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Abstract Background Cold stress poses a serious challenge to tropical fruit production, particularly in mango. N6-methyladenosine (m6A) modifications are key regulators of gene expression, enabling plants to respond to stress responses, enhance adaptation and improve resilience to environmental challenges. Results In our study, transcriptome-wide m6A methylation profiling under cold stress identified 6,499 differentially methylated m6A peaks and 2,164 differentially expressed genes (DEGs) in mango seedlings. Among these genes, six exhibited both significant increases in m6A modification levels and gene expression, 21 showed a significant increase in m6A levels but a concurrent downregulation of gene expression, and 26 showed reduced m6A levels but exhibited increased gene expression, highlighting distinct regulatory patterns in m6A-mediated gene expression control. Gene Ontology (GO) enrichment analysis revealed significant involvement in pathways such as potassium ion import, nitrate response, and transcription regulation. Notably, HSP70 was one of the upregulated genes in response to cold stress. RNA immunoprecipitation (RNA-IP) assays confirmed the association of HSP70 with m6A-modified RNAs in vivo, supporting its role in regulating stress-responsive transcripts. Additionally, immunofluorescence analysis demonstrated the formation of HSP70 condensates in plant cells under cold stress, indicating a potential mechanism for localized RNA stabilization. Fluorescence polarization assays demonstrated that HSP70 binds preferentially to m6A-modified RNAs, suggesting its role in forming protective condensates under cold conditions. This interaction between m6A modification and HSP70 points to a potential mechanism that helps stabilize stress-responsive transcripts, contributing to the plant’s enhanced cold tolerance. Conclusions m6A modifications play a vital role in regulating gene expression under cold stress, offering new insights into mango’s stress responses and potential breeding strategies for cold tolerance.

Abstract Purpose Multiple myeloma (MM) is the second most common hematologic malignancy, and there is no cure for this disease. This study aimed to explore the prognostic value of long noncoding RNAs (lncRNAs) in MM and to reveal related immune and chemotherapy resistance mechanisms. Methods In this study, lncRNA profiles from the Multiple Myeloma Research Foundation (MMRF) and Gene Expression Omnibus (GEO) databases were analyzed to identify lncRNAs linked to MM patient survival. A risk assessment model stratified patients into high- and low-risk groups, and survival was evaluated. Additionally, a triple-ceRNA (lncRNA–miRNA–mRNA) network was constructed, and functional analysis was performed. The research also involved immune function analysis and chemotherapy drug sensitivity assessment using oncoPredict and the GDSC dataset. Results We identified 422 lncRNAs significantly associated with overall survival in MM patients and ultimately focused on the 6 with the highest prognostic value. These lncRNAs were used to develop a risk score formula that stratified patients into high- and low-risk groups. Kaplan–Meier analysis revealed shorter survival in high-risk patients. We integrated this lncRNA signature with clinical parameters to construct a nomogram for predicting MM prognosis. Additionally, a triple-ceRNA network was constructed to reveal potential miRNA targets, coding genes related to these lncRNAs and significantly enriched pathways. Immune checkpoint gene expression and immune cell composition were also analyzed in relation to the lncRNA risk score. Finally, using the oncoPredict tool, we observed that high-risk patients exhibited decreased sensitivity to key MM chemotherapeutics, suggesting that lncRNA profiles are linked to chemotherapy resistance.

Abstract Background Pathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies. Methods Nine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them. Results Three of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn’t reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively. Conclusion Our study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.

Abstract Background We aimed to analyse genome‐wide transcriptome differences between Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients and identify biomarkers that correlate well with muscle magnetic resonance imaging (MRI) and histological fibrofatty replacement in both patients, which have not been reported. Methods One hundred and one male patients with dystrophinopathies (55 DMD and 46 BMD) were enrolled. Muscle‐derived genome‐wide RNA‐sequencing was performed in 31 DMD patients, 29 BMD patients, and 11 normal controls. Fibrofatty replacement was scored on muscle MRI and histological levels in all patients. A unique pipeline, single‐sample gene set enrichment analysis combined with Spearman's rank correlations (ssGSEA‐Cor) was developed to identify the most correlated gene signature for fibrofatty replacement. Quantitative real‐time PCR (qRT‐PCR) analysis, western blot analysis, and single‐nucleus RNA‐sequencing (snRNA‐seq) were performed in the remaining patients to validate the most correlated gene signature. Results Comparative transcriptomic analysis revealed that 31 DMD muscles were characterized by a significant increase of inflammation/immune response and extracellular matrix remodelling compared with 29 BMD muscles (P

Abstract Background N7-methylguanosine (m7G) is one of the most conserved modifications in nucleosides impacting mRNA export, splicing, and translation. However, the precise function and molecular mechanism of internal mRNA m7G methylation in adult hippocampal neurogenesis and neurogenesis-related Alzheimer’s disease (AD) remain unknown. Results We profiled the dynamic Mettl1/Wdr4 expressions and m7G modification during neuronal differentiation of neural stem cells (NSCs) in vitro and in vivo. Adult hippocampal neurogenesis and its molecular mechanisms were examined by morphology, biochemical methods and biological sequencing. The translation efficiency of mRNA was detected by polysome profiling. The stability of Sptbn2 mRNA was constructed by RNA stability assay. APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as model of AD. Morris water maze was used to detect the cognitive function. Methods We found that m7G methyltransferase complex Mettl1/Wdr4 as well as m7G was significantly elevated in neurons. Functionally, silencing Mettl1 in neural stem cells (NSCs) markedly decreased m7G modification, neuronal genesis and proliferation in addition to increasing gliogenesis, while forced expression of Mettl1 facilitated neuronal differentiation and proliferation. Mechanistically, the m7G modification of Sptbn2 mRNA by Mettl1 enhanced its stability and translation, which promoted neurogenesis. Importantly, genetic defciency of Mettl1 reduced hippocampal neurogenesis and spatial memory in the adult mice. Furthermore, Mettl1 overexpression in the hippocampus of APP/PS1 mice rescued neurogenesis and behavioral defects. Conclusion Our findings unravel the pivotal role of internal mRNA m7G modification in Sptbn2-mediated neurogenesis, and highlight Mettl3 regulation of neurogenesis as a novel therapeutic target in AD treatment.

Distributed drive electric vehicles improve steering response and enhance overall vehicle stability by independently controlling each motor. This paper introduces a control framework based on Adaptive Model Predictive Control (AMPC) for coordinating handling stability, consisting of three layers: the dynamic supervision layer, online optimization layer, and low-level control layer. The dynamic supervision layer considers the yaw rate and maneuverability limits when establishing the β−β˙ phase plane stability boundary and designs variable weight factors based on this stability boundary. The online optimization layer constructs the target weight-adaptive AMPC strategy, which can adjust the control weights for maneuverability and lateral stability in real time based on the variable weight factors provided by the dynamic supervision layer. The low-level control layer precisely allocates the driver’s requested driving force and additional yaw moment by using torque distribution error and tire utilization as the cost function. Finally, experiments are conducted on a Simulink-CarSim co-simulation platform to assess the performance of AMPC. Simulation results show that, compared to the traditional MPC strategy, this control strategy not only enhances maneuverability under normal conditions but also improves lateral stability control under extreme conditions.

Providing safe, smooth, and efficient trajectories for autonomous vehicles has long been a question of great interest in the field of autopiloting. In dynamic and ever-changing urban environments, safe and efficient trajectory planning is fundamental to achieving autonomous driving. Nevertheless, the complexity of environments with multiple constraints poses challenges for trajectory planning. It is possible that behavior planners may not successfully obtain collision-free trajectories in complex urban environments. Herein, this paper introduces spatio–temporal joint optimization-based trajectory planning (SJOTP) with multi-constraints for complex urban environments. The behavior planner generates initial trajectory clusters based on the current state of the vehicle, and a topology-guided hybrid A* algorithm applied to an inflated map is utilized to address the risk of collisions between the initial trajectories and static obstacles. Taking into consideration obstacles, road surface adhesion coefficients, and vehicle dynamics constraints, multi-constraint multi-objective coordinated trajectory planning is conducted, using both differential-flatness vehicle models and point-mass vehicle models. Taking into consideration longitudinal and lateral coupling in trajectory optimization, a spatio–temporal joint optimization solver is used to obtain the optimal trajectory. The simulation verification was conducted on a multi-agent simulation platform. The results demonstrate that this methodology can obtain optimal trajectories safely and efficiently in complex urban environments.

Most pathogenic DMD variants are detectable and interpretable by standard genetic testing for dystrophinopthies. However, approximately 1∼3% of dystrophinopthies patients still do not have a detectable DMD variant after standard genetic testing, most likely due to structural chromosome rearrangements and/or deep intronic pseudoexon-activating variants. Here, we report on a boy with a suspected diagnosis of Becker muscular dystrophy (BMD) who remained without a detectable DMD variant after exonic DNA-based standard genetic testing. Dystrophin mRNA studies and genomic Sanger sequencing were performed in the boy, followed by in silico splicing analyses. We successfully detected a novel deep intronic disease-causing variant in the DMD gene (c.2380 + 3317A > T), which consequently resulting in a new dystrophin pseudoexon activation through the enhancement of a cryptic donor splice site. The patient was therefore genetically diagnosed with BMD. Our case report further emphasizes the significant role of disease-causing splicing variants within deep intronic regions in genetically undiagnosed dystrophinopathies.

Abstract N7-methylguanosine (m7G) modification signature has recently emerged as a crucial regulator of tumor progression and treatment in cancer. However, there is limited information available on the genomic profile of lower-grade gliomas (LGGs) related to m7G methylation modification genes’ function in tumorigenesis and progression. In this study, we employed bioinformatics methods to characterize m7G modifications in individuals with LGG from The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). We used gene set enrichment analysis (GSEA), single sample GSEA (ssGSEA), CIBERSORT algorithm, ESTIMATE algorithm, and TIDE to evaluate the association between m7G modification patterns, tumor microenvironment (TME) cell infiltration properties, and immune infiltration markers. The m7G scoring scheme using principal component analysis (PCA) was employed to investigate the m7G modification patterns quantitatively. We examined the m7G modification hub genes' expression levels in normal samples, refractory epilepsy samples, and LGG samples using immunohistochemistry, western-blotting, and qRT-PCR. Our findings revealed that individuals with LGG could be categorized into two groups based on m7G scores (high and low) according to the properties of m7G. Moreover, we observed that high m7G score was associated with significant clinical benefit and prolonged survival duration in the anti-PD-1 cohort, while low m7G score was associated with improved prognostic outcomes and increased likelihood of complete or partial response in the anti-PD-L1 cohort. Different m7G subtypes also showed varying Tumor Mutational Burden (TMB) and immune profiles and might have distinct responses to immunotherapy. Furthermore, we identified five potential genetic markers that were highly correlated with the m7G score signature index. These findings provide insight into the features and classification associated with m7G methylation modifications and may aid in improving the clinical outcome of LGG.

Previous research has suggested a link between gut microbiota and attention deficit hyperactivity disorder (ADHD), but their causal relationship has not been elucidated. Aiming to comprehensively investigate their causal relationship and to identify specific causal microbe taxa for ADHD, we conducted a two-sample Mendelian randomization (MR) analysis. Instrumental variables of 211 gut microbiota taxa were obtained from gene wide association study (GWAS), and Mendelian randomization study was carried out to estimate their effects on ADHD risk from PGC GWAS (20,183 ADHD cases and 35,191 controls) and FinnGen GWAS (830 ADHD cases and 215,763 controls). Wald ratio (WR), inverse variance weighted (IVW), MR-Egger, and weighted median were the main methods to analyze causality, and MR results are verified by several sensitivity analysis analyses. At locus-wide significance level (p 0.05) and pleiotropy (p > 0.05) confirmed the robustness of MR results. We demonstrated that there was a potential causal relationship between gut microbiota and ADHD. Our research provides a foundation for understanding the causal relationship between gut microbiota and ADHD, and the several gut bacteria found in this study that may reduce the occurrence of ADHD may have potential in the prevention and treatment of ADHD.

Shear thickening fluids (STFs) can effectively enhance the ballistic performance of Kevlar. Considering that the unique shear thickening effect of STF is the key factor to enhance the impact resistance of fabrics, this study sought to reveal the impact resistance mechanism of STF-Kevlar and guide its further design by using a numerical simulation method of fluid–structure interaction. The ballistic limits of neat Kevlar and STF-Kevlar in the ballistic tests were 55.14 m/s and 72.40 m/s, respectively, and the simulation predictions were 55.58 m/s and 70.40 m/s, which indicated that the established finite element model has high accuracy for predicting the ballistic performance curve of the fabric. The results of numerical simulation showed that STF-Kevlar has smaller deformation during the impact process than neat Kevlar. Due to the strengthening effect of STF, the resistance of STF-Kevlar to the elastomer was greater than that of neat fabric. With the increase of the impact velocity, the STF-Kevlar increasingly relied on STF to absorb energy. In engineering practice, through the fluid–structure interaction numerical simulation method, the prediction of the ballistic performance of the composite fabric can be realized in the early stage of manufacture, and guide further design and optimization.

The study aimed to research the effects of innovative running shoes (a high heel-to-toe drop and special structure of midsole) on the biomechanics of the lower limbs and perceptual sensitivity in female runners. Fifteen healthy female runners were recruited to run through a 145-m runway with planted force plates at one peculiar speed (3.6 m/s ± 5%) with two kinds of shoe conditions (innovative running shoes vs. normal running shoes) while getting biomechanical data. The perception of shoe characteristics was assessed simultaneously through a 15-cm visual analog scale. The statistical parametric mapping technique calculated the time-series parameters. Regarding 0D parameters, the ankle dorsiflexion angle of innovative running shoes at touchdown was higher, and the peak dorsiflexion angle, range of motion, peak dorsiflexion velocity, and plantarflexion moment on the metatarsophalangeal joint of innovative running shoes during running were significantly smaller than those of normal running shoes (all p < 0.001). In addition, the braking phase and the time of peak vertical force 1 of innovative running shoes were found to be longer than those of normal running shoes (both p < 0.05). Meanwhile, the average vertical loading rate 1, peak vertical loading rate 1, peak braking force, and peak vertical force 1 in the innovative running shoes were lower than those of the normal running shoes during running (both p < 0.01). The statistical parametric mapping analysis exhibited a higher ankle dorsiflexion angle (0–4%, p < 0.05), a smaller knee internal rotation angle (0–6%, p < 0.05) (63–72%, p < 0.05), a decreased vertical ground reaction force (11–17%, p = 0.009), and braking anteroposterior ground reaction force (22–27%, p = 0.043) for innovative running shoes than normal running shoes. Runners were able to perceive the cushioning of innovative running shoes was better than that of normal running shoes. These findings suggested combining the high offset and structure of the midsole would benefit the industrial utilization of shoe producers in light of reducing the risk of running injuries for female runners.

Abstract Background The prevalence of myopia and associated risk factors among children in Chongqing has not yet been determined. This study investigated the prevalence of myopia and possible relationships between myopia and several related factors among school children in Chongqing. Methods This cross-sectional study assessed a sample of 997 children (7–13 years of age) attending primary school in Chongqing. Data were obtained from visual acuity and refractive error measurements and a structured questionnaire. Myopia was defined as visual acuity

When the single-phase reclosing of the high-voltage circuit, there will be tremendous negative sequence current generation. The connection of inverter-type new energy sources may increase the negative sequence current of the power system. The risks will be greatly increased if a large negative sequence current invades the generator, and it will cause the general stator damaged and offline. Based on the chain STATCOM compensation, a new strategy of negative sequence current coordinated control protection on the generator extremity is put forward. This strategy can predict the operation time of inverse time negative sequence current protection by monitoring the negative sequence current on the generator extremity. Once it is determined that the negative sequence current has an effect on the power system, according to the relationship between the STATCOM capacity and the magnitude of negative sequence current, two schemes of full compensation and incomplete compensation are proposed. The negative sequence current output by STATCOM suppresses the magnitude of the negative sequence current invading the generator. It eliminates or prolongs the operation time of the negative sequence current protection and gets more time for power system security and stability control. Finally, the simulation results verify the correctness and feasibility of the proposed strategy.

Background and objective. The cell cycle-related and expression-elevated protein in tumor (CREPT) is overexpressed in several human cancers. Establishing a method for purifying CREPT from mouse ascites is vital for further research. This study was aimed at establishing a method for purifying CREPT from mouse ascites. Methods. Cells were cultivated properly to obtain 3E10 CREPT monoclonal antibody cells in the logarithmic growth stage. Monoclonal antibody cells were injected into the abdominal cavity of sensitized mice. The flowing ascites were observed for 7-15 days. The antibody protein was obtained by collection, filtration, dilution, loading, and chromatography. Furthermore, its binding force was detected by SDS-PAGE and Western blot techniques. Results. The antibody protein was successfully obtained with a purity of 1895 μg/mL with high liveness. Conclusion. This study establishes a one-step purification method for obtaining monoclonal antibody with high liveness and purity for CREPT ascites antibody. This method is simple to perform and lays a foundation for the preparation and purification of humanized monoclonal antibodies in the future. In addition, it provides a basis for further research to investigate how CREPT affects the occurrence and development of different tumors.

Abstract Background Dystrophin-glycoprotein complex (DGC)-related muscular dystrophies may present similar clinical and pathological features as well as undetectable mutations thus being sometimes difficult to distinguish. We investigated the value of muscle magnetic resonance imaging (MRI) in the differential diagnosis of DGC-related muscular dystrophies and reported the largest series of Chinese patients with sarcoglycanopathies studied by muscle MRI. Results Fifty-five patients with DGC-related muscular dystrophies, including 22 with confirmed sarcoglycanopathies, 11 with limb-girdle muscular dystrophy 2I (LGMD2I, FKRP-associated dystroglycanopathy), and 22 with dystrophinopathies underwent extensive clinical evaluation, muscle biopsies, genetic analysis, and muscle MRI examinations. Hierarchical clustering of patients according to the clinical characteristics showed that patients did not cluster according to the genotypes. No statistically significant differences were observed between sarcoglycanopathies and LGMD2I in terms of thigh muscle involvement. The concentric fatty infiltration pattern was observed not only in different sarcoglycanopathies (14/22) but also in LGMD2I (9/11). The trefoil with single fruit sign was observed in most patients with dystrophinopathies (21/22), and a few patients with sarcoglycanopathies (4/22) or LGMD2I (2/11). Hierarchical clustering showed that most patients with sarcoglycanopathies or LGMD2I can be distinguished from dystrophinopathies based on the concentric fatty infiltration pattern and trefoil with single fruit sign at the thigh level on muscle MRI. Conclusions Muscle MRI at the thigh level potentially allows distinction of sarcoglycanopathies or FKRP-associated dystroglycanopathy from dystrophinopathies.

Phosphate rock has been considered as one of the most significant secondary rare-earth resource, and the utilization of rare earth elements (REEs) in phosphate rock has attracted increasing attention. In this study, the leaching kinetics of REEs from a phosphate ore from China was studied with the variation of temperature and phosphoric acid concentration under the conditions: ratio of liquid to solid of 12 mL/g, stirring speed of 120 r/min, and phosphate particle size of −0.074 mm amounts 61.1%. The results suggest that there were two distinct stages in leaching process and kinetics of both stages followed shrinking core model. At fast reaction stage, the semi-empirical equation describing the kinetics was 1 − 3(1 − α)2/3 + 2(1 − α) = 1.885CH3PO40.89exp(−11220/8.31T)t. The semi-empirical equation for slow reaction stage was 1 − 3(1 − α)2/3 + 2(1 − α) = 0.299CH3PO42.50exp(−18720/8.31T)t. Using shrinking core model and time-to-a-given-fraction method, we found that leaching rate of fast reaction stage was controlled by solid product layer diffusion, and both solid product layer diffusion and chemical reaction determined slow reaction stage.

Pasteurella multocida is a leading cause of respiratory diseases in many host species. To understand the genetic characteristics of P. multocida strains isolated from different host species, we sequenced the genomic DNA of P. multocida isolated from pigs and analyzed the genetic characteristics of strains from avian species, bovine species, pigs, and rabbits using whole genome sequence (WGS) data. Our results found that a capsular: lipopolysaccharide (LPS): multilocus sequence typing (MLST) genotype A: L1: ST129 (43.75%) was predominant in avian P. multocida; while genotypes B: L2: ST122 (60.00%) and A: L3: ST79 (30.00%) were predominate in bovine P. multocida; genotype D: L6: ST50 (37.50%) in porcine P. multocida; and genotype A: L3: ST9 (76.47%) in rabbit P. multocida. Comparative genomic analysis of P. multocida from different host species found that there are no genes in the P. multocida genome that are specific to any type of host. Phylogenetic analysis using either whole-genome single nucleotide polymorphisms (SNPs) or the set of SNPs present in all single-copy core genes across genomes showed that P. multocida strains with the same LPS genotype and MLST genotype were clustered together, suggesting the combining both the LPS and MLST typing schemes better explained the topology seen in the P. multocida phylogeny.