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Abstract Studies focusing on the kinematics of the ankle joint complex (AJC) have long been a key area of interest for biomechanists and orthopedic surgeons. However, it is not clear how additional weight-bearing walking affects the motion of the AJC compared to walking with a normal body weight (BW) or what adjustments the AJC would instinctively make to accommodate the additional load. To address this gap in knowledge, advanced dynamic biplane radiography combined with a model-based 2D-3D tracking technique was employed to elucidate the inherent kinematics of the AJC during the stance phase while walking with and without additional weight-bearing. It was found that walking with additional 50% body weight (BW + 50%) resulted in a greater dispersion of instantaneous axes of rotation in the talocrural and subtalar joints during the stance phase of gait. The talocrural joint is more plantarflexed and anteriorly translated during the early and late stance phases than during the midstance phases, which suggests that additional weight-bearing affects the stability of the AJC. Moreover, walking with BW + 50% showed that the center of rotation of the talocrural joint was positioned more superiorly and posteriorly during the foot flat to heel-off phase. This, accordingly, increases the ankle-foot gear ratio and the force of the dorsiflexors.

Abstract Background Assay of Transposase Accessible Chromatin Sequencing (ATAC-seq) is a high-throughput sequencing technique that detects open chromatin regions across the genome. These regions are critical in facilitating transcription factor binding and subsequent gene expression. Herein, we utilized ATAC-seq to identify key molecular targets regulating the development and progression of hepatocellular carcinoma (HCC) and elucidate the underlying mechanisms. Methods We first compared chromatin accessibility profiles between HCC and normal tissues. Subsequently, RNA-seq data was employed to identify differentially expressed genes (DEGs). Integrating ATAC-seq and RNA-seq data allowed the identification of transcription factors and their putative target genes associated with differentially accessible regions (DARs). Finally, functional experiments were conducted to investigate the effects of the identified regulatory factors and corresponding targets on HCC cell proliferation and migration. Results Enrichment analysis of DARs between HCC and adjacent normal tissues revealed distinct signaling pathways and regulatory factors. Upregulated DARs in HCC were enriched in genes related to the MAPK and FoxO signaling pathways and associated with transcription factor families like ETS and AP-1. Conversely, downregulated DARs were associated with the TGF-β, cAMP, and p53 signaling pathways and the CTCF family. Integration of the datasets revealed a positive correlation between specific DARs and DEGs. Notably, PRPF3 emerged as a gene associated with DARs in HCC, and functional assays demonstrated its ability to promote HCC cell proliferation and migration. To the best of our knowledge, this is the first report highlighting the oncogenic role of PRPF3 in HCC. Furthermore, ZNF93 expression positively correlated with PRPF3, and ChIP-seq data indicated its potential role as a transcription factor regulating PRPF3 by binding to its promoter region. Conclusion This study provides a comprehensive analysis of the epigenetic landscape in HCC, encompassing both chromatin accessibility and the transcriptome. Our findings reveal that ZNF93 promotes the proliferation and motility of HCC cells through transcriptional regulation of a novel oncogene, PRPF3.

SUMMARY: Purpose: The long-term fertility impact of cancer treatments is a significant concern for young breast cancer survivors. These reproductive concerns often become a persistent source of stress, negatively affecting their quality of life. This study aims to explore the reproductive concerns experienced by young breast cancer survivors post-treatment and the factors influencing their perceptions. Methods: This phenomenological study utilized semi-structured interviews to collect data. Eighteen participants were recruited from a tertiary hospital in Mainland China. The interviews were transcribed verbatim and analyzed using Colaizzi's method. Results: Data analysis revealed five themes and fourteen subthemes: (1) multiple emotional burdens interwoven with concerns about fertility; (2) concerns about risks associated with reproduction; (3) dilemma of childrearing; (4) the significance of reproduction; (5) support needs from family, peers, and professionals. Conclusion: Young breast cancer survivors in China face significant challenges related to reproductive issues. Reproductive health is a crucial aspect of breast cancer survivorship care. Healthcare providers must be attentive to the reproductive concerns of survivors, recognize the importance of multidimensional support for positive adaptation, and offer tailored and ongoing interventions to manage reproductive health in young breast cancer survivors.

Abstract Background Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy. Methods Using a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification. Results Our analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy. Conclusions This study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes.

Objective The present study evaluated the effect of flaxseed meal degraded by a protease, Lactobacillus plantarum, or both on the growth performance, nutrient digestibility, and health status of broilers. Methods There were four diets containing flaxseed meals in its non-degraded form (control, CON), degraded with 3,000 U/kg of protease (enzymatic, ELM), 1.0×109 CFU/kg of Lactobacillus plantarum (fermented, FLM), or both (dual-degraded, DLM). Each form of flaxseed meals was added at 15% of diet. A total of 480 yellow-feathered broilers at 22 d of age were distributed into 4 groups with 6 replicates of 20 chickens each. The feeding trial lasted for 42 d. Growth performance, apparent fecal digestibility (dry matter, energy, crude protein, and ash), and serum immunoglobins and antioxidases were determined at 42 and 63 d of age. Results Results showed that ELM, FLM, and DLM increased (p

IntroductionImmune checkpoint inhibitors (ICIs) are important systemic therapeutic agents for hepatocellular carcinoma (HCC), among which T-cell immunoglobulin and mucin-domain containing protein 3 (Tim-3) is considered an emerging target for ICI therapy. This study aims to evaluate the prognostic value of Tim-3 expression and develop a predictive model for Tim-3 infiltration in HCC.MethodsWe collected data from 424 HCC patients in The Cancer Genome Atlas (TCGA) and data from 102 pathologically confirmed HCC patients from our center for prognostic analysis. Multivariate Cox regression analyses were performed on both datasets to determine the prognostic significance of Tim-3 expression. In radiomics analysis, we used the K-means algorithm to cluster regions of interest in arterial phase enhancement and venous phase enhancement images from patients at our center. Radiomic features were extracted from three subregions as well as the entire tumor using pyradiomics. Five machine learning methods were employed to construct Habitat models based on habitat features and Rad models based on traditional radiomic features. The predictive performance of the models was compared using ROC curves, DCA curves, and calibration curves.ResultsMultivariate Cox analyses from both our center and the TCGA database indicated that high Tim-3 expression is an independent risk factor for poor prognosis in HCC patients. Higher levels of Tim-3 expression were significantly associated with worse prognosis. Among the ten models evaluated, the Habitat model constructed using the LightGBM algorithm showed the best performance in predicting Tim-3 expression status (training set vs. test set AUC 0.866 vs. 0.824).DiscussionThis study confirmed the importance of Tim-3 as a prognostic marker in HCC. The habitat radiomics model we developed effectively predicted intratumoral Tim-3 infiltration, providing valuable insights for the evaluation of ICI therapy in HCC patients.

Background Fetal arrhythmias frequently co-occur with congenital heart disease in fetuses. The peaks observed in M-mode fetal echocardiograms serve as pivotal diagnostic markers for fetal arrhythmias. However, speckles, artifacts, and noise pose notable challenges for accurate image analysis. While current deep learning networks mainly overlook cardiac cyclic information, this study concentrated on the integration of such features, leveraging contextual constraints derived from cardiac cyclical features to improve diagnostic accuracy. Methods This study proposed a novel deep learning architecture for diagnosing fetal arrhythmias. The architecture presented a loss function tailored to the cardiac cyclical information and formulated a diagnostic algorithm for classifying fetal arrhythmias. The training and validation processes utilized a dataset comprising 4440 patches gathered from 890 participants. Results Incorporating cyclic loss significantly enhanced the performance of deep learning networks in predicting peak points for diagnosing fetal arrhythmia, resulting in improvements ranging from 7.11% to 14.81% in F 1-score across different network combinations. Particularly noteworthy was the 18.2% improvement in the F 1-score for the low-quality group. Additionally, the precision of diagnosing fetal arrhythmia across four categories exhibited improvement, with an average improvement rate of 20.6%. Conclusion This study introduced a cyclic loss mechanism based on the cardiac cycle information. Comparative evaluations were conducted using baseline methods and state-of-the-art deep learning architectures with the fetal echocardiogram dataset. These evaluations demonstrated the proposed framework’s superior accuracy in diagnosing fetal arrhythmias. It is also crucial to note that further external testing is essential to assess the model’s generalizability and clinical value.

Trehalases (TREs), serving as crucial enzymes regulating trehalose and chitin metabolism in insects, represent prime targets for pest control strategies. We investigated the impact of three thioxothiazolidin compounds (1G, 2G, and 11G) on TRE activity and summarized their effects on the growth and development of Spodoptera frugiperda (Lepidoptera, Noctuidae). The experimental larvae of S. frugiperda were injected with the three thioxothiazolidin compounds (1G, 2G, and 11G), while the control group received an equivalent volume of 2% DMSO as a control. All three compounds had a strong effect on inhibiting TRE activity, significantly prolonging the pre-pupal development stage. However, compared with the 11G-treated group, the survival rate of larvae treated with 1G and 2G was significantly reduced by 31.11% and 27.78% respectively, while the occurrence of phenotypic abnormalities related to growth and development was higher. These results manifest that only the TRE inhibitors, 1G and 2G, modulate trehalose and chitin metabolism pathways of larvae, ultimately resulting in the failure molting and reduction of survival rates. Consequently, the thioxothiazolidin compounds, 1G and 2G, hold potential as environmentally friendly insecticides.

It is widely known that antibiotics can affect the structure and function of soil microbial communities, but the specific degree of impact and controlled factors on different indicators remain inconclusive. We conducted a multiple hierarchical mixed effects meta-analysis on 2564 observations that were extracted from 60 publications, to comprehensively assess the impact of antibiotics on soil microbiota. The results showed that antibiotics had significant negative effects on soil microbial biomass, α-diversity and soil enzyme activity. Under neutral initial soil, when soil was derived from agricultural land or had a fine-textured, the negative impacts of antibiotics on soil microbial community were exacerbated. Both single and mixed additions of antibiotics had significant inhibitory effects on soil microbial enzyme activities. The Random Forest model predicted the following key moderators involved in the effects of antibiotics on the soil microbiome, and antibiotics type, soil texture were key moderators on the severity of soil microbial biomass changes. Soil texture, temperature and single or combined application constitute of antibiotics were the main drivers of effects on soil enzyme activities. The reported results can be helpful to assess the ecological risk of antibiotics in a soil environment and provides a scientific basis for the rational of antibiotics use in the soil environment.

Mechanical rock breaking represented by boring machines is the direction of future development of vertical shaft and roadway excavation technology. In order to ensure the safety of rapid mechanical and intelligent excavation of shaft and roadway, advanced geological exploration is an essential link. The development status and characteristics of conventional advanced geological exploration technology and advanced geological exploration technology during excavation were classified and summarized from the aspects of detection range, applicable conditions, and advantages and disadvantages. Conventional advanced detection techniques each have a certain scope of application and have been well applied in the construction environment of blasting excavation method. When facing the complex construction environment of boring machines, conventional advanced detection techniques are difficult to apply. And advanced geological exploration technology during excavation can synchronously achieve excavation and advanced geological exploration, real-time prediction of unfavorable geology in front of the working face, which is the focus of research on advanced geological exploration technology for mechanized and intelligent excavation of shaft and roadway. The full face excavation machine for vertical shafts is the development direction and trend of comprehensive mechanized shaft sinking. However, its construction environment is very complex, and advanced geological detection based on seismic wave of boring machines rock breaking source is an effective prediction method. The difficulty of advanced detection method for rock breaking source of full face shaft boring machines lies in the dual complexity of construction environment and seismic wave field of rock breaking source. Solutions are proposed from multiple perspectives. For the source pilot signal, adopting multiple methods for joint denoising to suppress interference waves from rock breaking sources. For seismic record signals, a seismic record reconstruction method with cross correlation as the core is adopted to restore the effective wave field. Conduct research on full space three-dimensional detection and high-precision imaging of vertical shafts, etc. In addition, conducting joint inversion with multiple excavation geophysical methods can improve the reliability and interpretation accuracy of geological identification. The development of integrated equipment for excavation and exploration of vertical shaft tunneling machines is the direction of future in-depth research.

To address the problem that traditional cement-based slurry materials cannot meet the actual demand for grouting and reinforcement of large deformation roadways in coal mines, some high-performance composite slurry materials are obtained by modifying ordinary Portland cement with nano-silica sol, ethylene-vinyl acetate copolymer (EVA) and fly ash. The orthogonal test and extreme difference analysis are used to systematically study the variation of the physical and mechanical properties of the composite slurries, determine the optimal ratio, and further analyze the difference in the physical properties between the optimal ratio of composite slurries and pure cement, construct the hydration reaction mechanism model of the composite slurries, and elucidate the mechanical properties of the composite slurries for reinforcing broken rocks. The results of the study show that the optimum proportion of composite slurry is 0.7 water-cement ratio, 15% fly ash, 2% silica sol and 7.5% EVA. Compared with pure cement, the rheology of composite slurry is slightly decreased, but the stability and mechanical properties of the slurry are significantly improved, with the initial setting time shortened by 38.9%, the final setting time shortened by 53.8%, the precipitation rate reduced by 60%, the stone rate increased by 3.3%, the uniaxial compressive strength increased by 39.1%, the tensile strength increased by 97.2%, and the tensile/compression ratio increased by 41.7%. Silica sol and fly ash undergo volcanic ash reaction with Ca(OH)2 to generate more calcium silicate hydrate (C-S-H) and calcium aluminate hydrate (C-A-H) at different times, which promotes the hydration reaction of the composite slurry and accelerates the film formation of EVA to make the stone body more dense. The injection volume of the composite grout and the uniaxial compressive strength of the bonded body both increase with the increasing grouting pressure. With the increase in the Talbot index, the compressive strength first increases and then decreases. The failure mode is often characterized by bulging, and shear dilation deformation is pronounced. When the grouting pressure exceeds 2 MPa and the Talbot index is 0.5, the bond strength of the grout is higher, and the damage is reduced. This study provides a feasible way for early strength and toughening modification of ce-mentitious composite pastes.

Abstract Background Death anxiety is thought to cause a range of mental disorders among cancer patients, which may affect their mental health and even quality of life. This study sought to investigate experiential avoidance, meaning in life, and death anxiety among Chinese cancer patients and then explore the relationship between these 3 variables. Methods A total of 300 cancer patients recruited from a tertiary cancer hospital participated in this study from October to December 2021. A cross-sectional survey was conducted using a demographic and clinical characteristics questionnaire, the Acceptance and Action Questionnaire II, the Meaning in Life Questionnaire, and Templer’s Death Anxiety Scale. Correlation analysis, hierarchical regression analysis, and mediating effect analysis were used to analyze the relationship among experiential avoidance, meaning in life (including 2 dimensions: presence of meaning and search for meaning), and death anxiety. Results A total of 315 questionnaires were distributed, and 300 valid questionnaires were returned, resulting in a valid response rate of 95.2%. Experiential avoidance (r = 0.552, p

Janzen-Connell effects state that the accumulation of host-specific natural enemies near parent plants can negatively affect their offspring. Negative plant-soil feedbacks can produce patterns of seedling performance predicted by Janzen-Connell effects and influence plant populations, but their relevance in field conditions remains unclear. Here, using spatial point-pattern analysis, we examine the spatial distribution of Jacobaea vulgaris to assess whether distance- and density-dependent predictions of Janzen-Connell effects are evident in the field. We established 27 replicated 64 m2 plots at two grassland sites and mapped positions of rosette-bearing and flowering J. vulgaris plants within each plot. To investigate temporal distribution patterns, we tracked plant positions repeatedly in three plots during a single season. Additionally, we tested whether these patterns are soil-mediated. Soil samples were collected underneath flowering plants and at a distance of 0.5 meter, and used to compare seed germination, seedling survival, and growth under controlled conditions. Furthermore, we measured J. vulgaris growth in soil from patches with high J. vulgaris densities and in soil from areas outside these patches. The density of rosette-bearing plants was lower at close distances from flowering plants than expected from null models, suggesting negative distance-dependent plant recruitment. The degree of clustering decreased over time from rosette-bearing to flowering plants, indicating density-dependent self-thinning. Seed germination was higher in soil further away from flowering J. vulgaris plants than in soil underneath plants at one site, but soil distance was not an overall significant factor in explaining seed germination. However, seedling mortality and biomass did not differ between soils collected at the two distances, and plants produced similar biomass in soil collected from inside and outside J. vulgaris patches. Our study demonstrates conspecific distance- and density-dependent plant recruitment in J. vulgaris in the field, but we found no evidence this depends on belowground natural enemies.

Abstract Rapeseed is a critical cash crop globally, and understanding its distribution can assist in refined agricultural management, ensuring a sustainable vegetable oil supply, and informing government decisions. China is the leading consumer and third-largest producer of rapeseed. However, there is a lack of widely available, long-term, and large-scale remotely sensed maps on rapeseed cultivation in China. Here this study utilizes multi-source data such as satellite images, GLDAS environmental variables, land cover maps, and terrain data to create the China annual rapeseed maps at 30 m spatial resolution from 2000 to 2022 (CARM30). Our product was validated using independent samples and showed average F1 scores of 0.869 and 0.971 for winter and spring rapeseed. The CARM30 has high spatial consistency with existing 10 m and 20 m rapeseed maps. Additionally, the CARM30-derived rapeseed planted area was significantly correlated with agricultural statistics (R2 = 0.65–0.86; p

Abstract Anti‐inflammatory compounds, delivered as a payload to the gastrointestinal tract (GIT) by carriers, still cannot treat inflammatory bowel diseases without avoiding side effects. Here, we developed payload‐free protein nanoparticles (PNPs) that crossed GIT to retain in the colon and treat colitis by restoring intestinal barrier integrity by modulating gut microbiome and metabolome. Specifically, PNPs, orally administered to mice with acute colitis, reached the colon within three hours. Consequently, PNPs improve gut microbiota dysbiosis to reverse metabolism balance, suppressing the expression of tumor‐necrosis factor α and toll‐like receptor 4 that restores the intestinal barrier integrity. PNPs then ameliorated colon inflammation and attenuated gut microbiota dysbiosis by exerting probiotic effects on gut microbiota, treating colitis in a week more effectively than the clinically often used 5‐aminosalicylic acid without causing undesired side effects. Such PNPs represent safe, sustainable, and cost‐effective therapeutics for treating inflammatory and metabolic diseases by eliminating microbial and metabolomic imbalance.

Abstract Background and Aims Burn and scald injuries are the fourth most common type of trauma. Pediatric burns account for a high proportion of the total number of burn patients and impose a high burden on public health. Understanding the epidemiology of pediatric burns can help improve science education and reduce the incidence of burn injuries. Methods This study is a single‐center retrospective study. One thousand five hundred and twenty‐seven pediatric burn patients admitted to our burn center from January 2016 to December 2020 were included. Demographic and epidemiological data of included patients were extracted and analyzed. The correlations of categorical data were tested by the Chi‐square tests, and differences of continuous data were tested by the Kruskal–Wallis tests. A p‐value of less than 0.05 was considered to be statistically significant. Results The results showed that children under 3 years of age were most susceptible to burn and scald injuries. Burn injuries were most likely to occur in the season of winter and at the place of home. 56.6% of included patients did receive first aid measures, while 1.8% received gold‐standard first aid. Clinical variables related to the severity of injuries were statistically different between patients with and without cooling measures in first aid. Linear regression models showed that emergency treatment of burns in children and adolescents was associated with outcome indicators, including number of operations, total operation duration per total burn surface area (TBSA), cost per TBSA, and length of stay per TBSA. Conclusions This study summarized the epidemiology and outcomes of pediatric burn patients admitted to a burn center in northern China. Adopting cooling measures in first aid can reduce the severity of injuries and reduce the burden on the medical system. Education on burn prevention and first aid measures to caregivers of children, especially preschool children, should be strengthened.

Abstracts: Natural estrogens, including estrone (E1), 17β-estradiol (E2), and estriol (E3), are potentially carcinogenic pollutants commonly found in water and soil environments. Bacterial metabolic pathway of E2 has been studied; however, the catabolic products of E3 have not been discovered thus far. In this study, Novosphingobium sp. ES2–1 was used as the target strain to investigate its catabolic pathway of E3. The metabolites of E3 were identified by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) combined with stable 13C3-labeling. Strain ES2–1 could almost completely degrade 20 mg∙L−1 of E3 within 72 h under the optimal conditions of 30°C and pH 7.0. When inoculated with strain ES2–1, E3 was initially converted to E1 and then to 4-hydroxyestrone (4-OH-E1), which was then cleaved to HIP (metabolite A6) via the 4, 5-seco pathway or cleaved to the B loop via the 9,10-seco pathway to produce metabolite with a long-chain ketone structure (metabolite B4). Although the ring-opening sequence of the above two metabolic pathways was different, the metabolism of E3 was achieved especially through continuous oxidation reactions. This study reveals that, E3 could be firstly converted to E1 and then to 4-OH-E1, and finally degraded into small molecule metabolites through two alternative pathways, thereby reducing E3 pollution in water and soil environments.

Purposes The situation of post-disaster site of coal mine underground is complex. Aiming at the fact that traditional A* algorithm-based coal mine robot rescue path planning bears path insecurity, low efficiency, and other problems, and by combining with the raster map and the characteristics that the rescue robot can move along any direction, multi-faceted improvement of the traditional A* algorithm is realized. Methods First, the concept of robot size superimposed to obstacles is introduced to ensure the safety of the path. Second, the computational complexity is reduced by optimising the heuristic function to reduce the number of extensions that deviate from the optimal path nodes, and to reduce the redundant nodes and path transitions. Finally, a dynamic adjustment algorithm is used to round the corners of path turns, and the resulting path is smoothed to improve the operability of path. The optimised path with smaller path cost, shorter time consumption, and fewer turns is finally obtained. Based on the improved A* algorithm, the simulation test of rescue robot path planning under different sizes and different obstacle coverages is carried out by using MATLAB. Findings Compared with the traditional A* algorithm, the improved A* algorithm in rugged environment maps reduces the searching nodes by 26.51%, the computation time by 80.42%, the path length by 31.85%, and the number of turns by 44.44%, which improves the search efficiency and smoothness of the path. Conclusions The improved A* algorithm provides a theoretical basis for the rescue work of coal mine robots under complex working conditions.

Abstract The human organic cation transporter 1 (hOCT1), also known as SLC22A1, is integral to hepatic uptake of structurally diversified endogenous and exogenous organic cations, influencing both metabolism and drug pharmacokinetics. hOCT1 has been implicated in the therapeutic dynamics of many drugs, making interactions with hOCT1 a key consideration in novel drug development and drug–drug interactions. Notably, metformin, the frontline medication for type 2 diabetes, is a prominent hOCT1 substrate. Conversely, hOCT1 can be inhibited by agents such as spironolactone, a steroid analog inhibitor of the aldosterone receptor, necessitating a deep understanding of hOCT1–drug interactions in the development of new pharmacological treatments. Despite extensive study, specifics of hOCT1 transport and inhibition mechanisms remain elusive at the molecular level. Here, we present cryo-electron microscopy structures of the hOCT1-metformin complex in three distinct conformational states — outward open, outward occluded, and inward occluded as well as substrate-free hOCT1 in both partially and fully open states. We also present hOCT1 in complex with spironolactone in both outward and inward facing conformations. These structures provide atomic-level insights into the dynamic metformin transfer process via hOCT1 and the mechanism by which spironolactone inhibits it. Additionally, we identify a ‘YER’ motif critical for the conformational flexibility of hOCT1 and likely other SLC22 family transporters. Our findings significantly advance the understanding of hOCT1 molecular function and offer a foundational framework for the design of new therapeutic agents targeting this transporter.

Abstract Brain damage is a common tissue damage caused by trauma or diseases, which can be life-threatening. Stem cell implantation is an emerging strategy treating brain damage. The stem cell is commonly embedded in a matrix material for implantation, which protects stem cell and induces cell differentiation. Cell differentiation induction by this material is decisive in the effectiveness of this treatment strategy. In this work, we present an injectable fibroin/MXene conductive hydrogel as stem cell carrier, which further enables in-vivo electrical stimulation upon stem cells implanted into damaged brain tissue. Cell differentiation characterization of stem cell showed high effectiveness of electrical stimulation in this system, which is comparable to pure conductive membrane. Axon growth density of the newly differentiated neurons increased by 290% and axon length by 320%. In addition, unfavored astrocyte differentiation is minimized. The therapeutic effect of this system is proved through traumatic brain injury model on rats. Combined with in vivo electrical stimulation, cavities formation is reduced after traumatic brain injury, and rat motor function recovery is significantly promoted. Graphical Abstract

In most real world rehabilitation training, patients are trained to regain motion capabilities with the aid of functional/epidural electrical stimulation (FES/EES), under the support of gravity-assist systems to prevent falls. However, the lack of motion analysis dataset designed specifically for rehabilitation-related applications largely limits the conduct of pilot research. We provide an open access dataset, consisting of multimodal data collected via 16 electromyography (EMG) sensors, 6 inertial measurement unit (IMU) sensors, and 230 insole pressure sensors (IPS) per foot, together with a 26-sensor motion capture system, under different MOVEments and POstures for Rehabilitation Training (MovePort). Data were collected under diverse experimental paradigms. Twenty four participants first imitated multiple normal and abnormal body postures including (1) normal standing still, (2) leaning forward, (3) leaning back, and (4) half-squat, which in practical applications, can be detected as feedback to tune the parameters of FES/EES and gravity-assist systems to keep patients in a target body posture. Data under imitated abnormal gaits, e.g., (1) with legs raised higher under excessive electrical stimulation, and (2) with dragging legs under insufficient stimulation, were also collected. Data under normal gaits with low, medium and high speeds are also included. Pathological gait data from a subject with spastic paraplegia further increases the clinical value of our dataset. We also provide source codes to perform both intra- and inter-participant motion analyses of our dataset. We expect our dataset can provide a unique platform to promote collaboration among neurorehabilitation engineers.

Background Aminoacyl-tRNA synthetases (ARSs) are evolutionarily conserved enzymes that ensure the accuracy of the translation process. Isoleucyl-tRNA synthetase 2 (IARS2) gene is a type of ARS that encodes mitochondrial isoleucine-tRNA synthetase. Pathogenic variants in the IARS2 gene are associated with mitochondrial disease which involves several patients presenting broad clinical phenotypes. These clinical phenotypes include West syndrome, Leigh syndrome, and Cataract, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome. Only 29 cases have been reported worldwide. The patient manifested recurrent convulsions, and specific clinical manifestations included electrolyte disorders and recurrent infections.

This paper proposes a drone-assisted NOMA communication system equipped with a reconfigurable intelligent surface (RIS). Given the Line-of-Sight nature of the Air-to-Ground link, a more realistic Rician fading environment is chosen for the study of system performance. The user’s outage performance and secrecy outage probability of the RIS-UAV-assisted NOMA downlink communication under the Rician channels are investigated. Jointly considering the Line-of-Sight and Non-Line-of-Sight links, the closed-form expressions of each user’s outage probability are derived by approximating the composite channels as Rician distributions to characterize the channel coefficients of the system’s links. Considering the physical layer security in the presence of the eavesdropper, the secrecy outage probability of two users is further studied. The relationship between the system outage performance and the Rician factor of the channel, the number of RIS elements, and other factors are analyzed. The results of this study show that compared with Rayleigh fading, the Rician fading is more practical with the actual Air-to-Ground links; the user’s outage probability and the secrecy outage probability are lower over the Rician channels. The number of RIS elements and the power allocation factor by the base station for the users are inversely proportional to the user’s outage probability, and RIS element number, path loss index, and distance factor also have a greater impact on the outage probability. Compared with OMA, NOMA has a certain enhancement to the system performance.

Volleyball is a high-intensity sport characterized by repetitive jumping, sudden directional changes, and overhead movements, all of which significantly increase the risk of injuries, particularly to the shoulders, knees, and ankles. Despite the frequency of injuries caused by actions like blocking and spiking, there has been limited research focused on the specific biomechanical risk factors unique to volleyball. This study aimed to investigate the lower limb biomechanics during block jumps in both the dominant and non-dominant directions, under both anticipated and unanticipated conditions, in fifteen elite male volleyball players. Kinematic and kinetic data from the ankle, knee, and hip joints were recorded. Our results revealed statistically significant differences between the dominant and non-dominant directions at the ankle, knee, and hip joints. The non-dominant direction exhibited a greater ankle dorsiflexion angle and velocity, as well as higher knee flexion angle, velocity, moment, power, and abduction moment, along with increased hip flexion angle and power. Additionally, unanticipated movements led to increases in vertical ground reaction force (vGRF), hip extension moment, and flexion power, while ankle dorsiflexion plantarflexion velocity and knee flexion power decreased. It appears that movements in the dominant direction were stiffer and less cushioned, potentially increasing the risk of injury. While the non-dominant direction provided better shock absorption, it also elevated the knee valgus moment, which could increase the load on the knee. Furthermore, in unanticipated situations, athletes with short reaction times, unable to quickly adjust their automated movement patterns, faced a higher risk of limb overuse, thereby increasing the likelihood of injury. In practice, coaches should consider differences in limb coordination and movement direction, incorporating unilateral preventive exercises to reduce the risk of injury.

BackgroundPear black spot (PBS) is caused by Alternaria alternata and causes severe damage worldwide. It is particularly important to screen for synergistic fungicide combinations to address issues associated with the low efficacy of biocontrol agents, high dosage requirements and poor sustained effectiveness of chemical fungicides.MethodsIn vitro and in vivo studies were performed to determine the efficacy of a treatment for this important disease. Additionally, transcriptomic and metabolomic analyses were performed to determine the main molecular and biochemical mechanisms involved in the interaction.ResultsBacillus tequilensis 2_2a has a significant synergistic effect with difenoconazole, causing hyphal entanglement and spore lysis and inhibiting the formation of PBS lesions in vitro. In the field, the control effect of the combination was greater than 95%. The pathways associated with the synergistic effect on the mycelia of A. alternata were divided into two main types: one included glycolysis, oxidative phosphorylation, and MAPK signal transduction, while the other included glycolysis, the TCA cycle, coenzyme A biosynthesis, sterol synthesis, and fatty acid degradation. Both types of pathways jointly affect the cell cycle. The main functions of the key genes and metabolites that have been verified as being affected are glucose synthesis and oxidative respiration, as well as citric acid synthesis, acetyl-CoA synthesis, and sterol synthesis. Both functions involve intracellular pyridine nucleotide metabolism and adenine nucleotide transformation.ConclusionThis study helps to reveal the synergistic mechanisms underlying the combined efficacy of biological and chemical agents, providing a scientific basis for field applications.

Study area: China Study focus: Drought is an extremely serious disaster, typically characterized by slow onset, long duration, and cumulative impacts on multifaceted aspects. Developing a combined index that integrates its various characteristics can help deepen our understanding of drought evolution and provide accurate references for farmers to take drought mitigation measures. In this study, we proposed a Modified version of the Type Response-Aided Drought Index (MTRADI), simultaneously considering the various responses of different vegetation and the slow-varying properties of drought development. New hydrological insights for the regions: The suitability of MTRADI was evaluated through correlation analysis with Palmer Drought Severity Index (PDSI) and qualitative comparison with Meteorological Drought Composite Index (MCI) maps. The MTRADI achieved significantly higher correlation coefficients with the PDSI, outperforming other combined drought indices. Based on the run theory, Mann-Kendall (MK) test, and Sen’s slope, drought characteristics and trends in mainland China during 2001–2020 were analyzed and the results show that drought frequency and severity are relatively higher in eastern Inner Mongolia, North China Plain, and Northeast of China. Furthermore, areas with significant wetting trends are observed to be mainly distributed near the Hu line, indicating that the water conditions in China are gradually improving at the transition zone of arid and humid climate regions.

Vegetation Condition Index (VCI), as a widely used drought index for monitoring vegetation drought stress and estimating drought trends, is constructed by normalizing the long-term satellite-based Normalized Difference Vegetation Index (NDVI) data. However, under global greening, vegetation across different regions has shown an increasing trend in greenness, which may cause VCI to inherit the greening trend in NDVI and further hamper its ability in drought trend analysis. Therefore, this study quantitatively explored the underlying relationship among VCI, global greening, and drought from 2001 to 2021 to examine the utility of VCI in a changing environment. Multi-source indicators were employed as surrogates for vegetation greenness and drought, respectively. Particularly, the Leaf Area Index (LAI) and Net Primary Production (NPP) were used as proxies for vegetation greenness while the Root-Zone Soil Moisture (RZSM), Palmer Drought Severity Index (PDSI), and Standardized Precipitation-Evapotranspiration Index (SPEI) were used for drought indices. Based on Sen’s slope estimator, Mann-Kendall (MK) test, and partial correlation analysis, our results show that the proportion of pixels with an increasing trend in VCI is approximately 38.5%, which is similar to the greenness-related indices (i.e., NPP [26.47%] and LAI [59.14%]), and is significantly higher than the other drought indices (i.e., RZSM [19.83%], PDSI [10.38%], and SPEI [9.32%]). Furthermore, our results demonstrate that the VCI, as a drought index, exhibits a closer correlation with greenness-related indicators (LAI and NPP) than other drought indices (RZSM, PDSI, and SPEI). These results reveal the potential limitations in the practical applications of VCI and could enhance our understanding of vegetation dynamics and drought trends, especially in the current greening globe. Additionally, this study serves as a cautionary note for the scientific community involved in drought monitoring, emphasizing that the VCI may not be a suitable tool for evaluating long-term trends in drought impacts on vegetation.

BackgroundTuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are unclear.MethodsWe performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis. ResultsWe revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6. DiscussionWe proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by Mtb-infected tissues.

Artificial intelligence (AI) has made significant progress in the medical field in the last decade. The AI-powered analysis methods of medical images and clinical records can now match the abilities of clinical physicians. Due to the challenges posed by the unique group of fetuses and the dynamic organ of the heart, research into the application of AI in the prenatal diagnosis of congenital heart disease (CHD) is particularly active. In this review, we discuss the clinical questions and research methods involved in using AI to address prenatal diagnosis of CHD, including imaging, genetic diagnosis, and risk prediction. Representative examples are provided for each method discussed. Finally, we discuss the current limitations of AI in prenatal diagnosis of CHD, namely Volatility, Insufficiency and Independence (VII), and propose possible solutions.

Gastric-type endocervical adenocarcinoma (G-EAC) represents a rare variant of cervical mucinous adenocarcinoma that is typically unrelated to human papillomavirus (HPV) infection. G-EAC exhibits highly atypical clinical presentations and characteristics, and aggressive biological behavior often leads to challenges in timely diagnosis. Here, we present a case study involving a 74-year-old Chinese woman who experienced urinary incontinence for one month. Biopsy pathology confirmed the diagnosis of G-EAC, revealing stage IVa by imaging examinations. The patient subsequently underwent three cycles of chemotherapy, followed by adjuvant radiotherapy and surgical excision of residual tumor foci. This comprehensive treatment approach yielded a favorable survival outcome. For patients with advanced G-EAC, a multimodal therapeutic approach holds promise and warrants further exploration.

The quality and safety of agricultural products are related to people’s lives and health, economic development, and social stability, and have always been a hot issue of concern to the government and society. The rapid development of digital traceability technology in the digital environment has brought new opportunities for the supervision of agricultural product quality and safety, but the frequent occurrence of agricultural product safety incidents in recent years has exposed many problems such as the lack of governmental supervision, unstandardized production process of enterprises, and weak consumer awareness. To improve the cooperation efficiency of stakeholders and ensure the quality and safety of agricultural products, this paper proposes a dynamic model based on evolutionary game theory. The model incorporates the government, agricultural product producers, and farmers, and evaluates the stability and effectiveness of the system under different circumstances. The results of the study show that there are multiple evolutionary stabilization strategies in the tripartite evolutionary game model of agricultural product quality and safety supervision, and there are corresponding evolutionary stabilization conditions. There are several factors affecting the stability of the system, the most important of which are government regulation, severe penalties for agricultural product producers, and incentives. When these factors reach a certain threshold, the stakeholder cooperation mechanism can establish an evolutionarily stable strategy. This study contributes to the understanding of the operational mechanism of stakeholder cooperation in agricultural product quality and safety regulation in the digital environment and provides decision support and policy recommendations for stakeholders to promote the sustainable development and optimization of agricultural product quality and safety regulation.

Abstract Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F2α and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.

Developing environmentally friendly bulk materials capable of easily and thoroughly removing trace amounts of dye pollutants from water to rapidly obtain clean water has always been a goal pursued by researchers. Herein, a green material with a 3D architecture and with strong underwater rebounding and fatigue resistance ability was prepared by means of the assembly of biopolymer chitosan (CS) and natural caraganate fibers (CKFs) under freezing conditions. The CKFs can randomly and uniformly distribute in the lamellar structure formed during the freezing process of CS and CKFs, playing a role similar to that of “steel bars” in concrete, thus providing longitudinal support for the 3D-architecture material. The 2D layers formed by CS and CKFs as the main basic units can provide the material with a higher strength. The 3D-architecture material can bear the compressive force of a weight underwater for multiple cycles, meeting the requirements for water purification. The underwater compression test shows that the 3D-architecture material can quickly rebound to its original shape after removing the stress. This 3D-architecture material can be used to purify dye-containing water. When its dosage is 3 g/L, the material can remove 99.65% of the Congo Red (CR) in a 50 mg/L dye solution. The adsorption performance of the 3D architecture adsorbent for CR removal in actual water samples (i.e., tap water, seawater) is superior than that of commercial activated carbon. Due to its porous block characteristics, this material can be used for the continuous and efficient treatment of wastewater containing trace amounts of CR dye to obtain pure clean water, meaning that it has great potential for the effective purification of dye wastewater.

The MYB gene family, widely distributed across a variety of plants, plays a crucial role in the phenylpropane metabolic pathway. In this study, we identified 146 R2R3-MYB genes in the ‘NanGuo’ pear genome by screening its gene sequences. Phylogenetic analysis divided these genes into seven subfamilies, and we examined each for stability through analyses of conserved structural domains and motifs. In addition, differences in the expression levels between two varieties, the ‘NanGuo’ pear and its red bud sport variant ‘NanHong’ pear, were investigated using quantitative real-time PCR (qRT-PCR). The results revealed that the expression levels of 12 R2R3-MYB transcription factors (TFs) corresponded with the trends in anthocyanin content. Specifically, the expression trends of eight R2R3-MYB TFs positively correlated with anthocyanin accumulation, whereas four exhibited opposite trends, suggesting their negatively regulatory role in anthocyanin accumulation. This study not only enhances our understanding of the MYB gene family in the ‘NanGuo’ pear genome but also lays a solid foundation for future research into the functional roles of PuMYBs.

Surface electromyography (sEMG) is commonly used as an interface in human–machine interaction systems due to their high signal-to-noise ratio and easy acquisition. It can intuitively reflect motion intentions of users, thus is widely applied in gesture recognition systems. However, wearable sEMG-based gesture recognition systems are susceptible to changes in environmental noise, electrode placement, and physiological characteristics. This could result in significant performance degradation of the model in inter-session scenarios, bringing a poor experience to users. Currently, for noise from environmental changes and electrode shifting from wearing variety, numerous studies have proposed various data-augmentation methods and highly generalized networks to improve inter-session gesture recognition accuracy. However, few studies have considered the impact of individual physiological states. In this study, we assumed that user exercise could cause changes in muscle conditions, leading to variations in sEMG features and subsequently affecting the recognition accuracy of model. To verify our hypothesis, we collected sEMG data from 12 participants performing the same gesture tasks before and after exercise, and then used Linear Discriminant Analysis (LDA) for gesture classification. For the non-exercise group, the inter-session accuracy declined only by 2.86%, whereas that of the exercise group decreased by 13.53%. This finding proves that exercise is indeed a critical factor contributing to the decline in inter-session model performance.

With the intensification of global climate change, there is an increasing emphasis on protecting natural resources. Mangrove forests, critical to tropical and subtropical intertidal ecosystems, have garnered considerable attention in recent years for their strong carbon sink capacity, rich species diversity, and abundant natural resources. This study utilizes the 2020 global mangrove vector data as a baseline to construct a reasonable buffer zone by calculating the increase in mangrove crown width. The Google Earth Engine (GEE) platform and its Sentinel-2 data from 2022 are employed to acquire synthetic images across all regions using the mosaic algorithm. Then, mangrove forests are extracted using the Otsu algorithm, and a map depicting the global spatial distribution of mangrove forests in 2022 is obtained. The average overall accuracy of the extracted mangrove forests in this study reaches 92.4%, and it is determined that the global mangrove forest area expanded by 4920.6 km2 between 2020 and 2022, This study provides crucial data support for the global monitoring of mangrove changes and holds significant importance for protecting and restoring mangrove ecosystems.

Abstract Tislelizumab, an anti‐programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first‐in‐human, dose‐finding BGB‐A317‐001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5–10 mg/kg every 2 weeks (q2w), 2–5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune‐mediated AEs, and infusion‐related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure–response (E–R) analyses by logistic regression using data from study BGB‐A317‐001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018–2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E–R relationship. Overall, the totality of data, including efficacy, safety, and E–R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications.

Background: As the most common primary bone cancer, the therapy of osteosarcoma requires further study. An anthraquinone derivative, emodin, has been found to have anticancer potential. We proposed that emodin suppresses osteosarcoma by cell cycle regulation mediated by p53. Methods: This study determined the effect of emodin on viability and apoptosis of 6 osteosarcoma cell lines (p53 null cells MG63, G292, and A-673; p53 mutated cells HOS and SK-PN-DW; p53 expressing cells U2OS and 2 osteoblast cell lines), then knockdown p53 in U2OS, and observed the impacts of emodin on p53, p21, cyclin proteins, and cell cycle. Results: High dose emodin (40–160 μM) induced cell death and apoptosis of all the cell lines; medium dose emodin (20 μM) preferentially inhibited osteosarcoma cells; low dose emodin (1–10 μM) preferentially inhibited p53 expressing osteosarcoma cells. Emodin dose-dependently inhibited p53 and p21 in U2OS. Emodin at 10 μM decreased the expression of Cdk2, E2F, and Cdk1; and increased RB but had no effects on cyclin E and cyclin B. The knockdown of p53 almost eliminated all the impacts of 10 μM emodin on cell cycle proteins. Conclusions: Emodin suppresses U2OS by p53-mediated cell cycle regulation.

Summary: R-loops are three-stranded structures that can pose threats to genome stability. RNase H1 precisely recognizes R-loops to drive their resolution within the genome, but the underlying mechanism is unclear. Here, we report that ARID1A recognizes R-loops with high affinity in an ATM-dependent manner. ARID1A recruits METTL3 and METTL14 to the R-loop, leading to the m6A methylation of R-loop RNA. This m6A modification facilitates the recruitment of RNase H1 to the R-loop, driving its resolution and promoting DNA end resection at DSBs, thereby ensuring genome stability. Depletion of ARID1A, METTL3, or METTL14 leads to R-loop accumulation and reduced cell survival upon exposure to cytotoxic agents. Therefore, ARID1A, METTL3, and METTL14 function in a coordinated, temporal order at DSB sites to recruit RNase H1 and to ensure efficient R-loop resolution. Given the association of high ARID1A levels with resistance to genotoxic therapies in patients, these findings open avenues for exploring potential therapeutic strategies for cancers with ARID1A abnormalities.

Abstract Impacts occur everywhere, and they pose a serious threat to human health and production safety. Flexible materials with efficient cushioning and energy absorption are ideal candidates to provide protection from impacts. Despite the high demand, the cushioning capacity of protective materials is still limited. In this study, an integrated bionic strategy is proposed, and a bioinspired structural composite material with highly cushioning performance is developed on the basis of this strategy. The results demonstrated that the integrated bionic material, an S‐spider web‐foam, has excellent energy storage and dissipation as well as cushioning performance. Under impact loading, S‐spider web‐foam can reduce peak impact forces by a factor of 3.5 times better than silicone foam, achieving unprecedented cushioning performance. The results of this study deepen the understanding of flexible cushioning materials and may provide new strategies and inspiration for the preparation of high‐performance flexible cushioning materials.

Abstract The α1A-adrenergic receptor (α1AAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. α1AAR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human α1AAR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.9 Å to 3.5 Å. Our active and inactive α1AAR structures reveal the activation mechanism and distinct ligand binding modes for noradrenaline compared with other adrenergic receptor subtypes. In addition, we identified a nanobody that preferentially binds to the extracellular vestibule of α1AAR when bound to the selective agonist oxymetazoline. These results should facilitate the design of more selective therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family.

Abstract Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact of aberrant parental histone partition on human disease such as cancer is largely unknown. In this study, we construct a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast cancer cells. The resulting impaired histone inheritance reprograms the histone modification landscapes of progeny cells, especially the repressive histone mark H3K27me3. Lower H3K27me3 levels derepress the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. These epigenetic changes confer fitness advantages to some newly emerged subclones and consequently promote tumor growth and metastasis after orthotopic implantation. In summary, our results indicate that impaired inheritance of parental histones can drive tumor progression.

Abstract Photoelectrochemical water splitting has long been considered an ideal approach to producing green hydrogen by utilizing solar energy. However, the limited photocurrents and large overpotentials of the anodes seriously impede large-scale application of this technology. Here, we use an interfacial engineering strategy to construct a nanostructural photoelectrochemical catalyst by incorporating a semiconductor CdS/CdSe-MoS2 and NiFe layered double hydroxide for the oxygen evolution reaction. Impressively, the as-prepared photoelectrode requires an low potential of 1.001 V vs. reversible hydrogen electrode for a photocurrent density of 10 mA cm−2, and this is 228 mV lower than the theoretical water splitting potential (1.229 vs. reversible hydrogen electrode). Additionally, the generated current density (15 mA cm−2) of the photoelectrode at a given overpotential of 0.2 V remains at 95% after long-term testing (100 h). Operando X-ray absorption spectroscopy revealed that the formation of highly oxidized Ni species under illumination provides large photocurrent gains. This finding opens an avenue for designing high-efficiency photoelectrochemical catalysts for successive water splitting.

Abstract Objectives Many factors are related to oncology nurses’ professional values. However, the evidence on the relevance of professional values among oncology nurses in China remains sparse. This study aims to investigate the relationship between depression, self-efficacy, and professional values among Chinese oncology nurses and analyze the mediating effect of self-efficacy on this association. Methods It was a multicenter cross-sectional study designed with the STROBE guidelines. An anonymous online questionnaire recruited 2530 oncology nurses from 55 hospitals in six provinces of China between March and June 2021. Measures included self-designed sociodemographic and fully validated instruments. Pearson correlation analysis was employed to explore the associations between depression, self-efficacy, and professional values. Bootstrapping analysis by the PROCESS macro was used to examine the mediating effect of self-efficacy. Results The total scores of depression, self-efficacy, and professional values of Chinese oncology nurses were 52.75 ± 12.62, 28.39 ± 6.33, and 101.55 ± 20.43, respectively. About 55.2% of Chinese oncology nurses were depressed. Chinese oncology nurses’ professional values were generally intermediate. Their professional values were negatively related to depression and positively correlated with self-efficacy, while depression was negatively related to self-efficacy. Moreover, self-efficacy partially mediated the relationship between depression and professional values, accounting for 24.8% of the total effect. Conclusions Depression negatively predicts self-efficacy and professional values, and self-efficacy positively predicts professional values. Meanwhile, depression in Chinese oncology nurses has an indirect effect on their professional values through self-efficacy. Nursing managers and oncology nurses themselves should develop strategies aimed at relieving depression and improving self-efficacy to strengthen their positive professional values.

Abstract G protein-coupled receptors (GPCRs) within the same subfamily often share high homology in their orthosteric pocket and therefore pose challenges to drug development. The amino acids that form the orthosteric binding pocket for epinephrine and norepinephrine in the β1 and β2 adrenergic receptors (β1AR and β2AR) are identical. Here, to examine the effect of conformational restriction on ligand binding kinetics, we synthesized a constrained form of epinephrine. Surprisingly, the constrained epinephrine exhibits over 100-fold selectivity for the β2AR over the β1AR. We provide evidence that the selectivity may be due to reduced ligand flexibility that enhances the association rate for the β2AR, as well as a less stable binding pocket for constrained epinephrine in the β1AR. The differences in the amino acid sequence of the extracellular vestibule of the β1AR allosterically alter the shape and stability of the binding pocket, resulting in a marked difference in affinity compared to the β2AR. These studies suggest that for receptors containing identical binding pocket residues, the binding selectivity may be influenced in an allosteric manner by surrounding residues, like those of the extracellular loops (ECLs) that form the vestibule. Exploiting these allosteric influences may facilitate the development of more subtype-selective ligands for GPCRs.

This paper studies the impact of half-height infilled walls on the failure modes of frame columns through quasi-static tests of both frame models and half-height infilled wall frame models. Based on the experimental results, a seismic analysis model of reinforced concrete (RC) frame structures is established, and parametric studies are carried out to analyze the effects of masonry materials and masonry heights on the seismic performance of structures. The results show that the load-bearing capacity and stiffness of the structure are improved, while the ductility of the structure is reduced because of the existence of infilled walls. As the height of infilled walls increases, there is a notable decrease in the free height of frame columns. At a wall-to-column height ratio of 0.2, the masonry walls exert a negligible effect on the frame structure’s seismic performance. In contrast, at a ratio of 0.6, there is a transition in column failure modes from bending to shearing. When evaluated at consistent masonry heights, aerated concrete block-infilled walls demonstrate the least impact on the seismic performance of RC frame structures. Thus, in the absence of additional structural enhancements, the use of aerated concrete blocks is recommended to mitigate the negative implications of infilled walls on the seismic integrity of RC frames.

Spodoptera frugiperda was used to investigate its role as a trehalase inhibitor of three new thiothiazolidone compounds—6d, 6e, and 6f. The development and reproduction of S. frugiperda were investigated to evaluate the potential of these compounds as a novel pesticide for pest control. Compounds 6d, 6e, and 6f were injected into larvae and female pupae. Molecular changes in trehalose and chitin metabolism genes were monitored. Pupal trehalase activity, the female pupal emergence rate, ovarian development, and SfVg and SfVgR gene expression levels were assessed. The results revealed that all three compounds significantly inhibited trehalase activity in the larvae. The expression of TRE was significantly downregulated, and compounds 6d and 6f significantly downregulated the expression of TRE2. Treated larvae exhibited significantly decreased survival rates and a higher incidence of abnormalities. The egg production and hatching rates were markedly diminished by the inhibitors, and the ovaries displayed blackening and clumping. These compounds exhibit promise as eco-friendly insecticides, but further experiments are required to test their multifaceted capabilities.

In order to improve the seismic performance of reinforced concrete (RC) frames, carbon fiber-reinforced polymer (CFRP) was used to retrofit reinforced concrete frame structures. The comparison pseudo-static test results show that the peak load, initial stiffness and ductility of the CFRP retrofitted model were increased by 43.89%, 39.27% and 30.1%, respectively. Based on the parametric study of the finite element model, the contribution of CFRP to the seismic upgrading effect of RC columns was quantitatively revealed, and an optimized design of retrofitted CFRP was proposed. The results show that the peak load, ductility and energy dissipation capacity of the whole structure are improved by using CFRP full-wrap reinforcement and strip reinforcement models with different coverage areas. The damage degree of the column decreases, the damage degree of the beam increases, and the failure mode changes from “column hinge” to “beam hinge”. Simultaneously, different CFRP reinforcement areas and the distance between strip CFRP have different reinforcement effects on concrete structures. Based on the investigation results, the recommended ratio of CFRP strip to spacing is 1 to 1.25.

When launching a heavy-duty vehicle, torque and position control during automatic clutch engagement is critical, and the driver’s intention to launch and changes in the vehicle’s launching resistance make clutch control more complex. This paper analyses the automatic engagement process of automated mechanical transmission (AMT) clutches and proposes an optimal control of the clutch torque for launching heavy-duty vehicles. Firstly, a fuzzy neural network (FNN)-based vehicle launching states recognition (LSR) system is designed for distinguishing the driver’s launching intention and the vehicle’s launching equivalent moment of resistance. Secondly, jerk, friction work, and launching reserve power are taken as the performance indexes for clutch torque optimization, the weight coefficients of each performance index are adjusted according to the LSR results, and the optimal clutch torque is solved by using the minimum value principle based on the shooting method. Finally, simulations and tests are conducted to validate the strategy of optimizing clutch torque, and the impact of torque optimization on the position change during the engagement process is analyzed. The results indicate that under different driver’s intentions, vehicle masses, and road gradient conditions, the jerk, friction work, and slipping time of heavy vehicles during the launching process are improved by applying the optimization strategy.