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To accurately measure carbon emissions from open-pit mines in alpine ecologically fragile areas, a rigorous and comprehensive accounting method is essential. This method must account for both direct emissions from mining operations and indirect emissions from ecological disturbances. The unique challenges of high-altitude environments require a sophisticated carbon accounting approach that tracks emissions from both mining activities and their broader ecological impacts on carbon sinks and sources. This study begins by examining the carbon cycle mechanisms unique to open-pit mines in these fragile regions, characterized by high altitudes, low temperatures, and delicate ecosystems susceptible to disturbances. Leveraging life cycle theory, we define the accounting boundaries to encompass all stages of the mining life cycle, namely extraction, transportation, beneficiation, and auxiliary processes. A key aspect of this research is the meticulous examination of direct and indirect carbon emissions across various mining stages. The energy-intensive nature of mining, along with the substantial transportation requirements over challenging terrains, significantly contributes to the carbon footprint. Additionally, beneficiation processes involving the separation and refinement of raw materials are highly energy-consuming, increasing indirect emissions. By mapping these processes and analyzing their carbon emission contributions, we enhance the understanding of the carbon cycle’s impact owing to high-altitude mining. The study also elucidates the structure of carbon sources and sinks within these fragile ecosystems. We compile a detailed carbon emission source inventory for open-pit mines, providing a comprehensive reference for emission sources and natural carbon sinks, such as soil and vegetation, potentially compromised by mining activities. This inventory is instrumental in developing a more precise accounting model. We have developed a carbon emission accounting model that integrates mining production stages with changes in carbon sinks owing to mining-induced disturbances. This model specifically accounts for the increased energy consumption of mining equipment at high altitudes, leading to higher carbon emissions owing to reduced operational efficiency. The model offers a nuanced estimate of total emissions by incorporating these factors. The model was validated using a case study of an open-pit metal mine in Tibet, a region renowned for its alpine ecology and environmental fragility. Applying the model revealed total carbon emissions of 1.76295×105 t CO2 for 2023, reflecting the combined direct and indirect impacts of mining on the ecosystem. This case study demonstrates the model’s effectiveness and underscores the considerable carbon footprint of mining in alpine regions. This research provides a theoretical foundation for carbon emission accounting and management in high-altitude, ecologically sensitive mining areas. It presents a detailed and scientifically rigorous accounting method supporting sustainable mining practices. The findings and model offer practical insights for industry stakeholders and a data-driven framework for policymakers aiming to reduce the environmental footprint of mining in vulnerable ecosystems. This study paves the way for sustainable resource extraction in ecologically sensitive zones, supporting efforts to minimize the carbon footprint of mining operations in high altitudes.

Abstract Within the framework of a low-carbon transition and integrated mineral resource exploitation, this study presents an innovative system dynamics (SD) model designed to optimize decision-making and enhance profitability in underground gold mining operations. The novel approach seamlessly integrates critical subsystems, including reserves, mining, ore dressing, smelting, financial, and carbon reduction, offering a comprehensive framework for the analysis of efficiency and sustainability. Utilizing causal loop and system flow diagrams, the model elucidates the synergistic impacts of index variations on mine operational efficiency. The model is applied to a case study involving three mining areas within a specific gold mine in China, where sensitivity analysis identifies key indicators affecting profitability. Furthermore, it examines dynamic trends under varying carbon tax scenarios. The findings reveal that mining strategic adjustments can significantly enhance profitability, extend the operational lifespan of mines, and reduce emissions.

Spermatogonial cells are capable of transmitting genetic information to the next generation and have the potential for self-renewal. However, research on spermatogonial cells is generally limited by the paucity of cell surface markers, which are not universal among species. In this study, we developed a systematic screening strategy for germline regulatory pathways and spermatogonial surface markers in non-model organisms. This was achieved by combining weighted gene co-expression network analysis (WGCNA), differential expressed gene (DEG) overrepresentation analysis, and functional annotation. This strategy was employed to identify a spermatogonia-related module, which was found to be enriched with stem cell-related pathways in the scallop Patinopecten yessoensis. This module contained a transmembrane protein, fibroblast growth factor receptor (FGFR). A single copy of Fgfr (PyFgfr) was confirmed in the P. yessoensis genome, which exhibited the canonical functional domains of FGFRs. PyFgfr was universally expressed in multiple tissues, including the testis. The highest expression was observed at the resting stage of the testis, with exclusive localization in spermatogonia. To obtain antibodies that recognize the cell surface region, the extracellular domains of PyFGFR were used as an antigen to prepare antiserum. Western blotting, immunohistochemical, and immunofluorescent analyses demonstrated that the antiserum specifically detected PyFGFR in the spermatogonia. This study demonstrates the feasibility of this strategy for screening spermatogonial surface markers in the scallop. This approach will facilitate the culture and manipulation of spermatogonia in non-model organisms, which may contribute to genetic improvement in aquaculture.

Abstract Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases. Radiopharmaceutical therapy, which directly causes systematic and irreparable damage to targeted cells, has attracted increasing attention in the treatment of refractory diseases that are not sensitive to current therapies. As the Food and Drug Administration (FDA) approvals of [177Lu]Lu-DOTA-TATE, [177Lu]Lu-PSMA-617 and their complementary diagnostic agents, namely, [68Ga]Ga-DOTA-TATE and [68Ga]Ga-PSMA-11, targeted radiopharmaceutical-based theranostics (radiotheranostics) are being increasingly implemented in clinical practice in oncology, which lead to a new era of radiopharmaceuticals. The new generation of radiopharmaceuticals utilizes a targeting vector to achieve the accurate delivery of radionuclides to lesions and avoid off-target deposition, making it possible to improve the efficiency and biosafety of tumour diagnosis and therapy. Numerous studies have focused on developing novel radiopharmaceuticals targeting a broader range of disease targets, demonstrating remarkable in vivo performance. These include high tumor uptake, prolonged retention time, and favorable pharmacokinetic properties that align with clinical standards. While radiotheranostics have been widely applied in tumor diagnosis and therapy, their applications are now expanding to neurodegenerative diseases, cardiovascular diseases, and inflammation. Furthermore, radiotheranostic-empowered precision medicine is revolutionizing the cancer treatment paradigm. Diagnostic radiopharmaceuticals play a pivotal role in patient stratification and treatment planning, leading to improved therapeutic outcomes in targeted radionuclide therapy. This review offers a comprehensive overview of the evolution of radiopharmaceuticals, including both FDA-approved and clinically investigated agents, and explores the mechanisms of cell death induced by radiopharmaceuticals. It emphasizes the significance and future prospects of theranostic-based radiopharmaceuticals in advancing precision medicine.

Abstract The association between plasma low-density lipoprotein cholesterol (LDL-C) and atrial fibrillation (AF) recurrence after catheter ablation remains unclear. We aimed to assess the relationship between preprocedural LDL-C and the AF recurrence in patients undergoing catheter ablation. The cohort study consecutively included AF patients who underwent de novo catheter ablation between April 2021 and January 2023 in the Second Affiliated Hospital of Nanchang University in Jiangxi Province, China. Patients were divided into quartiles based on their baseline fasting LDL-C level (Q1-Q4). Multivariable Cox proportional hazards models were used to evaluate the relationship between LDL-C and AF recurrence. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and two-piecewise Cox proportional hazards models, to address the nonlinearity between preprocedural LDL-C and AF recurrence. A total of 482 AF patients with de novo catheter ablation were enrolled, with a median follow-up period of 15.00 months, AF recurrence occurred in 96 (19.92%) patients. The relationship between preprocedural LDL-C and AF recurrence after ablation presented as an L-shape, and the inflection point for the curve was found at the LDL-C level of 3.20 mmol/L (Log likelihood ratio P = 0.031). The hazard ratios (HR) [(95% confidence intervals (CI)] for AF recurrence were 0.50 (0.33–0.74) and 2.11 (0.76–5.89) to the left and right of the inflection point, respectively. Lower LDL-C level is associated with increased AF recurrence risk after catheter ablation were consistent across all subgroups.

Abstract Background Botrytis cinerea is a broad-host-range pathogen causing gray mold disease and significant yield losses of numerous crops. However, the mechanisms underlying its rapid invasion and efficient killing of plant cells remain unclear. Results In this study, we elucidated the dynamics of B. cinerea infection in Arabidopsis thaliana by live cell imaging and dual RNA sequencing. We found extensive transcriptional reprogramming events in both the pathogen and the host, which involved metabolic pathways, signaling cascades, and transcriptional regulation. For the pathogen, we identified 591 candidate effector proteins (CEPs) and comprehensively analyzed their co-expression, sequence similarity, and structural conservation. The results revealed temporal co-regulation patterns of these CEPs, indicating coordinated deployment of effectors during B. cinerea infection. Through functional screening of 48 selected CEPs in Nicotiana benthamiana, we identified 11 cell death-inducing proteins (CDIPs) in B. cinerea. Conclusions The findings provide important insights into the transcriptional dynamics and effector biology driving B. cinerea pathogenesis. The rapid infection of this pathogen involves the temporal co-regulation of CEPs and the prominent role of CDIPs in host cell death. This work highlights significant changes in gene expression associated with gray mold disease, underscoring the importance of a diverse repertoire of effectors crucial for successful infection.

The hybrid cascaded high-voltage direct current (HC-HVDC) system integrates the benefits of both LCC and MMC technologies. However, the inverter LCC is prone to suffer subsequent commutation failure (SCF) when an AC fault occurs. Therefore, a coordinated control strategy (CCS) based on the safety power range (SPR) is proposed in this paper. Firstly, the adverse effects of electrical quantity fluctuation and LCC’s reactive power demand on system recovery under different control modes are analyzed. Then, considering the role of the controller and MMC dynamic reactive power support, the SPR model is established under the coupling of multiple electrical quantities. Secondly, to realize the coordination of SCF suppression and rapid power recovery, a CCS based on the MMC’s reactive power outer loop and the LCC’s voltage-dependent current order limiter (VDCOL) is proposed by analyzing the power operating points in SPR. Finally, based on PSCAD/EMTDC, simulations and comparative analysis are conducted under different fault conditions. The findings demonstrate that the suggested approach can not only effectively suppress SCF, but also significantly increase power transmission, and the active power increase is up to 129 %, thus having a certain value for engineering applications.

Objective To examine recent patterns regarding oral anticoagulant (OAC) use among patients hospitalised with atrial fibrillation (AF) and quantify the impact of insurance coverage for non-vitamin K oral anticoagulants (NOACs) on quality of care and care inequality regarding OAC use among hospitalised patients with AF.Design Interrupted time series analysis.Setting Hospitals in China.Participants A total of 36 393 patients hospitalised with non-valvular AF were involved between 2015 and 2019 across China.Primary and secondary outcome measures Outcome was the impact of insurance coverage for NOACs on quality of care regarding OAC prescription using interrupted time series analysis with segmented regression models.Results OAC prescription rate during hospitalisation was 52.1% (31.3% for warfarin and 20.8% for NOACs) in patients with high-risk AF and 66.3% (29.8% for warfarin and 36.5% for NOACs) in low-risk patients. Insurance coverage for NOACs was associated with an immediate 10.9% (95% CI 7.6% to 14.3%) increase in NOAC prescription and a 0.33% (95% CI 0.08% to 0.58%) increase in the slope of the secular trend of NOAC prescription among all the patients. Disparities in NOAC prescription among hospitals decreased from 18.9 before the insurance coverage for NOACs to 3.4 after that. Similar results were found in patients with high risk of stroke.Conclusion A large gap exists between clinical practice and guideline recommendations regarding OAC prescription among patients hospitalised with AF in China. Insurance coverage may be an effective healthcare strategy to improve quality of care and reduce care disparities regarding OAC prescription among patients with AF.Trial registration number NCT02309398.

Encoding geospatial location is a fundamental problem for geospatial artificial intelligence (GeoAI) research. In recent years, some methods (such as Place2Vec, Space2Vec, and Sphere2Vec) were proposed to encode geospatial point as a high-dimensional vector. However, all these geospatial location encoders were designed to generate a real number vector. So, when applied to some of the brain-inspired neural networks, such as Hierarchical Temporal Memory (HTM), which required the input of a binary vector, the existing methods failed. To solve the problem, based on the research from neuroscience about place cell, we proposed a new geospatial location encoding method called PlaceField2BVec. The method used the place field model to encode a location. The place field was represented by the summation of four Gaussian functions, allowing it to be stretched or divided into multiple fields as the geospatial space expanded. Then we created an HTM and devised an experiment that simulated rats moving on tables of varying sizes. The moving trajectories were encoded by PlaceField2BVec and input to the HTM. After training, we found that the artificial neurons of HTM formed a place field similar to those of hippocampal neurons in the rat brain and the distribution patterns of the place field from the two kinds of neurons were consistent. At last, our method was compared with existing Space2BVec and Buffer2BVec in terms of location prediction accuracy and to demonstrate the robustness of the binary vector encoding methods, two brain-inspired artificial neural networks— HTM and BinaryLSTM were used. The result showed that, for HTM, in smaller geospatial space the PlaceField2BVec and Buffer2BVec had about the same accuracy on average but the highest accuracy of PlaceField2BVec is 100 %; when the geospatial space extended, our method had the highest accuracy and the average accuracy of PlaceField2BVec, Space2BVec, and Buffer2BVec is 83.9 %, 25.2 % and 69.7 % after 20 times’ training. For BinaryLSTM, PlaceField2BVec always had the highest accuracy in location prediction although the accuracy decreased as the space extended. Our research can be utilized for machine self-localization, navigation, and location-related GeoAI applications, and it also contributes to the theory of cognitive maps.

In clinical settings, regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods, restricted bone growth medications, and a scarcity of commercial bone grafts. To treat this life-threatening issue, improved biofunctional grafts capable of properly healing critical-sized bone defects are required. In this study, we effectively created anti-fracture hydrogel systems using spongy-like metal-organic (magnesium-phosphate) coordinated chitosan-modified injectable hydrogels (CPMg) loaded with a bioinspired neobavaisoflavone (NBF) component. The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphate-buffered saline. They also demonstrated prolonged and stable release profiles of Mg2+ and NBF. Importantly, CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells. To better understand the underlying mechanism of Mg2+ and NBF component, as well as their synergistic effect on osteogenesis, we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways. Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins (Runx2, OCN, OPN, BMPS and ALP). In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects. Based on these findings, we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.

Abstract Cancer-associated fibroblasts (CAFs) are a diverse stromal cell population within the tumour microenvironment, where they play fundamental roles in cancer progression and patient prognosis. Multiple lines of evidence have identified that CAFs are critically involved in shaping the structure and function of the tumour microenvironment with numerous functions in regulating tumour behaviours, such as metastasis, invasion, and epithelial-mesenchymal transition (EMT). CAFs can interact extensively with cancer cells by producing extracellular vesicles (EVs), multiple secreted factors, and metabolites. Notably, CAF-derived EVs have been identified as critical mediators of cancer therapy resistance, and constitute novel therapy targets and biomarkers in cancer management. This review aimed to summarize the biological roles and detailed molecular mechanisms of CAF-derived EVs in mediating cancer resistance to chemotherapy, targeted therapy agents, radiotherapy, and immunotherapy. We also discussed the therapeutic potential of CAF-derived EVs as novel targets and clinical biomarkers in cancer clinical management, thereby providing a novel therapeutic strategy for enhancing cancer therapy efficacy and improving patient prognosis.

Abstract Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.

The β-1–6-linked poly-N-acetylglucosamine (PNAG) polymer is a conserved surface polysaccharide produced by many bacteria, fungi, and protozoan (and even filarial) parasites. This wide-ranging expression makes PNAG an attractive target for vaccine development, as it potentially encompasses a broad range of microorganisms. Significant progress has been made in discovering important properties of the biology of PNAG expression in recent years. The molecular characterization and regulation of operons for the production of PNAG biosynthetic proteins and enzymes have been studied in many bacteria. In addition, the physiological function of PNAG has been further elucidated. PNAG-based vaccines and PNAG-targeting antibodies have shown great efficacy in preclinical research. Furthermore, clinical tests for both vaccines and antibodies have been carried out in humans and economically important animals, and the results are promising. Although it is not destined to be a smooth road, we are optimistic about new vaccines and immunotherapeutics targeting PNAG becoming validated and eventually licensed for clinical use against multiple infectious agents.

Aims: Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). Methods: A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. Results: The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. Conclusion: In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue. Cite this article: Bone Joint Res 2024;13(7):332–341.

IntroductionAldo-keto reductase 1B10 (AKR1B10) is a multifunctional enzyme, which is important in cancer development and progression, but the landscape of AKR1B10 in pan-cancers and in tumor microenvironment is unclear.MethodThis study integrated the sequencing data of 33 cancer types, including gastric cancer, from TCGA project to explored the expression pattern and genetic and epigenetic alterations of AKR1B10. The association of AKR1B10 expression with clinical progression of cancers was evaluated by Kaplan-Meier analysis; the potential role of AKR1B10 in tumor microenvironment (TME) and immune-related gene expression were analyzed by PURITY, ESTIMATE, TIMER and CIBERSORT algorithms. The expression of AKR1B10 and immune cell markers in gastric cancer were evaluated with multiplex immunofluorescence staining.ResultResults indicated that AKR1B10 was highly expressed in the gastrointestinal tract in health donors, but the expression of AKR1B10 was significantly changed in most of cancer types, which may be ascribed to DNA methylation in its promoter. The AKR1B10 expression in cancers and its value in disease progression was bidirectional and functionally enriched in metabolism in pan-cancers. In tumor microenvironment, AKR1B10 was significantly correlated with immune cell infiltrations and immune gene expression. In the stomach, along with the diminishing of AKR1B10 expression, CD68+ macrophage increased and CD19+ B cell decreased in gastric cancer.DiscussionThese data indicates that AKR1B10 may be an important factor in the development and progression and a potential therapeutic target for multiple cancers, but plays as a protector in the gastric tissues.

Investigating hidden hazards and implementing closed-loop management are essential strategies for accident prevention in the mining industry. This study tackles a key challenge in applying association rule mining to the development of hazard management plans for underground mines. The current approach mainly focuses on hazard description data, often underutilizing critical information such as hazard time and location. To address this, we integrate topic mining with association rule mining to uncover intrinsic association patterns among various attributes of mine safety hazards. Through a systematic analysis of standardized mining hazard attributes, five key analytical dimensions were identified: Hazard Type, Level, Time, Location, and Responsible Units. A topic mining model, utilizing the Biterm Topic Model, was constructed to reduce dimensionality and aggregate hazard description data. Evaluation indicators such as Standard Lift and Difference Degree were proposed, resulting in a multidimensional association rule mining model for mining safety hazards. In this research, 1387 valid rules were extracted based on hazard inspection data from an underground gold mine in China. The analysis revealed relatively strong associations between hazard location and hazard type, responsible unit, as well as hazard level, with association degrees of 1.934, 1.412, and 1.240, respectively. Additionally, 15 rules with a high degree of differentiation were identified to explore interesting correlations among different attributes. Based on this, corresponding control measures and improvement plans were developed for 19 locations. The results demonstrate that a multidimensional partition-based association rule mining approach for mining safety hazards can significantly enhance the specificity of safety training and improve the efficiency of safety hazard investigation.

ABSTRACTThe 20-year war in Afghanistan has had a catastrophic impact on agricultural planting and food security, but the assessment was difficult due to a lack of existing statistics. We used 30m Landsat data to extract the annual planting area and built the time series to measure the condition of agriculture, and used constant nighttime light data to quantify the impact of the war. Combined with climate, Digital Elevation Model (DEM) data, etc., we quantitatively analysis the impact of the war using regression model. From a time perspective, the total planting area reached peek during some period of relative pacification, but maintained a low level of planting most time. From a spatial perspective, the main planting areas shifted from east to west. Both poppy and wheat planting have a high correlation with non-natural factor, while wheat affected more by natural conditions compared with poppy. In addition, the cultivation of wheat is limited by poppy. As a verification, we collect relative history records to explain the rationality of the result of analysis. According to the result, we reveal the adverse effects of war on agricultural planting and food security in Afghanistan and provide a reference for relevant researches on war and agriculture.

Cadmium (Cd) is a neurotoxicant that gradually accumulates in the human body with age. High Cd burden is correlated with adult hippocampal neurogenesis (AHN) and memory deficits in mammals. However, little knowledge is known about the mechanism by which Cd exposure impairs neurogenesis and cognition. Here, we investigated the roles of store-operated calcium entry (SOCE)-mediated calcium dyshomeostasis in Cd-induced AHN and memory deficits as well as therapeutic potential for the prevention of Cd-induced neurotoxicity. To achieve this goal, 8 weeks-old C57BL/6 J mice were subjected to different concentrations of cadmium chloride (0, 5, 10, 20 ppm) in drinking water for 8 weeks, we then examined the AHN, calcium homeostasis, SOCE channel and memory in Cd-exposed mice by using immunohistochemistry, calcium imaging, Y-maze and fear conditioning test. Our results indicated that chronic Cd exposure markedly increased Cd levels in serum and cerebrospinal fluid by almost 10-fold, and inhibited the proliferation and differentiation of hippocampal adult neural stem cells in a dose-dependent manner. Additionally, Cd exposure impaired the maturation of hippocampal neural stem cells without inducing gliosis. Transcriptome analysis revealed that Cd exposure inhibited the proliferation of neuroblastoma via alteration of calcium signaling pathway, and attenuated SOCE channels played a pivotal role in mediating Cd-induced cytoplasmic calcium overload and depletion of endoplasmic reticulum calcium stores. Activation of SOCE by hyperforin, a natural derivative from medicinal plant, restored intracellular calcium homeostasis and improved AHN and memory in Cd-exposed mice. Together, this study provided novel insights into the mechanism that Cd exposure impaired AHN and memory by prompting neuronal SOCE-mediated calcium dyshomeostasis, and offered a new therapeutic approach for prevention of Cd-induced neurotoxicity.

For DC grid based on the hybrid modular multilevel converter (MMC), the traditional DC fault current clearance scheme takes a long time and greatly affects the active power transmission. A novel DC fault current clearance coordinated control strategy is proposed, which can quickly interrupt the fault current and reduce the impact of DC fault on the DC grid and AC system. For fault-line connected MMC (FLMMC), a negative DC voltage control is employed, which can improve the current attenuation speed and ensure reliable fault isolation. For non-fault-line connected MMC (NFLMMC), the active current-limiting control (ACLC) based on the virtual reactor is adopted, which can reduce the current flow to the fault location and further shorten fault isolation time. To reduce the impact on the AC system during the DC fault, a short-time active power support control is designed. Finally, a four-terminal DC grid simulation model is built based on the RT-LAB OP5600 real-time digital simulation platform. The simulation results show that the proposed coordinated control strategy for the DC grid can quickly clear DC fault current, shorten DC fault isolation time, and strengthen active power support capability.

Biological invasion poses a critical global issue, leading to substantial detrimental impacts on biodiversity, the environment, and the economy. The objective of the study is to offer a thorough understanding of how both climatic and human-induced elements impact the geographic richness of invasive plant species across the Loess Plateau. We evaluate the distribution of invasive plant species at the county level across the Loess Plateau by examining herbarium records from China. We incorporate 16 climatic and anthropogenic variables to depict the local environmental settings. Furthermore, we apply a classification and regression tree approach to investigate the correlation between the richness of invasive plant species and the identified factors. Our study demonstrates that a total of 401 invasive plant species are identified, which are spread across 249 genera and 61 families. Among these, the Asteraceae family stands out as the most prevalent, trailed by Poaceae and Fabaceae. The spatial distribution of invasive plant species richness reveals a notable trend, with the highest frequencies found in the southeastern parts of the region and the lowest in the northwestern areas. It is noteworthy that regions with higher levels of economic advancement tend to harbor a more significant abundance of invasive plant species. The richness of invasive plant species on the Loess Plateau is predominantly shaped by a combination of climatic and human variables, such as annual precipitation, gross domestic product, maximum temperature of warmest month, and minimum temperature of coldest month. To fully comprehend the ecological and biological mechanisms underlying the diversity of invasive plant species on the Loess Plateau, a pioneering conceptual framework has been established. Our study suggests that achieving a harmonious equilibrium among development, conservation, and invasion mitigation is essential for recognizing emerging risks associated with habitat alterations, climate change, and socio-economic advancements in arid regions.

Objective This study aims to explore a streamlined risk-adjusted cesarean section rate (RCSR) model and to compare its practical application effects with the traditional RCSR models. Methods Utilizing obstetric electronic health record (EHR) data from provincial multicenter hospitals, this study establishes a streamlined RCSR model alongside the traditional RCSR model and evaluates the efficacy of both models. Subsequently, the RCSRs of 56 hospitals within the province are calculated and ranked using both models. The consistency of these rankings is then quantified using Kendall's tau coefficient of concordance. Result Comparison of model effectiveness evaluation of the traditional RCSR model versus the streamlined RCSR model is as follows: AUC (0.840 vs 0.839), accuracy (0.875 vs 0.872), sensitivity (0.690 vs 0.685), specificity (0.898 vs 0.892), positive predictive value (0.908 vs 0.903), negative predictive value (0.664 vs 0.660), and Brier score (0.069 vs 0.067). In the test of the consistency of hospital rankings based on two models, Kendall's tau coefficients were observed to be 0.979 (year 2017), 0.978 (year 2018), and 0.978 (year 2019) over a span of 3 years, with an aggregate coefficient of 0.974. Conclusion In the realm of model performance evaluation as well as the pragmatic application within hospital settings, the streamlined model exhibits a substantial congruence with the traditional model. Therefore, the streamlined model can effectively serve as a viable surrogate for the traditional model, potentially establishing itself as a refined paradigm for the appraisal of quality in obstetric healthcare services.

Abstract Background A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis. Methods The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques. Results The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P

Abstract In this study, a new type of multi-arch tunnel construction method is proposed. This effort is undertaken due to the many disadvantages of the traditional multi-arch tunnel construction method. Furthermore, this method omits the construction of a middle pilot tunnel, and it has the advantages of safety, high efficiency, and being economical. When using the method of continuous arch tunneling without a middle pilot tunnel, the blasting of the first tunnel and the following tunnel has a greater impact on the surrounding rock damage, as well as on the supporting structure of the same cross-section. Therefore, this study uses LS-DYNA finite element software to construct a three-dimensional numerical model. In addition, the perimeter rock damage law and mechanical response characteristics of the supporting structure in the same cross-section of the first tunnel, as well as the following tunnel after blasting without a middle pilot tunnel, are analyzed. At the same time, the results of the study are based on optimizing the blasting program, and these are then applied to the field. Through the results, it is found that, after blasting a continuous arch tunnel without a medial pilot tunnel, the surrounding rock damage in the arch cross-region of the double-arch tunnel (where the arch top and the arch shoulder are more significant) and the effective stress of the supporting structure exceed the strength design value. In addition, the maximum adequate pressure is distributed in the medial diaphragm wall. With the optimized blasting scheme, the range of the peripheral rock damage is reduced by a maximum of 67%, and the effective stress in the supporting structure is reduced by 25.9–64.8%. The research results are of great significance in terms of improving construction safety, economic efficiency, and project quality, as well as in promoting the research and development of new work methods for double-arch tunnels.

Abstract Based on the macroscopic structure control theory, The slate with a significant bedding plane is a composite rock mass composed of rock blocks containing microscopic defects, joint surface closure elements, and shear deformation elements. Considering the coupling damage effect of water erosion and triaxial compressive load on bedding structure plane, the transversely isotropic damage constitutive model of slate under triaxial compressive load is derived with the dip angle of bedding and confining pressure as the variable. Firstly, based on the statistical theory of continuous damage mechanics and the maximum tensile strain criterion, the transversely isotropic deformation constitutive model of rock block with micro-defects is given; Secondly, based on the phenomenological theory of closed deformation and shear-slip deformation mechanism of layered structural plane under the coupling action of water erosion and triaxial compression load, the calculation formula of axial deformation of layered structural plane under the coupling action is given; Finally, to verify the accuracy of the established constitutive model, triaxial compression tests are carried out to study the influence of dip angle and confining pressure on the macroscopic mechanical properties and mechanism of slate. The results show that: the established triaxial compression damage constitutive model of bedding slate can accurately describe the stress–strain relationship of bedding slate after water environment erosion. With the increase of bedding dip angle, the strength and deformation capacity of the bedding slate first decreases and then increases, showing a U-shaped distribution as a whole. There are three main types of failure: tension shear composite failure, shear slip failure, and splitting tension failure.

The relationship between the stability of tool materials and their cutting performance is a critical technical challenge for the manufacturing industry, which is essential for selecting appropriate treatment processes to achieve superior treatment tool performance. In this paper, a standard cutting tool experiment was used to study the sharpness of the knife with different residual austenite content. The cutting edges of the knife were characterized by an optical microscope (OM), scanning electron microscope (SEM), electron back scattering diffraction (EBSD), and transmission electron microscope (TEM), to analyze the relationship between tool edge hardness and microstructure. The microstructure stability of the material was analyzed by a separated Hopkinson pressure bar (SHPB) experiment. The results show that the hardness and cutting performance of the knives are affected by the joint action of carbide and residual austenite, with an initial increase followed by decreases as the heat treatment quenching temperature increases. After the knife material is treated by cryogenic process, the hardness of the knife is increased by 3.89 HRC, the initial sharpness by 15.3%, and the sharpness and durability by 18.8%. The residual austenite in the knives was found to be unstable and easy to transformation during high-rate deformation processes. This study elucidates the effect of residual austenite content on the sharpness of the knives, providing a foundation for the reasonable control of residual austenite content in the actual production settings.

The heat transfer characteristics of smooth and honeycomb staggered labyrinth seals were investigated using the conjugate heat transfer method. Three pressure ratios (π = 1.2, 1.6, and 2.0), three rotational speeds (RPM = 0, 10,000, and 20,000), and two wall-to-fluid temperature ratios (TR = 0.4 and −0.67) are considered to explore the influence of centrifugal force and centrifugal buoyancy. The results indicate that the heat transfer coefficient of staggered labyrinth seals increases with pressure ratio due to the increased flow velocity and the thinner boundary layer. As a result of the interaction of inertia force and centrifugal force, some enhancement positions of heat transfer coefficient shift slightly. Notably, centrifugal buoyancy has a negative impact on heat transfer at TR = −0.67, but a positive impact at TR = 0.4. When TR = −0.67, there is a peak of the heat transfer coefficient with increased rotational speed due to centrifugal buoyancy. In addition, the heat transfer coefficient at TR = −0.67 is lower than that at TR = 0.4, especially at high rotational speeds. It is proposed that heat transfer correlations be developed by incorporating the Taylor number and rotating Grachev number.

The Loess Plateau plays a significant role in the implementation of China’s Grain for Green Project due to severe ecological damage in the region. In order to monitor and evaluate the effects of Grain for Green Project, a study was conducted in Wuqi County, which is representative of the Loess Plateau. The study utilized remote sensing (RS) and geographic information system (GIS) technologies to analyze the spatial and temporal patterns of Grain for Green Project and assess its effects. The findings indicate that the Grain for Green Project resulted in notable improvements in Wuqi County from 2000 to 2018. Firstly, there was a significant increase in vegetation coverage, accompanied by a reduction in soil erosion intensity. Secondly, approximately 64 % of cropland was converted, leading to an expansion of forest and grassland areas. Thirdly, the focus of vegetation restoration was primarily on converting cropland to grassland, indicating its suitability for the county compared to forestation. Lastly, the conversion of steep cropland (>25°) was influenced by the density of less steep cropland (

Carbon fiber (CF) is one of the conductive fillers with the best electrical conductivity, but it is expensive and difficult to disperse in cement matrix, which limits the application and development of CF conductive cement-based composites. Therefore, this paper took the conductive cement slurry with CF content of 1.0 % as the control group, and proposed to use low-cost graphite (G) and nano-carbon black (NCB) instead of some CFs to prepare conductive cement-based composites. The synergistic enhancement effect between different conductive fillers was explored to reduce the cost of materials while maintaining electrical conductivity. The results showed that the resistivity decreased first, then increased, then decreased and then increased with the increase of the proportion of particle conductive filler instead of CF. The resistivity of conductive cement slurry was 125.65 Ω·cm when G replaced 20 % CF, the resistivity of conductive cement slurry was 140.66 Ω·cm when NCB replaced 30 % CF, and the resistivity of conductive cement slurry was 122.05 Ω·cm when G and NCB replaced 30 % CF, which were close to the resistivity of the control group (122.35 Ω·cm). The purpose of reducing the cost of materials without affecting the conductivity of conductive cement slurry was achieved.

Background: Previous observational studies have indicated associations of physical activity (PA) and air pollution with mortality. A few studies have evaluated air pollution and PA interactions for health. Still, the trade-off between the harmful effects of air pollution exposure and the protective effects of PA remains controversial and unclear. Objective: This study aimed to investigate the joint association of air pollution and PA with mortality risks. Methods: This prospective cohort study included 322,092 participants from 2006 to 2010 and followed up to 2021 in the UK Biobank study. The concentrations of air pollutants (2006–2010), including particulate matter (PM) with diameters

Five stems of rapeseed with abundant black microsclerotia were collected from Huangyuan County of Qinghai Province, China, and fungal isolates were obtained from the stems. They were identified based on morphology, molecular features and specific PCR detection. The results showed that the 10 fungal isolates belonged to Verticillium longisporum lineage A1/D3. One of the 10 isolates (HW7-1) was tested for virulence on three species of rapeseed, including B. napus Zhongshuang 9, B. rapa Qingyou 9 and B. juncea Tayou 2 by conidia inoculation of HW7-1 on roots of young seedlings. Control seedlings were inoculated with V. dahliae conidia or water alone. The seedlings of these treatments were transplanted in culture mix and incubated in a growth chamber (20 ​°C). Results suggested that the control seedlings of three cultivars appeared quite healthy, while the seedlings inoculated with HW7-1 turned yellowing leaves, seedling stunting or even death after 22 days post-inoculation. V. longisporum was re-isolated from he yellow leaves, thus fulfilling Koch's postulates. Moreover, compared to the control treatments, inoculation with HW7-1 caused flowering delay and seed yield reduction on Tayou 2 with production of microsclerotia on the stems. To our knowledge, this is the first report of V. longisporum lineage A1/D3 on rapeseed in northwestern China.

Abstract Background Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes disability worldwide. Exosomes released by fibroblast-like synoviocytes in RA (RA-FLSs-Exos) play a role in the development of RA, and circular RNAs (circRNAs) are important for RA progression. This study aimed to investigate the molecular mechanisms underlying the effects of RA-FLSs-Exos in RA and identify the potential pathway responsible for these effects. Methods We initially conducted microarray analysis to identify dysregulated circRNAs in exosomes associated with RA. We then co-cultured isolated RA-FLSs-Exos with chondrocytes to examine their role in RA. In vivo experiments were performed using collagen-induced arthritis mouse models, and circFTO knockdown was achieved through intra-articular injection of AAV5 vectors. Results Our findings revealed increased expression of circFTO in both RA-FLSs-Exos and synovial tissues from patients with RA. Exosomal circFTO hindered chondrocyte proliferation, migration, and anabolism while promoting apoptosis and catabolism. Mechanistically, we discovered that circFTO facilitates the formation of methyltransferases complex to suppress SRY-related high-mobility group box 9 (SOX9) expression with assistance from YTH domain family 2 (YTHDF2) through an m6A-dependent mechanism. Furthermore, inhibition of circFTO improved symptoms of RA in vivo. Conclusion Taken together, our study demonstrates that exosomal circFTO derived from FLSs contributes to the progression of RA by targeting SOX9. These findings highlight a promising target for treating RA.

Although the hybrid powered underwater glider has the advantages of both typical underwater gliders and traditional vehicles, it also has disadvantages such as high energy consumption and inconvenient recovery. In the rapid propulsion mode, the existence of wings not only increases navigation resistance and reduces navigation stability but also is not conducive to the recovery and deployment of gliders. In view of this, a dual-hull hybrid powered underwater glider was proposed. The wings of the glider can be retracted according to the actual needs, which is different from the traditional fixed horizontal wing, so as to realize the reasonable distribution of energy and improve the comprehensive navigation performance of underwater gliders. In addition, the working mode, system composition, and wing retracting principle of the glider were introduced in detail, and a worm gear and worm glide wings retracting device was designed. The corresponding retracting mechanism was established. On this basis, the hydrodynamic performance of the wings was analyzed by numerical simulation method, and a reasonable shipborne configuration scheme was obtained.

A DC grid based on half-bridge modular multilevel converters (HB-MMC) is a feasible means to realize the friendly grid connection of renewable energy. To solve problems such as the high cost and technical difficulty of DC circuit breakers (DCCB), a coordinated control method for fault current suppression of DC grid connecting wind power is proposed. The key influencing factors of DC fault current are revealed by fault characteristics analysis, and an adaptive current-limiting control method for MMC is proposed, whose parameter selection principles are designed to ensure the safe operation of equipment while achieving effective suppression of fault current. In addition, a novel configuration method of dissipative resistors with the current-limiting function is proposed, which can solve the problem of surplus power in the DC grid and reduce the current stress of converter valves. Based on this, a coordination scheme of dissipative resistors, the adaptive current-limiting control method, and DCCBs are proposed to block fault current, effectively reducing the manufacturing difficulty and cost of DCCB. Finally, a four-terminal DC grid simulation model is built based on the RTLAB OP5600 real-time digital simulation platform, and the effectiveness and feasibility of the proposed methods are verified.

Abstract Objectives Lasiodiplodia pseudotheobromae is an important fungal pathogen associated with die-back, canker and shoot blight in many plant hosts with a wide geographic distribution. The aim of our study was to provide high-quality genome assemblies and sequence annotation resources of L. pseudotheobromae, to facilitate future studies on the systematics, population genetics and genomics of the fungal pathogen L. pseudotheobromae. Data description High-quality genomes of five L. pseudotheobromae isolates were sequenced based on Oxford Nanopore technology (ONT) and Illumina HiSeq sequencing platform. The total size of each assembly ranged from 43 Mb to 43.86 Mb and over 11,000 protein-coding genes were predicted from each genome. The proteins of predicted genes were annotated using multiple public databases, among the annotated protein-coding genes, more than 4,300 genes were predicted as potential virulence genes by the Pathogen Host Interactions (PHI) database. Moreover, the genome comparative analysis among L. pseudotheobromae and other closely related species revealed that 7,408 gene clusters were shared among them and 152 gene clusters unique to L. pseudotheobromae. This genome and associated datasets provided here will serve as a useful resource for further analyses of this fungal pathogen species.

Abstract Background Omental metastasis is the major cause of ovarian cancer recurrence and shortens patient survival, which can be largely attributed to the dynamic evolution of the fertile metastatic microenvironment driven by cancer cells. Previously, we found that adipose-derived mesenchymal stem cells (ADSCs) undergoing a phenotype shift toward cancer-associated fibroblasts (CAFs) participated in the orchestrated omental premetastatic niche for ovarian cancer. Here, we aim to elucidate the underlying mechanisms. Methods Small extracellular vesicles were isolated from ovarian cancer cell lines (ES-2 and its highly metastatic subline, ES-2-HM) and patient ascites using ultracentrifugation. Functional experiments, including Transwell and EdU assays, and molecular detection, including Western blot, immunofluorescence, and RT–qPCR, were performed to investigate the activation of ADSCs in vitro. High-throughput transcriptional sequencing and functional assays were employed to identify the crucial functional molecules inducing CAF-like activation of ADSCs and the downstream effector of miR-320a. The impact of extracellular vesicles and miR-320a-activated ADSCs on tumor growth and metastasis was assessed in subcutaneous and orthotopic ovarian cancer xenograft mouse models. The expression of miR-320a in human samples was evaluated using in situ hybridization staining. Results Primary human ADSCs cocultured with small extracellular vesicles, especially those derived from ES-2-HM, exhibited boosted migration, invasion, and proliferation capacities and elevated α-SMA and FAP levels. Tumor-derived small extracellular vesicles increased α-SMA-positive stromal cells, fostered omental metastasis, and shortened the survival of mice harboring orthotopic ovarian cancer xenografts. miR-320a was abundant in highly metastatic cell-derived extracellular vesicles, evoked dramatic CAF-like transition of ADSCs, targeted the 3′-untranslated region of integrin subunit alpha 7 and attenuated its expression. miR-320a overexpression in ovarian cancer was associated with omental metastasis and shorter survival. miR-320a-activated ADSCs facilitated tumor cell growth and omental metastasis. Depletion of integrin alpha 7 triggered CAF-like activation of ADSCs in vitro. Video Abstract Conclusions miR-320a in small extracellular vesicles secreted by tumor cells targets integrin subunit alpha 7 in ADSCs and drives CAF-like activation, which in turn facilitates omental metastasis of ovarian cancer. Graphical Abstract

Global urbanization has led to severe damage and even disappearance of traditional villages in large numbers, significantly impacting the diversity of cultural landscapes. To effectively protect and inherit the cultural landscape of traditional villages, this study proposes the “culture-landscape genes” theory and its double-chain model. Taking the traditional Tujia villages in Shizhu County, Chongqing Municipality, China as an example, we identify, extract, correspond, encode, and comprehensively evaluate their culture-landscape genes. Based on the evaluation and analysis results, corresponding protection and development strategies are formulated. The study indicates that: firstly, the identification, extraction, and correlation of genes directly influence the construction of the evaluation system and the assessment of the protection level. Secondly, the comprehensive evaluation system under the double-chain model is more scientific and reasonable compared to the single-gene model of cultural or landscape genes. The culture-landscape genes theory proposed in this study promotes the development of the gene theory of traditional villages, and its double-chain research model effectively supplements the current methods for the protection and sustainable development of traditional villages, demonstrating a wide range of application value.

Photovoltaic (PV) and battery energy storage systems (BESSs) are key components in the energy market and crucial contributors to carbon emission reduction targets. These systems can not only provide energy but can also generate considerable revenue by providing frequency regulation services and participating in carbon trading. This study proposes a bidding strategy for PV and BESSs operating in joint energy and frequency regulation markets, with a specific focus on carbon reduction benefits. A two-stage bidding framework that optimizes the profit of PV and BESSs is presented. In the first stage, the day-ahead energy market takes into account potential real-time forecast deviations. In the second stage, the real-time balancing market uses a rolling optimization method to account for multiple uncertainties. Notably, a real-time frequency regulation control method is proposed for the participation of PV and BESSs in automatic generation control (AGC). This is particularly relevant given the uncertainty of grid frequency fluctuations in the optimization model of the real-time balancing market. This control method dynamically assigns the frequency regulation amount undertaken by the PV and BESSs according to the control interval in which the area control error (ACE) occurs. The case study results demonstrate that the proposed bidding strategy not only enables the PV and BESSs to effectively participate in the grid frequency regulation response but also yields considerable carbon emission reduction benefits and effectively improves the system operation economy.