Search

In the context of cloud manufacturing, challenges related to trust, including malicious deception and dishonest feedback, are exacerbated by information asymmetry among platform participants. To address these issues, a novel approach for evaluating collaboration credibility among multi-service subjects within the cloud manufacturing framework is introduced. Initially, an evaluation index system is constructed, incorporating both internal and external data from the platform. This system is framed around four critical dimensions: subject characteristics, service characteristics, product characteristics, and task characteristics. The attribute weights are determined using an integrated assignment method. Subsequently, to effectively address the issues of ambiguity, uncertainty and randomness of evaluation information in the integrated evaluation process, this paper proposed a comprehensive evaluation model. This model capitalizes on the strengths of intuitionistic fuzzy sets (IFSs) and cloud models in converting qualitative assessments into quantitative evaluations, and leverages the method of approximation of the order of ideal solutions (TOPSIS) to carry out a comprehensive assessment of the degree of trustworthy collaboration of the service subject. The practicality and validity of the proposed methodology are demonstrated through a case study analysis, which confirms the model's effectiveness in enhancing the reliability of collaborative evaluations under the cloud manufacturing model.

Abstract Objective This study aimed to assess the feasibility of computer model-based evaluation of knee joint functional capacity in comparison with manual assessment. Methods This study consisted of two phases: (1) developing an automatic knee joint action recognition and classification system on the basis of improved YOLOX and (2) analyzing the feasibility of assessment by the software system and doctors, identifying the knee joint function of patients, and determining the accuracy of the software system. We collected 40–50 samples for use in clinical experiments. The datasets used in this study were collected from patients admitted to the Joint Surgery Center. In this study, the knee joint assessment items included stair climbing, walking on uneven surfaces, and knee joint function. To assess the computer model’s automatic evaluation of knee joint function, MedCalc 20 statistical software was used to analyze the consistency of the Lequesne functional index between the computer model’s automated determinations and manual independent assessments. Results The weighted kappa coefficients between the doctors’ assessments and the software system’s assessments were 0.76 (95% confidence intervals:0.59 ~ 0.92) for climbing up and down stairs, 0.64 (95% confidence intervals:0.45 ~ 0.82) for walking on uneven floors, and 0.68 (95% confidence intervals:0.53 ~ 0.84) for the Lequesne functional index, indicating good consistency between the assessments of the software system and doctors. Conclusion This paper introduces an automatic knee joint action recognition and classification method based on improved YOLOX. By comparing the results obtained by orthopedic doctors and the software system, the feasibility of this software system was validated in the clinic.

Abstract Ordered intermetallic alloys are renowned for their impressive mechanical, chemical, and physical properties, making them appealing for various fields. However, practical applications of them have long been severely hindered due to their severe brittleness and poor fabricability. It is difficult to fabricate such materials into components with complex geometries through traditional subtractive manufacturing methods. Here, we proposed a strategy to solve these long-standing issues through the additive manufacturing of chemically complex intermetallic alloy (CCIMA) based on laser powder bed fusion (LPBF). The developed CCIMA exhibits good printability, enabling a crack-free microstructure with a low porosity of 0.005%. More importantly, a good combination of high tensile strength (~1.6 GPa) and large uniform elongation (~35%) can be achieved, which has not been reported in the existing additive-manufactured alloys. Such properties are attributed to the structural and chemical features of highly ordered superlattice grain decorated with disordered interfacial nanolayer, as well as dynamic evolutions and interactions of multiple dislocation substructures. These findings could provide references for developing high-performance intermetallic alloys and accelerating their practical applications.

Abstract Background Excessive tachycardia is associated with impaired hemodynamics and worse outcome in critically ill patients. Previous studies suggested beneficial effect of β-blockers administration in ICU patients, including those with septic shock. However, comparisons in ICU settings are lacking. Our study aims to compare Landiolol and Esmolol regarding heart rate control and hemodynamic variables in general ICU patients. Methods This retrospective, observational study was conducted in a 56-bed ICU at a university hospital. A propensity score matching (PSM) was employed to balance baseline differences. Generalized estimating equations (GEE) were used to compare heart rate between two drugs. The primary outcome was heart rate control, while secondary outcomes included hemodynamic response, hospital length of stay (HLOS) and ICU length of stay (ICULOS). Results From June 2016 to December 2022, 438 patients were included after PSM, (292 in the Esmolol group and 146 the in Landiolol group). Baseline heart rate was similar between groups (Landiolol:120.0 [110.2, 131.0] bpm vs. Esmolol:120.0 [111.0, 129.0] bpm, p = 0.925). During 72 h. of β-blocker infusion, Landiolol reduced heart rate by 4.7 (1.3, 8.1) bpm, more than Esmolol (p = 0.007), while preserving a comparable proportion of patients able to stabilize vasopressor doses within the first 24 h. (82.9 vs. 80.8%, respectively, p = 0.596). Norepinephrine doses and lactate levels were similar between groups over 72 h., while the Landiolol group exhibited notably higher minimal ScvO2 levels (72% [63%, 78%] vs 68% [55%, 73%], respectively, p = 0.006) and a lower maximal PCO2 gap compared to the Esmolol group (7.0 [6.0, 9.0] vs. 8.0 [6.0, 10.0] mmHg, respectively, p = 0.040). Patients in the Landiolol group were observed to experience shorter HLOS than patients in the Esmolol group (26.5 [13.0, 42.0] vs 30.0 [17.0, 47.2] days, respectively, p = 0.044) and ICULOS (4.9 [2.8, 10.0] vs.6.7 [3.4, 13.1] days, respectively, p = 0.011). Conclusion Landiolol provides superior heart rate control in critically ill patients with tachycardia compared to Esmolol, without increasing vasopressor requirements during the first 24 h. Findings from ScvO2 levels and PCO2 gap suggest that Landiolol may exert less impact on cardiac output than Esmolol. Further studies, incorporating comprehensive hemodynamic monitoring, are warranted to clarify the clinical implications of heart rate control with β-blockers in ICU patients with tachycardia.

In order to solve the problems of frequent high energy microearthquakes and large roadway deformation in full-mechanized caving “segmented and stratified” combined mining in Yanbei Coal Mine with large dip angle and extra-thick coal seam, theoretical analysis, numerical simulation and field measurement are used to study the bearing stress characteristics of coal pillars and the instability mechanism of coal pillars. The load-bearing mechanical model of composite mining coal pillar is established, and the load-bearing stress distribution under the influence of coal pillar width is analyzed in three forms: asymmetric saddle shape, asymmetric platform shape and single peak shape, and it is determined that the load-bearing stress of coal pillar is more prone to instability when it is presented in asymmetric platform shape. The simulation results show that under the influence of pre-abutment pressure in inclined stratified mining, the section coal pillar is in a state of high stress, and the stress change rate is the most significant. The main cause of pillar instability is the local stress concentration in the combined mining of “segmented and stratified” coal seam with large dip angle; based on the instability mechanism of coal pillar in the composite mining area with large dip angle and ultra-thick coal seam, the prevention and control idea of rock burst of working face and key areas, the plan of the deep hole pre-splitting blasting in the roof and the combining of near and far blasting in the coal body, pressure relief in batches and shock absorption and shock prevention is formulated, which effectively reduces the stress and energy level of the gob side and significantly reduces the “segmented and stratified” composite mining of large dip angle and ultra-thick coal seam.

Abstract Background and objective Gastric cancer (GC) remains a significant global health challenge, characterized by high incidence and mortality rates, particularly in East Asia. A comprehensive understanding of the disease burden of gastric cancer is crucial for developing effective prevention and treatment strategies. However, comprehensive global assessments of the disease burden of gastric cancer remain limited. This study, based on the Global Burden of Disease (GBD) framework, systematically analyzes global trends in gastric cancer from 1990 to 2021 and projects future trends through 2035, aiming to provide scientific evidence for policymaking. Methods The data were derived from the Global Burden of Disease (GBD) Study 2021, covering gastric cancer (GC) incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs), and age-standardized DALY rates (ASRs) across 204 countries and regions from 1990 to 2021. The Bayesian age-period-cohort model was employed to project trends up to 2035. Results In comparison with 1990, both the incidence and mortality of GC rose in 2021, with over 1.23 million new cases recorded globally, resulting in 954,373.60 deaths and 22,786,633.10 DALYs. Between 1990 and 2021, the ASIRs, ASDRs, and ASRs decreased by 42% (ranging from 49 to 35%), 49% (ranging from 55 to 43%), and 53% (ranging from 58 to 47%), respectively. The peak ASIRs and ASDRs in 2021 were seen in the high-middle SDI quintile. Males exhibited higher rates of ASDRs, ASIRs, and ASRs compared to females. In 2021, East Asia and high-income North America bore the largest burden of smoking-related GC, while Central Europe experienced the highest burden from high-sodium diets. Forecasts toward 2035 indicate a continued decline in both ASIRs and ASDRs. Conclusions Despite notable reductions in both incidence and mortality, GC remains a substantial global burden, affecting various regions and countries. Deaths and DALYs related to high-sodium diets and smoking have shown an overall decline. However, substantial regional and age-related disparities persist. Targeted interventions, such as smoking control and promoting the intake of fresh fruits and vegetables, are essential in diminishing GC risk.

Abstract Emotions play a crucial role in human thoughts, cognitive processes, and decision-making. EEG has become a widely utilized tool in emotion recognition due to its high temporal resolution, real-time monitoring capabilities, portability, and cost-effectiveness. In this paper, we propose a novel end-to-end emotion recognition method from EEG signals, called MSDCGTNet, which is based on the Multi-Scale Dynamic 1D CNN and the Gated Transformer. First, the Multi-Scale Dynamic CNN is used to extract complex spatial and spectral features from raw EEG signals, which not only avoids information loss but also reduces computational costs associated with the time-frequency conversion of signals. Then, the Gated Transformer Encoder is utilized to capture global dependencies of EEG signals. This encoder focuses on specific regions of the input sequence while reducing computational resources through parallel processing with the improved multi-head self-attention mechanisms. Third, the Temporal Convolution Network is used to extract temporal features from the EEG signals. Finally, the extracted abstract features are fed into a classification module for emotion recognition. The proposed method was evaluated on three publicly available datasets: DEAP, SEED, and SEED_IV. Experimental results demonstrate the high accuracy and efficiency of the proposed method for emotion recognition. This approach proves to be robust and suitable for various practical applications. By addressing challenges posed by existing methods, the proposed method provides a valuable and effective solution for the field of Brain-Computer Interface (BCI).

ABSTRACT Rapeseed protein, as a valuable plant protein, holds great potential as a natural emulsifier for construction of food‐grade high internal phase emulsions (HIPEs). In this work, rapeseed protein, obtained through salt extraction combined with ultrafiltration, was employed as a sole stabilizer to formulate algae oil‐based HIPEs. The effects of protein concentration and pH changes on the physicochemical properties of HIPEs are systematically evaluated. The results show that a protein concentration of 0.5 wt% is sufficient to form stable and self‐supporting HIPEs. As the protein concentration increases, the droplet size of HIPEs gradually decreases, leading to a more robust structure and enhanced stability. Compared to neutral conditions (pH 7.0), the HIPEs under acidic pH 3.5 exhibit more densely packed emulsion droplets with smaller size and more uniform distribution, contributing to superior mechanical properties (higher G′ and yield stress) as well as preferable thixotropic and creep recovery behaviors, which thereby improve their physical stability during storage, thermal processing, and freeze‐thaw cycles. Furthermore, the rapeseed protein‐stabilized HIPEs inhibit the oxidation of algae oil, especially at pH 3.5. The results of oral lubrication indicate that the reduction in the friction coefficient is mainly associated with an increase in protein concentration, with minor effect from pH variation. These findings suggest that rapeseed protein is an effective emulsifier for preparing stable and processable HIPEs, especially under acidic conditions, which have great potential for applications in semi‐solid emulsion foods or edible oil structuring.

Lithium-ion batteries (LIBs) gradually occupied the energy storage market due to their long cycling life, high working voltage, as well as energy density. However, LIBs have high costs due to the limited lithium resource and difficulty to exploit. Potassium ion batteries (PIBs) have aroused extensive attention over the past few years since they possess considerable potassium salt resources while exhibiting similar electrochemical properties to LIBs. The electrode material takes on great significance in determining the properties exhibited by the batteries. Zinc-based chalcogenides have served as the most suitable anode materials for their numerous raw material resources, low prices, and environmental friendliness. Nevertheless, the application of Zinc-based chalcogenides has been continuously hindered by sluggish diffusion kinetics, low electrical conductivity, as well as huge volume variation. Several effective strategies have been explored to settle the above matters (e.g., designing nanostructures, constructing carbon composite structures, as well as doping anions or cations to construct heterojunction). In this review, the recent advance of zinc-based chalcogenides (e.g., electrochemical mechanisms, challenges, and perspectives) are summarized. This review can provide novel insights into the development of transition metal chalcogenides for PIBs.

Abstract Piezoelectric electronics possess great potential in flexible sensing and energy harvesting applications. However, they suffer from low electromechanical performance in all-organic piezoelectric systems due to the disordered and weakly-polarized interfaces. Here, we demonstrated an all-polymer piezo-ionic-electric electronics with PVDF/Nafion/PVDF (polyvinylidene difluoride) sandwich structure and regularized ion-electron interfaces. The piezoelectric effect and piezoionic effect mutually couple based on such ion-electron interfaces, endowing this electronics with the unique piezo-ionic-electric working mechanism. Further, owing to the massive interfacial accumulation of ion and electron charges, the electronics obtains a remarkable force-electric coupling enhancement. Experiments show that the electronics presents a high d33 of ~80.70 pC N−1, a pressure sensitivity of 51.50 mV kPa−1 and a maximum peak power of 34.66 mW m−2. It is applicable to be a transducer to light LEDs, and a sensor to detect weak physiological signals or mechanical vibration. This work shows the piezo-ionic-electric electronics as a paradigm of highly-optimized all-polymer piezo-generators.

Background The AQP4-AS1/miR-4476-ALOX15 regulatory axis was discovered in previous studies. We aimed to investigate the regulatory mechanism of the ferroptosis-related regulator ALOX15 by AQP4-AS1 and miR-4476 in lung adenocarcinoma (LUAD) and find new targets for clinical treatment.

Joint action by strong winds and high-intensive rainfall leads to serious soil erosion problems in large sediment generating and coarse sediment class areas of the middle Yellow River. Investigating the variation of trend and alternating wind and rainfall energy is an important prerequisite for controlling regional sediment transport problems. We calculated the wind and rainfall erosion energies by using the aerodynamic energy and rainfall kinetic energy formulas. The Mann-Kendall (MK) trend test and Theil-Sen approach were used to analyze the spatial-temporal variation and alternation of joint erosion energy during the last 40 years (1979–2018). The results show the following. 1) Wind erosion energy increased and rainfall erosion energy decreased. However, the former is larger than the latter. 2) The dominant erosive energy varies for different seasons. Wind erosive energy dominates in spring, and rainfall erosive energy dominates in summer. 3) There is a regular wind-rainfall-wind alternation of erosive energy. The wind-rainfall energies were alternately distributed in May–July and the rainfall-wind energies were alternately distributed in September–December. Furthermore, the dominant time of rainfall erosive energy decreased when wind erosive energy increased. The results can help decision makers to develop soil erosion control strategies to reduce soil erosion when it occurs in wind and water staggered areas.

Abstract In the cost function of model predictive torque control (MPTC) of permanent magnet synchronous motor (PMSM), torque and flux linkage have different dimensions, and the weighting factor needs to be properly adjusted to optimise the control performance. Therefore, based on the discrete mathematical model of PMSM, the torque predictive error and flux predictive error expressions are mapped to the two‐phase static coordinate system, which is equivalent to the distance expressions from the endpoint of the voltage vector to the straight line and to the circle respectively. Because they have the same dimension, they can be directly superimposed to form the cost function proposed, which eliminates the selection process of the weighting factor. Then, the candidate voltage vector is substituted into the cost function in turn, and the optimal voltage vector with the minimum cost function is selected as the voltage input of the next control cycle. Finally, the simulation model and an experimental platform are established to compare the steady‐state and dynamic performance of the geometric solution‐based weighting factor determined method proposed with other MPTC methods.

Abstract Rock-filled concrete (RFC) construction technology is to construct a force-transferring skeleton with large-size rocks, and to use self-compacting concrete (SCC) as the filling and bonding material. In which the defects with different distributions and sizes contained in SCC are often the key factors determining the mechanical properties and damage behaviors of RFC. In this research, by utilizing the excellent properties of super absorbent polymer (SAP), such as water absorption and expansion and dehydration shrinkage, non-introduction of impurities, and not easy suspension or settlement in concrete, RFC and SCC specimens with different numbers and sizes of defects were precisely prepared and subjected to unconfined uniaxial compression physical tests. The effects of porosity and pore aperture on the compressive strength and damage pattern of the specimens were studied. The mechanical behavior of the defective concrete specimens under compressive loading was analyzed from a mesoscopic perspective by using a combination of physical tests and numerical simulation using the Realistic Failure Process Analysis (RFPA) method to reveal the internal damage phenomenon and damage destabilization mechanism of RFC and SCC. The results show that: SAP material can accurately construct concrete specimens with stable and uniform defects; under the same porosity and aperture, the compressive strength of RFC is greater than that of SCC; the compressive strength of the specimen decreases linearly with the growth of porosity for the same aperture, the compressive strength of the specimen decreases with the increase of aperture for the same porosity and the trend tends to be flat, and the sensitivity of the compressive strength to porosity is higher than that of aperture. In addition, it was found that the internal penetrating shear damage during the fracturing process of SCC was the core cause of the overall damage. For RFC, the tensile fracture that penetrated through the force transmission skeleton of the stacked rock was the key factor causing the overall instability.

Revealing plasticity-evolved behaviors of laser-arc hybrid welding welds is indispensable for controlling high-reliability Ti–6Al–4V welded joints used in marine equipment. The relationship between dual heat source coupling and the plasticity of welded joints in thick plate titanium alloy is analyzed in this research. The plasticity-enhancing mechanisms based on the action of the keyhole are also elucidated. The results underscore that due to the faster cooling rate, the keyhole effect weakens the texture strengths of the β and α′ phases by 65.8% and 70.3%, respectively, and improves the ductility of the keyhole-affected region by 20% compared to the keyhole-free region. Furthermore, the keyhole region facilitates the generation of small-sized brittle phase α′, an increase in the number of small-angle grain boundaries, and easily activated pyramidal-slip systems {10 1‾ 1}, implying improved grain deformability and plasticity. These results have provided valuable insights into the plasticity-enhancing behaviors of thick Ti–6Al–4V laser-arc hybrid welded joints, offering guidance for subsequently regulating the performance of welded joints to achieve superior plasticity welded joints.

Abstract Certain immune-checkpoint inhibitors have a narrow therapeutic window (TW) as cancer therapeutics, and engineered dual-/multi-targeting agents could potentially widen the TW to bring true clinical benefits. We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. This resulted in an IgG4-based “2 × 2” symmetric structure but with an intentionally-reduced CD47-binding affinity, suggesting a novel candidate cancer immunotherapy. Specifically, HX009 has binding affinity constant of 8.951 × 10–9 M for human PD1 and 2.557 × 10–8 M for human CD47, respectively, where the CD47 binding is significantly weaker as compared to the binding affinity of HX008 to PD1 as well as the binding affinity of SIRPα-Fc to CD47, leading to little binding to RBCs and platelets and is contrasting to many CD47-agents in development. However, HX009 effectively and simultaneously binds to the PD1 and CD47 on PD1+CD47+ T-cells via cis-binding and elicits enhanced T cell activation compared to the parental HX008. HX009 caused little cytokine-release in human peripheral blood mononuclear cells. HX009 cross-species binds to cynomolgus monkey PD1/CD47 but not to rodents, making cynomolgus monkeys the choice of species to investigate the pharmacokinetics (PK) and toxicology of HX009. HX009’s anti-tumor activities were confirmed in several humanized preclinical mouse models by determining either its anti-PD1 (humanized hu-CD47-MC38 models) or anti-CD47 (HuT-102 lymphoma CDX and three PDX-AML models) functions, although limited available humanized models have hindered broadly demonstration of enhanced anti-tumor activities contributed from the dual targeting of the BsAb. The expanded DLBCL-PDX trial data suggested that both EBV-status and OX40 expression could potentially be two positive predictors for response to HX009. An intravenous (IV) infusion PK study in cynomolgus monkey revealed its largely vasculature distribution, terminal half-life (T1/2) of ~ 50 h, and dose-proportional exposure without accumulation. The anti-drug antibody (ADA) was observed in all monkeys as expected, affecting the PK parameters of repeated administration. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009’s candidacy for its clinical development.

Abstract To address coal pillar instability, the study focuses on the 3−1 coal seam coal pillar at Nanliang Coal Mine. It analyzes the bending deformation energy of the main roof and the pre-yield elastic energy of the coal pillar’s elastic zone through theoretical analysis, similar simulation, and field measurements. The formula for the bending elastic energy of the main roof is derived by establishing the mechanical model of the roadway’s main roof near the goaf side. Based on the side abutment stress distribution of the coal pillar, the calculation of the pre-yield elastic energy distribution along the width direction of the coal pillar’s elastic zone is conducted, leading to the derivation of the instability energy criterion for the coal pillar. The range analysis method is used to analyze the influencing factors and distribution patterns of the bending elastic energy of the main roof and the pre-yield elastic energy of the coal pillar’s elastic zone. Findings indicate that the main roof’s tensile strength is the primary factor influencing bending elastic energy. Higher tensile strength of the main roof, and smaller load, larger thickness and elastic modulus on the overlying strata, lead to higher bending elastic energy in the main roof. The internal friction angle, width of the coal pillar, and elastic modulus of the coal seam notably impact the pre-yield elastic energy of the coal pillar’s elastic zone. A larger internal friction angle and coal pillar width, along with a smaller elastic modulus, result in higher pre-yield elastic energy in the coal pillar’s elastic zone. Using the working face of 3−1 coal seam in Nanliang Coal Mine as the engineering context, the study calculates the minimum coal pillar width required for stability. Physical simulations and field monitoring demonstrate that with a 9 m—wide coal pillar, there is no apparent deformation or failure in the surrounding rock of the roadway, indicating good internal rock stability.

Abstract Congenital heart disease (CHD) is the most common birth defect in newborns, often requiring cardiac surgery with concomitant thymectomy that is known to increase disease susceptibility later in life. Studies of γδ T cells, which are one of the dominant T cells in the early fetal human thymus, are rare. Here, we provide a comprehensive analysis of the γδ T cell compartment via flow cytometry and next-generation sequencing in children and infants with CHD, who underwent cardiac surgery shortly after birth. A perturbation of the γδ T cell repertoire is evident, and Vδ1 T cell numbers are reduced. However, those cells that are present, do retain cytotoxicity. In contrast, GZMA+CD28+CD161hi innate effector Vγ9Vδ2 T cells are found in higher proportions. TCR-seq identifies an increase in TRDJ3+ γδ T cell clones in children with CHD, but not in a confirmatory group of neonates prior to CHD surgery, which overall points to a persistence of fetal-derived effector γδ T cells in children with CHD.

Abstract Oral tolerance is essential for intestinal homeostasis and systemic immune function. However, our understanding of how oral tolerance is maintained is inadequate. Here we report that food-derived nucleic acids promote oral tolerance through innate sensing pathways. We find that dietary nucleic acids, but not microbiota, expand the natural intraepithelial lymphocyte (IEL) pool, specifically in the small intestine. TGF-β1, produced by natural IELs, then promotes activation of gut CD103+ dendritic cells to support the induction of antigen-specific Treg cells in a mouse model of OVA-induced oral tolerance. Mechanistically, MAVS and STING are redundantly required for sensing dietary RNAs and DNAs to activate downstream TBK1 signalling to induce IL-15 production, which results in the accumulation of natural IELs. Thus, our study demonstrates a key role of food-triggered innate sensing pathways in the maintenance of natural IELs and oral tolerance.

Abstract The nucleus pulposus (NP) plays a vital role in intervertebral disc degeneration (IVDD). Previous studies have revealed cellular heterogeneity in NP tissue during IVDD progression. However, the cellular and molecular alterations of diverse cell clusters during IVDD remain to be fully elucidated. NP tissues were isolated from patients with different grades of IVDD undergoing discectomy, and then subjected to single-cell RNA sequencing (scRNA-seq). Cell subsets were identified based on unbiased clustering of gene expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the molecular features of diverse cell clusters. Monocle analysis was used to illustrate the differentiation trajectories of chondrocytes. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocytes and other cells during IVDD. Based on the expression profiles of 47,610 individual cells, eight putative clusters including chondrocytes, endothelial cells, fibroblasts, macrophages, mural cells, osteoclasts, proliferating stromal cells and T cells were identified. The chondrocyte cluster was classified into three subsets, C1-C3, which were associated with stress-resistance, fibrosis and inflammatory responses, respectively. Pseudo-time trajectories suggested that chondrocytes gradually differentiated into fibroblasts during IVDD. Immune cells including cDC2s, macrophages and monocytes were identified. Further analysis showed that chondrocytes might communicate with immune cells via the MIF, TNFSF9, SPP1 and CCL4L2 signaling pathways. In addition, we found that invading endothelial cells might interact with chondrocytes through the COL4A1, CXCL12, VEGFA and SEMA3E signaling pathways. Our results reveal the cellular complexity and phenotypic characteristics of NP tissues at single-cell resolution, which will contribute to the in-depth investigation of preventative and regenerative strategies for IVDD.

In a view of application of porous materials in wearable electronics and self-powered systems, reduced graphene oxide (rGO) foams modified by Mn or/and Bi were produced in this study to be used as electrodes for supercapacitors. The hydrothermal method and the freeze-drying processes were used for the preparation of the materials further morphologically, elementally and structurally analyzed. Based on the electrochemical characterization, Bi-modified rGO foam was found to be more a promising material for capacitive electrodes in comparison to the other prepared materials.

1D/2D g-C3N5/g-C3N4 heterojunction photocatalysts were prepared by a direct thermal polymerization method using melamine and 3-amino-1，2，4-triazole as raw materials. The crystal form， chemical composition， morphology and photoelectric chemical properties of the photocatalytic materials were characterized by XRD， XPS， SEM. Photocatalytic activity of 1D/2D g-C3N5/g-C3N4 heterojunction photocatalyst was studied using methyl orange（MO）as target pollutant and 500 W xenon lamp as visible light source. The active substances of the system were studied by active substance capture experiment and ESR characterization. The results show that the disordered stacking of one-dimensional g-C3N5 nanorods and two-dimensional g-C3N4 nanosheets increases the number of active sites. The formation of Z-scheme heterojunction between g-C3N5 and g-C3N4 improves the absorption intensity and spectral range of visible light， and inhibits the recombination of photoelectrons and holes. The superposition of π-π * conjugated systems similar to g-C3N5 and g-C3N4 reduces the mass transfer resistance of charge transfer and improves its photocatalytic activity. Under visible light irradiation for 30 min， 20 mg of 1D/2D g-C3N5/g-C3N4 photocatalytic material almost completely degraded 50 mL of 10 mg/L MO solution， and the apparent rate constant is 0.14836 min-1. After 5 cycles， the photocatalytic degradation rate of 1D/2D g-C3N5/g-C3N4 photocatalytic material for MO is 92.2%， indicating its good stability. The capture experiment of active substances and ESR characterization show that the main active substances in the photocatalytic degradation of MO system by g-C3N5/g-C3N4 photocatalyst are •O2- and h+， and the photocatalytic degradation of MO was a complex bond breaking and oxidation process.

Abstract Severe friction on wheel/rail contact interface in the process of a train emergency braking can cause significant thermal and mechanical phenomena. Obvious friction heat and serious material damage will appear on the contact surface. In this article, the variation law of temperature and surface damage during a wheel sliding contact process are investigated. To achieve the research objective, a three-dimensional (3D) thermo-mechanical coupling contact finite element model (FEM) is established, and the temperature-dependent material parameters are used. The FEM is adopted to analyze the temperature distribution law on the contact surface. At the same time, a sliding contact testing machine is used to study the damage of materials in the contact area during the sliding contact. The study results indicate, the highest temperature of wheel and rail material is respectively 1014 ℃ and 461.8 ℃ during sliding contact. High temperatures are located at the subsurface and surface areas of contact region. When the distance to contact surface exceeds 1.4 mm, the temperature changes slightly. The types of damage on wheel surface are grooves and material peeling, while the flaky spalling, corrosive pitting, adhesion and grooves appear on the rail surface. Meanwhile, many cracks can be found on the contact surface, which is a major factor leading to material damage. The research results of this article are of great significance for understanding the thermal and mechanical damage of wheel/rail materials.

Abstract Background Hepatic venous pressure gradient (HVPG) is considered the gold standard for diagnosing portal hypertension (PHT). Laparoscopic splenectomy plus esophagogastric devascularization (LSED) is an important surgery for treating PHT. However, the variation trend of HVPG after surgery is not clear. Moreover, whether HVPG can provide precise prognostic information for patients undergoing surgery remains to be further studied. This study aimed to investigate the independent prognostic value of HVPG in LSED. Methods From January 2016 to March 2023, 135 patients with PHT underwent LSED at our hospital were retrospectively evaluated. We analyzed the correlations between clinical indicators and history of upper gastrointestinal bleeding (UGIB). Among them, 57 patients remeasured postoperative HVPG. We further investigated the postoperative alterations of HVPG and correlative factors, as well as the relationship between the HVPG and postoperative UGIB. Results In this study, we found that 94 patients with preoperative UGIB (16.27 ± 5.73 mmHg) had a higher baseline HVPG than the other 41 patients without (14.02 ± 5.90 mmHg) (p = 0.04). The mean postoperative HVPG significantly decreased (-3.57 ± 8.09 mmHg, p = 0.001) compared to the baseline, and 66% of patients (38/57) experienced a decreased HVPG-response after surgery. The baseline HVPG and preoperative CTP class B were associated with the decreased HVPG-response (p20% from baseline exhibited better recurrent hemorrhage-free survival rates than those without (log-rank, p = 0.013). Conclusion We found that LSED led to a significantly decreased HVPG, and patients with postoperative HVPG decreased >20% obtained better UGIB-free survival benefits than those without.

Abstract Aims The present study aims to develop a nano-delivery system that encapsulates berberine (BBR) into PLGA-based nanoparticles (BPL-NPs), to treat ulcerative colitis (UC). Furthermore, the therapeutic efficacy and molecular targeting mechanisms of BPL-NPs in the management of UC are thoroughly examined. Methods Emulsion solvent-driven methods were used to self-assemble BBR and PLGA into nanoparticles, resulting in the development of the nano-delivery system (BPL-NPs). The therapeutic effectiveness of BPL-NPs was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice and a lipopolysaccharide (LPS)-induced model of inflammation in THP-1 macrophages. The interaction between Mφs and NCM-460 cells was investigated using a co-culture system. The molecular targeting ability of BPL-NPs in the treatment of UC was validated through in vitro as well as in vivo experiments. Results The BPL-NPs demonstrated a particle size of 184 ± 22.4 nm, enhanced dispersibility in deionized water, and a notable encapsulation efficiency of 31.1 ± 0.2%. The use of BPL-NPs clearly improved the clinical symptoms and pathological changes associated with UC in mice while also ensuring minimal toxicity. In addition, BPL-NPs improved intestinal epithelial cell apoptosis and enhanced the function of the intestinal barrier by inhibiting M1 Mφs infiltration and IL-6 signaling pathway in mice with UC. Furthermore, the BPL-NPs were found to selectively target the IL-6/IL-6R axis during the M1 Mφs-induced apoptosis of NCM460 cells. Conclusion The BPL-NPs were confirmed to harbor anti-inflammatory effects both in vitro and in vivo, along with enhanced water solubility and bioactivity. In addition, the precise targeting of the IL-6/IL-6R axis was confirmed as the mechanism by which the BPL-NPs exerted therapeutic effects in UC, as demonstrated in both in vitro as well as in vivo studies. Graphical Abstract

Abstract Background Robotic computer-assisted implant surgery (r-CAIS) is a revolutionary innovation in oral implantation; however, the clinical feasibility of r-CAIS for immediate implant placement (IIP) in posterior teeth has not been verified. Thus, this study aimed to evaluate the accuracy of r-CAIS for IIP in posterior tooth regions. Methods Patients with posterior teeth to be extracted and indicated to undergo r-CAIS were evaluated. The patients had positioning markers installed in the oral cavity and underwent cone-beam computed tomography (CBCT). Subsequently, minimally invasive tooth extractions were performed, and an individualised surgical plan was generated in the robotic software. After marker registration, implantation surgery was performed by the robotic arm under the supervision and assistance of the surgeons. Finally, the deviations between the planned and placed implants were evaluated based on preoperative and postoperative CBCT data. Results A total of 12 patients were evaluated. No adverse events occurred during the surgery. The mean global coronal, global apical, and angular deviations were 0.46 ± 0.15 mm (95%CI:0.36 to 0.56 mm), 0.46 ± 0.14 mm (95%CI:0.37 to 0.54 mm), and 1.05 ± 0.55° (0.69 to 1.40°), respectively. Conclusions Under the limited conditions of this study, the r-CAIS exhibited high accuracy in posterior teeth IIP surgery. Further multicentre randomised controlled studies are required to confirm the feasibility of this technology.

In order to scientifically and accurately calculate the water surface evaporation in the central Yunnan region， based on the monthly meteorological data from Yuxi Meteorological Station near the 'Three Lakes' basin in Central Yunnan from 2014 to 2021， the effectiveness of the FAO PPP-17 Penman formula in calculating water evaporation in this area and the error sources is analyzed through comparative analysis and correlation analysis.On this basis， aiming at the sources of calculation errors and the characteristics of seasonal changes， the water surface reflectance and the solar radiation parameters in the Penman formula are dynamically modified with the season changes using Morton empirical formula and other methods.Furthermore， based on the principle of heat balance， a new estimation model of water surface heat flux was derived by using error inverse derivation.The water surface heat flux term is added to the FAO PPP-17 Penman formula to correct the heat balance of the water surface.The results showed that： （1） The water evaporation calculated by the FAO PPP-17 Penman formula in the study area was generally overestimated， with a mean relative error of +15.2%.The error has seasonal characteristics of small in winter and large in summer， and periodic variation characteristics which is similar to a sine curve.The calculation error mainly stems from the inappropriate value of solar short-wave radiation parameters in the formula and the neglect of the influence of water surface heat flux， resulting in an imbalance in the heat budget.（2） After dynamically improving the parameters of the FAO PPP-17 Penman formula and adding the water surface heat flux to it， the calculation accuracy is significantly improved.Compared to the unrevised version， the accuracy with relative errors within ± 5%， ± 10%， and ± 20% increased by 40.6%， 42.7%， and 32.3%， respectively.The results of off-site tests show that the optimized Penman equation exhibits high fitting accuracy in the ‘Three Lakes’ basin of central Yunnan， and the model's accuracy with relative errors within ±10% is over 75%.（3） This study developed a nonlinear estimation model for water surface heat flux， which can reasonably simulate the nonlinear response of water storage heat to seasonal variations and water surface radiation intensity.Furthermore， the model has demonstrated satisfactory results in evaporation calculations within the "Three Lakes" region.

Abstract Background Hyperglycemia upon admission is associated with poor prognosis of many cardiovascular diseases. However, the relationship of stress hyperglycemia ratio (SHR), admission blood glucose (ABG), and hemoglobin A1c (HbA1c) with pulmonary hypertension has not been reported. This study aimed to explore the association of hyperglycemia indices with disease severity and long-term adverse outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). Methods This multi-center cohort study included 625 consecutive patients diagnosed with or treated for IPAH between January 2015 and June 2023. SHR was calculated using the followings: ABG (mmol/L)/(1.59 × HbA1c [%] − 2.59). The primary endpoint was defined as clinical worsening events. Multivariable Cox regression and restricted cubic spline analyses were employed to evaluate the association of SHR, ABG, and HbA1c with endpoint events. The mediating effect of pulmonary hemodynamics was evaluated to investigate the potential mechanism between hyperglycemia and clinical outcomes. Results During a mean follow-up period of 3.8 years, 219 (35.0%) patients experienced all-cause death or clinical worsening events. Hyperglycemia indices correlated with well-validated variables that reflected the severity of IPAH, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide levels. Multivariable Cox regression analyses indicated that SHR (hazard ratio [HR] 1.328, 95% confidence intervals [CI]: 1.185, 1.489 per 0.1-unit increment, P

Abstract Spatial distribution orientations of blocks can cause significant errors in the discrete element model (DEM) calculation of soil-rock mixture (SRM). To avoid this error, spherical harmonic (SH) series whose harmonization degrees fixed at 15 were proposed for block reconstruction. This research refers to the case-history of a deep excavation rift valley spanning from the Mabian to Zhaojue section of the Leshan-Xichang Expressway, mainly containing moderately-weathered silty mudstone, in the Leshan City, Sichuan Province, China. The appropriate degree of finite-term SH series is selected by the volume, surface area. 100 blocks were scanned on site, and sphericity and angularity of the blocks were calculated. The sphericity and angularity of 50 reconstructed blocks were considered for the error analysis of SH method. Moreover, stochastic polyhedron method was considered for comparing different block reconstructions. The maximum block placement angle was defined to control the spatial distribution orientations of the blocks. Large scale direct tests were carried. Numerical simulations of large-scale direct shear tests were conducted to study the influence of the spatial distribution orientations of the blocks on the mechanical properties of the SRMs. The results revealed that the finite-term SH series fixed at 15 accurately reflected the shape characteristics and mechanical behaviors of actual blocks. The spatial distribution orientations of the blocks had a minimal impact on the friction angle and cohesion of SRM constructed through the SH method. The SRMs developed via the SH method exhibited marginal variations in contact force and anisotropy index of contact across diverse block placement strategies. The evolution of coordination number was closer when employing the SH method under varied block placement methods. Blocks reconstructed by the SH method, could mitigate errors in DEM calculation caused by the spatial distribution orientations of the blocks.

Abstract Bone tissue engineering aims to harness materials to develop functional bone tissue to heal ‘critical-sized’ bone defects. This study examined a robust, coated poly(caprolactone) trimethacrylate (PCL-TMA) 3D-printable scaffold designed to augment bone formation. Following optimisation of the coatings, three bioactive coatings were examined, i) elastin-like polypeptide (ELP), ii) poly(ethyl acrylate) (PEA), fibronectin (FN) and bone morphogenetic protein-2 (BMP-2) applied sequentially (PEA/FN/BMP-2) and iii) both ELP and PEA/FN/BMP-2 coatings applied concurrently. The scaffold material was robust and showed biodegradability. The coatings demonstrated a significant (p

Abstract Background Synpolydactyly (SPD) is mainly caused by mutations of polyalanine expansion (PAE) in the transcription factor gene HOXD13 and the involved cell types and signal pathway are still not clear possible pathways and single-cell expression characteristics of limb bud in HOXD13 PAE mice was analyzed in this study. Method We investigated a previous study of a mouse model with SPD and conducted weighted gene co-expression network analysis (WGCNA) using a single-cell RNA sequencing dataset from limb bud cells of SPD mouse model of HOXD13 + 7A heterozygote. Results Analysis of WGCNA revealed that synpolydactyly-associated Hoxd13 PAEs alter the immune response and osteoclast differentiation, and enhance DNA replication. Bmp4, Hand2, Hoxd12, Lnp, Prrx1, Gmnn, and Cdc6 were found to play potentially key roles in synpolydactyly. Conclusions These findings evaluated the main genes related to SPD with PAE mutations in HOXD13 and advance our understanding of human limb development.

Introduction Previous studies have suggested that adolescents may smoke cigarettes to control weight, but relevant research is scarce in Chinese youth. This study was conducted to examine the associations of weight control related behaviors with cigarette smoking in Chinese students. Methods This was a secondary analysis of data for 24835 middle and high school students drawn from the 2022 Zhejiang Youth Risk Behavior Survey of China which collected self-reported information of cigarette smoking, weight control strategies and other health-related behaviors. Multivariable logistic regression models were used to estimate the adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for the study associations. Results Overall, there were 998 (4.02%) current cigarette smokers in this wave of the Zhejiang YRBS (2022). Neither trying to control weight nor healthy weight control behavior of exercising was associated with current cigarette smoking (AOR=1.15; 95% CI: 0.97–1.37 and AOR=1.01; 95% CI: 0.85–1.20, respectively). Meanwhile, unhealthy weight control behaviors of taking laxatives (AOR=1.52; 95% CI: 1.03–2.26), taking diet pills (AOR=1.82; 95% CI: 1.26–2.62), dieting (AOR=1.24; 95% CI: 1.04–1.49), and fasting (AOR=1.81; 95% CI: 1.40–2.34) were significantly associated with increased odds of current cigarette smoking. Conclusions Screening and developing interventions for unhealthy weight control behaviors should be considered as part of smoking prevention programs among adolescents.

Abstract Background Our previous genome‑wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated. Methods We assessed the association between variant rs912304 and T1D, as well as islet autoimmunity and islet function, stratified by the diagnosed age of 12. We used epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to prioritize the most likely functional variant and potential causal gene. We also performed functional experiments to evaluate the role of the causal gene on islet function and its related mechanisms. Results We identified rs912304 as a risk variant for T1D subgroups with diagnosed age ≥ 12 but not

Abstract Background Recently, the C3-epimer of 25-hydroxyvitamin D [C3-epi-25(OH)D] has become a topic of interest among 25-hydroxyvitamin D [25(OH)D] metabolites. Although it can lead to an overestimation of vitamin D storage, its relationship with disease occurrence remains controversial, possibly related to the great extent of tracking of 25(OH)D by C3-epi-25(OH)D over time. This study aimed to investigate the differential performance of C3-epi-25(OH)D3 and its percentage [%C3-epi-25(OH)D3] with respect to 20 common paediatric diseases. Methods This study involved 805 healthy children and adolescents and 2962 patients with common paediatric diseases. We investigated sex, age, and seasonal differences in C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 levels; their variations on 20 common paediatric diseases; and their degree of correlation with 25(OH)D3 levels and various diseases. Results Among the healthy underage participants, C3-epi-25(OH)D3 and %C3-epi-25(OH)D3 changed similarly, with no sex differences. Moreover, their levels were higher in the infant period than in the other periods (t = 5.329–5.833, t = 4.640–5.711, all Padj

In this study, a dense WS2 coating was deposited via high-power impulse magnetron sputtering (HiPIMS) after solving the glow discharge problem, and it was compared with WS2 coating deposited via radio frequency (RF) sputtering. The latter showed a columnar growth, with a loose and porous microstructure. The columnar crystal growth of the former was inhibited, resulting in a more compact coating structure and a more uniform, flatter and smoother surface. Therefore, the structure and tribological properties of WS2 coating prepared via HiPIMS were investigated under different loads and frictional frequencies. Under low loads (up to 15 N), the coefficient of friction (COF) decreased with polishing wear mechanism. Under a high load of 20 N, the COF rapidly increased, the wear rate was the highest, and the wear mechanism changed from polishing to abrasive wear. At low frequencies (5 and 10 Hz), the coating had a low and stable COF, good wear resistance and the wear mechanism was abrasive wear. At high frequencies (≥15 Hz), the COF and wear rates rapidly increased and the wear mechanism changed from abrasive to adhesive wear and plastic fracture. However, the friction and wear rates were similar across different wear mechanisms.

The effects of Nb and Ni contents on the precipitation of the Ni16Nb6Si7-G phase and the resulting hardening behavior in Fe–20Cr ferritic alloys were systematically investigated using micro-hardness, electron microscopy, and atom probe techniques. The results demonstrate that an optimal Nb content of ∼0.75 wt. % promotes the precipitation of the Ni16Nb6Si7-G phase, leading to a maximum micro-hardness of approximately 430 H V when aged at 560 °C for 24 h. Excess Nb content (>0.75 wt. %) introduces the Fe2Nb-Laves phase at grain boundaries and within the grains, which competes with the G-phase for precipitation. Conversely, an increase in Ni content effectively raises the dissolution temperature of the Ni16Nb6Si7-G phase to approximately 850 °C. The austenite phase begins to form when the Ni content exceeds 4 wt. %. Finally, the strengthening effect of the Ni16Nb6Si7-G phase and its underlying competition precipitation with the Fe2Nb-Laves phase as well as the possible benefit of inducing austenite phase was discussed in the context of developing 20Cr ferritic alloys with high strength and good ductility. These findings provide valuable insights into the influence of Nb and Ni contents on the microstructural evolution and mechanical properties of the newly developed 20Cr alloy, which may be helpful in guiding the design of high performance ferritic alloys by optimizing composition and heat treatment processes.

Objective To explore the predictive factors of ICU-acquired weakness in critically ill elderly patients and to investigate their predictive value in clinical diagnosis. Methods An observational cohort study was conducted on patients admitted to the department of critical care medicine at Beijing Fu xing Hospital Capital Medical University, from June 2017 to October 2018. Muscle strength was assessed using the medical research council score on the day the patients regained consciousness. Based on the clinical muscle strength assessment results, patients were divided into the experimental group (muscle strength score < 48 scores) and the control group (≥48 scores) . Relevant factors for both groups were collected and compared. Multivariate logistic regression analysis was used to assess the independent risk factors for ICU-acquired weakness in critically ill elderly patients. The predictive value of each indicator for ICU-acquired weakness on elderly patients was evaluated using ROC curves. Results A total of 62 awake elderly critically ill patients were collected. Among them, 30 patients diagnosed with ICU-acquired weakness (prevalence rate of 48.39% ) were designated as the experimental group, and 32 patients without ICU-acquired weakness were designated as the control group. Significant differences were found between the two groups in terms of acute physiology and chronic health evaluation (APACHE) Ⅱ scores, sequential organ failure assessment scores, duration of systemic inflammatory response syndrome, duration of sepsis, septic shock, duration of shock, multiple organ dysfunction and its duration, use of norepinephrine and its duration, duration of mechanical ventilation, use of neuromuscular blocking agents and their duration, hypocalcemia, and electrolyte disturbances (P < 0.05) . Multivariate logistic regression analysis indicated that APACHE Ⅱ score and duration of norepinephrine use were independent risk factors for ICU-acquired weakness in elderly critically ill patients (P < 0.05) . The ROC curve suggested that the optimal predictive performance was achieved when norepinephrine was used for more than 3 days and the APACHE Ⅱ score was greater than 20 points. Conclusion In elderly critically ill patients, APACHE Ⅱ score and duration of norepinephrine use are independent risk factors and good predictive indicators for ICU-acquired weakness.

Abstract By analyzing e + e − annihilation data corresponding to an integrated luminosity of 2.93 fb −1 collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, the first observation of the semileptonic decays D 0 → K S 0 π − π 0 e + ν e $$ {D}^0\to {K}_S^0{\pi}^{-}{\pi}^0{e}^{+}{\nu}_e $$ and D + → K S 0 π + π − e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^{+}{\pi}^{-}{e}^{+}{\nu}_e $$ is reported. In the hypothesis that all events correspond to K 1(1270) decays, the branching fractions are measured to be B D 0 → K 1 1270 − → K S 0 π − π 0 e + ν e = 1.69 − 0.46 + 0.53 ± 0.15 × 10 − 4 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}\left(\to {K}_S^0{\pi}^{-}{\pi}^0\right){e}^{+}{\nu}_e\right)=\left({1.69}_{-0.46}^{+0.53}\pm 0.15\right)\times {10}^{-4} $$ and B D + → K ¯ 1 1270 0 → K S 0 π + π − e + ν e = 1.47 − 0.40 + 0.45 ± 0.14 × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0\left(\to {K}_S^0{\pi}^{+}{\pi}^{-}\right){e}^{+}{\nu}^e\right)=\left({1.47}_{-0.40}^{+0.45}\pm 0.14\right)\times {10}^{-4} $$ with statistical significance of 5.4σ and 5.6σ, respectively. When combined with measurements of the K 1(1270) → K + π − π decays, the absolute branching fractions are determined to be B D 0 → K 1 1270 − e + ν e = 1.08 − 0.13 − 0.10 + 0.14 + 0.08 ± 0.21 × 10 − 3 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}{e}^{+}{\nu}_e\right)=\left({1.08}_{-0.13-0.10}^{+0.14+0.08}\pm 0.21\right)\times {10}^{-3} $$ and B D + → K ¯ 1 1270 0 e + ν e = 1.70 − 0.23 + 0.26 ± 0.13 ± 0.35 × 10 − 3 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0{e}^{+}{\nu}_e\right)=\left({1.70}_{-0.23}^{+0.26}\pm 0.13\pm 0.35\right)\times {10}^{-3} $$ . The first and second uncertainties are statistical and systematic, respectively, and the third uncertainties originate from the assumed branching fractions of the K 1(1270) → Kππ decays.

Abstract Interpreting the clinical significance of putative splice-altering variants outside canonical splice sites remains difficult without time-intensive experimental studies. To address this, we introduce Parallel Splice Effect Sequencing (ParSE-seq), a multiplexed assay to quantify variant effects on RNA splicing. We first apply this technique to study hundreds of variants in the arrhythmia-associated gene SCN5A. Variants are studied in ‘minigene’ plasmids with molecular barcodes to allow pooled variant effect quantification. We perform experiments in two cell types, including disease-relevant induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The assay strongly separates known control variants from ClinVar, enabling quantitative calibration of the ParSE-seq assay. Using these evidence strengths and experimental data, we reclassify 29 of 34 variants with conflicting interpretations and 11 of 42 variants of uncertain significance. In addition to intronic variants, we show that many synonymous and missense variants disrupted RNA splicing. Two splice-altering variants in the assay also disrupt splicing and sodium current when introduced into iPSC-CMs by CRISPR-Cas9 editing. ParSE-seq provides high-throughput experimental data for RNA-splicing to support precision medicine efforts and can be readily adopted to study other loss-of-function genotype-phenotype relationships.

Abstract Background Older adults are vulnerable to social isolation due to declining physical and cognitive function, decreased interpersonal interactions, and reduced outdoor activities after retirement. This study aimed to develop and validate a predictive model to assess the risk of social isolation among older adults in China. Methods Using data from the 2011 China Health and Retirement Longitudinal Study (CHARLS). The study cohort was randomly divided into training and validation groups in a 70:30 ratio. We used least absolute shrinkage and selection operator (LASSO) regression analysis with tenfold cross-validation to identify optimal predictive factors and examined the correlates of social isolation using logistic regression. A nomogram was constructed for the predictive model, and its accuracy was assessed using calibration curves. The predictive performance of the model was assessed using area under the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results From the 2011 CHARLS database, 4,747 older adults were included in the final analysis, of whom 1,654 (34.8%) experienced social isolation. Multifactorial logistic regression identified educational level, marital status, gender, physical activity, physical self -maintenance ability, and number of children as predictive factors for social isolation. The predictive model achieved an AUC of 0.739 (95%CI = 0.722–0.756) in the training set and 0.708 (95%CI = 0.681–0.735) in the validation set. The Hosmer-Lemeshow test yielded P values of 0.111 and 0.324, respectively (both P > 0.05), indicating significant agreement between the nomogram and observed outcomes. The nomogram showed excellent predictive ability according to ROC and DCA. Conclusions The predictive model developed to assess the risk of social isolation in the Chinese older adults shows promising utility for early screening and intervention by clinical healthcare professionals.

Dishevelled 2 (Dvl2) is a key mediator of the Wingless/Wnt signaling pathway that regulates cell proliferation, migration, and immune function. However, little is known about the role of macrophage Dvl2 in modulating NOD1-mediated pyroptosis and hepatocyte death in oxidative stress-induced inflammatory liver injury. In a mouse model of oxidative stress-induced liver inflammation, mice with myeloid-specific Dvl2 knockout (Dvl2M−KO) displayed exacerbated ischemia/reperfusion (IR) stress-induced hepatocellular damage with increased serum ALT levels, oxidative stress, and proinflammatory mediators. Unlike in Dvl2FL/FL controls, Dvl2M−KO enhanced NOD1, caspase-1, GSDMD, and NF-κB activation in liver macrophages after IR. Interestingly, IR stress enhanced YAP colocalized with HSF1 in Dvl2FL/FL macrophages, while macrophage Dvl2 deficiency reduced YAP and HSF1 colocalization in the nucleus under inflammatory conditions. Importantly, Dvl2 deletion diminished nuclear YAP interacted with HSF1 and augmented NOD1/caspase-1 and GSDMD activation in response to inflammatory stimulation. However, Dvl2 activation increased YAP interaction with HSF1 and activated HSF1 target gene eEF2, inhibiting NOD1/caspase-1, GSDMD, and NF-κB activity. Moreover, macrophage eEF2 deletion increased the NOD1-caspase-1 interaction, GSDMD activation, HMGB1 release, and hepatocyte LDH release after macrophage/hepatocyte co-culture. Adoptive transfer of eEF2-expressing macrophages in Dvl2M−KO mice alleviated IR-triggered liver inflammation and hepatocellular damage. Therefore, macrophage Dvl2 deficiency promotes NOD1-mediated pyroptosis and exacerbates IR-induced hepatocellular death by disrupting the YAP-HSF1 axis. eEF2 is crucial for modulating NOD1-driven pyroptosis, inflammatory response, and hepatocyte death. Our findings underscore a novel role of macrophage Dvl2 in modulating liver inflammatory injury and imply the therapeutic potential in organ IRI and transplant recipients.

With the increasing annual production of Lentinula edodes, the residues of Lentinus edodes are mass produced and wasted every year. In order to further explore the added value and effective utilization of Lentinus edodes, we studied the lipid-lowering efficacy and liver protective effect of Lentinus edodes soluble dietary fiber in mice on high-fat diet. Project team from Lentinus edodes extracted soluble dietary fiber, and its physicochemical properties, selected 30 male mice, randomly divided into normal group (N), high fat diet group (F), add low dose dietary fiber high fat diet (FL), add medium dose dietary fiber high fat diet group (FM), add high dose dietary fiber high fat diet group (FH) five groups. After 4 weeks, we assessed general state, organ conditions, liver status, blood parameters, expression of hepatic lipid metabolism genes, mRNA levels of key hepatic lipid metabolism genes. The results showed that the molecular weight of soluble dietary fiber is about 17.029 kDa, and the monosaccharides such as galactose, glucose and mannitol are connected by β-glycosidic bond. The soluble dietary fiber of Lentinus edodes can effectively slow the weight growth due to high-fat diet, delay liver tissue lesions, reduce the levels of ALT, AST, ACP, LDL-C, TG, TV, FFA, SOD, GSH and MDA, and increase the levels of γ-GT, HDL-C and CAT in blood. Lentinus edodes soluble dietary fiber decreased the expression of AMPKα and SREBP-2 in the liver, and increased the expression of PPARα, ACS, CPT1a, CYP7A1. It is proved that the soluble dietary fiber of Lentinus edodes can alleviate the organ fat accumulation caused by high-fat diet to some extent, effectively combat the liver injury, oxidative stress pressure and lipid metabolism disorder caused by high-fat diet, and provide an experimental basis for the subsequent effective use of soluble dietary fiber of Lentinus edodes in fat reduction.

In order to study the seismic performance of Dowel-Slot Grouting Assembly Station, the displacement and stress changes of the station and the cast-in-place station under horizontal, vertical and horizontal-vertical coupled earthquakes were compared by the finite element numerical simulation method based on a subway station in Changchun. The results indicate that the two stations have the same stress concentration position and the same weak point under different seismic actions, and both meet the aseismic requirements. Compared with the traditional cast-in-place station, the assembly station has obvious advantages in vertical seismic performance, but the horizontal seismic ability is relatively weak, and the difference of the displacement Angle between layers is 20%~60%. Compared with the difference of 46.43% in the maximum seismic stress and 28.51% in the vertical seismic time, the difference of 58.02% in the coupled seismic action shows that the stress concentration is more obvious. It provides reference for further optimization of assembly station.

IntroductionNightmares and depression are prevalent issues among adolescents. This study explores the relationship between nightmares and depression, focusing on the mediating role of anxiety and the moderating effect of ageMethodsA total of 210 adolescents aged 13 to 24 were surveyed using the Nightmare Distress Questionnaire (NDQ-CV), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). They also underwent niacin skin flushing response (NSFR) testing to explore physiological correlations. A moderated mediation model was applied to assess the relationships between nightmares, anxiety, and depression. Spearman correlation analysis was used to analyze the relationship between nightmares and NSFRResultsNightmares did not directly lead to depression, but anxiety served as a full mediator in this relationship. Age had no significant moderating effect. Additionally, a significant negative correlation between nightmares and NSFR was observedConclusionNightmares contribute to anxiety, which can lead to depression in adolescents, suggesting that clinicians can identify and intervene with nightmares in adolescents to minimize the onset of psychological disorders. The study also highlights a possible connection between nightmares and NSFR, suggesting further research is needed to understand the physiological mechanisms

Abstract Respiratory diseases pose a significant global health burden, with challenges in early and accurate diagnosis due to overlapping clinical symptoms, which often leads to misdiagnosis or delayed treatment. To address this issue, we developed LungDiag, an artificial intelligence (AI)‐based diagnostic system that utilizes natural language processing (NLP) to extract key clinical features from electronic health records (EHRs) for the accurate classification of respiratory diseases. This study employed a large cohort of 31,267 EHRs from multiple centers for model training and internal testing. Additionally, prospective real‐world validation was conducted using 1142 EHRs from three external centers. LungDiag demonstrated superior diagnostic performance, achieving an F1 score of 0.711 for top 1 diagnosis and 0.927 for top 3 diagnoses. In real‐world testing, LungDiag outperformed both human experts and ChatGPT 4.0, achieving an F1 score of 0.651 for top 1 diagnosis. The study emphasizes the potential of LungDiag as an effective tool to support physicians in diagnosing respiratory diseases more accurately and efficiently. Despite the promising results, further large‐scale multicenter validation with larger sample sizes is still needed to confirm its clinical utility and generalizability.

ObjectiveThis study aims to investigate the associations between MTNR1B rs724030 A>G variant and prediabetes risk, along with their correlations with clinical features, including plasma glucose and serum insulin levels during oral glucose tolerance test (OGTT), islet function, insulin resistance, and plasma lipid levels. In particular, we investigated whether there are sex dimorphisms in the impact of this variant on islet function/insulin resistance.MethodsWe included 3415 glucose-tolerant healthy and 1744 prediabetes individuals based on OGTT. Binary logistic regression was performed to evaluate the relationships between rs724030 in MTNR1B and prediabetes under the additive model. Additionally, multiple linear regression was utilized to investigate the associations between this variant and glycemic-related quantitative traits and lipid levels.ResultsWhile no association was observed between the rs724030 variant in MTNR1B and prediabetes risk in the overall cohort (P > 0.05), we found the G allele of this variant was associated with higher fasting and 30-minute plasma glucose levels, decreased Insulinogenic Index (IGI), and oral disposition index (DIo) (P = 0.009, 0.001, 0.001, and 0.007, respectively) in the normal glucose tolerance (NGT) individuals with normal BMI levels. Furthermore, we also found significant associations between this variant and IGI, corrected insulin response (CIR), and DIo (All P < 0.001) in female individuals whose waist-to-hip ratio (WHR) is greater than 0.85, with considerable heterogeneity (Phet = 0.009, 0.030, and 0.049, respectively) to male participants in the NGT individuals, but not in the impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) individuals. Additionally, no association was observed between this variant and insulin clearance (All P > 0.05).ConclusionsThe MTNR1B rs724030 variant contributes to glycemic traits and islet function, and its effects have sex dimorphisms in the NGT individuals after stratifying by WHR. All these findings provide a basis for accurately assessing islet function in healthy populations and offer a new perspective on precision prevention.

Abstract Bone tissue engineering seeks to develop treatment approaches for nonhealing and large bone defects. An ideal biodegradable scaffold will induce and support bone formation. The current study examines bone augmentation in critical‐sized bone defects, using functionalized scaffolds, with the hypothesized potential to induce skeletal cell differentiation. 3D printed, porous poly(caprolactone) trimethacrylate (PCL‐TMA900) scaffolds are applied within a murine femur defect, stabilized by a polyimide intramedullary (IM) pin. The PCL‐TMA900 scaffolds are coated with i) elastin‐like polypeptide (ELP), ii) poly(ethyl acrylate) (PEA)/fibronectin (FN)/bone morphogenetic protein‐2 (PEA/FN/BMP‐2), iii) both ELP and PEA/FN/BMP‐2, or iv) Laponite nanoclay binding BMP‐2. Sequential microcomputed tomography (µCT) and histological analysis are performed. PCL‐TMA900 is robust and biocompatible and when coated with the nanoclay material Laponite and BMP‐2 induce consistent, significant bone formation compared to the uncoated PCL‐TMA900 scaffold. Critically, the BMP‐2 is retained, due to the Laponite, producing bone around the scaffold in the desired shape and volume, compared to bone formation observed with the positive control (collagen sponge/BMP‐2). The ELP and/or PEA/FN/BMP‐2 scaffolds do not demonstrate significant or consistent bone formation. In summary, Laponite/BMP‐2 coated PCL‐TMA900 scaffolds offer a biodegradable, osteogenic construct for bone augmentation with potential for development into a large scale polymer scaffold for clinical translation.

ObjectiveFermented foods (FFs) may theoretically benefit irritable bowel syndrome (IBS) symptoms, but the role of FFs for IBS patients in the real world is inconsistent and has not been systematically assessed. We performed a systematic review and meta-analysis to examine this issue.MethodsPubMed, MEDLINE, Embase and Cochrane Library databases were searched up to August 2024. Randomized controlled trials (RCTs) investigating the efficacy of FFs in IBS were eligible for the analysis. Two authors independently screened studies and extracted data. Data were pooled using relative risk (RR) of dichotomous data and standardized mean difference (SMD) for continuous data.ResultsA total of 16 RCTs with 1,264 IBS patients were included. There were 12 RCTs involving 975 patients providing primary outcomes which was defined as symptom relief. The proportion of symptom relief was associated with the administration of FFs (RR 1.22, 95% CI 1.04–1.42, p = 0.01, I2 = 0%). For secondary outcomes, FFs also exerted a beneficial effect on global symptoms scores (SMD = −0.15; 95% CI −0.29 to −0.02, p = 0.02, I2 = 46%), but no significant improvement on abdominal pain scores and bloating scores. Subgroup analysis showed that fermented milk had a beneficial effect on symptom relief (RR 1.19, 95% CI 1.01 to 1.39, p = 0.04, I2 = 0%).ConclusionFermented foods, especially fermented milk with probiotics properties, appear to be efficacious in irritable bowel syndrome. However, given the limitations of current evidence, this conclusion should be interpreted with caution.Systematic Review RegistrationThis study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42024576608.

ObjectiveTo assist in the rapid clinical identification of brain tumor types while achieving segmentation detection, this study investigates the feasibility of applying the deep learning YOLOv5s algorithm model to the segmentation of brain tumor magnetic resonance images and optimizes and upgrades it on this basis.MethodsThe research institute utilized two public datasets of meningioma and glioma magnetic resonance imaging from Kaggle. Dataset 1 contains a total of 3,223 images, and Dataset 2 contains 216 images. From Dataset 1, we randomly selected 3,000 images and used the Labelimg tool to annotate the cancerous regions within the images. These images were then divided into training and validation sets in a 7:3 ratio. The remaining 223 images, along with Dataset 2, were ultimately used as the internal test set and external test set, respectively, to evaluate the model’s segmentation effect. A series of optimizations were made to the original YOLOv5 algorithm, introducing the Atrous Spatial Pyramid Pooling (ASPP), Convolutional Block Attention Module (CBAM), Coordinate Attention (CA) for structural improvement, resulting in several optimized versions, namely YOLOv5s-ASPP, YOLOv5s-CBAM, YOLOv5s-CA, YOLOv5s-ASPP-CBAM, and YOLOv5s-ASPP-CA. The training and validation sets were input into the original YOLOv5s model, five optimized models, and the YOLOv8s model for 100 rounds of iterative training. The best weight file of the model with the best evaluation index in the six trained models was used for the final test of the test set.ResultsAfter iterative training, the seven models can segment and recognize brain tumor magnetic resonance images. Their precision rates on the validation set are 92.5, 93.5, 91.2, 91.8, 89.6, 90.8, and 93.1%, respectively. The corresponding recall rates are 84, 85.3, 85.4, 84.7, 87.3, 85.4, and 91.9%. The best weight file of the model with the best evaluation index among the six trained models was tested on the test set, and the improved model significantly enhanced the image segmentation ability compared to the original model.ConclusionCompared with the original YOLOv5s model, among the five improved models, the improved YOLOv5s-ASPP model significantly enhanced the segmentation ability of brain tumor magnetic resonance images, which is helpful in assisting clinical diagnosis and treatment planning.