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To examine mental health status, COVID-19 vaccine intention and barriers among college students in the U.S. Participants: Students (n = 337) registered at a large public university in 2021. Methods: Cross-sectional survey data were collected online and analyzed using independent samples t test, chi-square test, and one-way ANOVA. Results: Compared to male students, females reported greater anxiety (p < 0.05) and fear (p < 0.01). Hispanic participants reported increased anxiety level and the least positive pandemic coping strategies (both p < 0.05) across the ethnic groups. Black students were the racial group with the lowest trust in the safety and effectiveness of COVID-19 vaccine (p < 0.05). Vaccine intention was positively correlated with factors such as vaccine safety measures, and perceptions toward vaccination (both p < 0.001). Conclusions: These gender- and ethnicity- based mental health struggles should be addressed immediately for better health and vaccine promotion outcomes amid the COVID-19 pandemic.

Abstract Optical Kerr effect, in which input light intensity linearly alters the refractive index, has enabled the generation of optical solitons, supercontinuum spectra, and frequency combs, playing vital roles in the on-chip devices, fiber communications, and quantum manipulations. Especially, terahertz Kerr effect, featuring fascinating prospects in future high-rate computing, artificial intelligence, and cloud-based technologies, encounters a great challenge due to the rather low power density and feeble Kerr response. Here, we demonstrate a giant terahertz frequency Kerr nonlinearity mediated by stimulated phonon polaritons. Under the influences of the giant Kerr nonlinearity, the power-dependent refractive index change would result in a frequency shift in the microcavity, which was experimentally demonstrated via the measurement of the resonant mode of a chip-scale lithium niobate Fabry-Pérot microcavity. Attributed to the existence of stimulated phonon polaritons, the nonlinear coefficient extracted from the frequency shifts is orders of magnitude larger than that of visible and infrared light, which is also theoretically demonstrated by nonlinear Huang equations. This work opens an avenue for many rich and fruitful terahertz Kerr effect based physical, chemical, and biological systems that have terahertz fingerprints.

Abstract Background Inadequate nerve regeneration and an inhibitory local microenvironment are major obstacles to the repair of spinal cord injury (SCI). The activation and differentiation fate regulation of endogenous neural stem cells (NSCs) represent one of the most promising repair approaches. Metformin has been extensively studied for its antioxidative, anti-inflammatory, anti-aging, and autophagy-regulating properties in central nervous system diseases. However, the effects of metformin on endogenous NSCs remains to be elucidated. Methods The proliferation and differentiation abilities of NSCs were evaluated using CCK-8 assay, EdU/Ki67 staining and immunofluorescence staining. Changes in the expression of key proteins related to ferroptosis in NSCs were detected using Western Blot and immunofluorescence staining. The levels of reactive oxygen species, glutathione and tissue iron were measured using corresponding assay kits. Changes in mitochondrial morphology and membrane potential were observed using transmission electron microscopy and JC-1 fluorescence probe. Locomotor function recovery after SCI in rats was assessed through BBB score, LSS score, CatWalk gait analysis, and electrophysiological testing. The expression of the AMPK pathway was examined using Western Blot. Results Metformin promoted the proliferation and neuronal differentiation of NSCs both in vitro and in vivo. Furthermore, a ferroptosis model of NSCs using erastin treatment was established in vitro, and metformin treatment could reverse the changes in the expression of key ferroptosis-related proteins, increase glutathione synthesis, reduce reactive oxygen species production and improve mitochondrial membrane potential and morphology. Moreover, metformin administration improved locomotor function recovery and histological outcomes following SCI in rats. Notably, all the above beneficial effects of metformin were completely abolished upon addition of compound C, a specific inhibitor of AMP-activated protein kinase (AMPK). Conclusion Metformin, driven by canonical AMPK-dependent regulation, promotes proliferation and neuronal differentiation of endogenous NSCs while inhibiting ferroptosis, thereby facilitating recovery of locomotor function following SCI. Our study further elucidates the protective mechanism of metformin in SCI, providing new mechanistic insights for its candidacy as a therapeutic agent for SCI.

A substantial reduction in groundwater level, exacerbated by coal mining activities, is intensifying water scarcity in western China’s ecologically fragile coal mining areas. China’s national strategic goal of achieving a carbon peak and carbon neutrality has made eco-friendly mining that prioritizes the protection and efficient use of water resources essential. Based on the resource characteristics of mine water and heat hazards, an intensive coal–water–thermal collaborative co-mining paradigm for the duration of the mining process is proposed. An integrated system for the production, supply, and storage of mining companion resources is achieved through technologies such as roof water inrush prevention and control, hydrothermal quality improvement, and deep-injection geological storage. An active preventive and control system achieved by adjusting the mining technology and a passive system centered on multi-objective drainage and grouting treatment are suggested, in accordance with the original geological characteristics and dynamic process of water inrush. By implementing advanced multi-objective drainage, specifically designed to address the “skylight-type” water inrush mode in the Yulin mining area of Shaanxi Province, a substantial reduction of 50% in water drillings and inflow was achieved, leading to stabilized water conditions that effectively ensure subsequent safe coal mining. An integrated-energy complementary model that incorporates the clean production concept of heat utilization is also proposed. The findings indicate a potential saving of 8419 t of standard coal by using water and air heat as an alternative heating source for the Xiaojihan coalmine, resulting in an impressive energy conservation of 50.2% and a notable 24.2% reduction in carbon emissions. The ultra-deep sustained water injection of 100 m3·h−1 in a single well would not rupture the formation or cause water leakage, and 7.87 × 105 t of mine water could be effectively stored in the Liujiagou Formation, presenting a viable method for mine–water management in the Ordos Basin and providing insights for green and low-carbon mining.

Abstract Mine water inflow is an important basis for the formulation of mining plans and the utilization of groundwater resources. The mine water inflow is the result of the combined influence of many factors. The weight value of the influencing factors is calculated by the entropy method, and the order of importance of the factors is: precipitation > mining depth > cumulative mined-out area > aquifer thickness > mining area > mining height. The optimal univariate nonlinear regression model of mine water inflow to each influencing factor is obtained by factor scatter analysis and Matlab function programming. On this basis, combined with the weight values of factors, a multivariate nonlinear regression prediction model of mine water inflow based on weighting is innovatively established, which overcomes the defect that the traditional water inflow prediction method that cannot reflect the relative importance differences of various influencing factors. The multivariate weighted nonlinear regression model is used to predict the mine water inflow of typical coal mines, and the prediction results are compared with the linear regression model and the measured value. The results show that the prediction model of mine water inflow based on weighted multivariate nonlinear regression is accurate higher, with higher practical application value.

Abstract Random tensor networks (RTNs) have proved to be fruitful tools for modelling the AdS/CFT correspondence. Due to their flat entanglement spectra, when discussing a given boundary region R and its complement R ¯ $$ \overline{R} $$ , standard RTNs are most analogous to fixed-area states of the bulk quantum gravity theory, in which quantum fluctuations have been suppressed for the area of the corresponding HRT surface. However, such RTNs have flat entanglement spectra for all choices of R, R ¯ $$ \overline{R} $$ , while quantum fluctuations of multiple HRT-areas can be suppressed only when the corresponding HRT-area operators mutually commute. We probe the severity of such obstructions in pure AdS3 Einstein-Hilbert gravity by constructing networks whose links are codimension-2 extremal-surfaces and by explicitly computing semiclassical commutators of the associated link-areas. Since d = 3, codimension-2 extremal-surfaces are geodesics, and codimension-2 ‘areas’ are lengths. We find a simple 4-link network defined by an HRT surface and a Chen-Dong-Lewkowycz-Qi constrained HRT surface for which all link-areas commute. However, the algebra generated by the link-areas of more general networks tends to be non-Abelian. One such non-Abelian example is associated with entanglement-wedge cross sections and may be of more general interest.

Abstract Background β-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the β-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation. Results In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of β-catenin. Our analysis showed that a truncated β-catenin lacking both N- and C-terminal domains (ΔN148C) could robustly rescue the DE formation, whereas hyperactive β-catenin mutants with S33Y mutation or N-terminal deletion (ΔN90) had limited ability to induce DE lineage. Notably, the ΔN148C mutant exhibited significant nuclear translocation that was positively correlated with successful DE rescue. Transcriptomic analysis further uncovered that two weak β-catenin mutants lacking the C-terminal transactivation domain (CTD) activated primitive streak (PS) genes, whereas the hyperactive β-catenin mutants activated mesoderm genes. Conclusion Our study uncovered an unconventional regulatory function of β-catenin through weak transactivation, indicating that the levels of β-catenin activity determine the lineage bifurcation from mesendoderm into endoderm and mesoderm.

The exploitation of coal resources will destroy the aquifer structure, disturb the groundwater system and produce a new water cycle model. As the focus of coal supply and production, the western mining area is short of water resources and fragile in ecology. High-intensity and large-scale mining aggravates this disturbance and makes the hydrochemical process such as water-rock interaction more intense. The coal mining-motivated effect of groundwater system hydrochemistry behind it is a key scientific problem related to the prediction accuracy of coal mine safety mining and the protection of groundwater environment in green mining. In view of this, taking the Caojiatan coal mine in western Yushen mining area as an example, using the principles and methods of hydrogeochemistry, from the perspective of ‘what it is’, ‘why it is’ and ‘how it changes’, the results of mining-motivated effect, the process of mining-motivated effect, and the evolution trend of hydrochemistry are systematically studied. The results show that the groundwater in the study area can be divided into five clusters. Cluster Ⅰ represents the shallow groundwater dominated by Quaternary and weathered bedrock aquifers in the west wing of the mine field after coal mining. Cluster Ⅱ represents the mixing of groundwater before and after mining. Cluster Ⅲ represents the groundwater before mining. Cluster Ⅳ and Cluster Ⅴ mainly represent the groundwater of Yan’an Formation after mining. After coal mining, the proportion of HCO3–Ca and HCO3–Mg in the groundwater samples of the fourth and fifth sections of Zhiluo Formation and Yan’an Formation increased, the shallow groundwater quality after mining in the west wing of the mine field was the best as a whole, and the water quality of each aquifer has a tendency to evolve well and is not sensitive to the response of coal mining. The groundwater in the study area is controlled by the ion exchange, and the groundwater in the fourth and above aquifers of Yan’an Formation before coal mining is controlled by the dissolution of carbonate and silicate rocks. The shallow groundwater in the west wing of the mine field after coal mining is controlled by the dissolution of carbonate rocks. The groundwater in the aquifers of the Zhiluo Formation and the fourth and fifth sections of the Yan’an Formation is mainly controlled by the dissolution of silicate rocks and the oxidation of FeS2. The groundwater in the aquifers of the third and lower sections of the Yan’an Formation is mainly controlled by the dissolution of evaporated salt. Coal mining accelerates the circulation speed of groundwater and the hydraulic connection between aquifers. The resulting dilution effect and the discharge measures after mine water treatment are the reasons for the hydrochemical characteristics and water quality evolution of the aquifers in the fourth section of Yan'an Formation and above. In the future, we should continue to do a good job in the discharge of mine water after treatment, and pay attention to the trend of groundwater characteristics in the fifth section of Zhiluo Formation and Yan’an Formation evolving to shallow groundwater, so as to avoid misjudgment of the results of water inrush sources.

To explore the influence of confining pressure on the macro-meso mechanical characteristics of gas hydrate bearing coal (GHBC) under different boundary conditions, the biaxial discrete element tests were carried out subjected to the confining pressures of 12，16 and 20 MPa for GHBC with saturation of 80%. Firstly, the biaxial numerical models of GHBC were established for flexible and rigid boundaries, using the linear model of the rolling resistance and the parallel bonding model. These numerical models incorporated the influences of particle shape effect, the hydrate cementation and the heat-shrinkable pipe. Then, the reliability of the numerical model was verified, by comparing with the indoor test results (stress-strain curves, bulk strain curves, internal friction angle cohesion and specimen failure modes). It is found that the flexible boundary can better reflect the deviatoric, stress-axial strain, the shear expansion and the strength characteristics of the sample. Based on the established numerical model, the roles of the confining pressure and the boundary condition on the macro-meso mechanical properties of GHBC were clarified from the perspectives of the internal displacement field, the mean mechanical coordination number, the mean porosity, the contact force chain and the hydrate bond failure. The results show that: ① with the increase of confining pressure, the numerical sample with the rigid boundary mostly exhibits the single inclined plane shear failure, while that with the flexible boundary varies from the single fork shear failure to the single inclined plane shear failure. ② With the increase of confining pressure, for the two boundaries, the mean mechanical coordination numbers increase and the mean porosity decrease, leading to a denser and higher strength of the sample. ③ With the increase of confining pressure, the normal contact force between particles continues to increase, and the sample strength increases. The normal contact force distributed near the axial direction increases, while that near the horizontal direction varies weakly. The higher the confining pressure is, the more difference between the vertical and the horizontal normal contact forces have, the more prominent the anisotropy is. The normal contact force increases by 54.50%, at the flexible boundary, and increases by 45.70%, at the peak strength point, with the confining pressure increasing from 12 MPa to 20 MPa. ④ Under different confining pressures and boundary conditions, the samples fail with two different failure modes, tensile and shear. The samples mainly crack from the shear between the hydrate and coal. The research results reveal the mechanism of the influence of confining pressure on the strength deformation and failure of GHBC on the mesoscale.

Abstract Background Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR). Methods To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran’s Q-test and the MR Egger intercept test. Results The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209–2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044–1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062–2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039–1.425, P = 0.015). Conclusions Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.

Abstract Intrinsically stretchable organic photovoltaics have emerged as a prominent candidate for the next-generation wearable power generators regarding their structural design flexibility, omnidirectional stretchability, and in-plane deformability. However, formulating strategies to fabricate intrinsically stretchable organic photovoltaics that exhibit mechanical robustness under both repetitive strain cycles and high tensile strains remains challenging. Herein, we demonstrate high-performance intrinsically stretchable organic photovoltaics with an initial power conversion efficiency of 14.2%, exceptional stretchability (80% of the initial power conversion efficiency maintained at 52% tensile strain), and cyclic mechanical durability (95% of the initial power conversion efficiency retained after 100 strain cycles at 10%). The stretchability is primarily realised by delocalising and redistributing the strain in the active layer to a highly stretchable PEDOT:PSS electrode developed with a straightforward incorporation of ION E, which simultaneously enhances the stretchability of PEDOT:PSS itself and meanwhile reinforces the interfacial adhesion with the polyurethane substrate. Both enhancements are pivotal factors ensuring the excellent mechanical durability of the PEDOT:PSS electrode, which further effectively delays the crack initiation and propagation in the top active layer, and enables the limited performance degradation under high tensile strains and repetitive strain cycles.

Background: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Introduction: Cartilage defect (CD) is a common complication in osteoarthritis (OA). Impairment of chondrogenesis and cellular senescence are considered as hallmarks of OA development and caused failure of cartilage repair in most clinical CD cases. Exploring markers for cellular senescence in CD patients might provide new perspectives for osteoarthritic CD patients. In the present study, we aim to explore senescent markers in CD patients with OA to fabricate a senescence-targeted SMSC organoid hydrogel for cartilage repair. Methods: Clinical cartilage samples from cartilage defect patients were collected. Immunofluorescence staining of senescent markers and SA-β-Gal staining were used to detect the senescence state of SMSCs and chondrocytes in cartilage defect and OA patients. MicroRNA expression profiles of SMSC organoids and H2O2-treated SMSC organoids were analyzed and compared with high-throughput microRNA sequencing. Fluorescent in situ hybridization of miRNA were used to determine the expression level of miR-24 in SMSC organoids and cartilage samples. Interaction between miR-24 and its downstream target was analyzed via qRT-PCR, immunofluorescence and luciferase assay. Senescence-targeted miR-24 μS/SMSC organoid hydrogel (MSOH) was constructed for cartilage repair. Anti-senescence properties and chondrogenesis were determined in vitro for MSOH. Rats were used to evaluate the cartilage repair capacity of the MSOH hydrogel in vivo. Results: In this study, we found Osteoarthritic cartilage defect patients demonstrated upregulated cellular senescence in joint cartilage. MicroRNA sequencing demonstrated senescence marker miR-24 was negatively associated with cartilage impairment and cellular senescence in osteoarthritic CD patients. Moreover, miR-24 mimics alleviates cellular senescence to promote chondrogenesis by targeting downstream TAOK1. Also, miR-24 downregulated TAOK1 expression and promoted chondrogenesis in SMSC organoids. Senescence-targeted miR-24 μS/SMSC organoid hydrogel (MSOH) was constructed and demonstrated superior chondrogenesis in vitro. Animal experiments demonstrated that MSOH hydrogel showed better cartilage repairing effects and better maintained joint function at 24 weeks with low intra-articular inflammatory response after transplantation in rat joint. Single-cell RNA-seq of generated cartilage indicated that implanted MSOH could affect chondrocyte homeostatic state and alter the chondrocyte cluster frequency by regulating cellular glycolysis and OXPHOS, impacting cell cycle and ferroptosis to alleviate cellular senescence and prevent joint degeneration. Conclusion: Osteoarthritic cartilage defect patients demonstrated upregulated cellular senescence in joint cartilage. Senescence marker miR-24 was negatively associated with cartilage impairment in osteoarthritic CD patients. miR-24 attenuates chondrocytes senescence and promotes chondrogenesis in SMSC organoids through targeting TAOK1. Senescence-targeted miR-24 microsphere/SMSC organoid composite hydrogel could successfully repair cartilage defect in osteoarthritic microenvironment via enhanced miR-24/TAOK1 signaling pathway, suggesting MSOH might be a novel therapy for cartilage repair in osteoarthritic CD patients.

Abstract Disseminated intravascular coagulation (DIC) is considered to be the most common and lethal complication of sepsis. NLR-family pyrin domain-containing-3 (NLRP3) inflammasome plays an important role in host defense against microbial pathogens, and its deregulation may cause coagulation cascade and should be strictly managed. Here, we identified the deubiquitinase YOD1, which played a vital role in regulating coagulation in a NLRP3 inflammasome-dependent manner in sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA). YOD1 interacted with NLRP3 to remove K33-linked ubiquitination of NLRP3 based on its deubiquitinating enzyme activity and specifically inhibited expression of NLRP3 as well as activation of NLRP3 inflammasome. Deficiency of YOD1 expression enhanced NLRP3 inflammasome activation and coagulation both in vitro and in vivo. In addition, pharmacological inhibition of the NLRP3 effectively improved coagulation and alleviated organ injury in Yod1 −/− mice infected with MRSA. Thus, our study reported that YOD1 is a key regulator of coagulation during MRSA infection, and provided YOD1 as a potential therapeutic target for the treatment of NLRP3 inflammasome-related diseases, especially MRSA sepsis-induced DIC.

Abstract In this paper, we consider a little-studied observable in classical pure AdS3 gravity: the twist along a geodesic. The motivation is that the twist only supports on the geodesic so may be a candidate element in the center of the algebra in either entanglement wedge associated to the geodesic. We study the properties of the twist and get the following results. First, we get the system’s evolution generated by the twist, which exhibits a relative shift along the geodesic. Second, we show that the twist commutes with the length of the same geodesic, which supports the proposal that the twist is a candidate element in the center.

In order to explore the effect of hydrate formation and loading-unloading condition on the strain and permeability of gas hydrate bearing coal, the authors first measured the permeability of coal before and after gas hydrate formation, by using the triaxial testing machine for coupling action of stress, seepage, and chemical effect, as well as measured the strain and permeability of coal (three particle sizes: 0.425−0.850 mm (20−40 mesh), 0.250−0.425 mm (40−60 mesh), 0.180−0.250 mm (60−80 mesh) and three saturations: 40%, 60%, 80%) under the axial loading and confining unloading conditions. Then, the stress-strain curve was used to determine the deformation characteristic of coal during under loading and unloading conditions, the effect of hydrate formation, hydrate saturation and deviator stress on the coal permeability, the extend of coal permeability and volume expansion effect were quantitatively characterized by permeability loss rate formula and deformation angle formula. Furthermore, the influence mechanism of hydrate distribution mode was preliminarily discussed on the coal permeability with the theoretical permeability models. The results show that ① the influence of saturation on the variation law of coal permeability is more complicated. In general, with the increase of hydrate saturation, the greater the percentage of permeability reduction, the more significant the degree of blockage. The coal permeability obviously reduces after the formation of gas hydrate, with the range of reductions being 58.3%−83.3% (20−40 mesh), 61.5%−95.0% (40−60 mesh) and 81.8%−90.9% (60−80 mesh). The coal permeability decreases with the increase of hydrate saturation with a reduction between 55.6% and 86.1%. ② The axial strains of the coal exhibit three-stage process, including stability increasing, slowly increasing, and rapidly increasing with the increase of time. There is a certain correlation between the permeability and the strain of coal, and the permeability varies with the increase of deviator stress, in terms of quadratically increasing, decreasing and first increasing and then decreasing, the quadratic function can better predict the permeability variation law of gas hydrate bearing coal under mining stress disturbance. ③ Introducing the permeability loss rate, the permeability loss rate increases with the increase of the deviator stress applied on the coal under the condition of the same hydrate saturation. ④ Introducing the expansion deformation angle, the coal expansion deformation angle decreases from 19.0°−63.9° to 0.2°−38.2° with the increase of hydrate saturation under the condition of the same deviator stress, which indicates that the lower the hydrate saturation, the more significant effect of the coal expansion.

China is the country with the most complicated coal-forming and occurrence conditions in the world. The roof water disaster, caused by the diversity and complexity of the hydrogeological conditions of the coal seam roof, the mutuality and time-varying coupling of the mining overburden fracture field and the seepage field, and the uniqueness and harmfulness of the coal mine roof water inrush, is one of the main mine disasters in China, especially in the western coal mining area. In order to better understand the roof water disaster, promote the existing technology and explore new technologies to prevent and control such mine disasters, based on the comprehensive analysis of the law of roof water disaster accidents in China’s coal mines in recent years and the occurrence conditions, water inrush mode, dynamic characteristics and mechanical behavior of roof water-filled aquifers, the types and characteristics of roof water disasters are systematically divided. The disaster mechanism of the main categories and the existing prevention and control technologies of roof water disasters are reviewed, and the future development direction of roof water disaster prevention and control is prospected. The study found that: ① The main structure of roof water disaster includes five types: gushing (leaching) water in thick bedrock aquifer, water-sand coupling inrush in weak cementation layer of thin bedrock, water storage and energy storage water inrush in abscission layer space, skylight recharge water inrush, and surrounding rock burning and permeability enhancement. They are concentrated in the north of the Qinling Mountains-Huaihe River. Shaanxi, Inner Mongolia and Ningxia are the main gathering places of roof water disasters. ② Mining-induced “Z” -type separation space is developed in the primary fractures of overlying strata under the super-thick bedrock aquifer, resulting in a large area of water gushing (leaching) in the stope. The fracture conditions of composite key strata are established, and the power source of water-sand coupling inrush disaster in weak cemented layer of thin bedrock is clarified. The critical criterion for assessing the instability of water inrush from bed separation is constructed, and the water inrush from bed separation is divided into three modes: static load disturbance, “dynamic+static” load composite disturbance and repeated disturbance of composite coal seam mining. The lack of laterite aquiclude and the mining-induced deterioration damage in the weak area of laterite are the main causes of skylight leakage recharge. The surrounding rock is burnt to increase permeability and porosity, and a new water-bearing structure is formed after receiving water supplement from adjacent water sources. Under the induction of mining, burnt rock water pours into stope and causes water disaster accidents. ③ The current prevention and control technology system of coal mine roof water disaster “exploration-discharge-treatment” is evaluated, and the future development direction is put forward, such as the conjugate linkage of upper and lower wells, the drilling-mining (excavation) high-level collaborative geological exploration system, the geological guarantee work guided by the “three zones” division of water prevention and control, the green mining and water prevention concept of “coal-water-ecology” multi-objective co-management, and the digital intelligence and transparent mine hydrogeological disaster information maintenance system.

Abstract Background Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM’s unique cell states and molecular landscape for targeted therapeutic interventions. Methods Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings. Results This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation. Conclusion Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.

Abstract Osteosarcoma (OS) is the most prevalent primary malignancy of bone in children and adolescents. It is extremely urgent to develop a new therapy for OS. In this study, the GSE14359 chip from the GEO database was used to screen differentially expressed genes in OS. DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferation and migration of OS cells in vitro, as well as the growth of tumors in vivo, while the apoptosis rate was increased. Bioinformatics analysis revealed that CD44 and Rac signaling pathway were the downstream molecule and pathway of POLE2, which were inhibited by knockdown of POLE2. POLE2 reduced the ubiquitination degradation of CD44 by acting on MDM2. Moreover, knockdown of CD44 inhibited the tumor-promoting effects of POLE2 overexpression on OS cells. In conclusion, POLE2 augmented the expression of CD44 via inhibiting MDM2-mediated ubiquitination, and then activated Rac signaling pathway to influence the progression of OS, indicating that POLE2/CD44 might be potential targets for OS treatment.

Since the economic reform and opening up, the exploitation of mineral resources has made significant contributions to the economic development of China. However, due to the non-renewable nature of most mineral resources, a considerable number of mines are facing resource depletion and closure. How to develop and utilize the positive environmental effects left by these mines will become a crucial support for extending the mining industry value chain, ensuring green and low-carbon energy development, and achieving China’s strategic goals of “carbon peak” and “carbon neutrality”. To scientifically develop environmentally positive resources in mines, this study focused on four categories of goals in the development and utilization of positive environmental effects in mines: resources, energy, popular science and entertainment, and ecological carbon sinks. Based on the “Supply - Demand - Development” (SDD) constraint combination of mining supply ontology characteristics, specific market demands, and development and utilization conditions, a comprehensive evaluation constraint system was developed, consisting of 6 first-level constraints and 38 second-level constraints of corresponding attributes. Following the principles of goal-oriented development and utilization, a single-goal evaluation index set with 18 implementation items was constructed. Also, a single-goal suitability evaluation model was built which introduced the triangular fuzzy numbers to determine the index weights, and classified suitability into “suitable, more suitable, more difficult and difficult” based on suitability indices. Furthermore, considering the systematic complexity of the positive effects development and utilization of the mine environment, the logical relationships between the development and utilization objectives were analyzed. In addition, a multi-goal linear evaluation theory was proposed based on the comprehensive optimal concept of economic, ecological and social benefits. By solving through the ideal point method or single-goal linear programming solution, the comprehensive optimal solution or the most suitable set for the positive effects development and utilization of the mine environment was obtained. Finally, from the perspectives of national strategy, social needs, watershed ecology, and positive effect market development, the study provides some insights into the significant implications of the implementation and systematic evaluation of mine environmental positive effects development and utilization.

Aiming at the real problems such as the occurrence of coal and gas outburst and based on the hypothesis of comprehensive action of coal and gas outburst, a method of gas hydration and solidification to prevent coal and gas outburst is proposed. The core of this method is to solidify the gas in coal seam to form gas hydrate, which can not only reduce the gas pressure, but also improve the coal strength, so as to reduce or eliminate the risk of coal and gas outburst. Based on the idea of “coal and gas outburst prevention using hydrate”, the test of gas hydrate formation in coal and the in-situ test of the mechanical property-permeability of gas hydrate bearing coal have been performed, with the numerical modeling technique of the triaxial compression of the gas hydrate bearing coal proposed. The techniques are implemented by comprehensively applying the methods of theoretical analysis, development of testing equipment, indoor test and numerical analysis. In terms of coal and gas outburst prevention, the thermodynamic and kinetic conditions of gas hydrate formation are its theoretical basis, the stable storage of gas hydrate is its technical precondition, and the reduction of gas pressure and the improvement of mechanical properties are its key measures. This paper focuses on the cross mechanics related to the gas hydrate bearing coal. The results show that: ① the theoretical framework of gas solidification technology by the hydrate method for outburst prevention has been initially formed, and the meso-mechanism of improving the mechanical characteristics of coal before and after gas hydration has been preliminarily explored by means of the numerical simulation. ② At present, it has been confirmed that the hydrate formation in coal can not only reduce the gas pressure, but also improve its mechanical properties. High saturation can obviously improve the peak strength of coal. ③ Gas hydrate formation experiences three stages: rapid, slow and stable stage. Additionally, the formation of hydrate will cause the gas seepage channel in the coal to be blocked, resulting in a decrease in its permeability. ④ High gas pressure and high CH4 concentration not only help to increase the saturation but also delay hydrate decomposition, which is conducive to the stable existence of the hydrate. However, a large number of repetitive experiments are still needed to verify the reliability of the method to build up a generalized database. By analyzing current research findings, the limitations and challenges that still exist are discussed, with further research interests pointed out.

Abstract Microfluidic flowmeters are a powerful and highly accurate tool, enabling precise monitoring and measurements of flows of gases and fluids in a range of applications. Here we proposed and experimentally demonstrated a whispering gallery modes flowmeter composed of a liquid crystal-filled nested capillary. Whispering gallery modes are excited by a tapered fiber coupled perpendicularly to the nested capillary. The air flowing through the capillary cools it down, which leads to a temperature-induced change of the refractive index of the nematic liquid crystals. This change in turn leads to a spectral shift of the whispering gallery modes resonances, which can be linked to the airflow rate in the capillary. The temperature change in the liquid crystals was simulated considering the heat transfer between the liquid crystals and airflow in the capillary, which indicated that the liquid crystals temperature decreases in a nonlinear manner with the increase of the airflow rate. A flowmeter with the maximum sensitivity of 0.3423 nm·min·mL−1 in the flowrate range from 0 to 2.52 nm·min·mL−1 and a resolution of 5.72 pm was demonstrated in our experiment. The proposed sensor provides a platform for whispering gallery modes flowmeters and offers the advantages of good stability, high sensitivity, and miniature size.

Abstract This study aims to develop a clinical diagnostic model for assessing the need for initial abdominal surgery in patients diagnosed with Crohn's disease (CD) and create a nomogram to facilitate clinical decision-making. A total of 164 surgical CD patients and 230 control CD patients were included in this retrospective analysis. Least Absolute Shrinkage and Selection Operator (Lasso) regression and binomial logistic regression were employed to select clinical variables. The 394 CD patients were randomly allocated to a training set and a validation set in a 7:3 ratio. The filtered variables were used to establish a diagnostic model and nomogram in the training set, subsequently validated in the testing set. Decision Curve Analysis (DCA) and clinical impact curve were constructed to validate the clinical applicability of the model. Binomial logistic regression analysis identified seven clinical variables with a p-value less than 0.01, including Biomarker (B), Waist-to-Height Ratio (WHtR), Intestinal obstruction, Albumin (ALB), Crohn's Disease Activity Index (CDAI), Myocardial Flow Index (MFI), and C-reactive protein (CRP). These variables were utilized to establish the diagnostic model. Calibration curves showed good alignment, with a C-index of 0.996 in the training set and 0.990 in the testing set. DCA and clinical impact curve demonstrated that the diagnostic model had good clinical efficiency and could provide clinical benefits. A validated diagnostic model for determining the timing of the first abdominal operation in CD patients was established and evaluated, showing high discriminative ability, calibration, and clinical efficiency. It can be utilized by clinicians to assess the optimal timing for transitioning CD patients from medical treatment to surgical intervention, providing valuable references for individualized treatment decisions for CD patients.

Abstract The high-frequency pulse flow, equivalent to the natural frequency of rocks, is generated by a self-excited oscillating cavity to achieve resonance rock-breaking. The flow field and oscillating mechanism of the self-excited oscillating cavity were simulated using the large eddy simulation method of Computational Fluid Dynamics (CFD). A field-scale testing apparatus was developed to investigate the impulse characteristics and verify the simulation results. The results show that the fluid at the outlet at the tool is deflected due to the pulse oscillation of the fluid. The size and shape of low-pressure vortices constantly change, leading to periodic changes in fluid impedance within the oscillating cavity. The impulse frequency reaches its highest point when the length–diameter ratio is 0.67. As the length–diameter ratio increases, the tool pressure loss also increases. Regarding the cavity thickness, the impulse frequency of the oscillating cavity initially decreases, then increases, and finally decreases again. Moreover, both the impulse frequency and pressure loss increase with an increase in displacement. The numerical simulation findings align with the experimental results, thus confirming the validity of the theoretical model. This research provides theoretical guidance for the practical application of resonance rock-breaking technology.

Abstract The blue and white porcelain produced in Jingdezhen during China’s Yuan Dynasty is an outstanding cultural heritage of ceramic art that has attracted wide attention for its identification. However, the traditional visual identification method is susceptible to misjudgment, thermoluminescence dating damages the samples, and the methods based on chemical analysis are limited by the accuracy and specificity of the elemental features. In this paper, we address the identification challenge by using machine learning techniques combined with portable X-ray Fluorescence Spectrometer (pXRF) analysis. We collect a large dataset of chemical compositions of Yuan blue and white porcelain from Jingdezhen using pXRF, and propose a graph anomaly detection method based on gradient attention map (GRAM) to identify the porcelain from different dynasties. We treat the porcelain produced in the Yuan dynasty as normal samples and those from other dynasties as abnormal samples. For GRAM, we merely train the variational graph autoencoder (VGAE) model with normal graphs and then use its encoder to extract graph features and compute the anomaly scores by utilizing the GRAM of the graph representations with respect to the node feature embeddings. Finally, we compare GRAM with state-of-the-art graph anomaly detection techniques and show that it achieves superior performance.

Abstract Background Cayratia albifolia C.L.Li (CAC), commonly known as “Jiao-Mei-Gu” in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established. Methods Twenty-four Sprague–Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot. Results CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA. Conclusions We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation. Graphical Abstract

Background: Type 2 diabetes mellitus (T2DM) presents a thrombotic environment, contributing to diabetic macroangiopathy and microangiopathy. In this study, the regulation of microthrombosis in T2DM was assessed. Methods: Platelets from T2DM patients and healthy controls were analyzed using 4D label-free proteomics and bioinformatics. The role of autophagy in T2DM platelet activation and conversion of platelet-derived angiotensinogen (AGT) was investigated. Results: The results showed that complement and coagulation cascades, platelet activation, metabolic pathways, endocytosis, autophagy, and other protein digestion-related pathways were enriched. The levels of the key protein AGT were increased in T2DM platelets. Chloroquine (CQ) inhibited ADP- or arachidonic acid (AA)-stimulated platelet aggregation and granule release in a dose-dependent manner, while the effects were less pronounced or even reversed for the proteasome inhibitor PYR-41 and the endocytosis inhibitor Pitstop 2. This indicated the dependence of platelet activation and the accompanying protein digestion on the autophagy-lysosome pathway. Mitophagy occurred in fresh T2DM platelets and ADP- or storage-stimulated platelets; mitophagy was inhibited by CQ. However, the mitophagy inhibitor Mdivi-1 failed to show effects similar to those of CQ. AGT, which could be transformed into ANGII in vitro by ADP-stimulated platelets, was upregulated in T2DM platelets and in MEG-01 cell-derived platelets cultured in a high-glucose medium. Finally, microthrombosis was alleviated as indicated by a reduction in the levels of red blood cells in the liver, spleen, heart, and kidney tissues of db/db mice treated with CQ or valsartan. Conclusion: In platelets, macroautophagy promotes protein digestion, subsequently facilitating platelet activation, ANGII-mediated vasoconstriction, and microthrombosis. Our results suggested that lysosome is a promising therapeutic target for antithrombotic treatment in T2DM.

Study objectiveRecent studies have shown that dexmedetomidine can be safely used in peripheral nerve blocks and spinal anesthesia. Epidural administration of dexmedetomidine produces analgesia and sedation, prolongs motor and sensory block time, extends postoperative analgesia, and reduces the need for rescue analgesia. This investigation seeks to identify the median effective concentration (EC50) of ropivacaine for epidural motor blockade, and assess how incorporating varying doses of dexmedetomidine impacts this EC50 value.DesignProspective, double-blind, up-down sequential allocation study.SettingOperating room, post-anesthesia care unit, and general ward.InterventionsOne hundred and fifty patients were allocated into five groups in a randomized, double-blinded manner as follows: NR (normal saline combined with ropivacaine) group, RD0.25 (0.25 μg/kg dexmedetomidine combined with ropivacaine) group, RD0.5 (0.5 μg/kg dexmedetomidine combined with ropivacaine) group, RD0.75 (0.75 μg/kg dexmedetomidine combined with ropivacaine) group, RD1.0 (1.0 μg/kg dexmedetomidine combined with ropivacaine) group. The concentration of epidural ropivacaine for the first patient in each group was 0.5%. Following administration, the patients were immediately placed in a supine position for observation, and the lower limb motor block was assessed every 5 min using the modified Bromage score within 30 min after drug administration. According to the sequential method, the concentration of ropivacaine in the next patient was adjusted according to the reaction of the previous patient: effective motor block was defined as the modified Bromage score > 0 within 30 min after epidural administration. If the modified Bromage score of the previous patient was >0 within 30 min after drug administration, the concentration of ropivacaine in the next patient was decreased by 1 gradient. Conversely, if the score did not exceed 0, the concentration of ropivacaine in the next patient was increased by 1 gradient. The up-down sequential allocation method and probit regression were used to calculate the EC50 of epidural ropivacaine.MeasurementsAdverse events, hemodynamic changes, demographic data and clinical characteristics.Main resultsThe EC50 of epidural ropivacaine required to achieve motor block was 0.677% (95% CI, 0.622–0.743%) in the NR group, 0.624% (95% CI, 0.550–0.728%) in the RD0.25 group, 0.549% (95% CI, 0.456–0.660%) in the RD0.5 group, 0.463% (95% CI, 0.408–0.527%) in the RD0.75 group, and 0.435% (95% CI, 0.390–0.447%) in the RD1.0 group. The EC50 of the NR group and the RD0.25 group were significantly higher than that of the RD0.75 and the RD1.0 groups, and the EC50 of the RD0.5 group was significantly higher than that of the RD1.0 group.ConclusionThe EC50 of epidural ropivacaine required to achieve motor block was 0.677% in the NR group, 0.624% in the RD0.25 group, 0.549% in the RD0.5 group, 0.463% in the RD0.75 group, and 0.435% in the RD1.0 group. Dexmedetomidine as an adjuvant for ropivacaine dose-dependently reduce the EC50 of epidural ropivacaine for motor block and shorten the onset time of epidural ropivacaine block. The optimal dose of dexmedetomidine combined with ropivacaine for epidural anesthesia was 0.5 μg/kg.

Background: Paraquat (PQ) is a widely used herbicide that poisons human by accident or intentional ingestion. PQ poisoning causes systemic inflammatory response syndrome (SIRS) resulting in acute lung injury (ALI) with an extremely high mortality rate. Blood trematode Schistosoma japonicum-produced cystatin (Sj-Cys) is a strong immunomodulatory protein that has been experimentally used to treat inflammation related diseases. In this study, Sj-Cys recombinant protein (rSj-Cys) was used to treat PQ-induced lung injury and the immunological mechanism underlying the therapeutic effect was investigated. Methods: PQ-induced acute lung injury mouse model was established by intraperitoneally injection of 20 mg/kg of paraquat. The poisoned mice were treated with rSj-Cys and the survival rate was observed up to 7 days compared with the group without treatment. The pathological changes of PQ-induced lung injury were observed by examining the histochemical sections of affected lung tissue and the wet to dry ratio of lung as a parameter for inflammation and edema. The levels of the inflammation related cytokines IL-6 and TNF-α and regulatory cytokines IL-10 and TGF-β were measured in sera and in affected lung tissue using ELISA and their mRNA levels in lung tissue using RT-PCR. The macrophages expressing iNOS were determined as M1 and those expressing Arg-1 as M2 macrophages. The effect of rSj-Cys on the transformation of inflammatory M1 to regulatory M2 macrophages was measured in affected lung tissue in vivo (EKISA and RT-PCR) and in MH-S cell line in vitro (flow cytometry). The expression levels of TLR2 and MyD88 in affected lung tissue were also measured to determine their role in the therapy of rSj-Cys on PQ-induced lung injury. Result: We identified that treatment with rSj-Cys significantly improved the survival rate of mice with PQ-induced lung injury from 30 % (untreated) to 80 %, reduced the pathological damage of poisoning lung tissue, associated with significantly reduced levels of proinflammatory cytokines (IL-6 from 1490 to 590 pg/ml, TNF-α from 260 to 150 pg/ml) and increased regulatory cytokines (IL-10 from360 to 550 pg/ml, and TGF-β from 220 to 410 pg/ml) in both sera (proteins) and affected lung tissue (proteins and mRNAs). The polarization of macrophages from M1to M2 type was found to be involved in the therapeutic effect of rSj-Cys on the PQ-induced acute lung injury, possibly through inhibiting TLR2/MyD88 signaling pathway. Conclusions: Our study demonstrated the therapeutic effect of rSj-Cys on PQ poisoning caused acute lung injury by inducing M2 macrophage polarization through inhibiting TLR2/MyD88 signaling pathway. The finding in this study provides an alternative approach for the treatment of PQ poisoning and other inflammatory diseases.

As a green building material, recycled aggregate concrete (RAC) can reduce construction solid waste and carbon emissions. In this paper, a combination of macroscale physical experiments of thermal performance and mesoscale numerical simulations of heat transfer were used to investigate the thermal conductivity (TC) of RAC. Firstly, the TC of RAC was measured using the steady-state method. Secondly, the mesoscale numerical analysis method of steady-state heat transfer of RAC was established by self-programming. Finally, by comparing with experimental results, the validity of the mesoscale numerical analysis method in this paper is verified. The results indicates that the TC of RAC is positively correlated with the recycled coarse aggregate dosage and the TC of each component, while it is negatively correlated with the water-binder ratio, the recycled fine aggregate replacement ratio, the old mortar adhesion ratio, the interface transition zone thickness, and the porosity. The six-phase mesoscale model of random convex polygonal aggregate for RAC constructed in this paper can effectively predict the TC of RAC, which provides a new idea for analyzing the TC of RAC.

Photoacoustic spectroscopy (PAS) has been rapidly developed and applied to different detection scenarios. The acoustic pressure detection is an important part in the PAS system. In this paper, an ultrahigh sensitivity Fabry-Perot acoustic sensor with a T-shaped cantilever was proposed. To achieve the best acoustic pressure effect, the dimension of the cantilever structure was designed and optimized by finite element analysis using COMSOL Multiphysics. Simulation results showed that the sensitivity of such T-shaped cantilever was 1.5 times higher than that based on a rectangular cantilever, and the resonance frequency of T-shaped cantilever were able to modulate from 800 Hz to 1500 Hz by adjusting the multi-parameter characteristics. Experimental sensing results showed that the resonance frequency of T-shaped Fabry-Perot acoustic sensor was 1080 Hz, yielding a high sensitivity of 1.428 μm/Pa, with a signal-to-noise ratio (SNR) of 84.8 dB and a detectable pressure limit of 1.9 μPa/Hz1/2@1 kHz. We successfully used such acoustic sensor to measure acetylene (C2H2) concentration in the PAS. The sensitivity of PAS for C2H2 gas was 3.22 pm/ppm with a concentration range of 50 ppm ∼100 ppm, and the minimum detection limit was 24.91ppb.

The Daba Mountain area is recognized as one of the global biodiversity hotspots. In recent years, human–wildlife conflicts (HWCs) in this region have intensified significantly. Understanding and mitigating the damage caused by wildlife is crucial for maintaining ecological balance and enhancing public welfare. We analyzed the current status of HWCs in the southern foothills of the Daba Mountains through semi-structured interviews and field surveys. Additionally, using the collected data on HWC occurrences, we predicted HWC hotspots using the maximum entropy (MaxEnt) model. The results: (1) A total of 449 cases of actual HWC incidents were investigated, primarily involving wild boars (Sus scrofa; 81.96%) and Asiatic black bears (Ursus thibetanus; 18.04%). The main types of HWC included crop destruction and attacks on beehives. (2) Incidents of damage caused by wild boars and Asiatic black bears were concentrated in the summer months, particularly from June to August. (3) In the study area, 21 out of 25 townships reported HWC cases. Notably, the townships of Fuxing, Gaoyan and Gaoguan were identified as the most affected, with Gaoyan and Fuxing experiencing the highest amounts of loss. (4) The variable of DTP (Distance to Protected Area) was found to have the greatest influence on the hotspot distributions of HWCs. The hotspot zone exhibited a strip-like distribution along the northwest–southeast axis in the central part of the study area. The total area of the HWC hotspots was 1352.56 km2. The largest hotspot areas were located in Xiuqi Town, Gaoyan Town, and Houping Township, accounting for 13.26%, 12.01%, and 7.83% of the total hotspot area, respectively. HWC hotspots require robust management measures to mitigate wildlife damage to local communities and enhance indigenous people’s engagement in wildlife conservation. Implementation of physical measures and compensation schemes may be necessary in these hotspots to alleviate the financial burden on indigenous populations. Our findings may provide valuable insights for the future formulation of biodiversity conservation policies and HWC mitigation strategies in the Daba Mountains.

Background: Multiple empirical investigations have indicated a connection between asthma and adverse pregnancy outcomes (APOs). Nevertheless, the effects of asthma on APOs remain uncertain. Methods: We performed bi-directional Univariable Mendelian randomization (UVMR) analyses using combined information obtained from genome-wide association studies (GWAS) data that is publicly accessible. The principal approach used to analyze the causal association between asthma or age when diagnosed and APOs was the inverse variance weighted (IVW) method. The two types of data regarding exposure originate from the IEU Open GWAS project, which includes 56,167 and 47,222 European asthma patients, respectively. The data of four APOs were acquired via the GWAS dataset of the FinnGen collaboration. In addition, we implemented multivariable Mendelian randomization (MVMR), controlling for confounding factors such as smoking status, frequent drinking, body mass index (BMI), and live birth quantity. Furthermore, we executed several meticulous sensitivity studies to ascertain the reliability of our MR results. Results: Following the implementation of the Bonferroni adjustment, the UVMR assessment revealed that in the IVW model, asthma was significantly linked to an elevated risk of spontaneous abortion (SA) (odds ratio [OR]: 1.115; 95 % confidence interval [CI]: 1.031–1.206; P = 0.006) and gestational diabetes mellitus (GDM) (OR: 1.125; 95 % CI: 1.037–1.220; P = 0.005). However, there was no causal correlation between asthma and preterm birth (PTB) (OR: 0.979; 95 % CI: 0.897–1.068; P = 0.629) or preeclampsia (PE) (OR: 1.059; 95 % CI: 0.951–1.179; P = 0.297). After adjusting for confounding factors, including smoking status, frequent drinking, BMI, and live birth quantity, the MVMR analysis shows a statistically significant causal relationship between asthma and SA or GDM. Furthermore, our investigation's findings did not reveal a substantial correlation between the age of asthma onset based on genetics and the likelihood of SA or GDM. The inverse MR outcomes indicate a lack of causal connection linking APOs to the incidence of asthma. The validity of these findings were verified by sensitivity analyses. Conclusions: The evidence provided by this study proves that genetically determined asthma is linked to a higher likelihood of SA and GDM. Further research is required to examine potential pathways. However, no conclusive evidence has been found to support the increased risk of SA and GDM in early asthma diagnosis or the interaction between asthma and PTB or PE, indicating that confounding factors may affect the results of previous observational studies.

Abstract Objectives EGFR‐tyrosine kinase inhibitor (TKI) is used to treat recurrent and metastatic nasopharyngeal carcinoma (rmNPC). This meta‐analysis aims to study the efficacy and safety of EGFR‐TKI in treating patients with rmNPC. Methods We conducted a systematic search of PubMed, Embase, and Web of Science up to November 2023, and included literature that met the criteria. We extracted objective response rate (ORR), disease control rate (DCR), median progression‐free survival (mPFS), median overall survival (mOS), and adverse reaction‐related events and performed meta‐analysis using Stata 14.0. Results A total of nine articles were included. The summary results showed that the ORR for patients treated with EGFR‐TKI for rmNPC was 38% (95% CI = 27%–49%), the DCR was 71% (95% CI = 61%–80%), the mPFS was 6.29 months (95% CI = 5.22–7.35), and the mOS was 15.94 months (95% CI = 14.68–17.20). The most common grade 3–4 adverse reaction events in these patients were mucositis, nasopharyngeal necrosis, and oral ulceration. We found an incidence rate of 49% (95% CI = 38%–61%) for grade 3–4 adverse events (AEs). The anti‐PD1 combined with TKI treatment method is more effective than the EGFR‐TKI alone for treating rmNPC. Conclusion The study shows that EGFR‐TKI has good efficacy in treating rmNPC but does not translate into survival benefits and owns a high incidence of grade 3–4 AEs. More RCT trials are needed in the future to verify the efficacy of anti‐PD1 combined with TKI treatment method.

BackgroundIn recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM2.5) on obesity, but their relationship remains ambiguous.MethodsUtilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM2.5 exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings.ResultsThe UVMR analysis demonstrated a significant association between PM2.5 exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881–21.968; PFDR = 0.005). Additionally, PM2.5 concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244–2.776; PFDR = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092–5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106–2.841; PFDR = 0.019). Furthermore, PM2.5 exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269–3.022; PFDR = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34–4.649; PFDR = 0.007). Finally, a significant negative association was observed between PM2.5 concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025–0.89; PFDR = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM2.5 levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21.ConclusionOur MR study demonstrates conclusively that higher PM2.5 concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.

BackgroundWe aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China.MethodsThis is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention.Results2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals.ConclusionThe LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period.Clinical trial registrationClinicalTrials.gov, identifier NCT05745545.

This study examined the applicability of indocyanine green (ICG) fluorescence imaging to assist the laparoscopic resection of retroperitoneal tumors in pediatric patients via an abdominal approach. Conducted prospectively at the Guangzhou Women and Children's Medical Center from May to September 2023, the research included three pediatric cases, for whom laparoscopic retroperitoneal tumor resections were performed utilizing ICG fluorescence imaging. In each case, ICG was intravenously administered (0.3 mg/kg) prior to surgery, enabling the visualization of vital vascular structures through real-time fluorescence imaging. The trocar's placement was guided by a “four-hole” technique from the healthy side in a 70-degree lateral decubitus position. The operations were accomplished successfully without any complications. Pathological analysis of the patients identified one case of Wilms tumor of the embryonal type, one ganglioneuroblastoma of the mature type without N-MYC gene amplification, and one mature cystic teratoma. The findings suggest that with careful patient selection and skilled surgical execution, the utilization of ICG fluorescence imaging in the laparoscopic resection of retroperitoneal tumors is both safe and effective in children. This approach significantly improves the visualization of critical blood vessels, thus enhancing surgical safety.

BackgroundThis study aimed to compare the clinical outcomes of Zero-P and ROI-C devices applied to anterior cervical discectomy and fusion (ACDF) surgery of cervical degenerative disc disease (CDDD).MethodsFrom January 2020 and December 2020, 56 patients with CDDD who underwent ACDF using Zero-P or ROI-C were included in this retrospective study. The outcomes included visual analogue scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI) score, Cobb angle, dysphagia, and bone fusion rate. Dysphagia was assessed using the Bazaz grading system. The comparison of outcomes between the two groups was based on the 2-year follow-up time point, which was defined as the last follow-up visit.ResultsThe Zero-P group included 16 males and 14 females, with a mean age of 56.2 (range, 35–65) years. The ROI-C group included 11 males and 15 females, with a mean age of 57.4 (range, 36–67) years. There was no significant difference in gender and mean age between the two groups. There were no significant differences in VAS score, JOA score, NDI score, Cobb angle, dysphagia, and bone fusion rate between two groups at the last follow up visit. In the Zero-P group, the duration of surgeries involving C3–4 or C6–7 segments was significantly longer than those including C4–5 or C5–6 segments (135.0 ± 19.0 vs. 105.6 ± 17.5 min, P 0.05). The Cobb angle in the last follow-up visit in the Zero-P group (24.4 ± 4.5°) was significantly higher than that in the ROI-C group (18.1 ± 2.3°) (P