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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 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.

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.

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.

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.

The effects of projectile/target impedance matching and projectile shape on energy, momentum transfer and projectile melting during collisions are investigated by numerical simulation. By comparing the computation results with the experimental results, the correctness of the calculation and the statistical method of momentum transfer coefficient is verified. Different shapes of aluminum, copper and heavy tungsten alloy projectiles striking aluminum, basalt, and pumice target for impacts up to 10 km/s are simulated. The influence mechanism of the shape of the projectile and projectile/target density on the momentum transfer was obtained. With an increase in projectile density and length-diameter ratio, the energy transfer time between the projectile and targets is prolonged. The projectile decelerates slowly, resulting in a larger cratering depth. The energy consumed by the projectile in the excavation stage increased, resulting in lower mass-velocity of ejecta and momentum transfer coefficient. The numerical simulation results demonstrated that for different projectile/target combinations, the higher the wave impedance of the projectile, the higher the initial phase transition velocity and the smaller the mass of phase transition. The results can provide theoretical guidance for kinetic impactor design and material selection.

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.

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

As the market increases for Artificial Intelligence and High-Performance Computing applications, the geometry of 3-Dimensional Integrated Circuit packages becomes more complicated; therefore, predicting the thermal distributions of the structures becomes not only more important but also more challenging. The physics governing the thermal distribution is a 3-dimensional partial differential equation. In order to predict the thermal distributions, various approaches such as the layer modeling method have been invented. While practical, these approaches solve a simplified version of the differential equation placing an inherent limitation on their capabilities which may be improved upon. In this research we solve the actual differential equation using Finite Element Analysis. Finite Element Analysis is known to produce accurate solutions, albeit being computationally intensive, and may take days to run even with a powerful computer, making it impractical for some applications. In this paper, we present case studies of computing the thermal distributions of large scale 3-dimensional integrated circuit models using XSim. We find that XSim’s solving capabilities are capable of computing accurate thermal distributions of large-scale models in minutes instead of days. This suggests a new way to compute the thermal distributions rapidly and accurately for large 3-Dimensional Integrated Circuit packages, which may bring potential benefits in research, design and development of 3-Dimensional Integrated Circuit packages.

This paper aims to establish a model that can reasonably reflect the mechanical properties of coal containing gas under different water content and confining pressure conditions. Firstly, the stress-strain characteristics of coal containing gas under different water content and confining pressure conditions are analyzed based on triaxial tests. Afterwards, this paper obtains the Duncan-Chang model parameters by combining the Duncan-Chang model and Janbu formula. Moreover, it establishes the fitting formulas of initial elastic modulus failure stress and various influencing factors, and conducts an improved Duncan-Chang model to characterize the deformation law of coal containing gas under different stress levels. Finally, this paper verifies the improved model and evaluate the accuracy of the mode. The results show that the increase of water content is an important reason for the dynamic change of coal model parameters of coal containing gas. The prediction curve of the improved model is in good agreement with the actual test curve, and the improved model can accurately reflect the stress-strain characteristics of coal containing gas under different confining pressures and water contents.

Abstract To analyze the relationship between macro and meso parameters of the gas hydrate bearing coal (GHBC) and to calibrate the meso-parameters, the numerical tests were conducted to simulate the laboratory triaxial compression tests by PFC3D, with the parallel bond model employed as the particle contact constitutive model. First, twenty simulation tests were conducted to quantify the relationship between the macro–meso parameters. Then, nine orthogonal simulation tests were performed using four meso-mechanical parameters in a three-level to evaluate the sensitivity of the meso-mechanical parameters. Furthermore, the calibration method of the meso-parameters were then proposed. Finally, the contact force chain, the contact force and the contact number were examined to investigate the saturation effect on the meso-mechanical behavior of GHBC. The results show that: (1) The elastic modulus linearly increases with the bonding stiffness ratio and the friction coefficient while exponentially increasing with the normal bonding strength and the bonding radius coefficient. The failure strength increases exponentially with the increase of the friction coefficient, the normal bonding strength and the bonding radius coefficient, and remains constant with the increase of bond stiffness ratio; (2) The friction coefficient and the bond radius coefficient are most sensitive to the elastic modulus and the failure strength; (3) The number of the force chains, the contact force, and the bond strength between particles will increase with the increase of the hydrate saturation, which leads to the larger failure strength.

Abstract CTCF plays an important role in 3D genome organization by adjusting the strength of chromatin insulation at TAD boundaries, where clustered CBS (CTCF-binding site) elements are often arranged in a tandem array with a complex divergent or convergent orientation. Here, using Pcdh and HOXD loci as a paradigm, we look into the clustered CTCF TAD boundaries and find that, counterintuitively, outward-oriented CBS elements are crucial for inward enhancer-promoter interactions as well as for gene regulation. Specifically, by combinatorial deletions of a series of putative enhancer elements in mice in vivo or CBS elements in cultured cells in vitro, in conjunction with chromosome conformation capture and RNA-seq analyses, we show that deletions of outward-oriented CBS elements weaken the strength of long-distance intra-TAD promoter-enhancer interactions and enhancer activation of target genes. Our data highlight the crucial role of outward-oriented CBS elements within the clustered CTCF TAD boundaries in developmental gene regulation and have interesting implications on the organization principles of clustered CTCF sites within TAD boundaries.

Abstract Background Recent studies have shown that, owning to its cohesive cleavage, Cas9-mediated CRISPR gene editing outcomes at junctions of chromosomal rearrangements or DNA-fragment editing are precise and predictable; however, the underlying mechanisms are poorly understood due to lack of suitable assay system and analysis tool. Results Here we developed a customized computer program to take account of staggered or cohesive Cas9 cleavage and to rapidly process large volumes of junctional sequencing reads from chromosomal rearrangements or DNA-fragment editing, including DNA-fragment inversions, duplications, and deletions. We also established a sensitive assay system using HPRT1 and DCK as reporters for cell growth during DNA-fragment editing by Cas9 with dual sgRNAs and found prominent large resections or long deletions at junctions of chromosomal rearrangements. In addition, we found that knockdown of PolQ (encoding Polθ polymerase), which has a prominent role in theta-mediated end joining (TMEJ) or microhomology-mediated end joining (MMEJ), results in increased large resections but decreased small deletions. We also found that the mechanisms for generating small deletions of 1bp and >1bp during DNA-fragment editing are different with regard to their opposite dependencies on Polθ and Polλ (encoded by the PolL gene). Specifically, Polθ suppresses 1bp deletions but promotes >1bp deletions, whereas Polλ promotes 1bp deletions but suppresses >1bp deletions. Finally, we found that Polλ is the main DNA polymerase responsible for fill-in of the 5′ overhangs of staggered Cas9 cleavage ends. Conclusions These findings contribute to our understanding of the molecular mechanisms of CRISPR/Cas9-mediated DNA-fragment editing and have important implications for controllable, precise, and predictable gene editing.

Highlights Alkyl-tailored Y-SMAs named YR-SeNF series with near-infrared absorption, different molecular crystallinity and self-assembly abilities are developed. The related organic solar cells (OSCs) with an active layer processed from halogen-free solvents and spin-coating-free technologies achieve a ~ 19% efficiency. Ternary OSCs offer a robust operating stability under MPP tracking and well-keep > 80% of the initial efficiency for even over 400 h.

Abstract Objective: To determine if customer purchases at small food stores are associated with healthfulness of the diet as approximated by skin carotenoids. Design: This is a cross-sectional survey of customers in small food stores regarding demographics and food purchases. Food and beverage purchases were classified as ‘healthy’ or ‘non-healthy’ and ‘carotenoid’ v. ‘non-carotenoid’ using a systematic classification scheme. Fruit and vegetable intake was objectively assessed using a non-invasive device to measure skin carotenoids. Associations between variables of interest were examined using Pearson’s correlation coefficients, t tests and multiple linear regression analyses. Setting: Twenty-two small food retail stores in rural (n 7 stores) and urban (n 15) areas of North Carolina. Participants: Customers of small food stores Results: Of study participants (n 1086), 55·1 % were male, 60·0 % were African American/Black and 4·2 % were Hispanic, with a mean age of 43·5 years. Overall, 36 % purchased at least one healthy item, and 7·6 % of participants purchased a carotenoid-containing food/beverage. Healthy foods and beverages purchased included produce, lean meats, 100 % juices, plain popcorn, plain nuts, milk and yogurt. Unhealthy items included non-100 % juices, crackers, chips, candy, cakes and donuts. Purchase of a healthy or carotenoid-containing item was positively associated with skin carotenoid scores (P = 0·002 and 0·006, respectively). Conclusions: A relatively small proportion of customers purchased any healthy or carotenoid-containing foods and beverages, and those who did purchase healthy options had higher skin carotenoid scores. Future research should confirm these findings in different populations.

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.

Background: Immunotherapy has changed the treatment landscape for lung cancer. This study aims to construct a tumor mutation-related model that combines long non-coding RNA (lncRNA) expression levels and tumor mutation levels in tumor genomes to detect the possibilities of the lncRNA signature as an indicator for predicting the prognosis and response to immunotherapy in lung adenocarcinoma (LUAD). Methods: We downloaded the tumor mutation profiles and RNA-seq expression database of LUAD from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were extracted based on the cumulative number of mutations. Cox regression analyses were used to identify the prognostic lncRNA signature, and the prognostic value of the five selected lncRNAs was validated by using survival analysis and the receiver operating characteristic (ROC) curve. We used qPCR to validate the expression of five selected lncRNAs between human lung epithelial and human lung adenocarcinoma cell lines. The ImmuCellAI, immunophenoscore (IPS) scores and Tumor Immune Dysfunction and Exclusion (TIDE) analyses were used to predict the response to immunotherapy for this mutation related lncRNA signature. Results: A total of 162 lncRNAs were detected among the differentially expressed lncRNAs between the Tumor mutational burden (TMB)-high group and the TMB-low group. Then, five lncRNAs (PLAC4, LINC01116, LINC02163, MIR223HG, FAM83A-AS1) were identified as tumor mutation-related candidates for constructing the prognostic prediction model. Kaplan‒Meier curves showed that the overall survival of the low-risk group was significantly better than that of the high-risk group, and the results of the GSE50081 set were consistent. The expression levels of PD1, PD-L1 and CTLA4 in the low-risk group were higher than those in the high-risk group. The IPS scores and TIDE scores of patients in the low-risk group were significantly higher than those in the high-risk group. Conclusion: Our findings demonstrated that the five lncRNAs (PLAC4, LINC01116, LINC02163, MIR223HG, FAM83A-AS1) were identified as candidates for constructing the tumor mutation-related model which may serve as an indicator of tumor mutation levels and have important implications for predicting the response to immunotherapy in LUAD.

Diabetic retinopathy (DR) is one of the major causes of visual impairment in adults with diabetes. Optical coherence tomography angiography (OCTA) is nowadays widely used as the golden criterion for diagnosing DR. Recently, wide-field OCTA (WF-OCTA) provided more abundant information including that of the peripheral retinal degenerative changes and it can contribute in accurately diagnosing DR. The need for an automatic DR diagnostic system based on WF-OCTA pictures attracts more and more attention due to the large diabetic population and the prevalence of retinopathy cases. In this study, automatic diagnosis of DR using vision transformer was performed using WF-OCTA images (12[Formula: see text]mm × 12[Formula: see text]mm single-scan) centered on the fovea as the dataset. WF-OCTA images were automatically classified into four classes: No DR, mild nonproliferative diabetic retinopathy (NPDR), moderate to severe NPDR, and proliferative diabetic retinopathy (PDR). The proposed method for detecting DR on the test set achieves accuracy of 99.55%, sensitivity of 99.49%, and specificity of 99.57%. The accuracy of the method for DR staging reaches up to 99.20%, which has been proven to be higher than that attained by classical convolutional neural network models. Results show that the automatic diagnosis of DR based on vision transformer and WF-OCTA pictures is more effective for detecting and staging DR.

Since the logic 28 nm technology and beyond, ArF immersion lithography has been widely used in manufacturing. To fully utilize the potential of the lithographic resolution, process simulation has been used since the lithography process setup step. The accuracy of the model prediction can be a key factor in the process stability, defectivity, and yield of the final product. To get better model prediction, it is very important to develop a process model with as many parameters as possible with physical meanings. Since the analysis of exposure data with a physical model can provide insights into the process and the photoresist material, it may greatly accelerate the photoresist formulation development or improvement process. From another aspect, as the function of the photoresist is to record the aerial image information on wafer, theoretically, the photoresist image should not deviate much from the aerial image or it will inevitably reduce the information content of the aerial image, i.e., through various kinds of averaging, mixing, etc. Since the emergence of Optical Proximity Correction (OPC), the time that takes to finalize a photolithography process has been significantly lengthened and made more complicated. To make the OPC model more reliable and less dependent on patches, a more physical OPC model is necessary. Therefore, it is clear that if we can develop a photoresist formulation to realize a more physical photoresist image, or a photoresist image closer to the aerial image, we can greatly improve the photolithography process performance and the time consumed for the process setup including OPC. In this paper, we focus on several physical model parameters for photoresist, especially the effective photoacid diffusion length and photo decomposable base parameters. We will show that these two parameters can provide a good description of photoresist imaging behavior, and the resist formulation can be improved to match the physical model prediction with more accuracy.

Abstract Introduction Developmental dysplasia of hip (DDH) is a hip joint disorder leading to subsequent osteoarthritis. Previous studies suggested collagen XI alpha 1 (COL11A1) as a potential gene in hip dysplasia and chondrocyte degeneration. However, no genetic association has reported COL11A1‐related cellular therapy as treatment of DDH and joint degeneration. Methods and Results We report identified genetic association between COL11A1 locus and DDH with genome‐wide association study (GWAS). Further exome sequencing for familial DDH patients was conducted in different populations to identify potential pathogenic Col11A1 variants for familiar DDH. Further studies demonstrated involvement of COL11A1 expression was down‐regulated in femoral head cartilage of DDH patients and Col11a1‐KO mice with induced DDH. Col11a1‐KO mice demonstrated aggravated joint degeneration and severe OA phenotype. To explore the underlying mechanism of Col11a1 in cartilage and DDH development, we generated scRNA‐seq profiles for DDH and Col11a1‐KO cartilage, demonstrating disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1–HIF1α‐mediated glycolysis–OXPHOS shift in chondrocytes. Genetically and biologically inspired, we further fabricated an intra‐articular injection therapy to preventing cartilage degeneration by generating a Col11a1‐over‐expressed (OE) SMSC mini‐organoids. Col11a1‐OE organoids demonstrated superior chondrogenesis and ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up‐regulated Col11a1/HIF1α‐mediated glycolysis in chondrocytes. Conclusion We reported association between COL11A1 loci and DDH with GWAS and exome sequencing. Further studies demonstrated involvement of COL11A1 in DDH patients and Col11a1‐KO mice. ScRNA‐seq for DDH and Col11a1‐KO cartilage demonstrated disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1–HIF1α‐mediated glycolysis–OXPHOS shift in chondrocytes. Genetically and biologically inspired, an intra‐articular injection therapy was fabricated to prevent cartilage degeneration with Col11a1‐OE SMSC organoids. Col11a1‐OE organoids ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up‐regulated Col11a1/HIF1α‐mediated glycolysis in chondrocytes.

Water level fluctuations (WLFs) are typical characteristic of floodplain lakes and dominant forces regulating the structure and function of lacustrine ecosystems. The sediment diazotrophs play important roles in contributing bioavailable nitrogen to the aquatic environment. However, the relationship between the diazotrophic community and WLFs in floodplain lakes is unknown. In this paper, we carried out a comprehensive investigation on the alpha diversity, abundance, composition and co-occurrence network of the sediment diazotrophs during different water level phases in Poyang Lake. There were no regular variation patterns in the alpha diversity and abundance of the sediment diazotrophs with the water level phase transitions. The relative abundance of some diazotrophic phyla (including Alphaproteobacteria, Deltaproteobacteri, Euryarchaeota, and Firmicutes) and genera (including Geobacter, Deferrisoma, Desulfuromonas, Rivicola, Paraburkholderia, Methylophilus, Methanothrix, Methanobacterium, and Clostridium) was found to change with the water level phase transitions. The results of ANOSIM, PerMANOVA, and DCA at the OTU level showed that the diazotrophic community structure in the low water level phase was significantly different from that in the two high water level phases, while there was no significant difference between the two high water level phases. These results indicated that the diazotrophic community was affected by the declining water level in terms of the composition, while the rising water level contributed to the recoveries of the diazotrophic community. The diazotrophs co-occurrence network was disrupted by the declining water level, but it was strengthened by the rising water level. Moreover, redundancy analysis showed that the variation of the diazotrophic community composition was mostly related to sediment total nitrogen (TN) and total phosphorous (TP). Interestingly, the levels of sediment TN and TP were also found to vary with the water level phase transitions. Therefore, it might be speculated that the WLFs may influence the sediment TN and TP, and in turn influence the diazotrophic community composition. These data can contribute to broadening our understanding of the ecological impacts of WLFs and the nitrogen fixation process in floodplain lakes.

Delivering high areal capacitance (CA) at high rates is crucial but challenging for flexible supercapacitors. CA is the product of areal loading mass (MA) and gravimetric capacitance (CW). Finding and understanding the balance between MA and CW of supercapacitor materials is significant for designing high-CA electrodes. Herein, we have systematically studied the correlation between MA and CW of the nanosheet arrays of NiCo−layered double hydroxide (NiCo−LDH), which were electrodeposited on carbon cloth with different heights to adjust the MA, accompanied by the interlayer distance regulation to improve the CW. The optimal CW performance is achieved at the best charge transfer kinetics for each of MA series. The NiCo−LDH electrode with the suitable MA (2.58 ​mg ​cm−2) and the relatively high CW (1918 F ​g−1 ​at 5 ​A ​g−1 and 400 ​F ​g−1 ​at 150 ​A ​g−1) present a high CA of 4948 ​mF ​cm−2 ​at 12.9 ​mA ​cm−2 and a record-high 1032 ​mF ​cm−2 among LDHs-based flexible electrodes at an ultrahigh current density of 387 ​mA ​cm−2. The corresponding flexible supercapacitor coupled with activated carbon delivers a high energy density of 0.28 ​mWh cm−2 ​at an ultrahigh power density of 712 ​mW ​cm−2, showing great potential applications.

The central and western coal resources have the highest degree of enrichment and superior development conditions in China. With the improvement of mining efficiency, the disturbance of high-intensity and large-mining-height mining mode to groundwater system also increases. In particular, the groundwater in the aquifer outside the disturbance range of the water-conducting fracture zone gradually participates in the mine water inflow process during the coal mining. Such mode leads to a series of problems such as large deviation of mine water inflow prediction, inaccurate evaluation of water inflow risk and unclear water hazard prevention measures, which brings great hidden risks to the current mine water hazard prevention and control. In this paper, a derivative mode of dynamic water inrush is summarized. With the coal mining, the evolution of groundwater system caused by overburden failure will induce new disaster sources, resulting in different forms of water inrush. Its connotation is to change the basis of defining the derivative dynamic water inrush model from the traditional static analysis before mining to the dynamic evaluation considering the change in the whole mining cycle. The derived dynamic water inrush model of the mine can be preliminarily divided into three categories, namely, “skylight leakage type”, “bed separation disaster type” and “channel permeability increase type”. This paper mainly discusses the derivative dynamic water inrush mode of “skylight leakage type”. Taking the Shanxi Yushen mining area, a shallow buried coal seam mining area with high strength and large mining height, as an example, the disaster-pregnant conditions of “skylight supply type” derivative disasters are discussed in depth. Through supplementary analysis of water-richness and hydraulic connection strength of indirect water-filled aquifer, the comprehensive evaluation of water inrush risk in roof aquifer is achieved, and the evaluation method system of disaster derivative model is put forward. Through the transformation of mining mode, the active prevention and control system is constructed. A passive prevention and control system is constructed by multi-objective advance drainage before mining and local grouting after mining. By further refining the mine water inrush disaster model, optimizing the evaluation system and establishing comprehensive prevention and control technology, it provides a scientific basis for the protection of groundwater resources and safe low-carbon mining in ecologically fragile areas.

Abstract Background The morbidity and mortality of community-acquired pneumonia (CAP) remain high among infectious diseases. It was reported that angiopoietin-like 4 (ANGPTL4) could be a diagnostic biomarker and a therapeutic target for pneumonia. This study aimed to develop a more objective, specific, accurate, and individualized scoring system to predict the severity of CAP. Methods Totally, 31 non-severe community-acquired pneumonia (nsCAP) patients and 14 severe community-acquired pneumonia (sCAP) patients were enrolled in this study. The CURB-65 and pneumonia severity index (PSI) scores were calculated from the clinical data. Serum ANGPTL4 level was measured by enzyme-linked immunosorbent assay (ELISA). After screening factors by univariate analysis and receiver operating characteristic (ROC) curve analysis, multivariate logistic regression analysis of ANGPTL4 expression level and other risk factors was performed, and a nomogram was developed to predict the severity of CAP. This nomogram was further internally validated by bootstrap resampling with 1000 replications through the area under the ROC curve (AUC), the calibration curve, and the decision curve analysis (DCA). Finally, the prediction performance of the new nomogram model, CURB-65 score, and PSI score was compared by AUC, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results A nomogram for predicting the severity of CAP was developed using three factors (C-reactive protein (CRP), procalcitonin (PCT), and ANGPTL4). According to the internal validation, the nomogram showed a great discrimination capability with an AUC of 0.910. The Hosmer–Lemeshow test and the approximately fitting calibration curve suggested a satisfactory accuracy of prediction. The results of DCA exhibited a great net benefit. The AUC values of CURB-65 score, PSI score, and the new prediction model were 0.857, 0.912, and 0.940, respectively. NRI comparing the new model with CURB-65 score was found to be statistically significant (NRI = 0.834, P

Abstract Background Compared to traditional fetal heart rate monitoring (FHR) for the outpatients in clinic, remote FHR monitoring shows real-time assessment of fetal wellbeing at home. The clinical function of remote FHR monitoring in pregnant wome in outpatient is still unclear. Objective To explore the feasibility of remote FHR self-monitoring in singleton pregnant women from southern China. Study design This prospective cohort study was conducted at one tertiary center in southern China. Pregnant women used a mobile cardiotocogram device to measure the FHR at least once a week until delivery in the remote group. For the control group, pregnant women underwent traditional FHR monitoring once a week in the outpatient clinic. The rate of cesarean section, risk of postpartum hemorrhage and adverse neonatal outcomes were compared between the two groups. All the pregnant women completed a questionnaire survey to evaluate their acquisition of remote FHR self-monitoring. Results Approximately 500 women were recruited in the remote FHR self-monitoring group (remote group), and 567 women were recruited in the traditional FHR monitoring group (control group). The women in the remote FHR monitoring group were more likely to be nulliparous (P

The primary causes of satellite breakups are hypervelocity impact and explosion, the research on satellite breakup can be used not only to evaluate the influence of breakup event on the space environment, but also to trace whether the satellite has been deliberately attacked. It is of great significance in both civil and military aspects. The study of satellite breakup behaviors and model is reviewed to summarize the research progress and insufficiency in recent decades, including the satellite breakup experiment, measurement and characterization of fragments, distribution characteristics of breakup fragments, satellite breakup model, etc. The classical studies are introduced in detail, and the limitations of the current research are pointed out. According to the current research results, the contemporary challenges and future directions for satellite breakup study are presented. The research on satellite breakup is developing in two directions: the miniaturization of satellite size and the complexity of satellite component. The study on satellite breakup needs to be explored and deepened on improving the experimental launch speed, expanding the model application range and breakup revealing the results under combined effect of impact and explosion.

This study investigates the anisotropy effect of Ta10W alloy manufactured by selective laser melting (SLM) on the microstructure and mechanical properties of the three butt welds. The welds were characterized by formation, microstructure, microhardness, room temperature (RT) strength, high temperature (HT) strength, and fracture morphology. Results indicate that Ta10W manufactured by SLM exhibits anisotropy in microstructure and properties, leading to notable differences in the welds' microstructure and mechanical properties. When the base metal's X-axis aligns with the welding direction, the weld forms columnar sub-grains, whereas aligning the base metal's Z-axis with the welding direction results in equiaxed sub-grains in the weld. These distinct microstructures influence the maximum RT strength, with the X + X weld displaying significantly higher strength (751.33 MPa) compared to the X + Z (672.00 MPa) and Z + Z (667.25 MPa) welds. Fracture analysis reveals a transition from cleavage fracture to intergranular fracture in three welds. The microhardness and HT strength of the welds exhibit an inapparent difference, with the microhardness of approximately 305 HV0.2/15 and the HT (1800 °C) strength of around 110.50 MPa.

Objectives With the gradual development of marine resources, the number of vehicles operating under the sea surface has rapidly increased, and the problem of the electromagnetic detection of underwater complex targets such as underwater vehicles needs to be solved urgently.MethodsBased on the total-field scattered-field source finite-difference time-domain method (TSS-FDTD) and the method of field value conversion on the sea surface, the spatial distribution of scattering fields generated by the underwater antenna array irradiation of target underwater vehicles is analyzed. The field distributions in the regions near the underwater antenna array and complex target, in the seawater and above the sea surface are obtained by calculation, and the spatial scattering fields of the three groups with different relative positions of target and source are compared and analyzed.ResultsThrough comparison and analysis, the scattering fields of the three groups in the seawater environment are clearly different, and the existence of the underwater target can be determined by observing the scattering fields. While the scattering fields of the three groups above the sea surface show little difference, the existence of the underwater target can be still determined by observing the value and energy distribution of the scattering fields.ConclusionsThe results of this analysis can provide numerical references for detection radar with similar working frequency bands, and provide technical support for the fields of underwater vehicle detection, underwater rescue and sunken ship salvage.

Abstract Pulmonary arterial hypertension‐targeted therapies in portopulmonary hypertension (PoPH) are scarce, let alone for patients with chronic liver failure (CLF) and hepatopulmonary syndrome (HPS). A 48‐year male was admitted to the hospital because of cirrhosis for 18 years, systemic oedema, and chest distress after exercise for 1 week. He was diagnosed with CLF, PoPH, and HPS. After 7 weeks of macitentan treatment, the patient's activity tolerance, pulmonary artery systolic pressure, arterial partial pressure of oxygen (PaO2), cTNI, and NT‐proBNP changes indicated gradual recovery, without hepatic safety concerns. This case indicated that administering macitentan in patients diagnosed as PoPH (with CLF and HPS) may be efficient and safe enough in a clinical setting.

This study aimed to explore the potential antioxidant activity and mechanism of oligopeptides from sauce-aroma Baijiu. The oligopeptides of Val-Leu-Pro-Phe (VLPF), Pro-Leu-Phe (PLF), Val-Gly-Phe-Cys (VGFC), Leu-Tyr-Pro (LYP), Leu-Pro-Phe (LPF), and Phe-Thr-Phe (FTF) were identified by liquid chromatography–mass spectrometry (LC–MS) from the mixed-distillate of Baijiu fermented grains and soy sauce residue (MDFS). The antioxidant mechanism of these oligopeptides on scavenging DPPH•, ABTS•+, and hydroxide radicals was investigated, respectively. Among them, VGFC had the strongest potential antioxidant activity, which was responsible for its hydrogen bonds with these radicals with high affinity. The binding energies between VGFC and these radicals were −1.26 kcal/mol, −1.33 kcal/mol, and −1.93 kcal/mol, respectively. Additionally, free radicals prefer to bind the oligopeptide composed of hydrophobic amino acid residues such as Leu, Val, Phe, and Pro, thus being scavenged for exerting antioxidant activity. It provided a new idea for the development and utilization of bioactive oligopeptides in sauce-aroma Baijiu.