver staining, and H. pylori immunohistochemical staining were conducted to confirm the colonization of H. pylori in the gastric mucosa of mice. Hematoxylin and eosin (HE) staining was performed to observe any histopathological changes in the gastric mucosa of mice. Immunohistochemistry was carried out to observe the expression of iNOS, IL-1β, and 3-Nitrotyrosine in the gastric mucosa of mice. Additionally, the structure of intestinal microflora was analyzed using 16S rRNA sequencing. Results: The successful establishment of H. pylori-infected mice. Lacidophilin improved the stomach histopathological morphology in mice with H. pylori-induced gastritis and inhibited iNOS, IL-1β, and 3-Nitrotyrosine expression in the gastric mucosa. The composition and structure of the gut microbiota among the lacidophilin group showed noticeable differences in comparison to the H. pylori-infected group. Lacidophilin augmented the diversity of intestinal microflora in H. pylori-infected mice by regulating the abundance of Firmicutes, Actinobacteriota, Bacteroidete, and Verrucomicrobiota. At the genus level, Lacidophilin resulted in significant growth stimulation of beneficial bacteria such as g_norank_f_Muribaculaceae, Akkermansia, and Alistipes, while suppressing the proliferation of inflammation-related bacteria such as Dubosiella, thereby improving the composition and structure of the gut microbiota. Conclusion: Lacidophilin has the potential to rebalance the composition and structure of gut microbiota that has been compromised by H. pylori infection. It may have a protective effect on mice with H. pylori-induced gastritis by promoting the growth of beneficial bacteria, reducing inflammatory reactions, and alleviating oxidative damage to the gastric mucosa.

Abstract Constipation is a major health problem worldwide that requires effective and safe treatment options. Increasing evidence indicates that disturbances in gut microbiota may be a risk factor for constipation. Administration of lacidophilin tablets shows promising therapeutic potential in the treatment of inflammatory bowel disease owing to their immunomodulatory properties and regulation of the gut microbiota. The focus of this study was on investigating the ability of lacidophilin tablets to relieve constipation by modulating the gut microbiome. Rats with loperamide hydrochloride induced constipation were treated with lacidophilin tablets via intragastric administration for ten days. The laxative effect of lacidophilin tablets was then evaluated by investigating the regulation of intestinal microflora and the possible underlying molecular mechanism. Our results reveal that treatment with lacidophilin tablets increased the intestinal advancement rate, fecal moisture content, and colonic AQP3 protein expression. It also improved colonic microflora structure in the colonic contents of model rats mainly by increasing Akkermansia muciniphila and decreasing Clostridium_sensu_stricto_1. Transcriptome analysis indicated that treatment with lacidophilin tablets maintains the immune response in the intestine and promotes recovery of the intestinal mechanical barrier in the constipation model. Our study shows that lacidophilin tablets improve constipation, possibly by promoting Akkermansia colonization and by modulating the intestinal immune response.

Ion chromatography was used to investigate the effects of γ-ray irradiation dose, vitamin C (VC) content and niacinamide content on nitrite degradation in aqueous solution and spiced donkey meat, and the volatile components of irradiated spiced donkey meat were analyzed by gas chromatography-ion mobility spectrometry. The results showed that γ-ray irradiation could effectively degrade nitrite in both aqueous solution and spiced donkey meat. A synergistic effect was observed when γ-ray irradiation and VC were used together. Nicotinamide had an inhibitory effect on the irradiation degradation of nitrite in aqueous solution, but had a synergistic effect on the irradiation degradation of nitrite in spiced donkey meat. Nitrite ions in aqueous solution were converted to nitrate ions by the irradiation. After 8 or 10 kGy irradiation, the contents of hexanal and heptanal increased, and donkey meat had an off-flavor. This study provides technical support and a theoretical basis for the degradation of nitrite in spiced donkey meat by γ-ray irradiation.

The aim of this study is designed an improved ResNet 50 network to achieve automatic classification model for pain expressions by elderly patients with hip fractures. This study built a dataset by combining the advantages of deep learning in image recognition, using a hybrid of the Multi-Task Cascaded Convolutional Neural Networks (MTCNN). Based on ResNet50 network framework utilized transfer learning to implement model function. This study performed the hyperparameters by Bayesian optimization in the learning process. This study calculated intraclass correlation between visual analog scale scores provided by clinicians independently and those provided by pain expression evaluation assistant(PEEA). The automatic pain expression recognition model in elderly patients with hip fractures, which constructed using the algorithm. The accuracy achieved 99.6% on the training set, 98.7% on the validation set, and 98.2% on the test set. The substantial kappa coefficient of 0.683 confirmed the efficacy of PEEA in clinic. This study demonstrates that the improved ResNet50 network can be used to construct an automatic pain expression recognition model for elderly patients with hip fractures, which has higher accuracy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shuang, Liangbo, Huiwen, Jing, Xiaoying, Siyi, Xiaoya and Wen.)