Cross-ancestry analysis of brain QTLs enhances interpretation of schizophrenia genome-wide association studies.

Research on brain expression quantitative trait loci (eQTLs) has illuminated the genetic underpinnings of schizophrenia (SCZ). Yet most of these studies have been centered on European populations, leading to a constrained understanding of population diversities and disease risks. To address this gap, we examined genotype and RNA-seq data from African Americans (AA, n = 158), Europeans (EUR, n = 408), and East Asians (EAS, n = 217). When comparing eQTLs between EUR and non-EUR populations, we observed concordant patterns of genetic regulatory effect, particularly in terms of the effect sizes of the eQTLs. However, 343,737 cis-eQTLs linked to 1,276 genes and 198,769 SNPs were found to be specific to non-EUR populations. Over 90% of observed population differences in eQTLs could be traced back to differences in allele frequency. Furthermore, 35% of these eQTLs were notably rare in the EUR population. Integrating brain eQTLs with SCZ signals from diverse populations, we observed a higher disease heritability enrichment of brain eQTLs in matched populations compared to mismatched ones. Prioritization analysis identified five risk genes (SFXN2, VPS37B, DENR, FTCDNL1, and NT5DC2) and three potential regulatory variants in known risk genes (CNNM2, MTRFR, and MPHOSPH9) that were missed in the EUR dataset. Our findings underscore that increasing genetic ancestral diversity is more efficient for power improvement than merely increasing the sample size within single-ancestry eQTLs datasets. Such a strategy will not only improve our understanding of the biological underpinnings of population structures but also pave the way for the identification of risk genes in SCZ.

Cannabidiol ameliorates cognitive decline in 5×FAD mouse model of Alzheimer's disease through potentiating the function of extrasynaptic glycine receptors.

Emerging evidence supports the therapeutic potential of cannabinoids in Alzheimer's disease (AD), but the underlying mechanism upon how cannabinoids impact brain cognition and AD pathology remains unclear. Here we show that chronic cannabidiol (CBD) administration significantly mitigates cognitive deficiency and hippocampal ß-amyloid (Aß) pathology in 5×FAD mouse model of AD. CBD achieves its curative effect mainly through potentiating the function of inhibitory extrasynaptic glycine receptor (GlyR) in hippocampal dentate gyrus (DG). Based on the in vitro and in vivo electrophysiological recording and calcium imaging, CBD mediated anti-AD effects via GlyR are mainly accomplished by decreasing neuronal hyperactivity of granule cells in the DG of AD mice. Furthermore, the AAV-mediated ablation of DG GlyRα1, or the GlyRα1S296A mutation that exclusively disrupts CBD binding, significantly intercepts the anti-AD effect of CBD. These findings suggest a GlyR dependent mechanism underlying the therapeutic potential of CBD in the treatment of AD.

CD74+ fibroblasts proliferate upon mechanical stretching to promote angiogenesis in keloids.

The healing of human skin wounds is susceptible to perturbation caused by excessive mechanical stretching, resulting in enlarged scars, hypertrophic scars, or even keloids in predisposed individuals. Keloids are fibro-proliferative scar tissues that extend beyond the initial wound boundary, consisting of the actively progressing periphery and the quiescent center. The stretch-associated outgrowth and enhanced angiogenesis are two features of the periphery of keloids. However, which cell population is responsible for transducing the mechanical stimulation to the progression of keloids remains unclear. Herein, through integrative analysis of single-cell RNA sequencing of keloids, we identified CD74+ fibroblasts, a previously unappreciated subset of fibroblasts with pro-angiogenic and stretch-induced proliferative capacities, as a key player in stretch-induced progression of keloids. Immunostaining of keloid cryosections depicted a predominant distribution of CD74+ fibroblasts in the periphery, interacting with the vasculature. In vitro tube formation assays on purified CD74+ fibroblasts ascertained their pro-angiogenic function. BrdU assays revealed that these cells proliferate upon stretching, through PIEZO1-mediated calcium influx and the downstream ERK and AKT signaling. Collectively, our findings propose a model wherein CD74+ fibroblasts serve as pivotal drivers of stretch-induced keloid progression, fueled by their proliferative and pro-angiogenic activities. Targeting the attributes of CD74+ fibroblasts holds promise as a therapeutic strategy for the management of keloids.

Improved Multi-Size, Multi-Target and 3D Position Detection Network for Flowering Chinese Cabbage Based on YOLOv8.

Accurately detecting the maturity and 3D position of flowering Chinese cabbage (Brassica rapa var. chinensis) in natural environments is vital for autonomous robot harvesting in unstructured farms. The challenge lies in dense planting, small flower buds, similar colors and occlusions. This study proposes a YOLOv8-Improved network integrated with the ByteTrack tracking algorithm to achieve multi-object detection and 3D positioning of flowering Chinese cabbage plants in fields. In this study, C2F-MLCA is created by adding a lightweight Mixed Local Channel Attention (MLCA) with spatial awareness capability to the C2F module of YOLOv8, which improves the extraction of spatial feature information in the backbone network. In addition, a P2 detection layer is added to the neck network, and BiFPN is used instead of PAN to enhance multi-scale feature fusion and small target detection. Wise-IoU in combination with Inner-IoU is adopted as a new loss function to optimize the network for different quality samples and different size bounding boxes. Lastly, ByteTrack is integrated for video tracking, and RGB-D camera depth data are used to estimate cabbage positions. The experimental results show that YOLOv8-Improve achieves a precision (P) of 86.5% and a recall (R) of 86.0% in detecting the maturity of flowering Chinese cabbage. Among them, mAP50 and mAP75 reach 91.8% and 61.6%, respectively, representing an improvement of 2.9% and 4.7% over the original network. Additionally, the number of parameters is reduced by 25.43%. In summary, the improved YOLOv8 algorithm demonstrates high robustness and real-time detection performance, thereby providing strong technical support for automated harvesting management.

Temporal dynamics of negative emotional memory reprocessing during sleep.

Memory reprocessing during sleep is a well-established phenomenon in numerous studies. However, it is unclear whether the intensity of memory reprocessing is consistently maintained throughout the night or exhibits dynamic changes. This study investigates the temporal dynamics of negative emotional memory reprocessing during sleep, with a specific focus on slow oscillation (SO)-spindle coupling and its role in memory reprocessing. In the first experiment (N = 40, mean age = 22.5 years), we detected the negative emotional memory reprocessing strength in each sleep cycle, we found that the 2nd sleep cycle after negative emotional memory learning constitute the most sensitive window for memory reprocessing, furthermore, SO-spindle coupling signals in this window plays a role in stabilizing negative emotional memory. To verify the role of SO-spindle coupling in negative emotional memory reprocessing, we utilized transcranial alternating current stimulation (tACS) to disrupt SO-spindle coupling during the 2nd sleep cycle (N = 21, mean age = 19.3 years). Notably, the outcomes of the tACS intervention demonstrated a significant reduction in the recognition of negative emotional memories. These findings offer new insights into the mechanisms that regulate emotional memory consolidation during sleep and may have implications for addressing psychiatric disorders associated with pathological emotional memory.

Targeting HPV for the prevention, diagnosis, and treatment of Cervical Cancer.

Despite advances in screening and prevention, cervical cancer (CC) remains an unresolved public health issue and poses a significant global challenge, particularly for women in low-income regions. Human papillomavirus (HPV) infection, especially with the high-risk strains, is a primary driver of cervical carcinogenesis. Emerging evidence indicates that integrating HPV testing with existing approaches, such as cervical cytology and visual inspection, offers enhanced sensitivity and specificity in CC screening. HPV infection-associated biomarkers, including HPV E6/E7 oncogenes, p16^INK4a, DNA methylation signatures, and non-coding RNAs, offer valuable insights into disease progression and the development of personalized interventions. Preventive and therapeutic vaccination against HPV, along with tertiary prevention strategies such as the use of antiviral and immune-modulating drugs for HPV-related lesions, show great clinical potential. At the mechanistic level, single-cell RNA sequencing analysis and the development of organoid models for HPV infection provide new cellular and molecular insights into HPV-related CC pathogenesis. This review focuses on the crucial roles of HPV in the prevention, diagnosis, and treatment of CC, with particular emphasis on the latest advancements in screening and disease intervention.

H3K14ac facilitates the reinstallation of constitutive heterochromatin in Drosophila early embryos by engaging Eggless/SetDB1.

Constitutive heterochromatin, a fundamental feature of eukaryotic nucleus essential for transposon silencing and genome stability, is rebuilt on various types of repetitive DNA in the zygotic genome during early embryogenesis. However, the molecular program underlying this process remains poorly understood. Here, we show that histone H3 lysine 14 acetylation (H3K14ac) is engaged in the reinstallation of constitutive heterochromatin in Drosophila early embryos. H3K14ac partially colocalizes with H3 lysine 9 trimethylation (H3K9me3) and its methyltransferase Eggless/SetDB1 around the mid-blastula transition. Concealing H3K14ac by either antibody injection or maternal knockdown of Gcn5 diminishes Eggless/SetDB1 nuclear foci and reduces the deposition of H3K9me3. Structural analysis reveals that Eggless/SetDB1 recognizes H3K14ac via its tandem Tudor domains, and disrupting the binding interface causes defects in Eggless/SetDB1 distribution and derepression of a subset of transposons. Therefore, H3K14ac, a histone modification normally associated with active transcription, is a crucial component of the early embryonic machinery that introduces constitutive heterochromatic features to the newly formed zygotic genome.

Structure and function of Mycobacterium tuberculosis EfpA as a lipid transporter and its inhibition by BRD-8000.3.

EfpA, the first major facilitator superfamily (MFS) protein identified in Mycobacterium tuberculosis (Mtb), is an essential efflux pump implicated in resistance to multiple drugs. EfpA-inhibitors have been developed to kill drug-tolerant Mtb. However, the biological function of EfpA has not yet been elucidated. Here, we present the cryo-EM structures of EfpA complexed with lipids or the inhibitor BRD-8000.3 at resolutions of 2.9 Å and 3.4 Å, respectively. Unexpectedly, EfpA forms an antiparallel dimer. Functional studies reveal that EfpA is a lipid transporter and BRD-8000.3 inhibits its lipid transport activity. Intriguingly, the mutation V319F, known to confer resistance to BRD-8000.3, alters the expression level and oligomeric state of EfpA. Based on our results and the observation of other antiparallel dimers in the MFS family, we propose an antiparallel-function model of EfpA. Collectively, our work provides structural and functional insights into EfpA's role in lipid transport and drug resistance, which would accelerate the development of antibiotics against this promising drug target.

Candida tropicalis-derived vitamin B3 exerts protective effects against intestinal inflammation by promoting IL-17A/IL-22-dependent epithelial barrier function.

Candida tropicalis-a prevalent gut commensal fungus in healthy individuals - contributes to intestinal health and disease. However, how commensal C. tropicalis influences intestinal homeostasis and barrier function is poorly understood. Here, we demonstrated that the reference strain of C. tropicalis (MYA-3404) ameliorated intestinal inflammation in murine models of chemically induced colitis and bacterial infection. Intestinal colonization of C. tropicalis robustly upregulated the expression of IL-17A and IL-22 to increase barrier function and promote proliferation of intestinal epithelial cells in the mouse colon. Metabolomics analysis of fecal samples from mice colonized with C. tropicalis revealed alterations in vitamin B3 metabolism, promoting conversion of nicotinamide to nicotinic acid. Although nicotinamide worsened colitis, treatment with nicotinic acid alleviated disease symptoms and enhanced epithelial proliferation and Th17 cell differentiation. Oral gavage of C. tropicalis mitigated nicotinamide-induced intestinal dysfunction in experimental colitis. Blockade of nicotinic acid production with nicotinamidase inhibitors lowered the protective effects against colitis in mice treated with C. tropicalis. Notably, a clinical C. tropicalis strain isolated from patients with candidemia lacked the protective effects against murine colitis observed with the reference strain. Together, our results highlight a novel role for C. tropicalis in resolving intestinal inflammation through the modulation of vitamin B3 metabolism.

• Protection against colitis conferred by intestinal colonization of Candida tropicalis depends on metabolic activity and strain• C. tropicalis MYA-3404 supplementation promotes intestinal epithelial barrier function through IL-17A and IL-22 expressed by Th17 cells, γδ T cells, and ILC3• MYA-3404 strain uses its enzymatic activity to modulate vitamin B3 metabolism for protective benefits.

Circular RNA circABCC4 as the ceRNA facilitates renal carcinoma progression.

PURPOSE: This study explores the role of circular RNA derived from the Multidrug Resistance Protein 4 (MRP4/ABCC4) gene, which is markedly elevated in renal cell carcinoma (RCC). Our objective is to clarify how this circular RNA contributes to the progression and development of RCC. METHODS: We quantified the presence of circular ABCC4 RNA in tissue samples, plasma and urine from patients diagnosed with RCC. In addition, the impact of this circular RNA on RCC tumour growth was assessed through studies in RCC cell lines and in animal models mimicking the disease. RESULTS: Our findings reveal that circular ABCC4 RNA, specifically the variant containing exons 25-29 (circABCC4e), is upregulated in RCC cell lines and tissues. This upregulation correlates with advanced tumor stages in RCC patients, suggesting circABCC4e's potential as a biomarker for RCC progression. Furthermore, the reduction in circABCC4e levels following tumor resection indicates its potential utility in monitoring treatment response. The mechanism by which circABCC4e promotes RCC tumor growth through the antagonism of tumor-suppressive microRNAs highlights its significance in RCC pathogenesis. These insights may inform the development of diagnostic and therapeutic strategies for RCC. CONCLUSION: This study demonstrates that circABCC4e accelerates RCC progression by inhibiting tumor-suppressive microRNAs. Its role as a diagnostic and prognostic biomarker for RCC underscores its potential value in improving RCC management.

Restoration of abnormal sleep EEG power in patients with insomnia disorder after 1Hz rTMS over left DLPFC.

Introduction: Hyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear. Methods>: Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated. Results: Abnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep. Discussion: The relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

GLP-1 analogue liraglutide attenuates CIH-induced cognitive deficits by inhibiting oxidative stress, neuroinflammation, and apoptosis via the Nrf2/HO-1 and MAPK/NF-κB signaling pathways.

Obstructive sleep apnea (OSA) is a common clinical condition linked to cognitive impairment, mainly characterized by chronic intermittent hypoxia (CIH). GLP-1 receptor agonist, known for promoting insulin secretion and reducing glucose levels, has demonstrated neuroprotective effects in various experimental models such as stroke, Alzheimer's disease, and Parkinson's disease. This study aims to investigate the potential role and mechanisms of the GLP-1 receptor agonist liraglutide in ameliorating OSA-induced cognitive deficits. CIH exposure, a well-established and mature OSA pathological model, was used both in vitro and in vivo. In vitro, CIH significantly activated oxidative stress, inflammation, and apoptosis in SH-SY5Y cells. Liraglutide enhanced the nuclear translocation of Nrf2, activating its downstream pathways, thereby mitigating CIH-induced injury in SH-SY5Y cells. Additionally, liraglutide modulated the MAPK/NF-κB signaling pathway, reducing the expression of inflammatory factors and proteins. In vivo, we subjected mice to an intermittent hypoxia incubator to mimic the pathogenesis of human OSA. The Morris water maze test revealed that CIH exposure substantially impaired spatial memory. Subsequent western blot analyses and histopathological examinations indicated that liraglutide could activate the Nrf2/HO-1 axis and inhibit the MAPK/NF-κB signaling pathway, thereby alleviating OSA-associated cognitive dysfunction in mice. These findings suggest that GLP-1 receptor agonists may offer a promising preventive strategy for OSA-associated cognitive impairment. By refining these findings, we provide new insights into GLP-1's protective mechanisms in combating cognitive deficits associated with CIH, underscoring its potential as a therapeutic agent for conditions linked to OSA.

Crosstalk between FTH1 and PYCR1 dysregulates proline metabolism and mediates cell growth in KRAS-mutant pancreatic cancer cells.

Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Inhibition of PRMT5 moderately suppresses prostate cancer growth in vivo but enhances its response to immunotherapy.

Protein arginine methylation is a common post-translational modification (PTM) catalyzed by nine protein arginine methyltransferases (PRMTs). As the major symmetric arginine methyltransferase that methylates both histone and non-histone substrates, PRMT5 plays key roles in a number of biological processes critical for development and tumorigenesis. PRMT5 overexpression has been reported in multiple cancer types including prostate cancer (PCa), but the exact biological and mechanistic understanding of PRMT5 in aggressive PCa remains ill-defined. Here, we show that PRMT5 is upregulated in PCa, correlates with worse patient survival, promotes corrupted RNA splicing, and functionally cooperates with an array of pro-tumorigenic pathways to enhance oncogenesis. PRMT5 inhibition via either genetic knockdown or pharmacological inhibition reduces stemness with paralleled differentiation and arrests cell cycle progression without causing appreciable apoptosis. Strikingly, the severity of antitumor effect of PRMT5 inhibition correlates with disease aggressiveness, with AR+ PCa being less affected. Molecular characterization pinpoints MYC, but not (or at least to a lesser degree) AR, as the main partner of PRMT5 to form a positive feedback loop to exacerbate malignancy in both AR+ and AR- PCa cells. Inspired by the surprising finding that PRMT5 negatively correlates with tumor immune infiltration and transcriptionally suppresses an immune-gene program, we further show that although PRMT5 inhibitor (PRMT5i) EPZ015666 or anti-PD-1 immunotherapy alone exhibits limited antitumor effects, combination of PRMT5i with anti-PD-1 displays superior efficacy in inhibiting castration-resistant PCa (CRPC) in vivo. Finally, to expand the potential use of PRMT5i through a synthetic lethality concept, we also perform a global CRISPR/Cas9 knockout screen to unravel that many clinical-grade drugs of known oncogenic pathways can be repurposed to target CRPC when used in combination with PRMT5i at low doses. Collectively, our findings establish a rationale to exploit PRMT5i in combination with immunotherapy or other targeted therapies to treat aggressive PCa.

Expression, regulation, and function of PD-L1 on non-tumor cells in the tumor microenvironment.

Antiprogrammed death ligand 1 (PD-L1) therapy is a leading immunotherapy, but only some patients with solid cancers benefit. Overwhelming evidence has revealed that PD-L1 is expressed on various immune cells in the tumor microenvironment (TME), including macrophages, dendritic cells, and regulatory T cells, modulating tumor immunity and influencing tumor progression. PD-L1 can also be located on tumor cell membranes as well as in exosomes and cytoplasm. Accordingly, the dynamic expression and various forms of PD-L1 might explain the therapy's limited efficacy and resistance. Herein a systematic summary of the expression of PD-L1 on different immune cells and their regulatory mechanisms is provided to offer a solid foundation for future studies.

Effects of high-definition tDCS targeting individual motor hotspot with EMG-driven robotic hand training on upper extremity motor function: a pilot randomized controlled trial.

BACKGROUND: Delivering HD-tDCS on individual motor hotspot with optimal electric fields could overcome challenges of stroke heterogeneity, potentially facilitating neural activation and improving motor function for stroke survivors. However, the intervention effect of this personalized HD-tDCS has not been explored on post-stroke motor recovery. In this study, we aim to evaluate whether targeting individual motor hotspot with HD-tDCS followed by EMG-driven robotic hand training could further facilitate the upper extremity motor function for chronic stroke survivors. METHODS: In this pilot randomized controlled trial, eighteen chronic stroke survivors were randomly allocated into two groups. The HDtDCS-group (n = 8) received personalized HD-tDCS using task-based fMRI to guide the stimulation on individual motor hotspot. The Sham-group (n = 10) received only sham stimulation. Both groups underwent 20 sessions of training, each session began with 20 min of HD-tDCS and was then followed by 60 min of robotic hand training. Clinical scales (Fugl-meyer Upper Extremity scale, FMAUE; Modified Ashworth Scale, MAS), and neuroimaging modalities (fMRI and EEG-EMG) were conducted before, after intervention, and at 6-month follow-up. Two-way repeated measures analysis of variance was used to compare the training effect between HDtDCS- and Sham-group. RESULTS: HDtDCS-group demonstrated significantly better motor improvement than the Sham-group in terms of greater changes of FMAUE scores (F = 6.5, P = 0.004) and MASf (F = 3.6, P = 0.038) immediately and 6 months after the 20-session intervention. The task-based fMRI activation significantly shifted to the ipsilesional motor area in the HDtDCS-group, and this activation pattern increasingly concentrated on the motor hotspot being stimulated 6 months after training within the HDtDCS-group, whereas the increased activation is not sustainable in the Sham-group. The neuroimaging results indicate that neural plastic changes of the HDtDCS-group were guided specifically and sustained as an add-on effect of the stimulation. CONCLUSIONS: Stimulating the individual motor hotspot before robotic hand training could further enhance brain activation in motor-related regions that promote better motor recovery for chronic stroke. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov (ID NCT05638464).

ERVcancer: a web resource designed for querying activation of human endogenous retroviruses across major cancer types.

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome, co-opted into the dynamic regulatory network of cellular potency in early embryonic development. In recent studies, resurgent HERVs' transcriptional activity has been frequently observed in many types of human cancers, suggesting their potential functions in the occurrence and progression of malignancy. However, a dedicated web resource for querying the relationship between activation of HERVs and cancer development is lacking. Here, we have constructed a database to explore the sequence information, expression profiles, survival prognosis, and genetic interactions of HERVs in diverse cancer types. Our database currently contains RNA sequencing data of 580 HERVs across 16246 samples, including that of 6478 tumoral and 634 normal tissues, 932 cancer cell lines, as well as 151 early embryonic and 8051 human adult tissues. The primary goal is to provide an easily accessible and user-friendly database for professionals in the fields of bioinformatics, pathology, pharmacology, and related areas, enabling them to efficiently screen the activity of HERVs of interest in normal and cancerous tissues and evaluate the clinical relevance. The ERVcancer database is available at http://kyuanlab.com/ervcancer/.

Development and External Validation of a Motor Intention-Integrated Prediction Model for Upper Extremity Motor Recovery After Intention-Driven Robotic Hand Training for Chronic Stroke.

OBJECTIVE: To derive and validate a prediction model for minimal clinically important differences (MCIDs) in upper extremity (UE) motor function after intention-driven robotic hand training using residual voluntary electromyography (EMG) signals from affected UE. DESIGN: A prospective longitudinal multicenter cohort study. We collected preintervention candidate predictors: demographics, clinical characteristics, Fugl-Meyer assessment of UE (FMAUE), Action Research Arm Test scores, and motor intention of flexor digitorum and extensor digitorum (ED) measured by EMG during maximal voluntary contraction (MVC). For EMG measures, recognizing challenges for stroke survivors to move paralyzed hand, peak signals were extracted from 8 time windows during MVC-EMG (0.1-5s) to identify subjects' motor intention. Classification and regression tree algorithm was employed to predict survivors with MCID of FMAUE. Relationship between predictors and motor improvements was further investigated. SETTING: Nine rehabilitation centers. PARTICIPANTS: Chronic stroke survivors (N=131), including 87 for derivation sample, and 44 for validation sample. INTERVENTIONS: All participants underwent 20-session robotic hand training (40min/session, 3-5sessions/wk). MAIN OUTCOME MEASURES: Prediction efficacies of models were assessed by area under the receiver operating characteristic curve (AUC). The best effective model was final model and validated using AUC and overall accuracy. RESULTS: The best model comprised FMAUE (cutoff score, 46) and peak activity of ED from 1-second MVC-EMG (MVC-EMG 4.604 times higher than resting EMG), which demonstrated significantly higher prediction accuracy (AUC, 0.807) than other time windows or solely using clinical scores (AUC, 0.595). In external validation, this model displayed robust prediction (AUC, 0.916). Significant quadratic relationship was observed between ED-EMG and FMAUE increases. CONCLUSIONS: This study presents a prediction model for intention-driven robotic hand training in chronic stroke survivors. It highlights significance of capturing motor intention through 1-second EMG window as a predictor for MCID improvement in UE motor function after 20-session robotic training. Survivors in 2 conditions showed high percentage of clinical motor improvement: moderate-to-high motor intention and low-to-moderate function; as well as high intention and high function.

Exploring plant growth promoting traits and biocontrol potential of new isolated Bacillus subtilis BS-2301 strain in suppressing Sclerotinia sclerotiorum through various mechanisms.

Sclerotinia sclerotiorum (Lib.) de Bary is the causative agent of stem white mold disease which severely reduces major crop productivity including soybean and rapeseed worldwide. The current study aimed to explore plant growth-promoting traits and biocontrol of new isolated Bacillus subtilis BS-2301 to suppress S. sclerotiorum through various mechanisms. The results indicated that the BS-2301 exhibited strong biocontrol potential against S. sclerotiorum up to 74% both in dual culture and partition plate experiments. The BS-2301 and its crude extract significantly suppressed S. sclerotiorum growth involving excessive reactive oxygen species (ROS) production in mycelia for rapid death. Furthermore, the treated hyphae produced low oxalic acid (OA), a crucial pathogenicity factor of S. sclerotiorum. The SEM and TEM microscopy of S. sclerotiorum showed severe damage in terms of cell wall, cell membrane breakage, cytoplasm displacement, and organelles disintegration compared to control. The pathogenicity of S. sclerotiorum exposed to BS-2301 had less disease progression potential on soybean leaves in the detached leaf assay experiment. Remarkably, the strain also demonstrated broad-range antagonistic activity with 70%, and 68% inhibition rates against Phytophthora sojae and Fusarium oxysporum, respectively. Furthermore, the strain exhibits multiple plant growth-promoting and disease-prevention traits, including the production of indole-3-acetic acid (IAA), siderophores, amylases, cellulases and proteases as well as harboring calcium phosphate decomposition activity. In comparison to the control, the BS-2301 also showed great potential for enhancing soybean seedlings growth for different parameters, including shoot length 31.23%, root length 29.87%, total fresh weight 33.45%, and total dry weight 27.56%. The antioxidant enzymes like CAT, POD, SOD and APX under BS-2301 treatment were up-regulated in S. sclerotiorum infected plants along with the positive regulation of defense-related genes (PR1-2, PR10, PAL1, AOS, CHS, and PDF1.2). These findings demonstrate that the BS-2301 strain possesses a notable broad-spectrum biocontrol potential against different phytopathogens and provides new insight in suppressing S. sclerotiorum through various mechanisms. Therefore, BS-2301 will be helpful in the development of biofertilizers for sustainable agricultural practices.