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Abstract This study investigates the particle’s geodesic motion and accretion around the spherically symmetric Reissner–Nordström black hole coupled with a nonlinear electrodynamics field. The formation of the disc-like structure in the accretion process arises from the geodesic motion exhibited by particles near the black hole. In the equatorial plane, we analyze the circular orbits of particles and their stability in detail. The analysis of the fluid’s critical flow, maximum accretion rate, radiant flux energy, radioactive efficiency, and radiant temperature are also examined near the central object. We analyze the perturbations experienced by particles throughout, employing restoring forces and the oscillatory behavior of the particles around the black hole. Our results show that the NED parameter $$\zeta $$ ζ affects the circular geodesics of particles and the maximum accretion rate of the Reissner–Nordström black hole coupled with nonlinear electrodynamics.

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.

ObjectivesPyrophyllite, as a sealed pressure medium, has been widely used in high-pressure research for laboratories and industrial synthesis. A highly efficient pressure transfer medium can generate higher cell pressure at the same loading force. The use of a highly efficient pressure transfer medium reduces the risk of anvil rupture and production costs. Therefore, it is important to develop a suitable and efficient pressure-transmitting pyrophyllite.MethodsThe pressure calibration of four pyrophyllites from different localities at room temperature was conducted in a 6 × 8 MN multi-anvil large-volume press. The relationship between loading force and cell pressure at room temperature was established. The influence of mineral composition changes in pyrophyllite on pressure-transmitting efficiency was studied using X-ray diffraction.ResultsBy investigating the influence of mineral composition changes in pyrophyllite on pressure-transmitting efficiency, the results are as follows: (1) When achieving the same cell pressure, the required loading force for Pyrophyllite 4 is 10% lower than those for the other three pyrophyllites, indicating that Pyrophyllite 4 has the best pressure-transmitting efficiency. (2) As cell pressure increases, the relationship between cell pressure and loading force begins to deviate from linearity, and the pressure-transmitting efficiency of pyrophyllite gradually decreases. When the cell pressure exceeds 5.00 GPa, applying higher loading force does not significantly increase the cell pressure. (3) Higher hardness minerals (such as Diaspore, Boehmite) in pyrophyllite can effectively improve pressure-transmitting efficiency in the low-pressure stage (cell pressure 2.55-3.68 GPa). When the minerals in pyrophyllite undergo phase transformation to form new minerals with higher hardness (such as Muscovite and Kaolinite) in the high-pressure stage (cell pressure of 5.50 GPa), pressure-transmitting efficiency can be effectively improved.ConclusionsPyrophyllite 4 has better pressure-transmitting efficiency than Pyrophyllite 2 does in the high-pressure stage, but it is prone to failure in sealing due to the changes in mineral composition. However, Pyrophyllite 2 shows good elastic recovery effect and sealing performance and can stably complete compression and decompression work. Considering both pressure-transmitting efficiency and sealing effect, Pyrophyllite 2 has better application value and economic benefits.

In order to systematically understand the various types of water hazards and standardize the management of water prevention and control work in coal mines, the National Mine Safety Administration in June 2022 extended the “three zones” management methodology for old goaf water prevention and control to more types of water hazards, such as roof water, floor water, and structural water. However, in the process of dividing the “three zones” of water prevention and control in coal mines, it is revealed that the water damage causing factors and water damage management situation are not closely linked with the division standard, and that technically different divisions are not made for different coal seams and mining areas, and there are inconsistencies in the scope of the division area, and the standardization and timeliness of the division results. Accordingly, combined with the purpose of water hazard prevention and control “three zones” division, compared the similarities and differences between the new and old “three zones” division work, this paper clarifies the degree of hydrogeological conditions survey, water hazard analysis, water hazard management as elements of the division principles, and determines the technical path of the division of the “three zones”. Combining the characteristics of five common types of water hazards in coal mines, the paper puts forward the division method of different types of water hazards, that is: surface water hazard should be divided according to the distribution and development characteristics of surface water bodies in the mining area and the degree of influence of atmospheric precipitation, landslides and other geological disasters in mining. The roof water hazard should be divided according to whether there is a strong water-rich aquifer, a medium water-rich but hydrostatic reservoir-rich aquifer, a loose aquifer. The floor water hazard should be divided according to the relationship between the thickness of the floor water barrier and the depth of the floor mine pressure damage zone in the coal seam pressure mining area, as well as the size of the floor water inrush coefficient. The old goaf water hazard should be divided according to the distribution range and amount of water in the mine and the surrounding mines. The structural water hazards should be divided according to the water-richness, water content, and water source conduction of geological structures and bad geological bodies such as faults, trap columns and caves in the mining area. The key points and difficulties of the division work include the clear division of time and space scope, the comprehensive analysis of division standards, the clear management responsibilities for the “three zones”, and the dynamic transformation of division results. On this basis, typical coal mines with various types of water hazards and complex hydrogeological conditions are selected as case studies. Following the principle of division, according to the division standard, the mineable zone, the slow mining zone and no-mining zone are divided by the method of separating coal seams and mining areas, and detailed explanations are given. The significance of carrying out the division of the “three zones” for water hazard prevention and control is clarified, which can enhance the comprehensive detection level, strengthen the prediction ability, and identify the direction of water hazard management in order to guide and standardize the division of the “three zones” for water prevention and control in the coal mines of China.

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 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.

Discrete element simulation of triaxial compression test was carried out to study the effects of confining pressure and saturation on the macro and meso mechanical properties of gas hydrate bearing coal (GHBC). Firstly, the numerical models of three kinds of GHBC with different saturations were established by particle flow program PFC3D, with the cementation of hydrate simulated by parallel bonding model. Then, the meso mechanical parameters were calibrated by using the results of the physical triaxial test. The stress-strain curves of the physical tests agree with the simulated results, with the failure strength and strength parameter error rate within 10%, which verifies the reliability of the established numerical model. Furthermore, the triaxial tests of GHBC were performed under different confining pressures to analyze the macro and meso-mechanical characteristics such as the stress-strain curve, velocity field, contact force chain, coordination number and porosity. The results show that the discrete element simulation results agree well with the indoor test results, especially simulating the strain hardening characteristics of the sample. The velocity field reveals a higher dilatancy degree under low saturation and a higher contraction degree under the high confining pressure of the samples. There is no obvious difference in the main chain transfer direction at the failure strength under different saturations and confining pressures. The contact force, the number of contact force chains, as well as the coordination number increase with the increase of confining pressure and saturation, while the porosity tends to decrease, which enhances the strength of the samples. The friction is an important factor to maintain the stability of the meso mechanical system of the samples. The influence mechanism of saturation and confining pressure on the strength deformation and failure of GHBC is revealed from the microscale, which provides a theoretical reference for the discrete element simulation of GHBC triaxial test and for the prevention of coal and gas outburst by hydrate technology.

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.

We present a novel method for investigating laser-driven dynamic fragmentation in tin using in situ X-ray diffraction. Our experimental results demonstrate the feasibility of the method for simultaneously identifying the phase and temperature of fragments through analysis of the diffraction pattern. Surprisingly, we observe a deviation from the widely accepted isentropic release assumption, with the temperature of the fragments being found to be more than 100 K higher than expected, owing to the release of plastic work during dynamic fragmentation. Our findings are further verified through extensive large-scale molecular dynamics simulations, in which strain energies are found to be transferred into thermal energies during the nucleation and growth of voids, leading to an increase in temperature. Our findings thus provide crucial insights into the impact-driven dynamic fragmentation phenomenon and reveal the significant influence of plastic work on material response during shock release.

Against the backdrop of China’s initiative to construct a new power system focusing on new energy, optimizing power grid investment holds significant importance. This study aims to investigate whether the application of artificial intelligence (AI) contributes to power grid investment efficiency. By considering diverse factors, power grid investment efficiency in China is assessed by using a Slack-based measure model. Then we analyze the relationship between AI and power grid investment efficiency, as well as their nonlinear threshold effect. We find a notable increase in China’s power grid investment efficiency, accompanied by evident regional differences. In addition, the utilization of AI exerts a significantly positive effect on power grid investment efficiency. Particularly, such a promoting effect is more pronounced in the China Southern Power Grid cohort and remains significant during the 12th Five-Year Plan period. Moreover, grid investment exhibits a double-threshold effect, and it diminishes the contributing effect of AI on power grid investment efficiency. AI shows a single threshold effect on power grid investment efficiency as electricity sales increase, and the positive impact manifests only when electricity sales surpass a specific threshold. These insights are important for the strategic deployment of power grid projects through using AI.

Carbon storage in terrestrial ecosystems varies with land use changes, and exploring the impact of land use changes on carbon storage in regional terrestrial ecosystems is important for maintaining regional carbon balance. Data on Dalian City’s land use types from 2000 to 2020 are used in this research, to evaluate the spatio-temporal evolution of carbon storage in Dalian. Furthermore, with the scenarios of urban development, natural development, cultivated land protection, and ecological protection in 2030, this study combines the PLUS and InVEST models to emulate the dynamic adjustment at land-use types and the spatio-temporal evolution regarding carbon storage in Dalian City. The investigation shows that: 1) The carbon storage of terrestrial ecosystem in Dalian has been altered as a consequence of changes in land use, and now it shows a general decline during 2000–2020, with reductions amounting to 5.39 × 106 t. 2) From 2000 through 2020, Dalian’s land resources that are utilized for farming, forestry, and grassland decreased to different degrees. The total construction land area increased by 796.47 km2, or 6.38 %, whereas there has been no substantial improvement in water or unused land. 3) The carbon storage reduction in 2030 in comparison to 2020 for the natural development, cultivated land protection, and urban development scenarios, among which the urban development scenario was the largest, was 1.36 × 106t. It suggests that the rapid rate of urbanization and expansion of construction land is an important cause of the decline in carbon storage. 4) The cultivated land protection scenario (CPS) yields the smallest reduction of 6.50 × 105t. The structure of Dalian’s land use type is optimum under the ecological protection scenario (EPS), as seen by the 3.90 × 105t increase in carbon storage under this scenario. It speeds up the rate of recovery of carbon storage and improves the function of carbon sinks in urban terrestrial ecosystems. Hoping to provide the reference to decision makers for ecosystem carbon storage optimization from the view of land use, which is vital for making future land use policies and realizing the “dual carbon” strategic goal.

Abstract Objectives Glioblastoma (GBM) is the most aggressive of intracranial gliomas. Despite the maximal treatment intervention, the median survival rate is still about 14–16 months. Nuclear receptor‐binding protein 1 (NRBP1) has a potential growth‐promoting role on biology function of cells. In this study, we investigated whether NRBP1 promotes GBM malignant phenotypes and the potential mechanisms. Methods The correlation between NRBP1 and glioma grade, prognosis in TCGA/CGGA databases and our clinical data were analyzed. Next, we conducted knockout and overexpression of NRBP1 on GBM cells to verify that NRBP1 promoted cell proliferation, invasion, and migration in vitro and in vivo. Finally, we detected the impact of NRBP1 on PI3K/Akt signaling pathway and EMT. Results There was a correlation between elevated NRBP1 expression and advanced stage glioma, as well as decreased overall and disease‐free survival. The suppression of proliferation, invasion, and migration of tumor cells was observed upon NRBP1 knockout, and in vitro studies also demonstrated the induction of apoptotic cell death. Whereas, its overexpression is associated with high multiplication rate, migration, invasion, and apoptotic escape. GO enrichment and KEGG analysis revealed that NRBP1 regulated differentially expressed gene clusters are involved in PI3K/Akt signaling pathway, as well as EMT mediated by this pathway. Moreover, the effects of NRBP1 knockdown and overexpression on GBM were mitigated by MK‐2206 and SC79, both of which respectively function as an inhibitor and an activator of the PI3K/Akt signaling pathway. Similarly, the suppression of NRBP1 led to a decrease in tumor growth, whereas its overexpression promoted tumor growth in a mouse model. Conclusions This study shows that NRBP1 promotes malignant phenotypes in GBM by activating PI3K/Akt pathway. Hence, it can function as both a predictive indicator and a new target for therapies in GBM treatment.

IntroductionThe connection between aging and cancer is complex. Previous research has highlighted the association between the aging process of lung adenocarcinoma (LUAD) cells and the immune response, yet there remains a gap in confirming this through single-cell data validation. Here, we aim to develop a novel aging-related prognostic model for LUAD, and verify the alterations in the genome and immune microenvironment linked to cellular senescence.MethodsWe integrated a comprehensive collection of senescence genes from the GenAge and CellAge databases and employed the least absolute shrinkage and selection operator (LASSO) Cox analysis to construct and validate a novel prognostic model for LUAD. This model was then utilized to examine the relationship between aging, tumor somatic mutations, and immune cell infiltration. Additionally, we explored the heterogeneity of senescence and intercellular communication within the LUAD tumor microenvironment (TME) through single-cell transcriptomic data analysis.ResultsBy exploring the expression profiles of 586 cellular senescence-related genes in 428 LUAD patients, we constructed an aging-related genes (ARGs) risk model included 10 ARGs and validated it as an independent prognostic predictor for LUAD patients. Notably, patients with low aging scores (LAS group) exhibited better survival, lower tumor mutation burden (TMB), lower somatic mutation frequency, lower tumor proliferation rate, and an immune activated phenotype compared to patients with high aging scores (HAS group). While the HAS group was enriched in tumor cells and showed a lower infiltration of CD8-CCR7, CD8- CXCL13, CD8-GNLY, FCGR3A NK cells, XCL1 NK cells, plasma cell (PC) and other immune subsets. Furthermore, the SPP1 and TENASCIN pathways, associated with tumor immune escape and tumor progression, were also enriched in the HAS group. Additionally, our study also indicated that senescence levels were heterogeneous in the LUAD tumor microenvironment (TME), especially with tumor cells in the LAS group showing higher age scores compared to those in the HAS group.ConclusionsCollectively, our findings underscore that ARRS through ARGs serves as a robust biomarker for the prognosis in LUAD.

This study investigates the effect of financial inclusion (FI), considering micro and macro indicators as well as micro- and macro-FI separately, on the stability of Asian banks and examines the moderating effect of bank competition (BC) on this relationship. Using data from 2011 to 2021, this study examines the relationship between FI, BC, and bank stability (BS). The hypotheses were tested using a “two-step system-GMM framework”. The findings were also authenticated using the panel OLS approach. The results indicate that FI (considering micro- and macro-indicators) and micro- and macroFI have significant positive effects on the stability of Asian banks. However, the impact of micro-FI is greater than that of macro-FI on the BS in Asia. Furthermore, the results manifest that BC has a significant positive impact on BS and positively moderates the relationship between micro-FI and BS, whereas it negatively moderates the relationship between macro-FI and BS. The findings of this study have practical implications for regulators, bankers, and policymakers involved in formulating strategies to enhance Asian banks’ stability.

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.

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.

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.

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.

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

Flexible photodetector is crucial for the intelligent industrial applications. However, the optical-sensitive materials are usually grown in a high temperature and then transferred onto the flexible substrate. This paper reported a directly fabricated flexible photodetector based on TiO2-doped Graphene Nanosheets Embedded Carbon (GNEC)film. An Electron Cyclotron Resonance (ECR) system was employed to in-situ deposit TiO2-doped GNEC film on a polyimide substrate, which were subsequently sensitized with N719 dye to fabricate the TiO2@GNEC photodetector. The GNEC film contains vertically aligned Graphene Nanosheets (GNs), which exhibit high-density edge states. The edge states suppress the recombination rate of photo-generated electron-hole pairs, thereby significantly enhancing the photo-responsive performance. The photodetector demonstrates a high photo responsivity of 0.82 mA/W and a response time of 1.93 seconds. Due to the in-situ manufacturing capabilities of the ECR system, which avoids defects from secondary material transfers, the photodetector array exhibits excellent consistency and achieves clear recognition of light patterns in both flat and bent states.

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.