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Abstract cGAS plays an important role in regulating both tumor immune responses and DNA damage repair. Nevertheless, there was little research that comprehensively analyzed the correlation between cGAS and the tumor microenvironment, immune cell infiltration, and DNA damage repair in different cancers. In this study, The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) data were used to analyze the mRNA expression and genomic alterations of cGAS in pan-cancer. The HPA database was used to explore the protein levels of cGAS in normal tissues and cancers. Correlation analysis were performed to explore the role of cGAS in interferon expression, immune cell infiltrations, DNA damage repair, and predictive immune markers. The prognostic value of cGAS was analyzed using survival data from the TCGA, Kaplan-Meier plotter database, and PrognoScan database. Lastly, the role of cGAS in DNA damage repair signaling and interferon signaling was validated in NSCLC cell lines. The results showed that cGAS was widely expressed in human normal tissues and various cancers, and the expression of cGAS was significantly upregulated in almost all of the solid cancers. Genomic analysis indicated that the expression of cGAS was positively correlated with copy number levels, while negatively correlated with the methylation levels of cGAS promoter. In addition, the level of cGAS was positively correlated with type I interferons expression, infiltration levels of most immune cell types, TMB and MSI levels, stromal and immune scores, and DNA damage repair gene sets including nonhomologous end joining and homologous recombination pathway. Survival analysis indicated that cGAS levels were associated with patient prognosis in several cancers. Lastly, in vitro study showed knockdown of cGAS expression inhibits the DNA damage repair signaling pathway and interferon signaling in NSCLC. In conclusions, cGAS is wildly activated in human cancers, which might participate in regulating cancer immunity and DNA damage repair. cGAS could be used as an effective target for cancer treatment and might be a potential predictive immune marker.

Abstract The precise fabrication and regulation of the stable catalysts with desired performance still challengeable for single atom catalysts. Here, the Ru single atoms with different coordination environment in Ni3FeN lattice are synthesized and studied as a typical case over alkaline methanol electrooxidation. The Ni3FeN with buried Ru atoms in subsurface lattice (Ni3FeN-Ruburied) exhibits high selectivity and Faradaic efficiency of methanol to formate conversion. Meanwhile, operando spectroscopies reveal that the Ni3FeN-Ruburied exhibits an optimized adsorption of reactants along with an inhibited surface structural reconstruction. Additional theoretical simulations demonstrate that the Ni3FeN-Ruburied displays a regulated local electronic states of surface metal atoms with an optimized adsorption of reactants and reduced energy barrier of potential determining step. This work not only reports a high-efficient catalyst for methanol to formate conversion in alkaline condition, but also offers the insight into the rational design of single atom catalysts with more accessible surficial active sites.

Abstract Background Stemona tuberosa, a vital species in traditional Chinese medicine, has been extensively cultivated and utilized within its natural distribution over the past decades. While the chloroplast genome of S. tuberosa has been characterized, its mitochondrial genome (mitogenome) remains unexplored. Results This paper details the assembly of the complete S. tuberosa mitogenome, achieved through the integration of Illumina and Nanopore sequencing technologies. The assembled mitogenome is 605,873 bp in size with a GC content of 45.63%. It comprises 66 genes, including 38 protein-coding genes, 25 tRNA genes, and 3 rRNA genes. Our analysis delved into codon usage, sequence repeats, and RNA editing within the mitogenome. Additionally, we conducted a phylogenetic analysis involving S. tuberosa and 17 other taxa to clarify its evolutionary and taxonomic status. This study provides a crucial genetic resource for evolutionary research within the genus Stemona and other related genera in the Stemonaceae family. Conclusion Our study provides the inaugural comprehensive analysis of the mitochondrial genome of S. tuberosa, revealing its unique multi-branched structure. Through our investigation of codon usage, sequence repeats, and RNA editing within the mitogenome, coupled with a phylogenetic analysis involving S. tuberosa and 17 other taxa, we have elucidated its evolutionary and taxonomic status. These investigations provide a crucial genetic resource for evolutionary research within the genus Stemona and other related genera in the Stemonaceae family.

Abstract Hypertension-induced myocardial remodelling encompasses both structural and functional changes in cardiac muscle tissue, such as myocardial hypertrophy, fibrosis, and inflammation. These alterations not only impair the systolic and diastolic functions of the heart but also elevate the risk of cardiovascular events and heart failure. One of the primary contributors to hypertensive cardiomyopathy (HTN-CM) is the over-activation of the renin-angiotensin-aldosterone system (RAAS), which subsequently induces myocardial remodeling. Although conventional therapeutic strategies aim to suppress RAAS and slow the progression of heart failure, the primary challenge in treating HTN-CM remains the lack of sensitive and specific biomarkers for early detection of myocardial remodelling. Combined multi-omics analyses, complemented by experimental validation, offer a systematic understanding of the landscape of gene/protein/metabolite expression in HTN-CM, revealing the underlying mechanisms of angiotensin II (Ang II)-induced myocardial remodeling in HTN-CM. Transcriptomic analysis revealed that differentially expressed genes (DEGs) are implicated in sphingolipid metabolic processes and are associated with collagen synthesis and inflammatory responses, collectively contributing to myocardial remodeling in HTN-CM. Proteomic analysis demonstrated that differentially expressed proteins (DEPs) are also involved in inflammatory and fibrotic processes, with associations to sphingolipid signaling pathways, particularly manifested through elevated expression of IL6, COL4A1, FGG, FGB, CREBBP and SPHK2 proteins. Metabolomic profiling further elucidated the increased expression of bioactive sphingolipid metabolites S1P and Sa1P in the myocardium of HTN-CM. Integrative multi-omics analysis revealed that HTN-CM is primarily influenced by the sphingolipid signaling pathway, with additional associations to the HIF-1α and FoxO signaling pathways. Correlation analysis has highlighted strong associations between sphingolipids and genes/proteins related to fibrosis and inflammation, as well as their connection to the HIF-1α and FoxO signalling pathways. Furthermore, certain key indicators were validated through ELISA and Western blot analyses in both plasma and myocardial tissue. In conclusion, the findings of this study suggest that excessive Ang II may induce abnormalities in sphingolipid metabolism, resulting in increased levels of S1P in both circulating and myocardial tissues. This elevation in S1P is implicated in myocardial inflammatory and fibrotic alterations, highlighting its pivotal role in myocardial remodeling. The specific mechanism underlying the sphingolipid signaling pathway in myocardial remodeling may involve downstream biological processes, including oxidative stress and excessive mitochondrial autophagy, mediated by HIF-1α and FoxO.

Abstract Background To evaluate the utility of glucose chemical exchange saturation transfer (glucoCEST) MRI with non-contrast injection in predicting the histological grade of rectal cancer. Methods This prospective analysis included 60 patients with preoperative rectal cancer who underwent pelvic glucoCEST, amide proton transfer-weighted imaging (APTWI), and diffusion-weighted imaging (DWI). In total, 21 low-grade and 39 high-grade cases were confirmed by postoperative pathology. The MTRasym (1.2 ppm), MTRasym (3.5 ppm), and apparent diffusion coefficient (ADC) values of lesions between the low-grade and high-grade groups were compared. The area under the receiver operating characteristic curve (AUC) was generated to evaluate the diagnostic performance of each technique. Logistic regression (LR) analysis was applied to determine independent predictors and for multi-parameter combined diagnosis. Results Elevated MTRasym (1.2 ppm), MTRasym (3.5 ppm) values and lower ADC values were observed in the high-grade group compared with low-grade cases (all p

Abstract The digital twin model of mine ventilation system (DTMVS) plays an important role in intelligent safety management. However, the uncertainty of the ventilation resistance coefficient, which is the core parameter of the model, makes it challenging to accurately construct a DTMVS. In this study, Latin Hypercube Sampling (LHS) and ventilation resistance coefficient estimation models (VRCEMs) are used to analyze the uncertainty. First, the LHS method was used to explore the effect of uncertainty in the simulated airflow by continuously increasing the level of uncertainty in the ventilation resistance coefficients. Subsequently, the ventilation resistance coefficients were estimated using the VRCEMs, and the uncertainty of the ventilation resistance coefficient and the simulated airflow was analyzed. The results showed that the ventilation resistance coefficients with a 5% coefficient of variation can cause the DTMVS to lose 34% of the real airflow data points. The degree of uncertainty in the ventilation resistance coefficients estimated by the VRCEM-GA (VRCEM using genetic algorithm) and VRCEM-DE (VRCEM using differential evolution algorithm) methods was enhanced by 27.4% and 4.4%, respectively, compared with VRCEM-ES (VRCEM using evolutionary strategy algorithm). The VRCEM-ES model had the least influence on the uncertainty of the simulated airflow of DTMVS. The simulated airflow of the DTMVS constructed based on VRCEMs fluctuated normally within the confidence interval. VRCEMs had a higher sensitivity to the ventilation resistance coefficients of branches with low coefficients of variation.

Abstract Aiming at the problems of traditional ship cold chain monitoring systems being easily affected by environmental factors, difficult to achieve real‐time monitoring in the open sea without network signals, and low efficiency in transmitting Beidou short message data, a multi‐link compressed transmission ship cold chain monitoring system was designed by combining 5G technology, Beidou short message transmission technology, and multi‐protocol transmission technology. The system can adaptively switch the strength of wireless signals to ensure that information transmission is not lost. At the same time, a Beidou short message compressed transmission method was proposed to improve transmission efficiency. Test results show that the system can accurately complete data collection and processing, with small system errors, effectively improving the reliability and efficiency of the monitoring system, and has high application value.

Abstract Atmospheric rivers are important transport vehicles for Earth’s water cycle. Using a high-resolution, eddy-resolving Earth System Model, atmospheric river impacts on the upper ocean are investigated by analyzing historical and climate change simulations. For atmospheric rivers along the North American coastline, strong winds cause significant dynamic and thermodynamic upper ocean responses. They push ocean water towards the coast, measured by sea surface height, a process that is amplified under climate change. Mixed layers are deeper upstream of atmospheric rivers, and shallower downstream, however for climate change, shoaling downstream is subdued. Air-sea heat fluxes tend to promote ocean cooling upstream and warming downstream, although different regions have different climate change heat flux signals. Southern California heat flux changes due to warming are driven by evaporative processes and strengthen the ocean responses seen in historical simulations. The regions north are primarily dominated by sensible heat flux changes and counter the historical patterns.

Abstract Objectives To describe the essential competencies required for patient engagement in their own safety. Method We adopted a phenomenological approach in qualitative research to conduct semi-structured interviews with nurses (n = 14) and adult patients (n = 13) from different departments. By deeply exploring their experiences and feelings about patient engagement in patient safety, we sought to understand their views on the qualities that patients need to possess in order to participate in their own safety. Results From the interviews, we identified six major themes, including competence of information sharing, competence of taking patient engagement as responsibility and right, competence of making equal communication, competence of maintaining trust relationship with health personnels, competence of accepting non-punitive safety culture, need of resource support, five of them showed essential competences for patients and one of them showed patients’ need for promoting their engagement. Conclusion The findings of this study show necessary competence and needs in patient engagement process of patient, offer a foundational reference for constructing a measurement tool for patient engagement in patient safety competence in the future, so that medical staff and patients can provide reference for the future targeted construction of patient competence improvement programs. At the same time, improving patient competence and engagement to better achieve safety goals requires the joint efforts of patients, medical staff, medical institutions, the government, and society.

Abstract The mine wind speed sensor is an important intelligent sensing equipment in the mine intelligent ventilation system that can provide accurate and key wind speed parameters for the intelligent ventilation system. The turbulent pulsation characteristics of the airflow in the underground tunnel are a major factor for the inaccurate measurement of mine wind speed. Therefore, according to the random non-stationary characteristics of a turbulent pulsation signal, a denoising method based on adaptive complete ensemble empirical mode decomposition (CEEMDAN) combined with the wavelet threshold is proposed for suppressing the turbulent pulsation noise in the wind speed signal. First, the CEEMDAN algorithm is used for decomposing the wind speed signal into a series of IMF components. Second, the continuous mean square error criterion is used for determining the high-frequency IMF components with more noise. The wavelet threshold denoising method is used for denoising the high-frequency IMF components with more noise. Finally, the denoised IMF components and remaining low-frequency IMF components are reconstructed for obtaining the denoised signal. The results of the denoising analysis of measured turbulent pulsation signals, comparative analysis of denoising of simulated turbulent pulsation signals by different joint denoising methods, and denoising analysis of actual mine wind speed sensor data indicate that the joint denoising method proposed in this study has a higher signal-to-noise ratio and lower root mean square error of the wind speed signal after denoising. Compared with the EMD-wavelet threshold and EEMD-wavelet threshold denoising methods, the denoising method proposed in this study is better and has higher denoising accuracy, which provides a new method for processing actual mine wind speed sensor data.

Abstract Autonomous mobile clinics (AMCs) have the potential to revolutionize healthcare delivery by bringing healthcare services to patients at the order of patient’s fingertips. Particularly, AMCs can act as an essential touch point of integrated care, which is a worldwide response to the fragmented delivery of health by focusing on more coordinated and integrated forms of care provision. However, the impact of AMCs on the health satisfaction outcome effectiveness still remains unknown. In this article, in collaboration with United Family Healthcare (UFH), we study the potential effectiveness improvement of integrated care delivery through AMCs.

Abstract Background Epigenome‐wide association studies have identified multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. This study aimed to test the hypothesis that an alcohol consumption epigenetic risk score (ERS) is associated with blood pressure (BP) traits. Results We implemented an ERS based on a previously reported epigenetic signature of 144 alcohol-associated CpGs in meta-analysis of participants of European ancestry. We found a one-unit increment of ERS was associated with eleven drinks of alcohol consumed per day, on average, across several cohorts (p

Abstract Lettuce (Lactuca sativa L., Asteraceae) is one of the most important vegetable crops, known for its various horticultural types and significant morphological variation. The first reference genome of lettuce, a crisphead type (L. sativa var. capitata cv. Salinas), was previously released. Here, we reported a near-complete chromosome-level reference genome for looseleaf lettuce (L. sativa var. crispa). PacBio high-fidelity sequencing, Oxford Nanopore, and Hi-C technologies were employed to produce genome assembly. The final assembly is 2.59 Gb in length with a contig N50 of 205.47 Mb, anchored onto nine chromosomes, containing 14 recognizable telomeres and only 11 gaps. Repetitive sequences account for 77.11% of the genome, and 41,375 protein-coding genes were predicted, with 99.10% of these assigned functional annotations. This chromosome-level genome enriched genomic resources for various horticultural types of lettuce and will facilitate the characterization of morphological variation and genetic improvement in lettuce.

Abstract Pseudomonas aeruginosa is a widespread nosocomial pathogen with a significant to cause both severe planktonic acute and biofilm-related chronic infections. Small RNAs (sRNAs) are noncoding regulatory molecules that are stabilized by the RNA chaperone Hfq to trigger various virulence-related signaling pathways. Here, we identified an Hfq-binding sRNA in P. aeruginosa PAO1, PqsS, which promotes bacterial pathogenicity and pseudomonas quinolone signal quorum sensing (pqs QS) system. Specifically, PqsS enhanced acute bacterial infections by inducing host cell death and promoting rhamnolipid-regulated swarming motility. Meanwhile, PqsS reduced chronic infection traits including biofilm formation and antibiotic resistance. Moreover, PqsS repressed pqsL transcript, increasing PQS levels for pqs QS. A PQS-rich environment promoted PqsS expression, thus forming a positive feedback loop. Furthermore, we demonstrated that the PqsS interacts and destabilizes the pqsL mRNA by recruiting RNase E to drive degradation. These findings provide insights for future research on P. aeruginosa pathogenesis and targeted treatment.

Abstract Freeze–thaw (F–T) cycling poses a significant challenge in seasonally frozen zones, notably affecting the mechanical properties of soil, which is a critical consideration in subgrade engineering. Consequently, a series of unconfined compressive strength tests were conducted to evaluate the influence of various factors, including fiber content, fiber length, curing time, and F–T cycles on the unconfined compression strength (UCS) of fiber-reinforced cemented silty sand. In parallel, acoustic emission (AE) testing was conducted to assess the AE characteristic parameters (e.g., cumulative ring count, cumulative energy, energy, amplitude, RA, and AF) of the same material under F–T cycles, elucidating the progression of F–T-induced damage. The findings indicated that UCS initially increased and then declined as fiber content increased, with the optimal fiber content identified at 0.2%. UCS increased with prolonged curing time, while increases in fiber length and F–T cycles led to a reduction in UCS, which then stabilized after 6 to 10 cycles. Stable F–T cycles resulted in a strength loss of approximately 30% in fiber-reinforced cemented silty sand. Furthermore, AE characteristic parameters strongly correlated with the stages of damage. F–T damage was segmented into three stages using cumulative ring count and cumulative energy. An increase in cumulative ring count to 0.02 × 104 times and cumulative energy to 0.03 × 104 mv·μs marked the emergence of critical failure points. A sudden shift in AE amplitude indicated a transition in the damage stage, with an amplitude of 67 dB after 6 F–T cycles serving as an early warning of impending failure.

Abstract Objective The systemic immunity-inflammation index (SII) is a newly developed biomarker that provides an integrated measure of inflammation in the body. We aim to evaluate the relationship between SII and body fat distribution. Methods Adults from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 were included. The SII was computed using lymphocyte (LC), neutrophil (NC), and platelet (PC) counts as its components. Body fat distribution was assessed by (total, android, gynoid) percentage fat, total abdominal fat area, subcutaneous adipose tissue area, visceral adipose tissue area, and the ratio of visceral to subcutaneous adipose tissue area (V/S ratio). Multivariable weighted linear regression and subgroup analysis were use to examine the relationships between fat distribution and SII. Restricted cubic splines (RCS) and threshold effect analysis were used to examine analyze nonlinear associations. Results After exclusions, a total of 11,192 adults with a weighted mean age of 38.46 ± 0.26 years were studied. In multivariable weighted linear regression, each level increase in log2SII was associated with increased of 0.23 SDs total percentage fat (95% CI = 0.03, 0.43) and 0.26 SDs android percentage fat (95% CI = 0.06, 0.47). Besides, the subgroup analysis showed that the positive association between SII and android percentage fat was mainly among obese individuals (BMI > 30 kg/m2) and non-obese individuals without DM or hypertension. Meanwhile, the relationship between SII and the V/S ratio was found to be significant in the female subgroup, the obese subgroup, individuals with non-alcoholic fatty liver disease (NAFLD), and those without diabetes mellitus. Finally, SII exhibited an inverted U-shaped relationship with total percentage fat, android percent fat and total abdominal fat. Accordingly, threshold effect analysis indicated a positive association between lower SII levels and total percentage fat, android percentage fat and total abdominal fat area. Conclusions In the nationwide study, it was observed that the SII exhibited a significant correlation with higher levels of body fat, specifically android fat. This association was particularly noticeable within specific subgroups of the population.

Abstract Brown planthopper (BPH) is the most destructive insect pest of rice. Drought is the most detrimental environmental stress. BPH infestation causes adaxial leaf-rolling and bulliform cells (BCs) shrinkage similar to drought. The BC-related abaxially curled leaf1 (ACL1) gene negatively regulates BPH resistance and drought tolerance, with decreased cuticular wax in the gain-of-function mutant ACL1-D. ACL1 shows an epidermis-specific expression. The TurboID system and multiple biochemical assays reveal that ACL1 interacts with the epidermal-characteristic rice outermost cell-specific (ROC) proteins. ROC4 and ROC5 positively regulate BPH resistance and drought tolerance through modulating cuticular wax and BCs, respectively. Overexpression of ROC4 and ROC5 both rescue ACL1-D mutant in various related phenotypes. ACL1 competes with ROC4/ROC5 in homo-dimer and hetero-dimer formation, and interacts with the repressive TOPLESS-related proteins. Altogether, we illustrate that ACL1–ROC4/5 complexes synergistically mediate drought tolerance and BPH resistance through regulating cuticular wax content and BC development in rice, a mechanism that might facilitate BPH-resistant breeding.

Abstract Background Lipids and thyroid hormones (TH) are closely interrelated. However, previous studies have not mentioned the linkage encompassing the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) alongside TH level, as well as sensitivity indices. Methods This cross-sectional study leverages expansive datasets from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012. Weighted multivariate linear regression, smoothed curve fitting and sensitivity analyses were used to investigate the associations of the NHHR with the thyroid. Subgroup analyses and interaction tests were conducted to determine the robustness of the findings across diverse segments of the population, ensuring the consistency and generalizability of the observed associations. Results The NHHR was significantly positively correlated with free triiodothyronine (FT3) levels, thyroid-stimulating hormone (TSH) levels, the FT3 to FT4 ratio (FT3/FT4), and the quantile-based thyroid feedback index for FT3 (TFQIFT3) and negatively correlated with free thyroxin (FT4) levels [0.17(0.07–0.27), P = 0.001; 0.60 (0.03–1.17), P = 0.040; 0.06 (0.04–0.08), P

Objective: To study the effect and mechanism of luteoloside on the differentiation and lipid metabolism of 3T3-L1 preadipocytes. Methods: The cytotoxicity of different concentrations of luteoloside on 3T3-L1 preadipocyte was detected using methyl thiazolyl tetrazolium (MTT) assay. Cell differentiation was induced by the cocktail method, and lipid droplets were observed by oil red O staining. The contents of triglyceride and total cholesterol in differentiated cells, as well as the secretion of related inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, leptin (LEP) and Adiponectin (ADPN) were measured. The relative expression levels of peroxisome proliferators activated receptor (PPAR) γ, CCAAT-enhancer-binding proteins (C/EBP)-α, sterol regulatory element-binding protein 1 (SREBP1), PPARα, uncoupling protein 1 (UCP-1), and carnitine palmitoyltransferase 1 (CPT-1) were analyzed by Western blotting. Results: The survival rate of 3T3-L1 preadipocytes decreased with the increase in luteoloside concentration, being above 80% at luteoloside concentrations of 5–60 μg/mL. Treatment with luteoloside significantly inhibited the differentiation of 3T3-L1 preadipocytes and reduced lipid accumulation. Luteoloside down-regulated the contents of TC and TG, the secretion of TNF-α, IL-6 and LEP, but up-regulated the secretion of IL-10 and ADPN. Luteoloside down-regulated the protein expression levels of PPARγ, C/EBP-α and SREBP1, but up-regulated those of PPARα, UCP-1 and CPT-1. Conclusion: Luteoloside can suppression the differentiation and lipid metabolism of 3T3-L1 preadipocytes. The mechanism may be that luteoloside down-regulates the protein expression of PPARγ, C/EBP-α, and SREBP1 to inhibit fat synthesis. Furthermore, it activates PPARα to upregulate downstream proteins and promote fat consumption. Luteoloside may also regulate the secretion of cytokines and promote cellular lipolysis, thus improving lipid metabolism imbalance.

Quantifying the urban heat island (UHI) effect and its impact on summer heat-related risk is important for both urban environment and human well-being. Existing studies frequently adopt the static (fixed) urban boundary to define urban/rural area in UHI measurement, overlooking the exacerbation of the urbanization-induced warming during long-term urban expansion and the consequent increase in urban heat risks. Here we measured the global surface UHI (SUHI) intensity up to 7,554 urban patches during 2000–2015 using every five-year dynamic urban boundary, followed by a two-stage analysis based on a Distributed Lag Non-linear Model (DLNM) to quantify the additional heat-related risks caused by the urbanization-induced warming. Our results show that the global average SUHI intensity increased by approximately 10 % in 15 years with distinct seasonal and diurnal variations. The global urban expansion from 2000 to 2015 resulted in an average increase of 0.61℃ (95 % CI = 0.56℃-0.66℃) in summer UHI intensity for newly built-up areas. This urbanization-induced warming further leads to a 20 % (95 % CI = 14.8 %-25.2 %) increase in summer heat relative risk (RR) on average, which implied an average increase of 20 % (95 % CI = 14.8 %-25.2 %) in annual heat-related mortality for the newly built-up areas. Furthermore, over 2.3 % of the world population would experience an RR increase greater than 10 %. This study highlights the importance of dynamic urban boundary for long-time span UHI measurements, providing a deeper understanding of the role of urbanization-induced warming on urban heat risk.

Sediment resuspension primarily occurs within the bottom boundary layer (BBL) of water bodies, particularly in silty coastal environments, and helps form the fluid mud layer (FML). In this study, we report data on the water level, waves, currents, and suspended sediment concentration (SSC) collected from the Bohai Sea over one year, at a vertical resolution of 4 cm, by using the acoustic wave and current profiler, acoustic Doppler current profiler, and an acoustic backscattering system. The aim was to investigate the mechanisms of formation and disappearance of the FML as driven by wave–current interactions on silty seabeds The findings revealed a thin and stable FML within 4–12 cm of the seabed in shallow waters. Strong waves contributed more significantly to sediment resuspension than strong currents. Moreover, the SSC near the seabed was generally governed by the currents, while waves were predominant in this regard in stormy conditions. The index of intensity of the bottom shear β—defined as the ratio of the wave–current-induced shear stress to the critical shear stress—was identified as a sensitive indicator of variations in the SSC. Significant sediment resuspension occurred in case of the coupling of large wave and current events on the fine-grained seabed, when the value of β exceeded 10 for more than 20 h and the Rouse number persisted below 0.01 for over 30 h. Following the storm (β < 10), the sediment gradually accumulated, and this led to the formation of the FML. Prolonged periods in which the value of β surpassed 10 for over 10 h while that of the Rouse number remained below 0.01 for more than 30 h resulted in considerable sediment resuspension and the destruction of the FML. Our results highlight the profound impacts of wave–current interactions on the formation and disappearance of the FML within the BBL in silty, shallow marine environments. The work here offers critical insights into the dynamics of fine-particle sediment, and provides suggestions for mitigating the negative effects associated with the FML.

BackgroundErectile dysfunction (ED) is characterized by the inability to achieve or maintain penile erection sufficient for intercourse. While previous research suggests a potential link between ED and prostate pathologies, the association between benign prostatic hyperplasia (BPH), prostatitis, prostatic cancer (PCa), and ED remains to be elucidated.MethodsData from participants (40-80 years, n=2225) were extracted from the NHANES 2001-2004 for this observational study. The investigation encompassed the following aspects: assessment of ED prevalence within subgroups, comparison of baseline characteristics between individuals with and without ED, analysis of associations between BPH, prostatitis, PCa, and ED using multivariable weighted logistic regression in the 40-60 and 60-80 age groups and subgroup analysis based on body mass index, hypertension, diabetes, and smoking status.ResultsAmong the 2225 participants, the weighted prevalence of ED was 27.47%, with 16.17% in the 40-60 years age group and 56.98% in the 60-80 years age group. BPH had an ED prevalence of 47.57%, prostatitis 34.62%, and PCa 85.62%. Comparative analysis between ED and non-ED groups revealed significant differences in education levels, PIR, smoking and alcohol status, creatinine, total cholesterol, LDL cholesterol, diabetes, hypertension, BPH, and PCa. Multivariate logistic regression analysis identified BPH as an independent risk factor for ED in the 60-80 years age group (OR=1.93; 95% CI, 1.18-3.18, P=0.02), and PCa was positively associated with ED in both the 40-60 years group (OR=11.90; 95% CI, 1.41-100.50, P=0.03) and the 40-80 years group (OR=7.30; 95% CI, 2.12-25.08, P=0.01). No clear correlation was found between prostatitis and ED. Subgroup analyses indicated that the association between BPH and ED was significant in non-diabetic, overweight/obese, and smoking groups, while the association between PCa and ED was more pronounced in non-diabetic, hypertensive individuals across all body mass index (BMI) categories, and in both smoking and non-smoking groups. Prostatitis showed no significant relationship with ED in any subgroup.ConclusionThe study established BPH and PCa as significant risk factors for ED, with no substantial link detected between prostatitis and ED. This finding highlights the necessity for tailored screening and management protocols for individuals with BPH and PCa to mitigate the burden of ED.

1-Bromopropane (1-BP) has become a new air pollutant in occupational and living environments due to its advantages in industrial applications and as a representative compound of volatile organic compounds (VOCs). As an irritant, its damaging effects on respiratory epithelium are worthy of further study. This study aimed to explore the damage effects of 1-BP on respiratory epithelial cells and reveal its underlying mechanisms. We found that exposure to 1-BP markedly reduced the viability of respiratory epithelial cells in a dose-dependent manner, and induced oxidative stress and vacuolation changes in respiratory epithelial cells. Subsequently, through RNA-seq analysis, we identified that the 1-BP-induced damage of respiratory epithelial cells was related to the mitochondrial function pathway and further verified that 1-BP caused mitochondrial damage of respiratory epithelial cells, which was manifested as ultrastructural damage, decreased membrane potential, ATP, and MFN2 levels. These damages were associated with cellular oxidative stress responses. Pretreating cells with the agonists of PGC-1α and PPARα, we revealed that 1-BP affected the expression of PGC-1α and interfered with its coactivator PPARα levels, causing an increase in the expression of lipid-producing genes and a decrease in the expression of lipid-decomposing genes, thus leading to a lipid accumulation in respiratory epithelial cells. Meanwhile, the imbalance of lipid metabolism in respiratory epithelial cells induced by 1-BP further caused mitochondrial damage, and the effect was bidirectional. These findings suggested that 1-BP has a potential role in inducing respiratory epithelial cell damage and is associated with the PGC-1α/PPARα signaling pathway.

Abstract Understanding and predicting “droughts” in wind and solar power availability can help the electric grid operator planning and operation toward deep renewable penetration. We assess climate models' ability to simulate these droughts at different horizontal resolutions, ∼100 and ∼25 km, over Western North America and Texas. We find that these power droughts are associated with the high/low pressure systems. The simulated wind and solar power variabilities and their corresponding droughts during historical periods are more sensitive to the model bias than to the model resolution. Future climate simulations reveal varied future change of these droughts across different regions. Although model resolution does not affect the simulation of historical droughts, it does impact the simulated future changes. This suggests that regional response to future warming can vary considerably in high‐ and low‐resolution models. These insights have important implications for adapting power system planning and operations to the changing climate.

F-box and WD repeat domain-containing 7 (FBXW7), formerly known as hCdc4, hAGO Fbw7, or SEL10, plays a specific recognition function in SCF-type E3 ubiquitin ligases. FBXW7 is a well-established cancer suppressor gene that specifically controls proteasomal degradation and destruction of many key oncogenic substrates. The FBXW7 gene is frequently abnormal in human malignancies especially in gastrointestinal cancers. Accumulating evidence reveals that mutations and deletions of FBXW7 are participating in the occurrence, progression and treatment resistance of human gastrointestinal cancers. Considering the current therapeutic challenges faced by gastrointestinal cancers, elucidating the biological function and molecular mechanism of FBXW7 can provide new perspectives and references for future personalized treatment strategies. In this review, we elucidate the key molecular mechanisms by which FBXW7 and its substrates are involved in gastrointestinal cancers. Furthermore, we discuss the consequences of FBXW7 loss or dysfunction in tumor progression and underscore its potential as a prognostic and therapeutic biomarker. Lastly, we propose potential therapeutic strategies targeting FBXW7 to guide the precision treatment of gastrointestinal cancers.

Abstract Astrocytic processes minutely regulate neuronal activity via tripartite synaptic structures. The precision‐tuning of the function of astrocytic processes is garnering increasing attention because of its significance in promoting brain repair following ischemic stroke. Microdomain calcium (Ca2+) transients in astrocytic processes are pivotal for the functional regulation of these processes. However, the understanding of the alterations and regulatory mechanism of microdomain Ca2+ transients during stroke remains limited. In the present study, a fast high‐resolution, miniaturized two‐photon microscopy is used to show that the levels of astrocytic microdomain Ca2+ transients are significantly reduced in the peri‐infarct area of awake ischemic stroke mice. This finding correlated with the behavioral deficits shown by these mice under freely‐moving conditions. Mitochondrial Ca2+ activity is an important factor driving the microdomain Ca2+ transients. DEAD Box 1 (DDX1) bound to circSCMH1 (a circular RNA involved in vascular post‐stroke repair) facilitates the formation of membrane‐associated RNA‐containing vesicles (MARVs) and enhances the activity of astrocytic microdomain Ca2+ transients, thereby promoting behavioral recovery. These results show that targeting astrocytic microdomain Ca2+ transients is a potential therapeutic approach in stroke intervention.

Ischemic stroke is a high-mortality disease that urgently requires new therapeutic strategies. Insufficient cerebral blood supply can induce poly (ADP-ribose) polymerase (PARP) activation and mitochondrial dysfunction, leading to tissue damage and motor dysfunction. We demonstrate that the expression of TCDD inducible PARP (TIPARP) is elevated in ischemic stroke patients and mice. Knockdown of Tiparp reduces brain infarction and promotes recovery of motor function in ischemic stroke mice. A rationally designed TIPARP inhibitor, XG-04-B1, promotes repair of brain injury and recovery of motor function in ischemic stroke mice. Mechanistically, XG-04-B1 increases neuronal plasticity and inhibits astrocyte activation in ischemic stroke mice. In addition, eukaryotic translation initiation factor 3 subunit B (EIF3B) is a direct target of TIPARP. TIPARP interacts with EIF3B through nucleoplasmic redistribution, leading to mitochondrial dysfunction. Knockdown of Tiparp and inhibition of TIPARP via XG-04-B1 restore mitochondrial homeostasis in ischemic stroke mice. Taken together, TIPARP activation contributes to mitochondrial dysfunction and subsequent brain injury, and is therefore a promising therapeutic target for stroke.

Objectives Dietary inflammatory index (DII) is utilized to determine the inflammatory effects of nutrients and foods on various diseases. Inflammation is a potential risk factor for anemia. We hypothesize that pro-inflammatory diets boost the incidence of anemia, as indicated by high DII.Methods 41, 360 Americans were included in this study from the U.S. National Health and Nutrition Survey (NHANES) from 2003–2018. Multivariable logistic regression models were employed to examine the association between DII and anemia.Results After adjustment for all the covariates, the odds ratios (ORs) (95% CI) between the risk of anemia and DII across tertile 3 were 1.2556 (95% CI 1.0621, 1.4843; P = 0.0077), and the trend test was statistically significant (P for trend = 0.009). Furthermore, in the subgroup analysis stratified by gender. The ORs (95% CI) between the risk of anemia and DII across tertile 2 and 3 were 1.8071 (95% CI 1.1754, 2.7783; P = 0.0070) and 2.1591 (95% CI 1.4009, 3.3278; P = 0.0005) in men after multivariable adjustment. However, in women, this association was only significantly different (P

Adoptive cell therapy (ACT) has revolutionized the treatment of patients with cancer. The success of ACT depends largely on transferred T cell status, particularly their less-differentiated state with stem cell-like properties, which enhances ACT effectiveness. Stem cell-like memory T (TSCM) cells exhibit continuous self-renewal and multilineage differentiation similar to pluripotent stem cells. TSCM cells are promising candidates for cancer immunotherapies, whereas maintenance of a more stem-cell-like state before transfer is challenging. Here, we established a highly efficient protocol for generating CD8+ TSCM cells from peripheral blood mononuclear cells (PBMCs). The process involved activating PBMCs using anti-CD3 monoclonal antibody and RetroNectin, followed by a transient-resting culture period (24 h) and subsequent long-term expansion in vitro with interlukien-2. We report that this transient-resting culture after activation preserves CD8+ T cells in a stem memory phenotype (CD95+ CD45RA+ CCR7+) compared to the conventional culture method. Further, this approach reduces the expression of T cell immunoglobulin mucin-3, an exhaustion marker, and increases the expression of T cell factor-1, a master regulator of stemness even after long-term culture compared to the conventional culture method. In conclusion, our study presents a simplified and cost-effective method for generating and expanding CD8+ TSCM cells ex vivo. This approach streamlines the optimization of cancer immunotherapy using ACT.

Abstract Background Microglial activation has been suggested to be involved in the pathogenesis of depression and Alzheimer’s disease (AD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a marker of microglial activation. The purpose of this study was to investigate the interrelationships of cerebrospinal fluid (CSF) sTREM2, AD pathology, as well as minimal depressive symptoms (MDSs), and cognition. Methods A total of 545 non-demented individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort were included in our study. The average age of the total population was 72.6 years and the percentage of females was 42.6%. Linear regression models were conducted to investigate the linear relationships of MDSs with CSF sTREM2, AD pathology, cognition, and brain structure. Mediation models and structural equation models (SEM) were conducted to examine whether CSF sTREM2 mediated the relationships of MDSs with AD pathology and cognition. Results Results revealed that individuals with MDSs had lower CSF sTREM2 levels than normal controls. Linear regression showed that MDSs were linearly associated with CSF sTREM2 (P FDR = 0.012) and amyloid biomarkers (P FDR < 0.05), as well as cognitive scores (P FDR < 0.05) and hippocampal volume (P FDR = 0.003). Mediation analyses revealed that CSF sTREM2 mediated the association between MDSs and amyloid pathology, with the mediating proportions ranging from 6.030 to 18.894%. However, SEM failed to reveal that MDS affected cognition through CSF amyloid pathology and CSF sTREM2. Conclusions MDSs are associated with amyloid pathology and cognition. CSF sTREM2 may potentially be an intervenable target between depression and AD pathology.

Abstract True morels (Morchella) are globally renowned medicinal and edible mushrooms. White mold disease caused by fungi is the main disease of Morchella, which has the characteristics of wide incidence and strong destructiveness. The disparities observed in the isolation rates of different pathogens indicate their varying degrees of host adaptability and competitive survival abilities. In order to elucidate its potential mechanism, this study, the pathogen of white mold disease from Dafang county, Guizhou Province was isolated and purified, identified as Pseudodiploöspora longispora by morphological, molecular biological and pathogenicity tests. Furthermore, high-quality genome of P. longisporus (40.846 Mb) was assembled N50 of 3.09 Mb, predicts 7381 protein-coding genes. Phylogenetic analysis of single-copy homologous genes showed that P. longispora and Zelopaecilomyces penicillatus have the closest evolutionary relationship, diverging into two branches approximately 50 (44.3–61.4) MYA. Additionally, compared with the other two pathogens causing Morchella disease, Z. penicillatus and Cladobotryum protrusum, it was found that they had similar proportions of carbohydrate enzyme types and encoded abundant cell wall degrading enzymes, such as chitinase and glucanase, indicating their important role in disease development. Moreover, the secondary metabolite gene clusters of P. longispora and Z. penicillatus show a high degree of similarity to leucinostatin A and leucinostatin B (peptaibols). Furthermore, a gene cluster with synthetic toxic substance Ochratoxin A was also identified in P. longispora and C. protrusum, indicating that they may pose a potential threat to food safety. This study provides valuable insights into the genome of P. longispora, contributing to pathogenicity research.

Abstract With the rapid spread of the novel coronavirus (COVID-19), a sustained global pandemic has emerged. Globally, the cumulative death toll is in the millions. The rising number of COVID-19 infections and deaths has severely impacted the lives of people worldwide, healthcare systems, and economic development. We conducted a retrospective analysis of the characteristics of COVID-19 patients. This analysis includes clinical features upon initial hospital admission, relevant laboratory test results, and imaging findings. We aimed to identify risk factors for severe illness and to construct a predictive model for assessing the risk of severe COVID-19. We collected and analyzed electronic medical records of confirmed COVID-19 patients admitted to the Affiliated Hospital of Jiangsu University (Zhenjiang, China) between December 18, 2022, and February 28, 2023. According to the WHO diagnostic criteria for the novel coronavirus, we divided the patients into two groups: severe and non-severe, and compared their clinical, laboratory, and imaging data. Logistic regression analysis, the least absolute shrinkage and selection operator (LASSO) regression, and receiver operating characteristic (ROC) curve analysis were used to identify the relevant risk factors for severe COVID-19 patients. Patients were divided into a training cohort and a validation cohort. A nomogram model was constructed using the “rms” package in R software. Among the 346 patients, the severe group exhibited significantly higher respiratory rates, breathlessness, altered consciousness, neutrophil-to-lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) levels compared to the non-severe group. Imaging findings indicated that the severe group had a higher proportion of bilateral pulmonary inflammation and ground-glass opacities compared to the non-severe group. NLR and LDH were identified as independent risk factors for severe patients. The diagnostic performance was maximized when NLR, respiratory rate (RR), and LDH were combined. Based on the statistical analysis results, we developed a COVID-19 severity risk prediction model. The total score is calculated by adding up the scores for each of the twelve independent variables. By mapping the total score to the lowest scale, we can estimate the risk of COVID-19 severity. In addition, the calibration plots and DCA analysis showed that the nomogram had better discrimination power for predicting the severity of COVID-19. Our results showed that the development and validation of the predictive nomogram had good predictive value for severe COVID-19.

Abstract Background Vascular endothelial growth factor (VEGF) is an important proangiogenic factor and has been considered as a key target of antiangiogenetic therapy in oral squamous cell carcinoma (OSCC). However, clinical application of bevacizumab, a specific VEGF antibody, didn’t improve the survival rate of OSCC patients. One possible explanation is that VEGF gene expresses diverse isoforms, which associate with extracellular vesicles (EVs), and EVs potentially contribute to VEGF resistance to bevacizumab. However, clear solution is lacking in addressing this issue. Methods Expression of VEGF isoforms in OSCC cells was confirmed by reverse transcription and polymerase chain reaction (RT-PCR) and western blot. EVs isolated from OSCC cell’s conditioned medium (CM) were characterized by western blot, transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Flow cytometry, immunogold labeling and western blot were applied to study the VEGF on EVs. Tube formation assay and Matrigel plug angiogenesis assay were used for analyzing the angiogenesis capacity of EV-VEGF. Results The most popular isoforms expressed by VEGF gene are VEGF121, VEGF165 and VEGF189. In this study, we demonstrated that all three isoforms of mRNA could be detected at varying levels in OSCC cells, while only VEGF165 and VEGF189 proteins were found. CM derived from OSCC cells, both soluble and non-soluble forms of VEGF could be detected. We further confirmed the presence of VGEF189 bound to EVs as a non-soluble form. EV-bound VEGF189 presented angiogenic activity, which could not be neutralized by bevacizumab. It was found that VEGF189 bound to EVs by heparan sulfate proteoglycans (HSPG). In addition, the angiogenic effect of EV-VEGF could be reversed by surfen, a kind of HSPG antagonist both in vitro and in vivo. Conclusion Antagonists targeting HSPG might potentially overcome the resistance of EV-VEGF to bevacizumab and serve as an alternative for anti-VEGF therapy in OSCC.

This is an article in the field of mining engineering. As an important battery raw material in the field of new energy, the global demand for lithium is accelerating. For a long time, China has needed to import a large amount of lithium raw materials, and there is still expected to be a significant demand gap in the future. Unconventional brine sources such as geothermal brine, oil and gas field brine, and desalination wastewater in seawater containing contain considerable lithium resources and may become an effective supplement to conventional lithium resources. As a green and sustainable method for extracting lithium resources, the development of unconventional brine-type lithium resources faces significant opportunities. The discovery of abundant unconventional brine-type lithium resources in Sichuan, Xizang, Yunnan and other places in China will be of great help to solve the shortage of lithium raw material supply in China. By summarizing the current status and progress of unconventional brine-type lithium resource development and its key technologies both domestically and internationally, this article provides a reference for the development of unconventional brine-type lithium resources in China.

Abstract Processing spatiotemporal data sources with both high spatial dimension and rich temporal information is a ubiquitous need in machine intelligence. Recurrent neural networks in the machine learning domain and bio-inspired spiking neural networks in the neuromorphic computing domain are two promising candidate models for dealing with spatiotemporal data via extrinsic dynamics and intrinsic dynamics, respectively. Nevertheless, these networks have disparate modeling paradigms, which leads to different performance results, making it hard for them to cover diverse data sources and performance requirements in practice. Constructing a unified modeling framework that can effectively and adaptively process variable spatiotemporal data in different situations remains quite challenging. In this work, we propose hybrid spatiotemporal neural networks created by combining the recurrent neural networks and spiking neural networks under a unified surrogate gradient learning framework and a Hessian-aware neuron selection method. By flexibly tuning the ratio between two types of neurons, the hybrid model demonstrates better adaptive ability in balancing different performance metrics, including accuracy, robustness, and efficiency on several typical benchmarks, and generally outperforms conventional single-paradigm recurrent neural networks and spiking neural networks. Furthermore, we evidence the great potential of the proposed network with a robotic task in varying environments. With our proof of concept, the proposed hybrid model provides a generic modeling route to process spatiotemporal data sources in the open world.

Abstract Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer.

Myocardial ischemia is a serious threat to human health, and vascular dysfunction is its main cause. Buxu Tongyu (BXTY) Granule is an effective traditional Chinese medicine (TCM) for treating myocardial ischemia. However, the underlying mechanism of BXTY is still unclear. In this study, we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase (sGC)–3′,5′-cyclic guanosine monophosphate (cGMP)–protein kinase G (PKG) signaling pathway in vascular smooth muscle cells (VSMCs) to dilate the arteries. BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin. The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice, including electrocardiogram abnormalities and changes in plasma enzymes. In addition, BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner. These effects were eliminated by pre-incubating vascular rings with the sGC inhibitors NS 2028 or ODQ, or with the PKG inhibitor KT 5823. Moreover, BXTY increased the protein expression of sGC-β1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells (MOVAs). NS 2028 or ODQ reversed these effects of BXTY. The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY. NS 2028, ODQ, or KT 5823 also reversed this effect of BXTY. In conclusion, BXTY can improve the symptoms of acute myocardial ischemia in mice, and activating the sGC–cGMP–PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.

Atherosclerosis is a severe cardiovascular disease followed by the accumulation of atherosclerotic plaques within the lumen of blood vessels resulting in reduced blood flow thus initiating a series of events. Conventional therapies for atherosclerosis encounter multiple challenges, especially difficulty in precisely concentrating in certain affected regions and the potential for unwanted side effects. Consequently, scientists are focused on developing nanoformulations for atherosclerosis diagnosis and therapy. Peptide-based nanomedicines improve conventional therapies by offering improved structural and therapeutic stability and enabling target-specific delivery. Their inherent biocompatibility and biodegradability additionally render them desirable materials intended for in vivo use. This review manuscript aims to provide an in-depth overview of peptide-based nanomedicines for atherosclerosis, focusing on targeted cells like endothelial cells, macrophages, and monocytes and their interaction with different plaque components. Moreover, the manuscript also highlights the latest progress in multimodal techniques and provides a comprehensive overview of limitations associated with their practical implementation.

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens, thereby engaging with CD3 on the T cell receptor. This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells. These antibodies have emerged as one of the most promising avenues within tumor immunotherapy. However, despite success in treating hematological malignancies, significant advancements in solid tumors have yet to be explored. In this review, we aim to address the critical challenges associated with T cell-redirecting bispecific antibodies and explore novel strategies to overcome these obstacles, with the ultimate goal of expanding the application of this therapy to include solid tumors.

A physical mechanics simulation experiment is one of the important technical methods to study the inoculation mechanism and development laws of coal and gas outburst. A new type of coal and gas outburst simulation system has been developed, aiming at developing an advanced experimental design scheme with the help of existing advanced monitoring technology, combined with specific gas geology conditions, to realize the simulation of coal and gas outburst phenomenon in complex scenes, and to promote the study of coal and gas outburst mechanism. The physical mechanics simulation system consists of following seven parts: stress loading subsystem, test chamber subsystem, power traction subsystem, gas pressure control subsystem, induced equipment subsystem, simulated roadway subsystem, and measurement and control subsystem. The design of each subsystem has been improved to different degrees, and the whole system has formed a landmark innovation. The simulation system has the following characteristics: ① the high load loading and unloading function of the three-axis synchronous continuous non-uniform loading technical equipment is improved. The specimen loading is done by 10 independent indenters in X, Y, and Z directions. The size of the experimental chamber is 400 mm × 400 mm × 1200 mm, the maximum load strength is 25 MPa, and the maximum closed gas pressure is 6.0 MPa. Each of the above 10 indenters can operate asynchronously or synchronously for loading or unloading tasks according to instructions, and horizontal stress loading and unloading layered processing function is implemented. ② An integrated process of systematic sample preparation, sample packing, sealing, and loading has been formed completely. The experimental chamber is designed as a new type of split structure, and the dynamic traction system is used to assist the experimental chamber to complete the molding, stress loading and material handling, and the translation amount of the chamber structure is controlled accurately. ③ The four kinds of technologies for inducing coal and gas outburst are integrated and applied in the same simulation platform, and some equipment functional innovations are realized, such as the test chamber, the pressure relief window, etc. Many kinds of technology and equipment have been successfully developed, as original innovation products, the dynamic technology and the drilling equipment have been verified by the experimental simulation. ④ The design innovation of key device structure is realized. The problems of stress concentration and high pressure gas leakage under synchronous loading are solved by the design of double-layer steel plate chamber structure. The experimental efficiency is improved by the structural optimization of the launching cavity, the safety of the simulation system is significantly improved by the design of the pipe end structure, a combination of soft and hard material pipe structure, and the variable diameter drilling technology has achieved the engineering application of the Rouleauxs triangle theory. ⑤ Simulation test precision is generated by multivariate information. Advanced data acquisition systems (stress, gas pressure, temperature, etc.) and monitoring technology equipment including acoustic emission and high-speed cameras are used to achieve multi-data monitoring of coal and gas outburst. ⑥ The reliability of the experimental system has been verified by laboratory simulation. Through the case simulation of the “3·22 accident in Pingdingshan”, the overall test of the system function is completed, and the influence law of fault structure on in-situ stress, gas pressure and temperature in the process of coal and gas outburst is discovered in a new way. It is proved that the physical mechanics simulation system is reliable and could provide a platform to support the research on the coal and gas outburst mechanism.

The construction of heterojunction is an effective way to promote the photoinduced charge carrier separation in spatial, thus accelerating the photocatalytic reaction. However, the regulation of interface properties, as a crucial factor in affecting the charge carrier diffusion process, still remains a significant challenge. In this work, BiOBr/TpBD-COF heterojunction was successfully constructed via a novel phase transformation strategy. Specifically, perovskite Cs3Bi2Br9 was first synthesized and then in-situ transformed into BiOBr during the preparation of TpBD-COF procedure, thus obtaining BiOBr/TpBD-COF heterojunction with favorable interface. According to the in-situ X-ray photoelectron spectroscopy (XPS) characterization and electron paramagnetic resonance (EPR) analysis, the photogenerated electrons with weak reduction power transfer from BiOBr to TpBD-COF driven by the internal electric field under irradiation, conforming to S-scheme charge transfer mode. As a result, the photogenerated electrons and holes with strong redox abilities are spatially located on TpBD-COF and BiOBr surface, respectively, endowing the strong driving force toward the water splitting reaction. The optimized 10%BiOBr/TpBD-COF displayed remarkably enhanced photocatalytic hydrogen evolution rate (16.17 mmol⋅g−1⋅h−1) in comparison with TpBD-COF (5.18 mmol⋅g−1⋅h−1). This study will provide some novel inspirations for developing efficient COF-based S-scheme heterojunction photocatalysts.