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Abstract This Matters Arising article critically examines the study “Genetic susceptibility association between viral infection and colorectal cancer risk: a two-sample Mendelian randomization analysis” by Li et al., highlighting both its contributions and methodological limitations. Their study employed two-sample Mendelian randomization (MR) to explore potential causal links between viral infections and colorectal cancer (CRC), identifying significant associations with infections such as herpes simplex virus and measles. However, several aspects of the methodology warrant scrutiny, including the relaxation of instrumental variable selection thresholds, the handling of potential pleiotropy, and the interpretation of biologically implausible findings. While leveraging advanced MR techniques such as MR-RAPS, cML, ConMix, and dIVW to address challenges like pleiotropy and weak instruments, the study encountered issues related to heterogeneity, insufficient exploration of biological plausibility, and a lack of detailed reporting on instrumental variable (IV) selection and preprocessing. This Matters Arising calls for more rigorous sensitivity analyses, improved transparency in IV selection criteria and harmonization of genome-wide association study (GWAS) datasets, particularly in addressing differences between self-reported and clinically diagnosed infections. Additionally, the Matters Arising article calls for a deeper exploration of biological mechanisms, such as the role of immune modulation and inflammation, to better interpret the observed associations. By addressing these limitations, future MR studies can enhance methodological rigor, improve reproducibility, and provide more robust insights into the causal pathways linking viral infections to CRC risk.

Most acute ischemic stroke patients with large vessel occlusion require stent implantation for complete recanalization. Yet, due to ischemia-reperfusion injury, over half of these patients still experience poor prognoses. Thus, neuroprotective treatment is imperative to alleviate the ischemic brain injury, and a proof-of-concept study was conducted on “biodegradable neuroprotective stent”. This concept is premised on the hypothesis that locally released Mg2+/H2 from Mg metal within the bloodstream could offer synergistic neuroprotection against reperfusion injury in distant cerebral ischemic tissues. Initially, the study evaluated pure Mg's neuroactive potential using oxygen-glucose deprivation/reoxygenation (OGD/R) injured neuron cells. Subsequently, a pure Mg wire was implanted into the common carotid artery of the transient middle cerebral artery occlusion (MCAO) rat model to simulate human brain ischemia/reperfusion injury. In vitro analyses revealed that pure Mg extract aided mouse hippocampal neuronal cell (HT-22) in defending against OGD/R injury. Additionally, the protective effects of the Mg wire on behavioral abnormalities, neural injury, blood-brain barrier disruption, and cerebral blood flow reduction in MCAO rats were verified. Conclusively, Mg-based biodegradable neuroprotective implants could serve as an effective local Mg2+/H2 delivery system for treating distant cerebral ischemic diseases.

Variations in molecular evolutionary rate have been widely investigated among lineages and genes. However, it remains an open question whether fast rate of molecular evolution is driven by natural selection or random drift, and how the fast rate is linked to metabolic rate. Additionally, previous studies on fast molecular evolution have been largely restricted to concatenated matrix of genes or a few specifically selected genes, but less is known for individual genes at the genome-wide level. Here we addressed these questions using more than 5000 single-copy orthologous (SCO) genes through comparative genomic and phylogenetic analyses among fishes, with a special focus on a newly-sequenced clupeocephalan fish the Chinese hook snout carp Opsariichthys bidens. We showed O. bidens displays significantly higher mean substitution rate and more fast-evolving SCO genes (2172 genes) than most fishes studied here. The rapidly evolving genes are enriched in highly conserved and very basic functions such as translation and ribosome that are critical for biological fitness. We further revealed that ∼25 % of these fast-evolving genes exhibit a constant increase of substitution rate from the common ancestor down to the present, suggesting a neglected but important contribution from ancestral states. Model fitting showed that ∼85 % of fast-evolving genes exclusive to O. bidens and related species follow the adaptive evolutionary model rather than random-drift model, and 7.6 % of fast-evolving genes identified in O. bidens have experienced positive selection, both indicating the reflection of adaptive selection. Finally, metabolic rate was observed to be linked with substitution rate in a gene-specific manner. Overall, our findings reveal fast molecular evolution of SCO genes at genome-wide level in O. bidens, and uncover the evolutionary and ecological contributors to it.

Abstract To aid in the diagnosis, monitoring, and surveillance of bladder carcinoma, this study aimed to develop and test an algorithm that creates a referenceable bladder map rendered from standard cystoscopy videos without the need for specialized equipment. A vision-based algorithm was developed to generate 2D bladder maps from individual video frames, by sequentially stitching image frames based on matching surface features, and subsequently localize and track frames during reevaluation. The algorithm was developed and calibrated in a 2D model and 3D anthropomorphic bladder phantom. The performance was evaluated in vivo in swine and with retrospective clinical cystoscopy video. Results showed that the algorithm was capable of capturing and stitching intravesical images with different sweeping patterns. Between 93% and 99% of frames had sufficient features for bladder map generation. Upon reevaluation, the cystoscope accurately localized a frame within 4.5 s. In swine, a virtual mucosal surface map was generated that matched the explant anatomy. A surface map could be generated based on archived patient cystoscopy images. This tool could aid recording and referencing pathologic findings and biopsy or treatment locations for subsequent procedures and may have utility in patients with metachronous bladder cancer and in low-resource settings.

Abstract The cryo-electron microscopy (cryoEM) method has enabled high-resolution structure determination of numerous biomolecules and complexes. Nevertheless, cryoEM sample preparation of challenging proteins and complexes, especially those with low abundance or with preferential orientation, remains a major hurdle. We developed an affinity-grid method employing monodispersed single particle streptavidin on a lipid monolayer to enhance particle absorption on the grid surface and alleviate sample exposure to the air-water interface. Using this approach, we successfully enriched the Thermococcus kodakarensis mini-chromosome maintenance complex 3 (MCM3) on cryoEM grids through biotinylation and resolved its structure. We further utilized this affinity method to tether the biotin-tagged dsDNA to selectively enrich a stable MCM3-ATP-dsDNA complex for cryoEM structure determination. Intriguingly, both MCM3 apo and dsDNA bound structures exhibit left-handed open spiral conformations, distinct from other reported MCM structures. The large open gate is sufficient to accommodate a dsDNA which could potentially be melted. The value of mspSA affinity method was further demonstrated by mitigating the issue of preferential angular distribution of HIV-1 capsid protein hexamer and RNA polymerase II elongation complex from Saccharomyces cerevisiae.

Abstract Using waste rubber to partially replace fine aggregate to make rubber concrete can not only reduce black pollution to alleviate the dilemma of natural sand resource depletion, but also improve the frost resistance of concrete, which is undoubtedly a win–win solution. Aim to promote the application of rubber concrete seasonal cold regions, it is of great significance to evaluate and predict its frost-resistance. Different from ordinary concrete, the existence of rubber changes the inherent characteristics of concrete to varying degrees, which makes the durability of rubber concrete more complicated and the establishment of prediction models more challenging. In this paper, an artificial neural network (ANN) model was proposed to predict the frost-resistance of rubberized concrete. Using water-cement ratio, cement, sand, sand rate, rubber content and the number of freeze–thaw cycles as input variables and relative dynamic elastic modulus as output variables, a three-layer BP neural network (BPNN) prediction model with a hidden layer was established on the basis of a large number of experimental data of another author. The prediction results show that the proposed BPNN model has a strong ability to predict the frost resistance of rubberized concrete with satisfactory accuracy (R2 = 0.9825, MAPE = 1.5609%), which opens up a new way to improve the prediction accuracy of frost-resistance for rubberized concrete.

Abstract Objective To investigate the efficacy of physical activity as a crucial intervention for Autism spectrum disorder (ASD) in clinical settings, we conducted a network meta-analysis to evaluate the effect of various exercise interventions on sociability and communication in individuals with ASD. Our aim was to identify the exercise modalities most conducive to enhancing these essential skills. Methods We searched Web of Science, PubMed, Cochrane Library, Scopus, Embase, and searched Chinese databases from inception to April 2024. We included randomized controlled trials that assessed the effects of different exercise types on sociability and communication in individuals with ASD. Network meta-analysis (NMA) was performed using a frequentist approach, and the node-splitting method was applied to assess inconsistency. Results We included 38 original studies published between 2009 and 2024, with a total of 1,382 participants analyzed for sociability outcomes. Results indicated that sports games [SMD = 1.12, 95%CI (0.51, 1.73)], combination therapy [SMD = 1.11, 95%CI (0.13, 2.09)], group ball sports [SMD = 1.06, 95%CI (0.37, 1.75)], and outdoor exercise [SMD = 1.02, 95%CI (0.50, 1.55)] were more effective than passive controls. A total of 25 original literatures were included in the analysis of communication ability, involving 904 subjects, and the results showed that combination therapy [SMD = 1.57, 95% CI (0.74, 2.40)], sports games [SMD = 1.01, 95% CI (0.45, 1.56)], group ball games [SMD = 0.85, 95% CI (0.45, 1.26)], outdoor exercise [SMD = 0.79, 95% CI (0.48, 1.11)], and mind-body exercise [SMD = 0.79, 95% CI (0.29, 1.30)], all of which were more effective than passive controls. Conclusion Physical exercise plays a significant role in alleviating symptoms and enhancing sociability and communication in individuals with ASD. Our findings highlight that sports games, combination therapy, team ball sports, and outdoor exercise are particularly effective in improving sociability. In terms of communication skills, combination therapy, sports games, team ball sports, outdoor exercise, and mind-body exercise demonstrated the most substantial benefits. These results provide a robust foundation for future interventions aimed at improving the quality of life for individuals with ASD.

Abstract Background The global incidence of frozen shoulder (FS) (2% ~ 5%) and osteoporosis (OP) is high (9.1%-12.1%). Clinically, postmenopausal women are particularly at risk for both diseases. The main objective of this current research is to investigate the pathogenesis mechanism of FS and explore the connection between FS and OP. Methods We obtained FS and OP datasets from GEO and identified crosstalk genes. Following KEGG and GO enrich analysis, the p38 MAPK signaling pathway was focused and the specific p38α inhibitor TAK715 was screened out. We conducted flow cytometry, western blot, and PCR analyses to assess the treatment effect of TAK715 on FS synovium fibroblasts at different concentrations. Additionally, we employed SD rats to validate the treatment effects of TAK715 in vivo. Results TAK715 was useful in reversing fibrosis at the concentration of 1 μM, 5 μM and 10 μM. The unbalanced apoptosis process in frozen shoulder cell and the activation of osteoclast were inhibited at the concentration of 5 μM by TAK715. Then we successfully established a FS and OP rat model, with the FS with OP rat displaying less range of motion (ROM) and thicker shoulder capsule. In FS rat that was treated with TAK715, the frozen shoulder side was corrected in ROM and bone loss. Conclusions The frozen shoulder with osteoporosis may exhibit more severe symptoms, and TAK715 is effective in protecting fibrosis and osteoporosis both in vitro and vivo. The therapy to correct FS and OP simultaneously by TAK715 provides novel approach in FS treatment and study.

Abstract The tomato hind (Cephalopholis sonnerati) is an emerging economically important grouper in recent years. With the increasing maturity of sequencing technologies and assembly methodologies, a higher quality reference genome has become both accessible and necessary. In this study, we present two telomere-to-telomere (T2T) gap-free haplotype assemblies of the tomato hind with lengths of 1039.53 Mb (YSFRI_Csonn_HA_1.0, N50 43.83 Mb) and 1039.91 Mb (YSFRI_Csonn_HB_1.0, N50 44.09 Mb). Reads from next-generation sequencing, ONT ultra-long sequencing, and PacBio HiFi sequencing exhibited mapping rates exceeding 99.8% when aligned to these two assemblies. Evaluation using Merqury indicated high accuracy for both assemblies, with average quality values of 51.80 and 51.83, respectively. Percentages of 97.9% and 97.8% of complete BUSCOs were achieved, and a total of 23,270 and 23,184 protein-code genes were inferred in each assembly. Moreover, telomere identification, centromere prediction, and repetitive sequence annotation were also successfully performed. These two assemblies provide robust foundation for the genetic analysis and development of molecular genetic breeding technologies in C. sonnerati.

Abstract Background Evidence has accumulated to demonstrate that intestinal microbiome can inhibit viral infection. However, our knowledge of the signaling pathways and identity of specific commensal microbes that mediate the antiviral response is limited. Zebrafish have emerged as a powerful animal model for study of vertebrate-microbiota interactions. Here, a rhabdoviral infection model in zebrafish allows us to investigate the modes of action of microbiome-mediated antiviral effect. Results We observed that oral antibiotics-treated and germ-free zebrafish exhibited greater spring viremia of carp virus (SVCV) infection. Mechanistically, depletion of the intestinal microbiome alters TLR2-Myd88 signaling and blunts neutrophil response and type I interferon (IFN) antiviral innate immunity. Through 16S rRNA sequencing of the intestinal contents from control and antibiotic(s)-treated fish, we identified a single commensal bacterial species, Cetobacterium somerae, that can restore the TLR2- and neutrophil-dependent type I IFN response to restrict SVCV infection in gnotobiotic zebrafish. Furthermore, we found that C. somerae exopolysaccharides (CsEPS) was the effector molecule that engaged TLR2 to mediate the type I IFN-dependent antiviral function. Conclusions Together, our results suggest a conserved role of intestinal microbiome in regulating type I IFN antiviral response among vertebrates and reveal that the intestinal microbiome inhibits viral infection through a CsEPS-TLR2-type I IFN signaling axis in zebrafish. Video Abstract

Abstract Background Previous studies have found that the temporal duration required for males to perceive visual motion direction is significantly shorter than that for females. However, the neural correlates of such shortened duration perception remain yet unclear. Given that motion perception is primarily associated with the neural activity of the middle temporal visual complex (MT+), we here test the novel hypothesis that the neural mechanism of these behavioral sex differences is mainly related to the MT+ region. Methods We utilized ultra-high field (UHF) MRI to investigate sex differences in the MT+ brain region. A total of 95 subjects (48 females) participated in two separate studies. Cohort 1, consisting of 33 subjects (16 females), completed task-fMRI (drafting grating stimuli) experiment. Cohort 2, comprising 62 subjects (32 females), engaged in a psychophysical experiment measuring motion perception along different temporal thresholds as well as conducting structural and functional MRI scanning of MT+. Results Our findings show pronounced sex differences in major brain parameters within the left MT+ (but not the right MT+, i.e., laterality). In particular, males demonstrate (i) larger gray matter volume (GMV) and higher brain’s spontaneous activity at the fastest infra-slow frequency band in the left MT+; and (ii) stronger functional connectivity between the left MT+ and the left centromedial amygdala (CM). Meanwhile, both female and male participants exhibited comparable correlations between motion perception ability and the multimodal imaging indexes of the MT+ region, i.e., larger GMV, higher brain’s spontaneous activity, and faster motion discrimination. Conclusions Our findings reveal sex differences of imaging indicators of structure and function in the MT+ region, which also relate to the temporal threshold of motion discrimination. Overall, these results show how behavioral sex differences in visual motion perception are generated, and advocate considering sex as a crucial biological variable in both human brain and behavioral research.

Abstract Background Genetic biocontrol interventions targeting mosquito-borne diseases require the release of male mosquitoes exclusively, as only females consume blood and transmit pathogens. Releasing only males eliminates the risk of increasing mosquito bites and spreading pathogens while enabling effective population control. The aim of this study is to develop robust sex-sorting methods for early larval stages in mosquitoes, enabling scalable male-only releases for genetic biocontrol interventions. Methods To address the challenge of sex-sorting in the Asian malaria vector Anopheles stephensi, we engineer Sexing Element Produced by Alternative RNA-splicing of a Transgenic Observable Reporter (SEPARATOR). This dominant fluorescent-based method, previously proven effective in Aedes aegypti, exploits sex-specific alternative splicing of a reporter to ensure exclusive male-specific expression early in development. The sex-specific alternative RNA splicing of the doublesex gene was selected as a target for engineering SEPARATOR due to its evolutionary conservation in insects. To expand SEPARATOR’s applicability for genetic sexing, we assessed the cross-species sex-specific RNA splicing activity of the An. gambiae doublesex (AngDsx) splicing module in An. stephensi. Male-specific enhanced green fluorescent protein (EGFP) expression was verified throughout the mosquito life cycle using a fluorescent stereomicroscope. Results Our results confirm that SEPARATOR regulates male-specific EGFP expression in An. stephensi and enables reliable positive male selection from the first instar larval stages. Molecular analysis demonstrates that male-specific EGFP expression is dependent on doublesex sex-specific splicing events. Additionally, the splicing module from An. gambiae operates effectively in An. stephensi, demonstrating evolutionary conservation in sex-specific splicing events between these species. Conclusions SEPARATOR’s independence from sex-chromosome linkage provides resistance to breakage that could be mediated by meiotic recombination and chromosomal rearrangements, making it highly suitable for mass male releases. By enabling precise male selection from the first instar larval stages, SEPARATOR represents a significant advancement that will aid in the genetic biocontrol for Anopheles mosquitoes. Graphical Abstract

Objective Posterior condylar offset (PCO) and anterior condylar offset (ACO) exert an influence on the sagittal alignment in total knee arthroplasty (TKA). However, there is no common consensus that the variation range of posterior condylar offset (PCO) is associated with patient‐reported outcome measures (PROMs) and the optimum variation range of PCO. This study aims to investigate the correlation between PCO and the PROMs of primary TKA for osteoarthritis (OA) and find out the optimal variation range of the PCO. Methods In this study, we performed a radiographic analysis of 106 patients (112 knees) with primary TKA. Patients were divided into two cohorts (A and B) according to the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC). Correlations between the sagittal parameter and WOMAC were investigated using univariate and multivariate analysis. The receiver operating characteristic (ROC) curve was used to establish the cut‐off value for the optimal variation range. We then further investigated how different variation range affects the WOMAC subscale score and forgotten‐joint‐score‐12 (FJS‐12). Results Univariate analysis revealed a correlation between the variation range of PCO (p

Abstract The open‐circuit magnetic field of the V‐shaped interior PM (IPM) machine is predicted by the analytical method. The method is implemented following the basic principle of the subdomain method. The machine model is divided into five different regions, including rotor slot, magnetic barrier, air gap, stator slot, and stator slot opening. To perform the analytical prediction process in the polar coordinate system, these regions should be transformed into the appropriate subdomains. The last four regions can be transformed into the subdomains with the required shape based on the existing method. The rotor slot cannot be treated as a single subdomain, for the shape of which is irregular. Herein, the PM and vacuum region in the rotor slot is divided into several fan‐shaped subdomains. The division method is described clearly. Then, the boundary conditions alongside the interface between adjacent subdomains are derived based on function transformation. On this basis, the open‐circuit magnetic field of the IPM machine can be predicted. The magnetic field of the 6p/36 s V‐shaped IPM machine is obtained by the proposed method, finite element method simulation, and experiment, respectively. Additionally, the comparison results verify the accuracy and efficiency of the proposed method.

Overheating and the resultant tube failures of boiler high temperature heating surfaces such as waterwall is one of the sore major problems affecting the safe operation of coal-fired power generating units. Boiler tube overheating generally occurs at some localized areas of boiler heating surfaces. To alleviate tube overheating and avoid the resultant tube failures, it’s necessary to monitor the tube temperature distribution in real-time to make preventive boiler operation adjustment. Due to the limitation of measurement method and the huge time cost of numerical method, currently there are still lack of methods that can realize the real-time prediction of waterwall tube temperature distribution during boiler operation. Therefore, this paper integrated the coupled heat transfer model with neural network and established a typical database of a 350 MW supercritical boiler using the coupled model, which contains 220 different typical boiler operating cases generated by adjusting 46 key operating parameters. Then, 4 400 expansion cases were derived at extremely time cost by the quick expansion method proposed in this paper. The deep neural network model was then constructed with 46 boiler operating parameters and waterwall coordinates as the model input and the tube temperature at the corresponding locations as the output. The DNN model was trained based on the comprehensive database containing 220 typical cases and 4 400 expansion cases. The MSE of the DNN model on validation set was only 0.005 3, the AUC5 was 0.988 and the calculation time was within 0.1 s. It illustrates that the data-driven model realized the real-time prediction of the waterwall tube temperature distribution over the entire boiler operating conditions by means of generalizing the numerical simulation results of finite cases. In addition, a quick database expansion method was proposed to address the problem that the heat transfer deterioration is difficult to be accurately predicted due to the insufficient data of the heat deterioration, and the prediction accuracy of the heat deterioration problem was significantly improved. Both the accuracy and the response speed of the model meet the demand of coal-fired plants for a real-time monitoring of tube temperature distribution.

Static stretching (SS) may reduce maximal muscle force and power output, while short-duration, high-intensity conditioning contractions (CC) have the potential to increase force and power output. However, the precise effects of CC on athletic performance and lower limb muscle coordination after SS are not yet fully understood. This investigation sought to explore the effects of SS (four sets of 30 seconds each) and its combination with CC (10 repetitive drop jumps), denoted as SC, on the synergy patterns of key lower limb muscles and jump performance during squat jumps (SJ) executed at two distinct knee joint starting angles (90° and 120°). Eleven participants were randomly assigned to three experimental conditions, with each condition encompassing three SJs at both angles. A three-dimensional motion capture system, force platform, and electromyography (EMG) system were employed to quantify jump height, extract ground contact time, and perform non-negative matrix factorization. Our findings revealed that at a knee joint starting angle of 120°, both SS and SC altered the weighting of the five major muscles (cosine similarity: SS: r = 0.897; SC: r = 0.767) and augmented the activity strength of the primary synergy (SS: 59.6%; SC: 10.48%). Additionally, SC demonstrably advanced the phase shift (90°: 14%; 120°: 61%). Notably, neither SS nor SC exerted a statistically significant influence on jump height (p > 0.05). However, SS significantly increased ground contact time (p = 0.029). In conclusion, at a knee joint angle of 120°, both SS and CC were observed to alter lower limb muscle synergy patterns and influence ground contact time. While SS led to an increase in ground contact time, CC effectively countered this rise. These findings suggest that athletes in disciplines demanding rapid movements might benefit from omitting SS in isolation during warm-ups or consider combining SS with CC to optimize performance.

[Objective] Mining and urbanization have transformed the ecological and socioeconomic aspects of coal resource-based cities. This study aimed to measure the spatial characteristics of ecosystem services supply and demand matching in coal resource-based cities based on the urban-mining-rural tri-structure and to simulate future scenarios, and constructed the ecological protection and urban development pattern of Huainan City based on the supply and demand of ecosystem services. [Methods] This study focused on Huainan, a typical mature coal resource-based city in Anhui Province. Using land use data from 2005 to 2020, the PLUS model simulated future land changes in Huainan under four scenarios: natural, urban development, mining development, and ecological protection. The InVEST model then evaluated the supply-demand matching of six ecosystem services for 2035. [Results] (1) By 2035, the natural scenario increased construction land, while other lands decreased. Urban development significantly expanded urban land. Mining development boosted mining and subsidence areas. Ecological protection enhanced cropland, forest, grass, and water areas and construction land increase slowly. (2) Urban and mining scenarios improved matching for carbon sequestration and erosion prevention compared to the natural scenario., while ecological protection scenario enhanced water production, recreation and tourism, water purification, and food supply. (3) Urban development scenario expanded low matching degree areas but stimulated economic growth, whereas ecological protection scenario improved overall supply-demand balance and increased ecological land [Conclusion] The ecological protection scenario optimized supply-demand matching, while urban development degraded it but stimulated the economic growth of the Huainan City. The economic protection pattern of “one axis, three corridors, and multiple cores” and the urban development system of “one main, one auxiliary, and multiple nodes” are constructed. This study offers a foundation for balanced development in coal resource-based cities.

Abstract Phototherapy can offer a safe and non-invasive solution against infections, while promoting wound healing. Conventional phototherapeutic devices are bulky and limited to hospital use. To overcome these challenges, we developed a wearable, flexible red and blue LED (r&bLED) patch controlled by a mobile-connected system, enabling safe self-application at home. The patch exhibits excellent skin compatibility, flexibility, and comfort, with high safety under system supervision. Additionally, we synthesized a sprayable fibrin gel (F-gel) containing blue light-sensitive thymoquinone and red light-synergistic NADH. Combined with bLED, thymoquinone eradicated microbes and biofilms within minutes, regardless of antibiotic resistance. Furthermore, NADH and rLED synergistically improved macrophage and endothelial cell mitochondrial function, promoting wound healing, reducing inflammation, and enhancing angiogenesis, as validated in infected diabetic wounds in mice and minipigs. This innovative technology holds great promise for revolutionizing at-home phototherapy for chronic infected wounds.

Abstract GWASs have linked the 3p21.1 locus, which is associated with the expression levels of NEK4, to bipolar disorder. Here, we use integrative analyses of GWAS statistics and eQTL annotations to establish that elevated NEK4 expression in the hippocampus is associated with an increased risk of bipolar disorder. To further study this association, we generate transgenic male mice that conditionally overexpress NEK4 in the pyramidal neurons of the adult forebrain, or use AAV to overexpress NEK4 in the dorsal hippocampus. Compared to the control mice, male mice of both strains exhibit a shift from a diurnal anxiety state to a nocturnal normal or anxiolytic-like state. Overexpression of NEK4 also affects the circadian fluctuations in dendritic spine morphology and synaptic structure. Furthermore, we show that treatment with lithium ameliorates the effects of NEK4 overexpression in male mice. We then perform phosphoproteomic analyses to demonstrate that the diurnal and nocturnal phosphoproteomic profiles of male control and NEK4 overexpressing mice are different. These results suggest that male mice with different NEK4 expression levels may recapitulate some of the core features observed in patients with bipolar disorder, indicating that interruption of the homeostatic dynamics of synapses may underlie the emotional swings in bipolar disorder.

Abstract Background Given the characteristics of the rehabilitation therapy specialty and the drawback of the traditional didactic teaching approach, we developed the innovative teaching approach from the students’ perspective using the person–environment–occupation (PEO) model. The new model was developed from the original PEO model to be applied in pedagogical contexts and tailored to the characteristics of an application-oriented specialty, such as rehabilitation therapy. The present study aimed to examine the perceived effectiveness of the PEO innovative teaching model applied to rehabilitation therapy students. Methods A pre–post descriptive study was conducted to compare the perceived effectiveness of the PEO innovative teaching model for two consecutive student cohorts. A purposive sampling method was used to recruit students from two cohorts of junior medical students majoring in rehabilitation therapy in the spring semesters of 2020 and 2021. A questionnaire was developed to evaluate the perceived effectiveness of the PEO innovative teaching model. SPSS version 26.0 was used to perform data analysis. Results A total of 112 students were included in the study and completed both pre- and post-tests. Of 112 received questionnaires, 101 were considered as valid questionnaires after the quality check (effective rate 90.18%). In the 2020 and 2021 cohorts, students rated the PEO innovative teaching model significantly higher than the didactic teaching approach in the following aspects: the teaching content is highly professional and valuable; the course is extensively expounded; the clinical reasoning is strengthened; problem-solving ability is developed; communication skills are improved; and teamwork skills are developed. Conclusion The PEO innovative teaching model was perceived to be an effective teaching strategy to enhance students’ academic performance. In addition, three core skills including clinical reasoning, problem-solving ability, and communication skills were improved by the PEO innovative teaching model.

Understanding the response of solid combustibles under high radiant fluxes is critical in predicting the thermal damage from extreme scenarios. Unlike the more moderate radiant fluxes in conventional hydrocarbon fires, extreme events such as strong explosion, concentrated sunlight and directed energy can generate dynamic radiant fluxes at the MW/m2 level, creating a unique threat to materials. This study investigates the pyrolysis and spontaneous ignition behaviors of corrugated cardboard by using both experimental and numerical methods, under 10-cm dynamic high radiant fluxes ranging from 0.2 to 1.25 MW/m2 for 10 s. The spontaneous ignition process at dynamic high radiant fluxes was recorded and quantified. Two ignition modes were found at the critical radiant flux of 0.4 MW/m2, namely hot-gas spontaneous ignition and hot-residue piloted ignition. The latter is not the focus of this paper due to its extremely small probability of occurrence. The research reveals that the increase in flux intensity induces shorter delay times for both pyrolysis and ignition, lower ignition energy density, along with a corresponding rise in the critical mass flux and surface temperature at ignition moment. The simulation results are generally aligned with the experimental findings, despite some divergences may be attributed to model simplifications and parameter assumptions. The work contributes to a deeper insight into material behavior under extreme radiation, with valuable implications for fire safety and hazard assessment.

Abstract Navigating toward destinations with rewards is a common behavior among animals. The ventral tegmental area (VTA) has been shown to be responsible for reward coding and reward cue learning, and its response to other variables, such as kinematics, has also been increasingly studied. These findings suggest a potential relationship between animal navigation behavior and VTA activity. However, the deep location and small volume of the VTA pose significant challenges to the precision of electrode implantation, increasing the uncertainty of measurement results during animal navigation and thus limiting research on the role of the VTA in goal-directed navigation. To address this gap, we innovatively designed and fabricated low-curvature microelectrode arrays (MEAs) via a novel backside dry etching technique to release residual stress. Histological verification confirmed that low-curvature MEAs indeed improved electrode implantation precision. These low-curvature MEAs were subsequently implanted into the VTA of the rats to observe their electrophysiological activity in a freely chosen modified T-maze. The results of the behavioral experiments revealed that the rats could quickly learn the reward probability corresponding to the left and right paths and that VTA neurons were deeply involved in goal-directed navigation. Compared with those in no-reward trials, VTA neurons in reward trials presented a significantly greater firing rate and larger local field potential (LFP) amplitude during the reward-consuming period. Notably, we discovered place fields mapped by VTA neurons, which disappeared or were reconstructed with changes in the path–outcome relationship. These results provide new insights into the VTA and its role in goal-directed navigation. Our designed and fabricated low-curvature microelectrode arrays can serve as a new device for precise deep brain implantation in the future.

Abstract As one of the mainstream biodegradable materials, poly(butylene adipate-co-terephthalate) (PBAT) foams offer a sustainable alternative to traditional plastic foams, effectively reducing environmental pollution. However, the high cost and poor mechanical performance of PBAT foams impede their practical application. Herein, the glycidyl methacrylate-grafted biomass lignin (GML) was used to produce a PBAT/GML composite foam with good foaming performance and mechanical properties at high lignin-filling amounts by twin-screw melting free radical polymerization and supercritical CO2 foaming process. The compatibility of GML in the PBAT matrix was improved due to the formation of ester bonds in modified lignin, endowing the PBAT/GML (PGML) composite foam with exceptional foaming performance. Additionally, the mechanical properties of PGML composite foam were remarkably enhanced due to the introduction of the abundant aromatic structures of GML and the construction of a stable covalent crosslinking network. The compressive strengths and compression modulus of the PGML foam were improved by 2.53 times and 2.47 times, while its bending strength and bending modulus were improved by 1.27 times and 3.92 times compared to the neat PBAT. This research affords a new strategy for developing low-cost biodegradable biomass PBAT/lignin composite foam materials with good foaming performance and mechanical properties. Graphical abstract

The coupling factors of geological hazards such as rainfall are sufficient conditions for the occurrence of geological hazards. In this study, the distribution characteristics of Wuhan's geological disasters and their relationship with heavy rainfall by cluster analysis were investigated using multiple regression and other methods, based on Wuhan's geological disaster data, rainfall live grid data, and geological environment foundation during 2016-2022. Meanwhile, multi-source data fusion, machine learning, and other methods were employed to dynamically assess the vulnerability of geological disasters. The results are as follows. About 76.49% of geological disasters in Wuhan are induced by rainfall. The impact period of heavy rainfall on geological disasters in Wuhan is 13 days, and the possibility of geological disasters during the impact period is as high as 87.69%. A meteorological risk prediction model for geological disasters in Wuhan based on effective rainfall was established. This model can achieve a dynamic assessment of geological disaster-prone zoning by introducing the latest geological disaster occurrence, geological environment, and rainfall information. The 24-hour average accuracy rate can reach 79.51%. In the application of geological disaster prediction in 2022, the recognition rate reaches 90%, which shows good geological disaster prediction capabilities.

Abstract Parity-time (PT) symmetry is an active research area that provides a variety of new opportunities for different systems with novel functionalities. For instance, PT symmetry has been used in lasers and optoelectronic oscillators to achieve single-frequency lasing or oscillation. A single-frequency system is essentially a static PT-symmetric system, whose frequency is time-invariant. Here we investigate time-variant PT symmetry in frequency-scanning systems. Time-variant PT symmetry equations and eigenfrequencies for frequency-scanning systems are developed. We show that time-variant PT symmetry can dynamically narrow the instantaneous linewidth of frequency-scanning systems. The instantaneous linewidth of a produced frequency-modulated continuous-wave (FMCW) waveform is narrowed by a factor of 14 in the experiment. De-chirping and radar imaging results also show that the time-variant PT-symmetric system outperforms a conventional frequency-scanning one. Our study paves the way for a new class of time-variant PT-symmetric systems and shows great promise for applications including FMCW radar and lidar systems.

Abstract The immunosuppressive tumor microenvironment (TME) significantly inhibits the effective anti-tumor immune response, greatly affecting the efficacy of immunotherapy. Most tumor-associated macrophages (TAMs) belong to the M2 phenotype, which contributes significantly to the immunosuppressive effects in non-small cell lung cancer (NSCLC) TME. The interaction between signal regulatory protein α (SIRPα) expressed on macrophages and CD47, a transmembrane protein overexpressed on cancer cells, activates the "eat-me-not" signaling pathway, inhibiting phagocytosis. In this study, a folic acid (FA)-modified ultrasound responsive gene/drugs delivery system, named FA@ PFP @ Fe3O4 @LNB-SIRPα siRNA (FA-PFNB-SIRPα siRNA), was developed using 1,2-dioleoacyl-3-trimethylammonium-propane (DOTAP), FA-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino (polyethylene glycol)2000] (DSPE-PEG2000-FA), cholesterol, and perfluoropentane (PFP), for the delivery of siRNA encoding SIRPα mRNA and immune adjuvant Fe3O4 nanoparticles. Under ultrasound conditions, the nanobubbles effectively transfected macrophages, inhibiting SIRPα mRNA and protein expression, promoting the phagocytosis of TAMs, and synergistically reversing M2 polarization. This system promotes the infiltration of T cells, enhances the proliferation and activation of cytotoxic T cells, and inhibits the infiltration of immunosuppressive cells in tumor tissues. Administration of FA-PFNB-SIRPα siRNA combined with ultrasound significantly inhibits NSCLC progression. The study highlights the potential of ultrasound nanotechnology-enabled delivery of SIRPα siRNA and Fe3O4 as an effective strategy for macrophage-based immunotherapy to reshape the immunosuppressive TME for cancer therapy. Graphical Abstract

Abstract Background The purpose of this study was to evaluate the advantages of robot navigation system-assisted intramedullary nail treatment for humeral shaft fractures and compare it’s efficacy with that of traditional surgical intramedullary nail treatment. Materials and methods This was a retrospective analysis of patients with humeral shaft fractures who received intramedullary nail treatment at our centre from March 2020 to September 2022. The analysis was divided into a robot group and a traditional surgical group on the basis of whether the surgery involved a robot navigation system. We compared the baseline data (age, sex, cause of injury, fracture AO classification, and time of injury-induced surgery), intraoperative conditions (surgery time, length of main nail insertion incision, postoperative fluoroscopy frequency, intraoperative bleeding), fracture healing time, and shoulder joint function at 1 year postsurgery (ASES score and Constant–Murley score) between the two groups of patients. Results There was no statistically significant difference in the baseline data or average fracture healing time between the two groups of patients. However, the robotic group had significantly shorter surgical times, longer main nail incisions, fewer intraoperative fluoroscopies, and less intraoperative blood loss than did the traditional surgery group (P

Abstract Tamoxifen (TAM) resistance is a major challenge in treating oestrogen receptor-positive (ER+) breast cancers. It is possible that the H2S synthase cystathionine-γ-lyase (CSE), which has been previously shown to promote tumour growth and metastasis in other cancer cells, is involved in this resistance. Therefore, we investigated CSE's role and potential mechanisms in TAM-resistant breast cancer cells. First, we examined the effect of CSE expression on TAM sensitivity and resistance in MCF7 (breast cancer) cells. The findings revealed that CSE was directly associated with TAM sensitivity and involved in TAM resistance in ER+ breast cancer cells, indicating that it may be useful as a biomarker. Next, we wanted to determine the molecular mechanism of CSE's role in TAM resistance. Using cell migration, co-immunoprecipitation, western blotting, and cell viability assays, we determined that the CSE/H2S system can affect the expression of PPARγ by promoting the sulfhydrylation of PPARγ, which regulates the transcriptional activity of ACSL1. ACSL1, in turn, influences STAT3 activation by affecting the phosphorylation, palmitoylation and dimerization of STAT3, ultimately leading to the development of TAM resistance in breast cancer. Finally, we examined the effect of CSE inhibitors on reducing drug resistance to determine whether CSE may be used as a biomarker of TAM resistance. We observed that the novel CSE inhibitor I194496 can reverse TAM resistance in TAM-resistant breast cancer via targeting the PPARγ/ACSL1/STAT3 signalling pathway. Overall, our data indicate that CSE may serve as a biomarker of TAM resistance and that the CSE inhibitor I194496 is a promising candidate for combating TAM resistance.

Abstract Objectives To analyze the lung structure of small airway dysfunction (SAD) defined by spirometry and parametric response mapping (PRM) using high-resolution computed tomography (HRCT), and to analyze the predictive factors for SAD. Methods A prospective study was conducted with 388 participants undergoing pulmonary function test (PFT) and inspiratory-expiratory chest CT scans. The clinical data and HRCT assessments of SAD patients defined by both methods were compared. A prediction model for SAD was constructed based on logistic regression. Results SAD was defined in 122 individuals by spirometry and 158 by PRM. In HRCT visual assessment, emphysema, tree-in-bud sign, and bronchial wall thickening have higher incidence in SAD defined by each method. (p

Abstract Many mammal species have declining populations, but the consequences of small population size on the genomic makeup of species remain largely unknown. We investigated the evolutionary history, genetic load and adaptive potential of the Cat Ba langur (Trachypithecus poliocephalus), a primate species endemic to Vietnam’s famous Ha Long Bay and with less than 100 living individuals one of the most threatened primates in the world. Using high-coverage whole genome data of four wild individuals, we revealed the Cat Ba langur as sister species to its conspecifics of the northern limestone langur clade and found no evidence for extensive secondary gene flow after their initial separation. Compared to other primates and mammals, the Cat Ba langur showed low levels of genetic diversity, long runs of homozygosity, high levels of inbreeding and an excess of deleterious mutations in homozygous state. On the other hand, genetic diversity has been maintained in protein-coding genes and on the gene-rich human chromosome 19 ortholog, suggesting that the Cat Ba langur retained most of its adaptive potential. The Cat Ba langur also exhibits several unique non-synonymous variants that are related to calcium and sodium metabolism, which may have improved adaptation to high calcium intake and saltwater consumption.

Abstract Objective To exploit the combination diagnostic performance of serum microRNA-134-5p (miR-134-5p) and color Doppler ultrasound in patients with endometriosis patients. Methods Quantitative real time polymerase chain reaction (qRT-PCR) analysis was applied to measure relative abundance of miR-134-5p in serum of patients with endometriosis and gynecological benign diseases. Calculation of uterine artery blood flow parameters was conducted using Color Doppler ultrasound. Receiver operating characteristic (ROC) curve was established to evaluate the diagnostic capacity of miR-134-5p and Doppler parameters. Kaplan-Meier method was used for the analysis of recurrence-free survival rate. Results Compared with the control group, serum miR-134-5p expression was remarkably diminished in endometriosis patients (P

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Due to the modal disparities between synthetic aperture radar (SAR) and optical images, effectively extracting modality-shared structural features is crucial for achieving accurate registration results. Considering that point features have a limited ability to describe the common structural features between SAR and optical images, graph topology is introduced to extract edge features to derive modality-shared structural features for reliable registration. In this article, we propose a registration network for multifeature alignment and matching (MFAM-RegNet) between SAR and optical images, which includes a multifeature alignment module (MFAM) and a multifeature matching module (MFMM). First, we construct an MFAM to extract and align point and edge features to mine modality-shared structural features. In MFAM, point features are extracted by graph neural networks, and edge features are constructed by the feature similarity between two keypoints. Inspired by graph matching, we design linear and quadratic contrastive learning to mine the correspondence of point and edge features of intramodal and intermodal images. Second, speckle noise in SAR images inevitably leads to some noise labels, which decreases the accuracy and robustness of our supervised algorithm. Therefore, we design an MFMM to modify noise labels and use bidirectional matching for robust matching. According to the essential relationships of features mined by the momentum contrastive learning strategy, the labels are adaptively modified to reduce the influence of the incorrect labels on the model's performance and achieve more stable matching results. Experiments on three publicly available SAR and optical datasets indicate that our proposed MFAM-RegNet outperforms the existing state-of-the-art algorithms.

BACKGROUND AND AIMS: Neuroprotection plays an important role in the treatment of brain disorders. In recent years, studies using rat models and clinical trials have demonstrated the positive effects of hydrogen treatment on neurological disorders and brain injuries. Hence, it is of great significance to shed light on this issue. In this article, CiteSpace is employed for visualization and bibliometric analysis of the research frontiers and evolving trends related to the neuroprotective effect of hydrogen. METHODS: All articles published from 2009 to 2023 that discussed the neuroprotective effects of hydrogen in cerebrovascular diseases were retrieved from the Web of Science. Using CiteSpace, a visualization analysis was conducted on aspects such as countries, institutions, authors, keywords, and Co cited references, which enables an intuitive observation of current research hotspots. RESULTS: After manual screening, a total of 106 articles were retrieved. Over time, The number of publications has increased annually. Regarding national contributions, the top three countries with the highest number of publications include China, the United States, and Japan. The Second Military Medical University is the institution that publishes the most articles and has significant influence in the field of hydrogen neuroprotection. Sun, Xuejun and Domoki, Ferenc were the most productive. The most common keywords include hydrogen, oxidative stress, inflammation, and apoptosis. Potential areas of focus for future research consist of early brain injury, hydrogen, ischemia-reperfusion injury and hypothermia treatment. CONCLUSION: The bibliometric study presented herein offers insights into the current status and trends of research on hydrogen in the field of cerebrovascular diseases. Future research trends suggest that hydrogen contributes significantly to the cerebrovascular domain through its anti-inflammatory, antioxidative, and anti-apoptotic mechanisms. This study can aid researchers in identifying hot topics and exploring new research directions.

Abstract Background The reference values of eNO have certain differences among people of different countries and races. We aimed to obtain the reference value of eNO in healthy children and adolescents (6–18 years old) in China and to explore the associations between the reference values with ages, gender, heights, BMI, and regions. Methods We measured FeNO50 levels in 5949 healthy Chinese children and adolescents, FeNO200 and CaNO levels in 658 participants from 16 provinces of 7 administrative areas in China aged 6–18. All persons were studied after obtaining informed consent from children and their parents. Results The mean FeNO50 of 5949 Chinese children and adolescents aged 6–18 years was 14.1 ppb, with a 95% confidence interval of 1-38.1 ppb. The mean FeNO200 of 658 persons was 6.9 ppb with a 95% upper confidence interval of 15.0 ppb, and the mean CaNO was 3.0 ppb with a 95% upper confidence interval of 11.2 ppb. In the 6–11 age group, age and height were correlated with the logarithm of FeNO50 (P 0.05). The logarithm of CaNO was correlated with gender (P

Abstract Objective To analyze the spatial autocorrelation and spatiotemporal clustering characteristics of severe fever with thrombocytopenia syndrome(SFTS) in Anhui Province from 2011 to 2023. Methods Data of SFTS in Anhui Province from 2011 to 2023 were collected. Spatial autocorrelation analysis was conducted using GeoDa software, while spatiotemporal scanning was performed using SaTScan 10.0.1 software to identify significant spatiotemporal clusters of SFTS. Results From 2011 to 2023, 5720 SFTS cases were reported in Anhui Province, with an average annual incidence rate of 0.7131/100,000. The incidence of SFTS in Anhui Province reached its peak mainly from April to May, with a small peak in October. The spatial autocorrelation results showed that from 2011 to 2023, there was a spatial positive correlation(P

Abstract Prokaryotic Argonautes (pAgos) provide bacteria and archaea with immunity against plasmids and viruses. Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids, while inactive pAgos lacking catalytic residues employ auxiliary effectors, such as nonspecific nucleases, to trigger abortive infection upon detection of foreign nucleic acids. Here, we report a unique group of catalytically active pAgo proteins that frequently associate with a phospholipase D (PLD) family protein. We demonstrate that this particular system employs the catalytic center of the associated PLD protein rather than that of pAgo to restrict plasmid DNA, while interestingly, its immunity against a single‐stranded DNA virus relies on the pAgo catalytic center and is enhanced by the PLD protein. We also find that this system selectively suppresses viral DNA propagation without inducing noticeable abortive infection outcomes. Moreover, the pAgo protein alone enhances gene editing, which is unexpectedly inhibited by the PLD protein. Our data highlight the ability of catalytically active pAgo proteins to employ auxiliary proteins to strengthen the targeted eradication of different genetic invaders and underline the trend of PLD nucleases to participate in host immunity.

For Nd2Fe14B/α-Fe nanocomposite magnets, which exhibit great superiority in theoretical energy products, it is a great challenge to obtain controlled nano-scale microstructural features while eliminating the harmful metastable phases due to the general metastable fabrication methods. Here, we report a strategy to control the nano-scale features and simultaneously eliminate metastable phases for Nd2Fe14B/α-Fe nanocomposites through low-temperature pre-deformation of amorphous alloys combined with subsequent thermal annealing. The resultant bulk Nd2Fe14B/α-Fe nanostructure exhibits desired ultrafine grain sizes, ∼20 nm for soft-magnetic α-Fe phase with a high fraction of Vα-Fe ≈ 30 wt% and ∼33 nm for hard-magnetic Nd2Fe14B phase. The desired microstructure results in a larger coercivity (Hci = 4.1 kOe) and higher saturation magnetization (Ms = 1.51 T) compared to those (Hci = 3.3 kOe and Ms = 1.35 T) of the counterpart without pre-deformation, contributing to a high energy density of 26.3 MGOe. This energy density is 200% larger than that of the counterpart without pre-deformation and far beyond that (around 20 MGOe) of previously reported bulk Nd2Fe14B/α-Fe nanocomposites with Vα-Fe ≥ 20 wt%. The superior property stems from the purposely introduced low-temperature pre-deformation that changed the structure and local chemistry of the amorphous alloy, facilitating the decomposition of harmful metastable phases and the formation of Nd2Fe14B phase during annealing processes, which lowers the temperature, from 750 to 700 °C for producing the Nd2Fe14B/α-Fe nanostructure and thus yields ultrafine nanograins. These results demonstrate an effective means to prepare high-performance bulk Nd2Fe14B/α-Fe nanocomposite magnets.

Abstract We include the quark to gluon and gluon to quark shock-wave transition operators into the small Bjorken-x evolution equations for helicity in the flavor-singlet channel derived earlier in [1–3]. While such transitions do not affect the large-N c version of the evolution equations for helicity, the large-N c & N f equations are affected. (N c and N f are the numbers of quark colors and flavors, respectively.) We derive the corresponding corrected large-N c & N f equations for the polarized dipole amplitudes contributing to the flavor-singlet quark and gluon helicity distributions in the double-logarithmic approximation (DLA), resumming powers of α s ln2(1/x) with α s the strong coupling constant. We solve these equations iteratively and extract the polarized splitting functions up to four loops. We show that our splitting functions agree with the fixed-order perturbative calculations up to and including the existing three-loops results [4–7]. Similar to the large-N c helicity evolution in the shock-wave approach [8], our large-N c & N f small-x splitting functions agree with those obtained in the infrared evolution equations framework from [9, 10] up to three loops, but appear to slightly disagree at four loops.

Titanium hydride (TiH2), a promising high-energy additive, is doped into PTFE/Al to optimize the energy output structure of the reactive jet and strive for better aftereffect damage ability to the target. Six types of PTFE/Al/TiH2 reactive liners with different TiH2 content are prepared by the molding and sintering method. The energy release characteristics of PTFE/Al/TiH2 reactive jet are tested by the transient explosion energy test, and are characterized from pressure and temperature. The reaction delay time, pressure history, and temperature history of the energy release process are obtained, then the actual value of released energy and reaction efficiency of the reactive jet are calculated. The results show that the peak pressure and temperature of the PTFE/Al/TiH2 jet initially increase and then decrease with increasing TiH2 content. When the TiH2 content is 10%, the actual value of released energy and reaction efficiency increased by 24% and 6.4%, respectively, compared to the PTFE/Al jet. The reaction duration of the reactive material is significantly prolonged as the TiH2 content increased from 0% to 30%. Finally, combined with the energy release behaviors of PAT material and the dynamic deformation process of liner, the enhancement mechanism of TiH2 on energy release of the reactive jet is expounded.

Abstract We investigated the potential correlation between miR‐223 and NAcHT, LRR, and PYd domain‐containing protein 3 (NLRP3) in the context of renal ischemia‐reperfusion injury (RIRI), which is a leading cause of acute renal failure with significant mortality rates. Additionally, miR‐223 has been implicated in renal inflammation, further highlighting its relevance to this study. C57BL/6 male mice were used as RIRI models. After successful modeling, pathological examinations and serum creatinine and miR‐223 levels were tested. Pro‐inflammatory cytokine (IL‐1β, IL‐6, IL‐8, NLPR3, TLR4) expression was detected in mice by western blot (kidney tissue) and enzyme‐linked immunosorbent assay (serum). HK‐2 cells were used for in vitro experiments. A hypoxia/reoxygenation (H/R) model was used, and miR‐223 and pro‐inflammatory cytokine levels were detected using PCR and western blot assays, respectively. A dual‐luciferase reporter assay was conducted to confirm the binding of miR‐223 to NLPR3. Next, NLRP3 was knocked down to determine whether the anti‐inflammatory function of miR‐223 is dependent on NLRP3. MiR‐223 expression was lower in RIRI mice than in the sham operation group. The level of miR‐223 negatively correlated with serum creatinine levels and the severity of tubule injury. Increased proinflammatory cytokine levels in RIRI mice were observed. In vitro, miR‐223 alleviated the inflammatory response in H/R treated cells by inhibiting proinflammatory cytokines. Dual‐luciferase reporter and western blot assays confirmed the binding of miR‐223 to NLRP3. NLRP3 knockdown reversed the anti‐inflammatory effects of miR‐223 in HK‐2 cells. MiR‐223 plays an anti‐inflammatory role in RIRI by targeting NLRP3 to repress pro‐inflammatory factors.

Abstract The construction of large reservoirs has modified the process of water and sediment transport downstream, resulting in changes in the morphology of the river cross-section. Changes in water and sand transport and cross-sectional morphology are reflected in the rating curve at the cross-section. This study analyzed the variations in the rating curve at the Huayuankou (HYK) section and their influencing factors, and conducted water level predictions based on this relationship. The findings revealed that while the annual mean water level has shown a declining tendency over the past 20 years, the annual mean discharge has shown a constant pattern. The rating curve at this stretch narrowed from a rope-loop type curve in its natural condition to a more stable single curve as a result of the construction of the dam upstream of the HYK section. The effect of pre-flood section morphology and the water–sediment process on the scattering degree of the rating curve is inverse; increasing roughness and hydraulic radius decreases scattering degree, while increasing sand content and sand transport rate increases scattering degree. Using the measured data from 2020 as an example, the feasibility of predicting cross-sectional water levels using the rating curve was verified. The prediction results were accurate when the flow was between 1000 and 2800 m3/s; However, when the flow was between 2800 and 4000 m3/s, the forecast results were typically slightly lower than the measured values. Overall, the method demonstrates good predictive accuracy. Insight from the method can be used to predict water levels to better inform decision making about water resources management, and flood emergency response in the lower Yellow River.

Abstract Aim The purpose of the present study was to evaluate the diagnostic performance of serum miR-4534 combined with Transvaginal Color Doppler Ultrasound (TVCDS) in cervical cancer patients. Methods Blood samples from 126 patients with cervical cancer and 83 patients with benign uterine lesions were retrospectively analyzed. Quantitative real time polymerase chain reaction (qRT-PCR) was applied to examine the relative abundances of serum miR-4534 in cervical cancer based on a case–control study. Chi-square test was adopted to analyze the association between serum miR-4534 and other clinicopathological factors. The blood flow of cervix was examined using TVCDS, and the blood flow resistance index (RI) of cervix was summarized. Receiver operating characteristic (ROC) curves were plotted to explore the diagnostic capacity of serum miR-4534 combined with blood flow RI. Logistic regression was employed to analyze the risk factors of cervical cancer. Results Serum miR-4534 was distinctly increased in the study group compared with the control group (P

Abstract Cytokinins, which play crucial roles in shoot development, substantially affect grain yield. In rice, the OsRopGEF10-OsRAC3 module is associated with cytokinin signaling and crown root development. However, the effects of RopGEF-mediated cytokinin signaling on rice shoot development and grain yield remain unclear. In this study, we investigated the role of OsRopGEF10 in SAM development and the underlying mechanism. We showed that overexpression of OsRopGEF10 inhibited SAM and panicle development, leading to decreased grain yield. Intriguingly, the overexpression of a specific amino acid mutant of OsRopGEF10, designated gef10-W260S, was found to promote panicle development and grain yield. Further analysis using the BiFC assay revealed that the gef10-W260S mutation disrupted the recruitment of rice histidine phosphotransfer proteins (OsAHP1/2) to the plasma membrane (PM), thereby promoting cytokinin signaling. This effect was corroborated by a dark-induced leaf senescence assay, which revealed an increased cytokinin response in the gef10-W260S ectopic expression lines, whereas the overexpression lines presented a suppressed cytokinin response. Moreover, we revealed that the enhanced panicle development in the gef10-W260S lines was attributable to the upregulated expression of several type-B response regulators (RRs) that are crucial for panicle development. Collectively, these findings revealed the negative regulatory function of OsRopGEF10 in the development of the shoot apical meristem (SAM) via interference with cytokinin signaling. Our study highlights the promising role of OsRopGEF10 as a potential target for regulating SAM and panicle development in rice, revealing a valuable breeding strategy for increasing crop yield.

Achieving diffraction-limited performance in fourth-generation synchrotron radiation sources demands monochromator crystals that can preserve the wavefront across an unprecedented extensive range. There is an urgent need for techniques of absolute crystal diffraction wavefront measurement. At the Beijing Synchrotron Radiation Facility (BSRF), a novel edge scan wavefront metrology technique has been developed. This technique employs a double-edge tracking method, making diffraction-limited level absolute crystal diffraction wavefront measurement a reality. The results demonstrate an equivalent diffraction surface slope error below 70 nrad (corresponding to a wavefront phase error of 4.57% λ) r.m.s. within a nearly 6 mm range for a flat crystal in the crystal surface coordinate. The double-edge structure contributes to exceptional measurement precision for slope error reproducibility, achieving levels below 15 nrad (phase error reproducibility < λ/100) even at a first-generation synchrotron radiation source. Currently, the measurement termed double-edge scan (DES) has already been regarded as a critical feedback mechanism in the fabrication of next-generation crystals.

Background: Hyperbaric oxygen (HBO) therapy is widely used to treat bone defects, but the correlation of high oxygen concentration and pressure to osteogenesis is unclear. Methods: Bilateral monocortical tibial defect surgeries were performed on 12-week-old Prrx1-Cre; Rosa26-tdTomato and Prrx1-Cre; Piezo1fl/+ mice. Daily HBO treatment was applied on post-surgery day (PSD) 1–9; and daily mechanical loading on tibia was from PSD 5 to 8. The mice were euthanized on PSD 10, and bone defect repair in their tibias was evaluated using μCT, biomechanical testing, and immunofluorescence deep-tissue imaging. The degree of angiogenesis–osteogenesis coupling was determined through spatial correlation analysis. Bone marrow stromal cells from knockout mice were cultured in vitro, and their osteogenic capacities of the cells were assessed. The activation of genes in the Piezo1–YAP pathway was evaluated using RNA sequencing and quantitative real-time polymerase chain reaction. Results: Lineage tracing showed HBO therapy considerably altered the number of Prrx1+ cells and their progeny in a healing bone defect. Using conditional knockdown mice, we found that HBO stimulation activates the Piezo1–YAP axis in Prrx1+ cells and promotes osteogenesis–angiogenesis coupling during bone repair. The beneficial effect of HBO was similar to that of anabolic mechanical stimulation, which also acts through the Piezo1–YAP axis. Subsequent transcriptome sequencing results revealed that similar mechanosensitive pathways are activated by HBO therapy in a bone defect. Conclusion: HBO therapy promotes bone tissue regeneration through the mechanosensitive Piezo1–YAP pathway in a population of Prrx1+ osteogenic progenitors. Our results contribute to the understanding of the mechanism by which HBO therapy treats bone defects. The Translational Potential of this Article: Hyperbaric oxygen therapy is widely used in clinical settings. Our results show that osteogenesis was induced by the activation of the Piezo1–YAP pathway in osteoprogenitors after HBO stimulation, and the underlying mechanism was elucidated. These results may help improve current HBO methods and lead to the formulation of alternative treatments that achieve the same functional outcomes.

The general purpose plugin for deep reinforcement learning is a type of algorithm that can be attached to most native algorithms and is compatible with other kinds of plugins. Under different environments, the original algorithm forms different variants after adding appropriate plugins, and achieves better results in training speed and stability. According to the commonness of the general plugins in the training process, the variants were divided into six categories, including the general network model, intrinsic reward, experience replay, self-play, imitation learning, and curriculum learning. The general plugins commonly used in these six kinds of algorithms were reviewed, and their application scenarios and main functions in deep reinforcement learning were also briefly introduced. The future research priorities were put forward: 1) to improve the efficiency of experience utilization; 2)to design and train a general neural network architecture; 3)to improve the efficiency of algorithm exploration in sparse reward environment; 4)to improve the ability of the algorithm to deal with various emergencies in reality.

This paper explored students’ experiences in an international virtual student mobility (VSM) program at a Japanese national university implemented in collaboration with partner universities in the Asia Pacific region and Europe. Through students’ narratives, the study discerned how students perceive “mobility” and the concept of “international students” after participating in a virtual student mobility program. Findings revealed a tension between students’ understanding of “mobility,” official narratives, and students’ actual experiences. While VSM programs facilitate communication and knowledge exchange across borders and develop cross-cultural communications, prevailing binary definitions in student mobility, such as “inbound” vs. “outbound,” “domestic” vs. “international,” or “study abroad” vs. “internationalization at home,” limit VSM potential to be fully realized. This misalignment of the traditional understanding of student mobility that emphasizes place and borders challenges the official narrative of student mobility and urges educators to re-align and re-frame how we understand “international students.”

In this work, molten salt method was used to prepare highly dispersed graphitic carbon nitride(WSGCN), and chemical reduction method was used to load Cu nanoparticles on WSGCN to prepare Cu-WSGCN composites. FTIR, XRD, XPS, TEM, SEM, ICP-AES, UV-vis DRS, PL spectroscopy, ESR and EIS characterization methods were carried out to investigate the structure and photoelectric properties of the photocatalyst. The results show that compared with WSGCN, Cu-WSGCN has a larger light absorption range and a narrower band gap. In addition, the presence of Schottky barriers at the interface between Cu nanoparticles and WSGCN promotes charge transfer and separation of photogenerated carriers, which improves the photocatalytic ability. The uranium removal rate of Cu-WSGCN composite is relatively high(81.07 %) when the load of Cu nanoparticles is 1%. After three cycles of photocatalytic uranium reduction experiments, the uranium removal rate by 1%Cu-WSGCN can still reach 75.96%, which provides a useful reference for the development of novel materials with high efficiency photocatalytic removal of uranium.

Abstract Type I CRISPR-Cas systems are widespread and have exhibited high versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems, with a total gene size smaller than that of SpCas9, can be developed for transcriptional activation in human cells. The efficiency of the engineered I-F2 tool can match or surpass that of dCas9. Additionally, we create a base editor using the I-F2 Cascade, which induces a considerably wide editing window (~30 nt) with a bimodal distribution. It can expand targetable sites, which is useful for disrupting functional sequences and genetic screening. This research underscores the application of compact type I systems in eukaryotes, particularly in the development of a base editor with a wide editing window.