Search

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.

Abstract Background and aims Uncertainty persists over the effects of blood pressure (BP) lowering in acute stroke. The INTEnsive ambulance-delivered blood pressure Reduction in hyper-Acute stroke Trial (INTERACT4) aims to determine efficacy and safety of hyperacute intensive BP lowering in patients with suspected acute stroke. Given concerns over the safety of this treatment in the pre-hospital setting, particularly in relation to patients with intracerebral hemorrhage, we provide an update on progress of the study and profile of participants to date. Methods INTERACT4 is an ongoing multicentre, ambulance-delivered, randomized, open-label, blinded endpoint trial of pre-hospital BP lowering in patients with suspected acute stroke and elevated BP in China. Patients are randomized via a mobile phone digital system to intensive (target systolic BP [SBP]

AbstractContext Current chemotherapeutic drugs cannot meet the treatment needs of patients with nasopharyngeal carcinoma (NPC), so urgent action is needed to discover novel chemotherapeutic agents. Our previous study revealed that garcinone E (GE) inhibited the proliferation and metastasis of NPC, suggesting that the compound might display promising anticancer activity.Objective To examine the mechanism underlying the anti-NPC activity of GE for the first time.Materials and methods For MTS assay, NPC cells were treated with 2.5-20 μmol/L GE or dimethyl sulfoxide for 24, 48, and 72 h. Colony formation capacity, cell cycle distribution, and in vivo xenograft experiment of GE were assessed. MDC staining, StubRFP-sensGFP-LC3 observation, LysoBrite Blue staining, and immunofluorescence examined the autophagy of NPC cells after GE exposure. Western blotting, RNA-sequencing, and RT-qPCR measured protein and mRNA levels.Results GE suppressed cell viability with an IC50 of 7.64, 8.83 and 4.65 μmol/L for HK1, HONE1 and S18 cells. GE inhibited colony formation and cell cycle, increased autophagosome number, and inhibited the autophagic flux partially by blocking lysosome-autophagosome fusion, and repressed S18 xenograft growth. GE dysregulated the expression of autophagy- and cell cycle-related proteins such as Beclin-1, SQSTM1/p62, LC3, CDKs, and Cyclins. Bioinformatics GO and KEGG pathway enrichment analysis of RNA-seq showed that autophagy was enriched in differentially expressed genes upon GE treatment.Discussion and conclusion GE acts as an autophagic flux inhibitor, which may have potential chemotherapeutic use for NPC treatment and may have an application in basic research to explore the mechanisms of autophagy.

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.

Objective αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). Methods αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Results Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3′-untranslated region (3′UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. Conclusion miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.

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.

Jamming recognition is a prerequisite for radar antijamming and actual radar deception jamming recognition; however, there is a problem of insufficient samples. To address this issue, we propose a multimodal radar active deception jamming recognition method based on small samples in this paper. This method is based on two modal information—feature parameters and time-frequency images extracted from radar signals—and utilizes prototype networks to train multimodal features. Furthermore, the model adopts the image denoising method and weighted Euclidean distance to improve the recognition performance at low signal-to-noise ratios. Thus, radar deception jamming recognition can be achieved under small sample conditions. Simulation results reveal that the proposed method achieves an average recognition accuracy of over 97% across 10 types of radar deception jamming when the jamming-to-signal ratio is 3 dB. Moreover, the test results from the simulator data verify the good generalization performance of the proposed method.

A 12-wk trial was conducted to compare the tolerance of tilapia to high carbohydrate and high lipid diets. Three isonitrogenous and isoenergetic diets, whose carbohydrate and lipid levels were the following: 35.0% and 8% (control), 44.2% and 4% (D1, high carbohydrate), and 25.8% and 12% (D2, high lipid), respectively. Three hundred tilapias (27 ± 0.11 g) were fed the diets for 10 wk (4 replicates per group); 72 fish from the D1 group were continually fed the D1 (D1D1) and 72 fish from the D2 were continually fed the D2 (D2D2) diet for 2 wk (3 replicates each group) to evaluate the tilapia's capacity to tolerate high carbohydrate and high lipid diets, respectively. Another 36 fish from D1 group were continually fed D2 (D1D2) for comparison with D1D1 and D2D2 groups. In phase 1, hepatosomatic index, liver triglycerides (TG), glucose tolerance (GT) and crude protein in the whole body in D1 group were higher than those in D2 group (P

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.

Abstract Background Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disease that is mainly caused by PHOX2B mutations. The purpose of this study is to analyze and summarize the clinical and genetic characteristics of CCHS patients in the Chinese population from our study and previous literature. Methods The potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype–phenotype correlations. Results We identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non‐polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p

Euphorbia factor L1 (EFL1) is a kind of lathyrane-type diterpenoid and is isolated from the medical herb Euphorbia lathyris L. (Euphorbiaceae); it has been reported with the toxicity that causes intestinal irritation, but the underlying mechanisms are still obscure. The objective of this study was to assess the EFL1-induced intestinal cytotoxicity in human colon adenocarcinoma Caco-2 cells. The Caco-2 cells were treated with EFL1, and the intracellular calcium ion concentration, mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP), adenosine 5′-triphosphate (ATP) content, ATPase activities, TGF-β1 concentration, and transepithelial electrical resistance (TEER) were detected. The interaction between EFL1 and the tight junction proteins Occludin, Claudin-4, Tricellulin, ZO-1, JAM-1, and E-cadherin was simulated by molecular docking. The expression of proteins involved in the energy metabolism, the ion transporters and aquaporins, the tight junction, and the F-actin cytoskeleton were detected by Western blotting and cell immunofluorescence. As a result, EFL1 decreased the intracellular Ca2+, MMP, mPTP, ATP content, and ATPase activities in the Caco-2 cells. The AMPK/SIRT1/PGC-1α signaling pathway, which regulates the energy metabolism, was inhibited. The ion transporters NEH and CFTR, as well as the aquaporins in the Caco-2 cells, were decreased. The tight junction proteins were down-regulated, and the integrity of the intestinal barrier was injured; TGF-β1 was compensatively increased; so, the intestinal permeability was increased and was characterized by decreased TEER. The morphology of the F-actin cytoskeleton was destroyed. These findings indicated that EFL1 caused cytotoxicity in the human intestinal Caco-2 cells through mitochondrial damage, inhibition of the energy metabolism, and suppression of the ion and water molecule transporters, as well as the down-regulation tight junction and cytoskeleton protiens.

Abstract Background Patients with hemorrhagic shock may develop emerging enterogenic sepsis due to damage to the intestinal mucosal barrier and translocation of intestinal bacteria and endotoxins caused by ischemic injury. Because of the dual effects of anesthesia state and hemorrhagic shock, perioperative emerging enterogenic sepsis is even more rare and insidious. Case presentation We reported a case of 56-year-old man who underwent right hepatectomy for intrahepatic bile duct stones. Severe hemorrhage occurred during the procedure and the hemodynamics neither improved nor worsened after rehydration therapy and vasoactive drug administration. Based on the patient’s history and clinical presentation, a possible enterogenic sepsis was considered. After anti-infective treatment and hormone supplementation, the patient’s circulation improved significantly and he had an uneventful recovery. Conclusion The possibility of emerging enterogenic sepsis in hemorrhagic shock must always be taken into consideration. Familiarity with the risk factors and pathophysiological alterations of enterogenic sepsis is a prerequisite for early recognition and sound clinical decision making.

Abstract Objective The majority of individuals with femoral neck fractures opt for total hip replacement to enhance their quality of life. However, this group frequently exhibits perioperative symptoms of pain, anxiety, and sadness, which extends recovery time to some extent. Esketamine, the right-handed monomer of ketamine, is more popular these days due to its sedative, analgesic, and antidepressant properties. There are currently few domestic and international research on the use of esketamine in elderly individuals who have undergone surgery for a femoral neck fracture. In order to further cut the length of the hospital stay and hasten postoperative recovery, this study investigates whether esketamine postoperative analgesia can lessen postoperative pain, anxiety, and depression in older patients having hip replacement. Methods 150 patients, ASA physical status I–II, aged ≥ 60 years, no limitation in gender, BMI 18–25 kg/cm2, who underwent selective total hip arthroplasty, according to random number table method, esketamine group (group A) and sufentanil group (group B) were randomized, 75 patients in each group. The two groups received general anesthesia method. At the end of the operation, PCIA was connected for analgesia. In group A, esketamine 2.5 mg/kg was mixed with normal saline to 100 ml. In group B, sufentanil 2.5 ug/kg was mixed with normal saline to 100 ml. Record the VAS scores after operation. Record the first ambulation time, ambulation distance and Patient-controlled Analgesia compression times after operation. The incidence of postoperative adverse reactions such as drowsiness, dizziness, nausea and vomiting, multilingual were recorded. ELISA was used to detect IL-6 and CRP in the morning, 24 h and 72 h after operation. The Hospital Anxiety and Depression Scale (HAD) score and Harris score at 3 days, 1 week and 1 month after operation were followed up. Results There was no significant difference in VAS score and PCA compression times (P > 0.05), but the incidence of nausea, vomiting and dizziness in group B was higher than that in group A (P 0.05). The Harris score of group A was higher than that of group B at 3 days, 1 week and 1 month after operation (P

Abstract Hematogenous metastasis is the main approach for colorectal cancer liver metastasis (CRCLM). However, as the gatekeepers in the tumor vessels, the role of TPCs in hematogenous metastasis remains largely unknown, which may be attributed to the lack of specific biomarkers for TPC isolation. Here, microdissection combined with a pericyte medium‐based approach is developed to obtain TPCs from CRC patients. Proteomic analysis reveals that TRP channel‐associated factor 2 (TCAF2), a partner protein of the transient receptor potential cation channel subfamily M member 8 (TRPM8), is overexpressed in TPCs from patients with CRCLM. TCAF2 in TPCs is correlated with liver metastasis, short overall survival, and disease‐free survival in CRC patients. Gain‐ and loss‐of‐function experiments validate that TCAF2 in TPCs promotes tumor cell motility, epithelial‐mesenchymal transition (EMT), and CRCLM, which is attenuated in pericyte‐conditional Tcaf2‐knockout mice. Mechanistically, TCAF2 inhibits the expression and activity of TRPM8, leading to Wnt5a secretion in TPCs, which facilitates EMT via the activation of the STAT3 signaling pathway in tumor cells. Menthol, a TRPM8 agonist, significantly suppresses Wnt5a secretion in TPCs and CRCLM. This study reveals the previously unidentified pro‐metastatic effects of TPCs from the perspective of cold‐sensory receptors, providing a promising diagnostic biomarker and therapeutic target for CRCLM.

Aim or Purpose: This study aimed to establish a homogeneous organic-inorganic composite scaffold (nHA@SIS) based on the ''polymer-induced liquid precursor'' (PILP) theory and explore its potential in bone tissue engineering. Materials and Methods: A fresh decellularized small intestine was subjected to a series of defatting and decellularization processes, followed by preparation of freeze-dried powder. The powder was then dissolved in acetic acid and pepsin, molded, and then subjected to a second round of freeze-drying to obtain the organic component (SIS) of the nHA@SIS scaffold. Physicochemical characterization and cell biology evaluation of the nHA@SIS composite scaffold were performed. Results: The results showed that nHA@SIS had good pore size, porosity, hydrophilic properties, appropriate degradation rate, and good protein adsorption ability. Successful deposition of calcium phosphate significantly improved the mechanical strength and thermodynamic resistance of the nHA@SIS composite scaffold. Compared with pure SIS scaffolds, nHA@SIS maintained excellent cell activity of the SIS and better guided the reorganization of the cell skeleton, achieving superior osteoconductivity and maintaining osteoinductivity at the protein and gene levels. Conclusions: In conclusion, nHA@SIS significantly improved bone regeneration in vitro, indicating the enormous potential of nHA@SIS in bone tissue engineering applications.

Abstract Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, raise the mortality rate with an incidence of up to 71%. Pathological neuroinflammation after sepsis leads to acute brain dysfunction, survivors may remain long-term cognitive impairment. At present, the evaluation of SAE severity and prognosis mainly depends on clinical manifestations and imaging features, but lack of effectiveness and timeliness. Biomarkers of nerve injuries nowadays, have shown good application value and perspectives in the diagnosis and evaluation of SAE. This article will review the current biomarkers for accurate diagnosis and evaluation, basing on the possible pathophysiological mechanism of different stages of SAE.

Abstract Background Fowl adenovirus is of major concern to the poultry industry worldwidely. In order to monitor the prevalent status of Fowl adenovirus in China, a total of 1920 clinical samples from apparently healthy birds in the 25 sites of poultry flocks, Slaughterhouse and living bird markets from 8 provinces in eastern China were collected and detected by PCR, sequencing, and phylogenetic analysis. Results The epidemiological survey showed that Fowl adenoviruses were detected in living bird markets, and circulating in a variety of fowl species, including chickens, ducks, goose and pigeons. Among the 1920 clinical samples, 166 samples (8.65%) were positive in the fowl adenovirus PCR detection. In this study, totally all the 12 serotypes (serotypes of 1, 2, 3, 4, 5, 6, 7, 8A, 8B, 9, 10 and 11) fowl adenoviruses were detected, the most prevalent serotype was serotype 1. Phylogenetic analysis indicated that 166 FAdVs of 12 serotypes were divided into 5 fowl adenovirus species (Fowl aviadenovirus A, B, C, D, E). Conclusions In the epidemiological survey, 8.65% of the clinical samples from apparently healthy birds were positive in the fowl adenovirus PCR detection. Totally all the 12 serotypes fowl adenoviruses were detected in a variety of fowl species, which provided abundant resources for the research of fowl adenoviruses in China. The newly prevalent FAdV serotypes provides valuable information for the development of an effective control strategy for FAdV infections in fowls.

Bacteremia frequently occurs in patients with acute cholangitis, which could increase the risk of mortality. This single-center retrospective observational study was conducted from July 2013 to July 2020 to evaluate the predictive value of platelet index for bacteremia at admission for acute cholecystitis. A total of 285 patients with acute cholangitis were divided into bacteremia group and non-bacteremia group. The incidence of bacteremia in acute cholangitis was 48.42%. The bacteremia group had more grade III patients, higher 30d mortality rate [17(12.32%) vs 8(5.44%), p = .040] and higher incidence of thrombocytopenia [76(55.07%) vs 35(23.81%), p

The effects of dietary supplementation of Clostridium butyricum (CB) on growth performance, serum biochemistry, antioxidant activity, mRNA levels of immune-related genes and resistance to hypoxia stress were studied in largemouth bass. Feed with CB0 (control, 0 CFU/kg), CB1 (4.3×108 CFU/kg), CB2 (7.5×108 CFU/kg), CB3 (1.5×109 CFU/kg) and CB4 (3.2×109 CFU/kg) CB for 56 days, and then a 3 h hypoxic stress experiment was performed. The results showed that dietary CB significantly increased the WGR (weight gain rate), SGR (specific growth rate), PDR (protein deposition rate) and ISI (Intestosomatic index) of largemouth bass (P

ABSTRACT Temperature dependency of viral diseases in ectotherms has been an important scientific issue for decades, while the molecular mechanism behind this phenomenon remains largely mysterious. In this study, deploying infection with grass carp reovirus (GCRV), a double-stranded RNA aquareovirus, as a model system, we demonstrated that the cross talk between HSP70 and outer capsid protein VP7 of GCRV determines temperature-dependent viral entry. Multitranscriptomic analysis identified HSP70 as a key player in the temperature-dependent pathogenesis of GCRV infection. Further biochemical, small interfering RNA (siRNA) knockdown, pharmacological inhibition, and microscopic approaches revealed that the primary plasma membrane-anchored HSP70 interacts with VP7 to facilitate viral entry during the early phase of GCRV infection. Moreover, VP7 functions as a key coordinator protein to interact with multiple housekeeping proteins and regulate receptor gene expression, concomitantly facilitating viral entry. This work illuminates a previously unidentified immune evasion mechanism by which an aquatic virus hijacks heat shock response-related proteins to enhance viral entry, pinpointing targeted preventives and therapeutics for aquatic viral diseases. IMPORTANCE The seasonality of viral diseases in ectotherms is a prevailing phenomenon in the aquatic environment, which causes huge economic losses every year worldwide and hinders sustainable development of the aquaculture industry. Nevertheless, our understanding of the molecular mechanism of how temperature determines the pathogenesis of aquatic viruses remains largely unexplored. In this study, by deploying grass carp reovirus (GCRV) infection as a model system, we demonstrated that temperature-dependent, primarily membrane-localized HSP70 interacts with major outer capsid protein VP7 of GCRV to bridge the virus-host interaction, reshape the host’s behaviors, and concomitantly facilitate viral entry. Our work unveils a central role of HSP70 in the temperature-dependent pathogenesis of aquatic viruses and provides a theoretical basis for the formulation of prevention and control strategies for aquatic viral diseases.

Chronic inflammation and elevated cytokine levels are closely associated with the progression of chronic kidney disease (CKD), which is responsible for the manifestation of numerous complications and mortality. In addition to conventional CKD therapies, the possibility of using natural compounds with anti-inflammatory potential has attracted widespread attention in scientific research. This study aimed to study the potential anti-inflammatory effects of a natural oil compound, farnesol, in primary human renal proximal tubule epithelial cell (RPTEC) culture. Farnesol was encapsulated in lipid-based small unilamellar vesicles (SUVs) to overcome its insolubility in cell culture medium. The cell attachment of empty vesicles (SUVs) and farnesol-loaded vesicles (farnesol-SUVs) was examined using BODIPY, a fluorescent dye with hydrophobic properties. Next, we used multiple protein, RNA, and protein phosphorylation arrays to investigate the impact of farnesol on inflammatory signaling in RPTECs. The results indicated that farnesol inhibits TNF-α/IL-1β-induced phosphorylation of the PI3 kinase p85 subunit and subsequent transcriptional activation of the inflammatory genes TNFRSF9, CD27, TNFRSF8, DR6, FAS, IL-7, and CCL2. Therefore, farnesol may be a promising natural compound for treating CKD.

Cyclin-dependent kinases (CDKs) are a large family of proteins exerting different regulatory functions in eukaryotic cells, including control over the cell cycle and gene transcription. CDK1 controls the cell cycle and promotes cell proliferation by regulating the initiation and transition of the G2/M phase. Similar to mammals, CDK1 has also been characterized in arthropods; however, its functions and physiological importance in crustaceans remain unknown. Our pervious transcriptomic data indicated that CDK1 was a candidate cold-stress response gene in the Pacific white shrimp (Litopenaeus vannamei). Therefore, in the present study, the full-length sequence of CDK1 (LvCDK1) was obtained from L. vannamei containing a conserved PSTAIRE sequence and ATP-binding region. The expression of LvCDK1 is tissue-specific, with relatively higher in the hepatopancreas. The in situ hybridization (ISH) signals for LvCDK1 were present in the distal zone of hepatopancreas and mainly located in the cytoplasm and nucleus. The expression of LvCDK1 in hepatopancreatic was sensitive to environmental temperature. Furthermore, under cold stress, knockdown of LvCDK1 led to increased mortality in shrimp. Our study provides the first evidence of LvCDK1 responding to cold stress in shrimps. This mechanism for modifying the transcriptional roles of LvCDK1 may show new light on the molecular regulation of crustaceans in response to cold stress.

Summary: Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130–140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target 150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018. Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24–36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616. Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24–36 h. Mean achieved systolic blood pressures over 1–24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24–36 h (0.3 [IQR 0.0–16.6] in the intensive group and 0.9 [0.0–12.5] in the guideline group; log Δmean −0.17, 95% CI −0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Interpretation: Intensive blood pressure lowering treatment to a systolic target

Shellfish plays an important role in aquatic products. Shellfish protein is rich in nutrition and has unique flavor and functional characteristics. However, because of shellfish products are limited by regions and prone to spoilage, its practical application in food industry is less. Studies have proved that the functional characteristics of shellfish protein can be further optimized by modifying properties, so that it can be better applied to food processing, thus solving the problem of resource shortage in protein. This paper discusses the mechanism, advantages and disadvantages of three kinds of shellfish protein modification technologies, namely physical modification, chemical modification and enzymatic modification, which not only provides theoretical support for improving shellfish protein modification technology and developing new shellfish products, but also provides a basis for broadening the application range of shellfish products in food industry.

Abstract Land subsidence is a global problem in urban areas. The main cause of land subsidence is the pumping of subsurface water. It is of great significance to study the subsurface settlement and water flow of the lands due to pumping. In this study, the probabilistic analysis of land subsidence due to pumping is performed by Biot’s poroelasticity and random field theory based on a case study. The results show that the change of deformation of the aquifer is far less significant than the hydraulic head over the years. When considering the spatial variability of soil strength, the land subsidence suffers from great uncertainty when the correlation length is large. Nevertheless, the spatial variability of soil strength on the uncertainty of hydraulic head can be ignored. When considering the spatial variability of soil hydraulic conductivity, the uncertainty of the hydraulic head is mainly located near the bedrock and increases markedly along with the rise of the correlation length. Time is another important factor to increase the uncertainty of the hydraulic head. However, its contribution to the uncertainty of displacement is insignificant.

Abstract Background To investigate the difference in the severity of illness, organ dysfunction, and prognosis of acute cholangitis due to different pathogenic bacterial infection types. Methods A retrospective observational study was performed. Patients who met the selection criteria according to blood culture and bile culture results of different pathogenic bacterial were divided into groups. The severity of illness, organ dysfunction, and prognosis of the groups were analyzed and compared comprehensively. Results A total of 424 patients were included, and no bacterial growth developed in 111 patients (26.2%). Among the 313 patients (73.8%) with bacterial growth, 155 patients had only Gram-negative bacteria cultured (49.5%), 48 patients had only Gram-positive bacteria cultured (15.3%), and 110 patients had both Gram-negative and Gram-positive bacteria cultured (35.1%). The proportion of Grade III patients and the APACHE II and SOFA scores of the mixed Gram-negative and positive group were the highest (p 0.05). Conclusions In acute cholangitis, mixed infection with Gram-negative and Gram-positive bacteria was more severe and was associated with a higher risk of death. There were no apparent differences between Gram-negative and Gram-positive bacterial infections.

Chiral metasurfaces have garnered significant interest as an emerging field of metamaterials, primarily due to their exceptional capability to manipulate phase distributions at interfaces. However, the on-demand design of chiral metasurface structures remains a challenging task. To address this challenge, this paper introduces a deep learning-based network model for rapid calculation of chiral metasurface structure parameters. The network achieves a mean absolute error (MAE) of 0.025 and enables the design of chiral metasurface structures with a circular dichroism (CD) of 0.41 at a frequency of 1.169 THz. By changing the phase of the chiral metasurface, it is possible to produce not only a monofocal lens but also a multifocal lens. Well-designed chiral metasurface lenses allow us to control the number and position of focal points of the light field. This chiral metasurface, designed using deep learning, demonstrates great multifocal focus characteristics and holds great potential for a wide range of applications in sensing and holography.

Inhibitory control plays an important role in controlling behaviors, and its impairment is a characteristic feature of schizophrenia. Such inhibitory control has been examined through the the stop-signal task, wherein participants are asked to suppress a planned movement when a stop signal appears. In this research, we constructed a two-layer spiking neural circuit model to study how N-methyl-D-aspartate receptor (NMDAR) hypofunction, a potential pathological mechanism in schizophrenia, impacts the inhibitory control ability in the stop-signal task. To find the possible NMDAR hypofunction effects in schizophrenia, all NMDA-mediated synapses in the model were set to be NMDAR hypofunction at different levels. Our findings revealed that the performances of the stop-signal task were close to the experimental results in schizophrenia when NMDAR hypofunction was present in the neurons of two populations that controlled the “go” process and the “stop” process of the stop-signal task, implying that the execution and inhibition of behaviors were both impaired in schizophrenia. Under a certain degree of NMDAR hypofunction, the circuit model is able to replicate the stop-signal task performances observed in individuals with schizophrenia. In addition, we have observed a predictable outcome indicating that NMDAR hypofunction can lower the saccadic threshold in the stop-signal task. These results provide a mechanical explanation for the impairment of inhibitory control in schizophrenia.

A new certified reference material (CRM) of D-mannitol (GBW(E) 100681) has been developed in this study. We describe the preparation, structure determination, characterization, homogeneity study, stability study, as well as uncertainty estimation. The main component was 99.91% ± 0.01%. The moisture content of the candidate CRM was 0.036% ± 0.002%, as measured by Karl Fischer titration. The nonvolatile and volatile impurities in the candidate CRM were all much less than 0.01%, which was determined by the ICP–MS and headspace GC–FID methods, respectively. The purity of the D-mannitol CRM was 99.9% ± 1.1% (k = 2), as measured by the two independent approaches involving the mass balance method (MB) and quantitative nuclear magnetic resonance technique (qNMR). The D-mannitol CRM was stable during the monitoring period for each temperature. It is stable for up to 48 months at room temperature and 28 days at 50 °C. The uncertainty was evaluated by combining the contributions from characterization, homogeneity, and stability. The developed D-mannitol CRM would effectively support method validation and proficiency testing, as well as effectively guarantee the accuracy, reliability, and comparability of results.