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Abstract Background Although previous studies have suggested a possible association between bone mineral density (BMD) and intervertebral disc degeneration (IDD), the causal relationship between them remains unclear. Evidence from accumulating studies indicates that they might mutually influence one another. However, observational studies may be affected by potential confounders. Meanwhile, Mendelian randomization (MR) study can overcome these confounders to assess causality. Objectives This Mendelian randomization (MR) study aimed to explore the causal effect of bone mineral density (BMD) on intervertebral disc degeneration (IDD). Methods Summary data from genome-wide association studies of bone mineral density (BMD) and IDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran’s Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. Multivariate MR (MVMR) analyses used multivariable inverse variance-weighted methods to individually and jointly adjust for four potential confounders, body mass index (BMI), Type2 diabetes, hyperthyroidism and smoking. A reverse MR analysis was conducted to assess potential reverse causation. Results In the univariate MR analysis, femoral neck bone mineral density (FNBMD), heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) had a direct causal effect on intervertebral disc degeneration (IDD) [FNBMD-related analysis: OR(95%CI) = 1.17 (1.04 to 1.31), p = 0.008, eBMD-related analysis: OR(95%CI) = 1.06 (1.01 to 1.12), p = 0.028, LSBMD-related analysis: OR(95%CI) = 1.20 (1.10 to 1.31), p = 3.38E-7,TB BMD-related analysis: OR(95%CI) = 1.20 (1.12 to 1.29), p = 1.0E-8]. In the MVMR analysis, it was revealed that, even after controlling for confounding factors, heel bone mineral density (eBMD), lumbar spine bone mineral density (LSBMD), and total body bone mineral density (TB BMD) still maintained an independent and significant causal association with IDD(Adjusting for heel bone mineral density: beta = 0.073, OR95% CI = 1.08(1.02 to 1.14), P = 0.013; Adjusting for lumbar spine bone mineral density: beta = 0.11, OR(95%CI) = 1.12(1.02 to 1.23), P = 0.03; Adjusting for total body bone mineral density: beta = 0.139, OR95% CI = 1.15(1.06 to 1.24), P = 5.53E − 5). In the reverse analysis, no evidence was found to suggest that IDD has an impact on BMD. Conclusions The findings from our univariate and multivariable Mendelian randomization analysis establish a substantial positive causal association between BMD and IDD, indicating that higher bone mineral density may be a significant risk factor for intervertebral disc degeneration. Notably, no causal effect of IDD on these four measures of bone mineral density was observed. Further research is required to elucidate the underlying mechanisms governing this causal relationship.

Rock deformation modulus is one of the key parameters for the design and construction of underground rock engineering. Obtaining accurate rock deformation modulus is crucial for a comprehensive analysis of the deformation behavior of the surrounding rock in deep rock engineering. To achieve this goal, the commonly used methods for calculating rock deformation modulus are systematically sorted out and summarized. Furthermore, the rock deformation modulus is inverse-calculated by simulating in-situ tests using the finite element method, and the results are verified and analyzed by comparing them with the in-situ test results. For the actual project of deep shaft, a numerical calculation model is established to conduct an inversion analysis of rock deformation modulus of different lithologies in the deep strata. Additionally, a sensitivity analysis is performed on different strength criteria, Poisson's ratio and rock cohesion on rock deformation modulus. Finally, the numerical simulation inversion results are compared and discussed with the empirical formula calculation results. The results show that the values of rock deformation modulus obtained from numerical inversion using finite element method are in good agreement with those calculated based on the experimental rigid plate load test; While Poisson's ratio does have some influence on rock deformation modulus, the sensitivity of rock deformation modulus to Poisson's ratio is generally low; When the cohesion of the rock mass is small, the choice of strength criterion has a significant influence on the inversion results of deformation modulus, and vice versa; the sensitivity of the rock deformation modulus to the changes of the rock cohesion varies depending on the depth and lithology of the strata; the deformation modulus of the rock mass obtained by numerical inversion has a good correlation with some empirical equations. Therefore, the numerical simulation and empirical formulae are useful during planning, design and development of deep rock projects to perform the inversion calculation of rock deformation modulus, thereby ensuring greater safety and economy.

Abstract Over the past two decades, more frequent and intense climate events have seriously threatened the operation of water transfer projects in the Pacific Rim region. However, the role of climatic change in driving runoff variations in the water source areas of these projects is unclear. We used tree-ring data to reconstruct changes in the runoff of the Hanjiang River since 1580 CE representing an important water source area for China’s south-north water transfer project. Comparisons with hydroclimatic reconstructions for the southwestern United States and central Chile indicated that the Pacific Rim region has experienced multiple coinciding droughts related to ENSO activity. Climate simulations indicate an increased likelihood of drought occurrence in the Pacific Rim region in the coming decades. The combination of warming-induced drought stresses with dynamic El Niño (warming ENSO) patterns is a thread to urban agglomerations and agricultural regions that rely on water transfer projects along the Pacific Rim.

In order to investigate the effect of intermediate principal stress on the progressive damage and permeability characteristics of unloading sandstone, the unloading test was carried out under different intermediate principal stress conditions based on a multifunctional true triaxial fluid-solid coupling test system with gas-bearing sandstone as the research object; the exponential permeability model related to the cracked volume strain and damage variable were obtained. The results show that the crack closure stress, crack initiation stress and damage stress increase with the increase of intermediate principal stress, and the percentage of elastic section and microcrack extension stage in the pre-peak strain increases. The deformation in the direction of the intermediate principal stress is restrained in the microcrack extension stage, and the compression effect on the direction of the minimum principal stress is enhanced with the increase of the intermediate principal stress; in the macroscopic crack extension stage, the damage stress is closer to the peak stress, and the damage of the specimen is brittle in character. With the increase of the intermediate principal stress, the initial permeability reduction shows a decreasing trend and the point of elevated permeability shifts backward.

Abstract Broad‐spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage‐displayed peptide onto a broad‐spectrum antimicrobial peptide and explored its structure–function relationship through one‐factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage‐derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

Abstract Background Cancer cells frequently evolve necroptotic resistance to overcome various survival stress during tumorigenesis. However, we have previously showed that necroptosis is widespread in head and neck squamous cell carcinoma (HNSCC) and contributes to tumor progression and poor survival via DAMPs-induced migration and invasiveness in peri-necroptotic tumor cells. This implicated an alternative strategy that cancers cope with necroptotic stress by reprogramming a pro-invasive necroptotic microenvironment (NME). Here, we aim to decipher how necroptotic cells shape the NME and affect HNSCC progression. Methods Both our pre-established cellular necroptotic model and newly established Dox-induce intratumoral necroptosis model were used to investigate how necroptosis affect HNSCC progression. Transcriptomic alterations in peri-necroptotic tumor cells were analyzed by RNA-seq and validated in the NME in mice and patients’ samples. The differential DAMPs compositon among apopotosis. Necrosis, and necroptosis were analyzed by label-free proteomic technique, and the necroptosis-specific DAMPs were then identified and validated. The potential receptor for ISG15 were simulated using molecular docking and further validated by in vitro assays. Then the ISG15-RAGE axis was blocked by either knockdown of necroptotic-ISG15 release and RAGE inhibitor FPS-ZM1, and the impact on tumor progression were tested. Last, we further tested our findings in a HNSCC-patients cohort. Results Necroptosis played a crucial role in driving tumor-cell invasiveness and lymphatic metastasis via tumor-type dependent DAMPs-releasing. Mechanistically, necroptotic DAMPs induced peri-necroptotic EMT via NF-κB and STAT3 signaling. Furthermore, intrinsic orchestration between necroptotic and cGAS-STING signaling resulted in producing a group of interferon stimulated genes (ISGs) as HNSCC-dependent necroptotic DAMPs. Among them, ISG15 played an essential role in reprogramming the NME. We then identified RAGE as a novel receptor for extracellular ISG15. Either blockage of ISG15 release or ISG15-RAGE interaction dramatically impeded necroptosis-driven EMT and lymphatic metastasis in HNSCC. Lastly, clinicopathological analysis showed high ISG15 expression in NME. Extensive necroptosis and high tumor-cell RAGE expression correlated with tumor progression and poor survival of HNSCC patients. Conclusions Our data revealed a previously unknown cGAS-ISG15-RAGE dependent reprogramming of the necroptotic microenvironment which converts the necroptotic stress into invasive force to foster HNSCC-cell dissemination. By demonstrating the programmatic production of ISG15 via necroptosis-cGAS orchestration and its downstream signaling through RAGE, we shed light on the unique role of ISG15 in HNSCC progression. Targeting such machineries may hold therapeutic potential for restoring intratumoral survival stress and preventing lymphatic metastasis in HNSCC. Graphical Abstract

Abstract Respiratory diseases constitute a major health problem for ruminants, resulting in considerable economic losses throughout the world. Parainfluenza type 3 virus (PIV3) is one of the most important respiratory pathogens of ruminants. The pathogenicity and phylogenetic analyses of PIV3 virus have been reported in sheep and goats. However, there are no recent studies of the vaccination of sheep or goats against PIV3. Here, we developed a purified inactivated ovine parainfluenza virus type 3 (OPIV3) vaccine candidate. In addition, we immunized sheep with the inactivated OPIV3 vaccine and evaluated the immune response and pathological outcomes associated with OPIV3 TX01 infection. The vaccinated sheep demonstrated no obvious symptoms of respiratory tract infection, and there were no gross lesions or pathological changes in the lungs. The average body weight gain significantly differed between the vaccinated group and the control group (P

Abstract How to effectively utilize renewable energy and improve the economic efficiency of microgrid system and its ability to consume renewable energy has become one of the main problems facing China at present. In response to this challenge, this paper establishes a multiobjective capacity optimization model with the minimum levelized cost of energy, the maximum proportion of renewable energy consumption, and the minimum comprehensive system cost. Based on this model, a new improved beluga whale optimization algorithm is proposed to solve the multiobjective optimization problem in the capacity allocation process of wind–solar–storage microgrid system with the goal of ensuring that the microgrid can meet the maximum load demand at different moments throughout the year. In this paper, opposition‐based learning, artificial bee colony, dynamic opposite, and beluga whale optimization are combined to improve the population diversity and convergence accuracy, thereby enhancing the optimization performance of the algorithm. Finally, after finding the optimal Pareto front solution, the Technique for Order Preference by Similarity to an Ideal Solution is used to help decision‐makers select the optimal solution. Using real load data and meteorological data, the results of this paper show that the multiobjective capacity allocation optimization method of grid‐connected scenic storage microgrid system based on the improved beluga whale optimization algorithm can improve the economics of the wind–solar–storage microgrid system and promote the photovoltaic consumption simultaneously, providing a solution for the realization of low‐carbon power and regional economic development. The best‐found levelized cost of energy for the wind–solar–storage microgrid system is 0.192 yuan/kWh.

Abstract The complete cp genomes of Pedicularis chinensis (GenBank accession number: OQ587614) and Pedicularis kansuensis (GenBank accession number: OQ587613) were sequenced, assembled, and annotated. Their chloroplast (cp) genome lengths were 146,452 bp, and 146,852 bp, respectively; 120 and 116 genes were identified, comprising 75 and 72 protein-coding genes (PCGs), 37 and 36 transfer RNA (tRNA) genes, and 8 and 8 ribosomal RNA (rRNA) genes, for P. chinensis and P. kansuensis, respectively. A simple sequence repeat (SSR) analysis revealed that the repetitive sequences were mainly composed of mononucleotide repeats (A/T motif) and dinucleotide repeats (AT/TA motif). Comparative genomics identified several variant genes (rpl22, rps19, rpl12, ycf1, trnH, psbA, and ndhH) and variant regions (trnS-GGA, trnV-UAC, ndhJ-trnV, ycf4-cemA, ndhE-nhdG, and rpl32-trnL) with a high Pi, indicating the potential to serve as deoxyribo nucleic acid (DNA) barcodes for Pedicularis species identification. The results show that the cp genomes of P. chinensis and P. kansuensis were the same as those of other plants in Pedicularis, with different degrees of AT preference for codons. Large differences in the number of SSRs and the expansion of the inverted repeat (IR) region showed strong variability and interspecific differentiation between these two species and other species represented in the genus Pedicularis. A phylogenetic analysis showed that P. kansuensis had the closest relationship with P. oliveriana, and P. chinensis had the closest relationship with P. aschistorhyncha. These results will facilitate the study of the phylogenetic classification and interspecific evolution of Pedicularis plants.

Abstract Chronic obstructive pulmonary disease (COPD) is characterised by persistent airway inflammation even after cigarette smoking cessation. Neutrophil extracellular traps (NETs) have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke (CS). However, whether and how NETs contribute to sustained airway inflammation in COPD remain unclear. This study aimed to elucidate the immunoregulatory mechanism of NETs in COPD, employing human neutrophils, airway epithelial cells (AECs), dendritic cells (DCs), and a long-term CS-induced COPD mouse model, alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice (cGAS -−/− , TLR9 −/− ); Additionally, bronchoalveolar lavage fluid (BALF) of COPD patients was examined. Neutrophils from COPD patients released greater cigarette smoke extract (CSE)-induced NETs (CSE-NETs) due to mitochondrial respiratory chain dysfunction. These CSE-NETs, containing oxidatively-damaged DNA (NETs-DNA), promoted AECs proliferation, nuclear factor kappa B (NF-κB) activation, NF-κB-dependent cytokines and type-I interferons production, and DC maturation, which were ameliorated/reversed by silencing/inhibition of cGAS/TLR9. In the COPD mouse model, blocking NETs-DNA-sensing via cGAS −/− and TLR9 −/− mice, inhibiting NETosis using mitoTEMPO, and degrading NETs-DNA with DNase-I, respectively, reduced NETs infiltrations, airway inflammation, NF-κB activation and NF-κB-dependent cytokines, but not type-I interferons due to IFN-α/β receptor degradation. Elevated NETs components (myeloperoxidase and neutrophil elastase activity) in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels, but not type-I interferon levels. In conclusion, NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced COPD. Therefore, targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.

Soil metabolomics is an emerging approach for profiling diverse small molecule metabolites, i.e., metabolomes, in the soil. Soil metabolites, including fatty acids, amino acids, lipids, organic acids, sugars, and volatile organic compounds, often contain essential nutrients such as nitrogen, phosphorus, and sulfur and are directly linked to soil biogeochemical cycles driven by soil microorganisms. This paper presents an overview of methods for analyzing soil metabolites and the state-of-the-art of soil metabolomics in relation to soil nutrient cycling. We describe important applications of metabolomics in studying soil carbon cycling and sequestration, and the response of soil organic pools to changing environmental conditions. This includes using metabolomics to provide new insights into the close relationships between soil microbiome and metabolome, as well as responses of soil metabolome to plant and environmental stresses such as soil contamination. We also highlight the advantage of using soil metabolomics to study the biogeochemical cycles of elements and suggest that future research needs to better understand factors driving soil function and health.

Abstract Background Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host–parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. Methods Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host–parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. Results This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. Conclusions Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals. Graphical Abstract

Abstract Background Epidermal patterning factor / -like (EPF/EPFL) gene family encodes a class of cysteine-rich secretory peptides, which are widelyfound in terrestrial plants.Multiple studies has indicated that EPF/EPFLs might play significant roles in coordinating plant development and growth, especially as the morphogenesis processes of stoma, awn, stamen, and fruit skin. However, few research on EPF/EPFL gene family was reported in Gossypium. Results We separately identified 20 G. raimondii, 24 G. arboreum, 44 G. hirsutum, and 44 G. barbadense EPF/EPFL genes in the 4 representative cotton species, which were divided into four clades together with 11 Arabidopsis thaliana, 13 Oryza sativa, and 17 Selaginella moellendorffii ones based on their evolutionary relationships. The similar gene structure and common motifs indicated the high conservation among the EPF/EPFL members, while the uneven distribution in chromosomes implied the variability during the long-term evolutionary process. Hundreds of collinearity relationships were identified from the pairwise comparisons of intraspecifc and interspecific genomes, which illustrated gene duplication might contribute to the expansion of cotton EPF/EPFL gene family. A total of 15 kinds of cis-regulatory elements were predicted in the promoter regions, and divided into three major categories relevant to the biological processes of development and growth, plant hormone response, and abiotic stress response. Having performing the expression pattern analyses with the basic of the published RNA-seq data, we found most of GhEPF/EPFL and GbEPF/EPFL genes presented the relatively low expression levels among the 9 tissues or organs, while showed more dramatically different responses to high/low temperature and salt or drought stresses. Combined with transcriptome data of developing ovules and fibers and quantitative Real-time PCR results (qRT-PCR) of 15 highly expressed GhEPF/EPFL genes, it could be deduced that the cotton EPF/EPFL genes were closely related with fiber development. Additionally, the networks of protein–protein interacting among EPF/EPFLs concentrated on the cores of GhEPF1 and GhEPF7, and thosefunctional enrichment analyses indicated that most of EPF/EPFLs participate in the GO (Gene Ontology) terms of stomatal development and plant epidermis development, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of DNA or base excision repair. Conclusion Totally, 132 EPF/EPFL genes were identified for the first time in cotton, whose bioinformatic analyses of cis-regulatory elements and expression patterns combined with qRT-PCR experiments to prove the potential functions in the biological processes of plant growth and responding to abiotic stresses, specifically in the fiber development. These results not only provide comprehensive and valuable information for cotton EPF/EPFL gene family, but also lay solid foundation for screening candidate EPF/EPFL genes in further cotton breeding.

Abstract Tuberculosis (TB) remains a significant global health threat, necessitating effective strategies for diagnosis, prognosis, and treatment. This study employs a multi-cohort analysis approach to unravel the immune microenvironment of TB and delineate distinct subtypes within pulmonary TB (PTB) patients. Leveraging functional gene expression signatures (Fges), we identified three PTB subtypes (C1, C2, and C3) characterized by differential immune-inflammatory activity. These subtypes exhibited unique molecular features, functional disparities, and cell infiltration patterns, suggesting varying disease trajectories and treatment responses. A neural network model was developed to predict PTB progression based on a set of biomarker genes, achieving promising accuracy. Notably, despite both genders being affected by PTB, females exhibited a relatively higher risk of deterioration. Additionally, single-cell analysis provided insights into enhanced major histocompatibility complex (MHC) signaling in the rapid clearance of early pathogens in the C3 subgroup. This comprehensive approach offers valuable insights into PTB pathogenesis, facilitating personalized treatment strategies and precision medicine interventions.

Abstract Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

To investigate the effects of different brine and fermentation methods on the quality characteristics of fermented chili peppers, this study employed four different fermentation methods: Natural fermentation with sterile water, co-inoculation fermentation (Lactiplantibacillus plantarum KUST-D1303:Pichia manshurica KUST-F1705=1:1) with sterile water, natural fermentation with aged brine and co-inoculation fermentation with aged brine. The quality characteristics of the fermented chili peppers were compared and analyzed. Results showed that compared to other fermentation methods, co-inoculation fermentation with aged brine significantly (P

Abstract The secretagogin (SCGN) was originally identified as a secreted calcium-binding protein present in the cytoplasm. Recent studies have found that SCGN has a close relationship with cancer. However, its role in the occurrence, progression, and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we utilized a mutual authentication method based on public databases and clinical samples to determine the role of SCGN in the progression and prognosis of ccRCC. Firstly, we comprehensively analyzed the expression characteristics of SCGN in ccRCC in several public databases. Subsequently, we systematically evaluated SCGN expression on 252 microarrays of ccRCC tissues from different grades. It was found that SCGN was absent in all the normal kidney tissues and significantly overexpressed in ccRCC tumor tissues. In addition, the expression level of SCGN gradually decreased with an increase in tumor grade, and the percentage of SCGN staining positivity over 50% was 86.7% (13/15) and 73.4% (58/79) in Grade1 and Grade2, respectively, while it was only 8.3% (12/144) in Grade3, and the expression of SCGN was completely absent in Grade4 (0/14) and distant metastasis group (0/4). Additionally, the expression of SCGN was strongly correlated with the patient's prognosis, with the higher the expression levels of SCGN being associated with longer overall survival and disease-free survival of patients. In conclusion, our results suggest that reduced expression of SCGN in cancer cells is correlated with the progression and prognosis of ccRCC.

Abstract Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.

Abstract Objective Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia. Methods This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used. Results During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis. Conclusions This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.

Abstract Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC–IRAK1–MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

In response to the poor active support effect of the surface protection components in soft coal roadway and the continuous expansion of the broken range of local exposed surrounding rock, which leads to the failure of anchor rod and cables, a mesh grouting surface type prestressed application technology has been developed. The authors conducted post mesh grouting tests on different specifications and models of metal mesh, and obtained the mechanical response characteristics of the support system during the application of active surface prestressing. Based on this, the post mesh grouting tests on the roof and two sides of the mesh under on-site conditions were carried out, verifying the applicability of post mesh grouting technology. The research results indicate that: ① There is a gap between the metal mesh and the coal wall, which leads to poor active support ability. The continuous expansion of the broken range of the exposed surrounding rock is the main controlling factor for the failure of anchor rod and anchor cable support. Filling the uneven structure around the contact surface between the metal mesh and the coal wall, increasing the active support ability of the protective surface components, and comprehensively sealing the surrounding rock are the technical means to improve the anchor mesh support system; ② Injecting and filling between the metal mesh and the surrounding rock can achieve the application of surface active pre-stress. The trend of surface stress change is mainly divided into: the initial stage of constant surface stress, the stage of increasing surface stress, and the stage of reducing surface stress to stable state; ③ During the process of grouting behind the mesh, the trend of changes in surface stress values is closely related to the grouting pressure and deformation of the metal mesh. During the process of increasing surface stress, the grouting pressure and deformation of the metal mesh also increase accordingly; ④ Grouting behind the mesh can effectively alleviate the stress concentration of the cable tray. During the process of increasing the surface stress value, the pre-tightening force of the cable with stress concentration can show a small decrease trend, while the pre-tightening force of the cable with relatively uniform stress shows a synchronous upward trend during the process of increasing the surface stress value. The technologies developed are expected to become supporting technologies for rock bolt support, providing technical and theoretical references for the treatment of complex and difficult roadway.

Abstract In this paper, we report a coherent beam combining (CBC) system that involves two thulium-doped all-polarization maintaining (PM) fiber chirped pulse amplifiers. Through phase-locking the two channels via a fiber stretcher by using the stochastic parallel gradient descent (SPGD) algorithm, a maximum average power of 265 W is obtained, with a CBC efficiency of 81% and a residual phase error of λ/17. After de-chirping by a pair of diffraction gratings, the duration of the combined laser pulse is compressed to 690 fs. Taking into account the compression efficiency of 90% and the main peak energy proportion of 91%, the corresponding peak power is calculated to be 4 MW. The laser noise characteristics before and after CBC are examined, and the results indicate that the CBC would degrade the low frequency relative intensity noise (RIN), of which the integration is 1.74% in [100 Hz, 2 MHz] at the maximum combined output power. In addition, the effects of the nonlinear spectrum broadening during chirped pulse amplification on the CBC efficiency are also investigated, showing that a higher extent of pulse stretching is effective in alleviating the spectrum broadening and realizing a higher output power with decent combining efficiency. Graphical Abstract

Abstract The innate immune molecule NLR family CARD domain-containing 5 (NLRC5) plays a significant role in endometrial carcinoma (EC) immunosurveillance. However, NLRC5 also plays a protumor role in EC cells. Mismatch repair gene deficiency (dMMR) can enable tumors to grow faster and also can exhibit high sensitivity to immune checkpoint inhibitors. In this study, we attempted to determine whether NLRC5-mediated protumor role in EC is via the regulation of dMMR. Our findings revealed that NLRC5 promoted the proliferation, migration, and invasion abilities of EC cells and induced the dMMR status of EC in vivo and in vitro. Furthermore, the mechanism underlying NLRC5 regulated dMMR was also verified. We first found NLRC5 could suppress nuclear factor-kappaB (NF-κB) pathway in EC cells. Then we validated that the positive effect of NLRC5 in dMMR was restricted when NF-κB was activated by lipopolysaccharides in NLRC5-overexpression EC cell lines. In conclusion, our present study confirmed the novel NLRC5/NF-κB/MMR regulatory mechanism of the protumor effect of NLRC5 on EC cells, thereby suggesting that the NLRC5-mediated protumor in EC was depend on the function of MMR.

Abstract Background The causal impact of lipid-lowering drugs on ovarian cancer (OC) and cervical cancer (CC) has received considerable attention, but its causal relationship is still a subject of debate. Hence, the objective of this study is to evaluate the impact of lipid-lowering medications on the occurrence risk of OC and CC through Mendelian randomization (MR) analysis of drug targets. Methods This investigation concentrated on the primary targets of lipid-lowering medications, specifically, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase kexin 9 (PCSK9). Genetic variations associated with HMGCR and PCSK9 were derived from published genome-wide association study (GWAS) findings to serve as substitutes for HMGCR and PCSK9 inhibitors. Employing a MR approach, an analysis was conducted to scrutinize the impact of inhibitors targeting HMGCR and PCSK9 on the occurrence of OC and CC. Coronary heart disease (CHD) risk was utilized as a positive control, and the primary outcomes encompassed OC and CC. Results The findings of the study suggest a notable elevation in the risk of OC among patients treated with HMGCR inhibitors (OR [95%CI] = 1.815 [1.316, 2.315], p = 0.019). In contrast, no significant correlation was observed between PCSK9 inhibitors and the occurrence of OC. Additionally, the analysis did not reveal any noteworthy connection between HMGCR inhibitors, PCSK9 inhibitors, and CC. Conclusion HMGCR inhibitors significantly elevate the risk of OC in patients, but their mechanism needs further investigation, and no influence of PCSK9 inhibitors on OC has been observed. There is no significant relationship between HMGCR inhibitors, PCSK9 inhibitors, and CC.

This paper focuses on the dynamic compaction experimental investigation of ADC12 alloy powder using laser impact, leveraging the high strain rate and controllable precision of pulsed lasers. The effects of varying laser energy (Em) and impactor thickness on the relative density, microstructure, and microhardness of the ADC12 alloy powder billets were examined. Utilizing 2D multi-particle finite element simulation (2D MPFEM), the densification mechanism of these billets was analysed with the help of coordination numbers. The simulation also provided insights into the particle velocity, equivalent plastic strain, and adiabatic temperature increase during compaction. Key findings include that a relative densification of up to 97.27% in the billets is achievable when the laser energy reaches 6J. Notably, a decrease in impactor thickness at constant laser energy leads to a more uniform microstructure and microhardness in the billet. Simulations with the 2D MPFEM demonstrate that thinner impactors allow billets to absorb more energy, thereby increasing particle velocity and plastic strain. This enhances both the relative density and mechanical properties of the billets. The simulation explores the stress distribution during compaction and captures the adiabatic temperature rise on the surface of the pressed billet that occurs in the transient, which is consistent with experimental revelations that heat softens or even locally melts the particles to produce sintering. This study offers new insights into the formation process of these billets from a microstructural standpoint, elucidating the relationship between processing conditions and the resulting material properties.

The environmental stability of infectious viruses in the laboratory setting is crucial to the transmission potential of human respiratory viruses. Different experimental techniques or conditions used in studies over the past decades have led to diverse understandings and predictions for the stability of viral infectivity in the atmospheric environment. In this paper, we review the current knowledge on the effect of simulated atmospheric conditions on the infectivity of respiratory viruses, mainly focusing on influenza viruses and coronaviruses, including severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus. First, we summarize the impact of the experimental conditions on viral stability; these involve the methods of viral aerosol generation, storage during aging and collection, the virus types and strains, the suspension matrixes, the initial inoculum volumes and concentrations, and the drying process. Second, we summarize and discuss the detection methods of viral infectivity and their disadvantages. Finally, we integrate the results from the reviewed studies to obtain an overall understanding of the effects of atmospheric environmental conditions on the decay of infectious viruses, especially aerosolized viruses. Overall, this review highlights the knowledge gaps in predicting the ability of viruses to maintain infectivity during airborne transmission.

Abstract Background The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. The aim of this study was to find new biomarkers related to MRGs in CAS. Methods This research utilized two CAS-related datasets (GSE40888 and GSE40732) and extracted 40 MRGs from the MitoCarta3.0 Database. Initially, differential expression analysis was performed on CAS and control samples in the GSE40888 dataset to obtain the differentially expressed genes (DEGs). Differentially expressed MRGs (DE-MRGs) were obtained by overlapping the DEGs and MRGs. Protein protein interactions (PPI) network of DE-MRGs was created and the top 10 genes in the degree ranking of Maximal Clique Centrality (MCC) algorithm were defined as feature genes. Hub genes were obtained from the intersection genes from the Least absolute shrinkage and selection operator (LASSO) and EXtreme Gradient Boosting (XGBoost) algorithms. Additionally, the expression validation was conducted, functional enrichment analysis, immune infiltration analysis were finished, and transcription factors (TFs)-miRNA-mRNA regulatory network was constructed. Results A total of 1505 DEGs were obtained from the GSE40888, and 44 DE-MRGs were obtained. A PPI network based on these 44 DE-MRGs was created and revealed strong interactions between ADCK5 and MFN1, BNIP3 and NBR1. Four hub genes (NDUFAF7, MTIF3, MRPS26, and NDUFAF1) were obtained by taking the intersection of genes from the LASSO and XGBoost algorithms based on 10 signature genes which obtained from PPI. In addition, hub genes-based alignment diagram showed good diagnostic performance. The results of Gene Set Enrichment Analysis (GSEA) suggested that hub genes were closely related to mismatch repair. The B cells naive cells were significantly expressed between CAS and control groups, and MTIF3 was most strongly negatively correlated with B cells naive. In addition, the expression of MTIF3 and MRPS26 may have influenced the inflammatory response in CAS patients by affecting mitochondria-related functions. The quantitative real-time polymerase chain reaction (qRT‒PCR) results showed that four hub genes were all down-regulated in the CAS samples. Conclusion NDUFAF7, MTIF3, MRPS26, and NDUFAF1 were identified as an MRGs-related biomarkers in CAS, which provides some reference for further research on CAS.

Material and structure made by additive manufacturing (AM) have received much attention lately due to their flexibility and ability to customize complex structures. This study first implements multiple objective topology optimization simulations based on a projectile perforation model, and a new topologic projectile is obtained. Then two types of 316L stainless steel projectiles (the solid and the topology) are printed in a selective laser melt (SLM) machine to evaluate the penetration performance of the projectiles by the ballistic test. The experiment results show that the dimensionless specific kinetic energy value of topologic projectiles is higher than that of solid projectiles, indicating the better penetration ability of the topologic projectiles. Finally, microscopic studies (scanning electron microscope and X-ray micro-CT) are performed on the remaining projectiles to investigate the failure mechanism of the internal structure of the topologic projectiles. An explicit dynamics simulation was also performed, and the failure locations of the residual topologic projectiles were in good agreement with the experimental results, which can better guide the design of new projectiles combining AM and topology optimization in the future.

The millimeter-sized glass (SiO2) shells play key roles in inertial confinement fusion (ICF) experiments, especially for the so-called ''direct-drive'' configuration. The preparation of large diameter/thickness ratio glass shells and the exploration of transformation mechanisms for silicon-doped glow discharge polymer (Si-GDP) to SiO2 still face challenges. Here, we prepared large diameter/thickness ratio glass shells with the diameter of ∼1200 μm and shell thickness of ∼5 μm by increasing the Si contents in Si-GDP precursors. The influence of Si contents in Si-GDP shells on the compositions, morphologies and geometrical properties of glass shells were carefully investigated. The formability and uniformity of micro morphologies of the glass shells will improve with the increase of Si contents in precursors. The chemical composition of the prepared glass shells is SiO2 with some carbides adsorbed on their surfaces and the compositions present negligible relationship with the Si contents. The sphericity, thickness uniformity and surface quality will increase with the increase of Si contents in precursors. Besides, the oxidation mechanisms for Si-GDP to SiO2 were explored by the combination of an in situ high temperature infrared spectroscopy and a simultaneous thermal analyzer.

Abstract Purpose The main objective is to quantify the lens nuclear opacity using spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with Lens Opacities Classification System III (LOCS-III) system, lens thickness (LT), and surgical parameters. The secondary objective is to assess the diagnostic model performance for hard nuclear cataract. Methods This study included 70 eyes of 57 adults with cataract, with 49 (70%) and 21 (30%) in training and validation cohort, respectively. Correlations of the average nuclear density (AND) /maximum nuclear density (MND) with LOCS-III scores, LT, and surgical parameters were analyzed. Univariate and multivariate logistic regression analysis, receiver operating characteristic curves and calibration curves were performed for the diagnostic of hard nuclear cataract. Results The pre-operative uncorrected distance visual acuity (UDVA), intraocular pressure (IOP), mean axial length (AL), and LT were 1.20 ± 0.47 log MAR, 15.50 ± 2.87 mmHg, 27.34 ± 3.77 mm and 4.32 ± 0.45 mm, respectively. The average nuclear opalescence (NO) and nuclear colour (NC) scores were 3.61 ± 0.94 and 3.50 ± 0.91 (ranging from 1.00 to 6.90), respectively. The average AND and MND were 137.94 ± 17.01 and 230.01 ± 8.91, respectively. NC and NO scores both significantly correlated with the AND (rNC = 0.733, p = 0.000; rNO = 0.755, p = 0.000) and MND (rNC = 0.643, p = 0.000; rNO = 0.634, p = 0.000). In the training cohort, the area under the curve (AUC) of the model was 0.769 (P

Abstract Background Growth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle. Methods This is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group. Results After PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1–1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2–3.3). Conclusions Women with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

High silicon steel has excellent soft magnetic properties, but a poor plasticity limits its practical application seriously. In this research, a novel FeSiCrNi alloy short for Fe-6.5Si–2Cr–12Ni (wt%) was designed and deformed via the local canning compression process at room temperature. It was shown that the FeSiCrNi alloy presents a relatively high plasticity in a triaxial compressive stress state. Geometrically necessary dislocations ensure the compatibility of plastic deformation for FeSiCrNi alloy. There are a small number of η and γ textures inside the FeSiCrNi sample. The intensity of η texture nearly keeps steady, while the intensity of γ texture increases slightly with the level of plastic deformation increasing. Additionally, the intensity of {112} copper texture increases with the increase of plastic deformation. Lath structures dominate the inhomogeneous plastic deformation of FeSiCrNi alloy and then integrate with the phase α-Fe. The main deformation mechanism of FeSiCrNi alloy is dislocation slip rather than twinning which has not been observed yet. The order degree of FeSiCrNi alloy continuously decreases, and deformation bands, dislocation walls and dislocation cells are successively formed, as the compression proceeds. It is feasible to produce FeSiCrNi components in cold forming process.

Recycling is presently the most environmentally friendly approach that deals with wood waste. Each year a huge amount of particleboard completes its service life and needs to be disposed of or recycled. Scrap particleboard has the potential to be reused as raw material for particleboard production. A crucial step for producing particleboards using scrap particleboards is to break down urea-formaldehyde (UF) resins in the scrap particleboards to obtain separated particles. In this study, liquid hot water (LHW) pretreatment was employed to decompose the UF resins to detach and recover wood particles from the scrap particleboards. The recovered wood particles and fresh industrial wood particles in different proportions were used as the raw material for the particleboard. The physical and mechanical properties of the recycled particleboards were evaluated. The modulus of rupture (MOR), modulus of elasticity (MOE), and internal bond (IB) of the recycled particleboards were lower than those of the particleboards made with fresh wood particles. However, the 2 h thickness swelling (TS) of the recycled particleboards was better than that of the fresh particleboards, indicating that the recycled particleboards were more dimensionally stable. The mechanical properties of the particleboards containing up to 40% recycled wood particles met the minimum Chinese National Standard requirements for general-purpose particleboards. Conclusively, scrap wood particleboards could be utilized as raw material in particleboard production.

Abstract Introduction Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR). Methods Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method. Results Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99–1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97–1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95–1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91–1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy. Conclusions This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

Chemical inhibition is one of the important measures for the prevention and control of coal spontaneous combustion. This paper proposed a quasi-ionic liquid inhibition method based on deep eutectic solvents (DES). First, seven kinds of room temperature deep eutectic solvents were prepared and screened using a heating method. The changes in the functional groups and thermodynamic characteristics of different DES-treated coal samples were analyzed. On this basis, the density functional theory was utilized to analyze the differences in the modification of coal's physicochemical properties by the hydrogen bond strength in the DES, and the inhibition mechanism of deep eutectic solvents and their optimal hydrogen bond strength were deduced. The results showed that after the DES treatment, the hydrogen bond network in coal was disrupted and rearranged. The relative abundance of aliphatic and aromatic hydrocarbons increased by 10%−37%, the content of aliphatic side chains decreased by 9.38%−20.65%, the relative abundance of oxygen-containing functional groups (C=O and C—O) decreased by 22.88%−56.94%, and free low-molecular compound and minerals were leached out. After the DES treatment, the mass loss during the evaporation and desorption stage of coal and the oxygen uptake during the oxygen absorption stage decreased. The heat release during the low temperature oxidation stage and the thermal decomposition stage was reduced by 8.94%−77.51% and 5.40%−26.20%, respectively. The stronger the electronegativity of the hydrogen bond acceptor site in the HBA, the greater the hydrogen bond strength formed between HBA and HBD. The hydrogen bond strength in the DES was positively correlated with the degree of destruction of the hydrogen bond network in coal, and was locally correlated with the oxygen uptake during the oxygen absorption stage, the heat release during low temperature oxidation, and the mineral removal rate. The DES weakened the low-temperature oxidation reactivity of coal by dissolving its active components, and increased the bond dissociation enthalpy of coal by promoting the rearrangement of hydrogen bonds into more thermally stable [OH]4 and OH—N hydrogen bonds. However, the excessive strong hydrogen bond strength would inhibit the removal and dissolution of active side chains. Therefore, the hydrogen bond strength of deep eutectic solvents used to inhibit coal spontaneous combustion should be controlled between 69.45 kJ/mol and 160.00 kJ/mol.

Methane explosion is one of the major disasters that seriously threaten the safety of coal mine production, the development of efficient methane explosion suppression technology can effectively improve the prevention and control level of methane explosion accidents, and its focus is on the function of explosion suppression materials. In order to systematically study the effect of typical haloalkanes extinguishing agents on methane explosion, the effects of typical haloalkanes such as heptafluoropropane (C3HF7), hexafluoropropane (C3H2F6) and trifluoromethane (CHF3) on the ignition and explosion characteristics of methane were systematically studied by combining experimental tests and theoretical analysis. The effects of haloalkanes on methane explosion pressure parameters and laminar burning velocity were tested by a 20 L spherical explosive vessel and a self-developed Bunsen burner laminar flame propagation velocity system. The variation laws of peak explosion pressure, maximum pressure rise rate, laminar burning velocity, and laminar flame morphology evolution were obtained. The results show that with the increase of the added volume fraction, the haloalkanes had a double effect of promoting and inhibiting the methane explosion process. Under the chemical equivalent condition, only C3HF7 can first promote and then inhibit the peak explosion pressure and maximum pressure rise rate of methane, while CHF3 and C3H2F6 can inhibit the effect. The three haloalkanes all showed inhibition on the combustion rate of methane laminar flow. In the oxygen-poor condition, the three haloalkanes inhibited the peak explosion pressure, the maximum pressure boost rate, and the laminar burning velocity of methane. In general, C3H2F6 and C3HF7 have better inhibition effects on methane explosion pressure characteristic parameters and laminar burning velocity than CHF3. The theoretical analysis results show that the double effect of promoting and inhibiting the haloalkanes with the increase of the mixture volume fraction can be attributed to the competition between the improvement of the heat release characteristics of the system reaction and the inhibition of the key free radicals such as H, O, and OH by the main intermediates containing F. The results of this paper provide a theoretical basis for the theoretical research and technical development of methane explosion prevention and control.

We confirm the previously revised stereochemistry of spiroviolene by X-ray crystallographically characterizing a hydrazone derivative of 9-oxospiroviolane, which is synthesized by hydroboration/oxidation of spiroviolene followed by oxidation of the resultant hydroxy group. An unexpected thermal boron migration occurred during the hydroboration process of spiroviolene that resulted in the production of a mixture of 1α-hydroxyspiroviolane, 9α- and 9β-hydroxyspiroviolane after oxidation. The assertion of the cis-orientation of the 19- and 20-methyl groups provided further support for the revised cyclization mechanism of spiroviolene.

This is an article in the field of mining engineering. Graphite is an inorganic nonmetallic material widely used in China, and it also plays an important role in chemical industry, electrical industry, national defense and high-tech fields. Graphite mining will produce a large number of tailings, it not only occupies a lot of land but also causes serious pollution to the ecological environment. By consulting a large number of documents, the current research status of graphite tailings resource utilization is summarized in this paper, and the problem of massive accumulation of graphite tailings is discussed, and some suggestions are put forward to help its resource utilization.

Abstract Background Two-tiered plant immune responses involve cross-talk among defense-responsive (DR) genes involved in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), effector-triggered immunity (ETI) and effector-triggered susceptibility (ETS). Bacterial leaf streak (BLS), caused by Xanthomonas oryzae pv. oryzicola (Xoc) is an important bacterial disease that causes serious threats to rice yield and quality. Transcriptomic profiling provides an effective approach for the comprehensive and large-scale detection of DR genes that participate in the interactions between rice and Xoc. Results In this study, we used RNA-seq to analyze the differentially expressed genes (DEGs) in susceptible rice after inoculation with two naturally pathogenic Xoc strains, a hypervirulent strain, HGA4, and a relatively hypovirulent strain, RS105. First, bacterial growth curve and biomass quantification revealed that differential growth occurred beginning at 1 day post inoculation (dpi) and became more significant at 3 dpi. Additionally, we analyzed the DEGs at 12 h and 3 days post inoculation with two strains, representing the DR genes involved in the PTI and ETI/ETS responses, respectively. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on the common DEGs, which included 4380 upregulated and 4019 downregulated genes and 930 upregulated and 1383 downregulated genes identified for the two strains at 12 h post inoculation (hpi) and 3 dpi, respectively. Compared to those at 12 hpi, at 3 dpi the number of common DEGs decreased, while the degree of differential expression was intensified. In addition, more disease-related GO pathways were enriched, and more transcription activator-like effector (TALE) putative target genes were upregulated in plants inoculated with HGA4 than in those inoculated with RS105 at 3 dpi. Then, four DRs were randomly selected for the BLS resistance assay. We found that CDP3.10, LOC_Os11g03820, and OsDSR2 positively regulated rice resistance to Xoc, while OsSPX3 negatively regulated rice resistance. Conclusions By using an enrichment method for RNA-seq, we identified a group of DEGs related to the two stages of response to the Xoc strain, which included four functionally identified DR genes.

ABSTRACTAccurate evaluation of terrestrial carbon balance is essential for designing climate change mitigation policies, and capabilities of remote sensing techniques in monitoring carbon fluxes are widely recognized for their great contributions to regional and global carbon budget accounting. In this review, we synthesized satellite-based data and methodologies to estimate the main flux components of terrestrial carbon balance and their uncertainties over the past two decades. The global gross primary production (GPP) during the period 2001–2022 is 134 ± 14 PgC yr−1, and nearly half of them occurs in tropical forest regions such as South America and Africa. Less than 2% of global GPP is converted into a net carbon sink of 2.28 ± 1.12 PgC yr−1 using satellite-based atmospheric inversion during 2015–2020, and this sink is comparable to the stock change-based estimate (2.49 PgC yr−1) but twice as large as model-based estimate (1.08 ± 0.78 PgC yr−1). By decomposing satellite-derived net carbon balance into different terms including satellite-derived carbon emissions from land-use change and wildfires (3.55 PgC yr−1), we inferred that ~ 43% of global GPP would be respired through soil microbes (57.1 PgC yr−1), but which is higher than the previous bottom-up estimate (39–46 PgC yr−1). We then propose that an accurate remote sensing of terrestrial carbon balance requires to enhance representations of photosynthetic responses to rising CO2 and disturbances, develop satellite-constrained belowground carbon dynamics and separate natural fluxes from anthropogenic CO2 emissions, by integrating multi-source satellite sensors in orbit, revolutionized remote sensing capabilities with focused field campaigns in data-scarce regions.

Abstract Background Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. Methods We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women’s Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria–diabetes associations are explained by altered metabolites and proteins. Results Seven gut bacterial genera were identified to be associated with diabetes (FDR-q

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract To study the aerodynamic performance and wind-induced response of carbon fiber-reinforced polymer (CFRP) cables, CFRP cable was designed by replacing a steel cable in a tied arch bridge based on stiffness, strength and area equivalent criteria, respectively. The aerodynamic performance and wind-induced response of CFRP cable and steel cable were studied and compared by computational fluid dynamics (CFD) model. Based on the computational results, optimal cable replacement criterion was proposed for CFRP cable to replace steel cable. In addition, surface modification was conducted by engrooving vertical symmetric (VS), vertical asymmetric (VA) and helical symmetric (HS) V-shaped grooves to improve the aerodynamic performance and wind-induced response of CFRP cable. Results showed that CFRP cables exhibited inferior aerodynamic performance and wind-induced response in most cases. However, CFRP cable based on stiffness equivalent criterion exhibited better aerodynamic performance and wind-induced vibration properties compared to the other two cable replacement criteria, thus is regarded as the optimal substitute for steel cable. In addition, HS grooves generated symmetric disturbances and caused approximately equivalent boundary layer separation delays uniformly and continuously along the cable length, thus exhibiting better effect in decreasing the reverse flow region, the maximum negative flow velocity, the vortex shedding frequency and the wind-induced vibration amplitude of CFRP cable. Hence, the stiffness equivalent criterion combined with surface modification with HS V-shaped grooves was proposed to replace steel cable with CFRP cable. This study can provide insights into the aerodynamic performance and wind-induced response of CFRP cable and instructions for cable replacement practice.

Abstract Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis.

Abstract We explore the controls of stress magnitude and orientation relative to bedding on the resulting morphology/topology of hydraulic fractures using a combined finite-discrete element method (FDEM). Behavior is shown conditioned by the ratio of principal stresses $$\lambda ={\sigma }_{3}/{\sigma }_{1}$$ λ = σ 3 / σ 1 and relative inclination of the bedding. When the lateral pressure coefficient ( $$\lambda$$ λ ) is less than 0.67, hydraulic fractures predominantly initiate as tensile fractures along the wellbore, aligning with the maximum principal stress direction. Conversely, for $$\lambda \ge 0.67$$ λ ≥ 0.67 , shear cracks are favored to initiate for the minor stress difference, leading to a less predictable initiation and extension direction. Simultaneously, diminished stress differences correspond to elevated reservoir breakdown pressures, displaying a linear correlation with lateral pressure coefficients and little influenced by equivalent bedding orientation. Bedding plane orientation significantly impacts the mode and morphology of hydraulic fracture propagation. Bedding parallel to the direction of the minimum principal stress ( $${\sigma }_{3}$$ σ 3 ) favors layer-penetrating and bifurcated fractures, whereas inclined bedding facilitates the emergence of numerous steering-type and capture-type fractures. Especially at steeper inclinations ( $$\beta =60^\circ$$ β = 60 ∘ ), hydraulic fractures readily extend along the bedding surface, inducing macroscopic shear slip failure. Under high-stress disparities, the breakdown pressure exhibits greater sensitivity to bedding inclination, and its influence pattern aligns with the variations in tensile strength, typically reaching maximum and minimum values at bedding inclination angles of 0° and 60°, respectively.

ABSTRACT Purpose: This study aims to evaluate the safety and efficacy of ultrasound-guided balloon dilation compared to non-balloon dilation for percutaneous nephrolithotomy (PCNL). Materials and methods: A systematic review and meta-analysis were conducted by searching PubMed, EMBASE, and the Cochrane Library. Results were filtered using predefined inclusion and exclusion criteria as described and meta-analysis was performed using Review Manager 5.4 software. Results: A total of six studies involving 1189 patients who underwent PCNL were included. The meta-analysis results demonstrated that compared to non-balloon dilation, balloon dilation was associated with reduced haemoglobin drop [mean difference (MD) = -0.26, 95% CI = -0.40 ~ -0.12, P = 0.0002], decreased transfusion rate [odds ratio (OR) = 0.47, 95% CI = 0.24 ~ 0.92, P = 0.03], shorter tract establishment time (MD = -1.30, 95% CI = -1.87 ~ -0.72, P < 0.0001) and shorter operation time (MD = -5.23, 95% CI = -10.19 ~ -0.27, P = 0.04). Conclusions: Overall, ultrasound-guided balloon dilatation offered several advantages in PCNL procedures. It facilitated faster access establishment, as evidenced by shorter access creation time. Additionally, it reduced the risk of kidney injury by minimizing postoperative haemoglobin drop and decreasing the need for transfusions. Moreover, it enhanced the efficiency of surgery by reducing the operation time. However, it is important to note that the quality of some included studies was subpar, as they did not adequately control for confounding factors that may affect the outcomes. Therefore, further research is necessary to validate and strengthen these findings.

Abstract Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p

Abstract Zinc-ion hybrid supercapacitors (ZHSCs) are attracting significant attention due to their high energies/power densities, safety, and low cost. In this review, recent advances in the development of ZHSCs are summarized. Particular emphasis is placed on state-of-the-art cathodes (including carbon, metal oxides, MXenes, and redox-active polymers), anodes (including Zn-based composites and Zn-free materials) and electrolytes for ZHSCs. Furthermore, the latest research on functional ZHSC devices with miniaturized ZHSCs, fiber-shaped ZHSCs, self-chargeable ZHSCs and self-healing devices is reported. Finally, further developments with ZHSCs are envisaged for future research in this thriving field.