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Tillage practices significantly influence crop yield and soil quality. This study investigated the impact of rotary tillage (RT) and deep tillage (DT) on soil properties, microbial diversity, and melon (Cucumis melo L.) root growth and yield. RT involved breaking up the topsoil to a depth of 15 cm using a rotary tiller, while DT employed a rotary tiller followed by a moldboard plow to turn the soil layer over to a depth of 35 cm. The melon variety “Nasimi” was used as the material. Our findings revealed a remarkable response of soil phosphorus to tillage practices. High-throughput sequencing results revealed a significant impact of tillage practices on the soil fungal composition, richness, and diversity but little impact on the bacterial communities. Compared to RT, DT markedly enhanced melon root length, root surface area, root volume, and mean root diameter by 47.42%, 56.70%, 58.83%, and 27.28%, respectively. Additionally, DT treatments significantly increased melon yield (53.46%) compared to RT. The results indicate that DT improves soil nutrient availability, affects soil fungal community characteristics, and optimizes root distribution in soil, thereby improving melon yield. The findings offer valuable theoretical insights for the implementation of effective tillage practices in open-field melon cultivation.

In this paper, we propose a model averaging estimation for the varying-coefficient partially linear models with missing responses. Within this context, we construct a HRCp weight choice criterion that exhibits asymptotic optimality under certain assumptions. Our model averaging procedure can simultaneously address the uncertainty on which covariates to include and the uncertainty on whether a covariate should enter the linear or nonlinear component of the model. The simulation results in comparison with some related strategies strongly favor our proposal. A real dataset is analyzed to illustrate the practical application as well.

This study investigated how salicylic acid (SA) mediates the response of melon (Cucumis melo) seeds to salt stress using physiological and transcriptomic methods. The effects of SA on the antioxidant enzymes, osmoregulatory substances, and transcriptome of melon seeds under salt stress were investigated using sodium chloride (NaCl, 100 mmol·L−1) as the stress stimulant and SA + NaCl (0.25 mmol·L−1 + 100 mmol·L−1) as the alleviation treatment. The results showed that SA positively influences salt tolerance by increasing the activity of superoxide dismutase activity (SOD) and catalase activity (CAT) while decreasing proline content (Pro). Differentially expressed genes (DEGs) were identified by transcriptome data analysis, of which 2958 were up-regulated, and 2157 were down-regulated. These genes were mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway and plant hormone signal transduction, lipid metabolism (linoleic and α-linolenic fatty acid metabolism), biosynthesis of secondary metabolites (phenylpropanoid pathway and flavonoid biosynthesis), and related pathways. Further analysis revealed that SA might alleviate salt stress by initiating a series of signaling pathways under salt stress, participating in lignin biosynthesis to improve cell wall stability, and positively regulating lipoxygenase (LOX) genes. These results provide valuable information and new strategies for future salt resistance cultivation and high melon yield.

In the past few decades, model averaging has received extensive attention, and has been regarded as a feasible alternative to model selection. However, this work is mainly based on parametric model framework and complete dataset. This paper develops a frequentist model-averaging estimation for semiparametric partially linear models with censored responses. The nonparametric function is approximated by B-spline, and the weights in model-averaging estimator are picked up via minimizing a leave-one-out cross-validation criterion. The resulting model-averaging estimator is proved to be asymptotically optimal in the sense of achieving the lowest possible squared error. A simulation study demonstrates that the method in this paper is superior to traditional model-selection and model-averaging methods. Finally, as an illustration, the proposed procedure is further applied to analyze two real datasets.

Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG) in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas.

BackgroundPatients with knee osteoarthritis (KOA) often present lower extremity motor dysfunction. However, traditional radiography is a static assessment and cannot achieve long-term dynamic functional monitoring. Plantar pressure signals have demonstrated potential applications in the diagnosis and rehabilitation monitoring of KOA. ObjectiveThrough wearable gait analysis technology, we aim to obtain abundant gait information based on machine learning techniques to develop a simple, rapid, effective, and patient-friendly functional assessment model for the KOA rehabilitation process to provide long-term remote monitoring, which is conducive to reducing the burden of social health care system. MethodsThis cross-sectional study enrolled patients diagnosed with KOA who were able to walk independently for 2 minutes. Participants were given clinically recommended functional tests, including the 40-m fast-paced walk test (40mFPWT) and timed up-and-go test (TUGT). We used a smart shoe system to gather gait pressure data from patients with KOA. The multidimensional gait features extracted from the data and physical characteristics were used to establish the KOA functional feature database for the plantar pressure measurement system. 40mFPWT and TUGT regression prediction models were trained using a series of mature machine learning algorithms. Furthermore, model stacking and average ensemble learning methods were adopted to further improve the generalization performance of the model. Mean absolute error (MAE), mean absolute percentage error (MAPE), and root mean squared error (RMSE) were used as regression performance metrics to evaluate the results of different models. ResultsA total of 92 patients with KOA were included, exhibiting varying degrees of severity as evaluated by the Kellgren and Lawrence classification. A total of 380 gait features and 4 physical characteristics were extracted to form the feature database. Effective stepwise feature selection determined optimal feature subsets of 11 variables for the 40mFPWT and 10 variables for the TUGT. Among all models, the weighted average ensemble model using 4 tree-based models had the best generalization performance in the test set, with an MAE of 2.686 seconds, MAPE of 9.602%, and RMSE of 3.316 seconds for the prediction of the 40mFPWT and an MAE of 1.280 seconds, MAPE of 12.389%, and RMSE of 1.905 seconds for the prediction of the TUGT. ConclusionsThis wearable plantar pressure feature technique can objectively quantify indicators that reflect functional status and is promising as a new tool for long-term remote functional monitoring of patients with KOA. Future work is needed to further explore and investigate the relationship between gait characteristics and functional status with more functional tests and in larger sample cohorts.

Abstract Objectives Motoric cognitive risk syndrome (MCR) is a pre-dementia condition characterized by subjective complaints in cognition and slow gait. Pain interference has previously been linked with cognitive deterioration; however, its specific relationship with MCR remains unclear. We aimed to examine how pain interference is associated with concurrent and incident MCR. Methods This study included older adults aged ≥ 65 years without dementia from the Health and Retirement Study. We combined participants with MCR information in 2006 and 2008 as baseline, and the participants were followed up 4 and 8 years later. The states of pain interference were divided into 3 categories: interfering pain, non-interfering pain, and no pain. Logistic regression analysis was done at baseline to examine the associations between pain interference and concurrent MCR. During the 8-year follow-up, Cox regression analysis was done to investigate the associations between pain interference and incident MCR. Results The study included 7120 older adults (74.6 ± 6.7 years; 56.8% females) at baseline. The baseline prevalence of MCR was 5.7%. Individuals with interfering pain had a significantly increased risk of MCR (OR = 1.51, 95% CI = 1.17–1.95; p = 0.001). The longitudinal analysis included 4605 participants, and there were 284 (6.2%) MCR cases on follow-up. Participants with interfering pain at baseline had a higher risk for MCR at 8 years of follow-up (HR = 2.02, 95% CI = 1.52–2.69; p

Abstract Background Knee osteoarthritis (KOA) is an irreversible degenerative disease that characterized by pain and abnormal gait. Radiography is typically used to detect KOA but has limitations. This study aimed to identify changes in plantar pressure that are associated with radiological knee osteoarthritis (ROA) and to validate them using machine learning algorithms. Methods This study included 92 participants with variable degrees of KOA. A modified Kellgren–Lawrence scale was used to classify participants into non-ROA and ROA groups. The total feature set included 210 dynamic plantar pressure features captured by a wearable in-shoe system as well as age, gender, height, weight, and body mass index. Filter and wrapper methods identified the optimal features, which were used to train five types of machine learning classification models for further validation: k-nearest neighbors (KNN), support vector machine (SVM), random forest (RF), AdaBoost, and eXtreme gradient boosting (XGBoost). Results Age, the standard deviation (SD) of the peak plantar pressure under the left lateral heel (f_L8PPP_std), the SD of the right second peak pressure (f_Rpeak2_std), and the SD of the variation in the anteroposterior displacement of center of pressure (COP) in the right foot (f_RYcopstd_std) were most associated with ROA. The RF model with an accuracy of 82.61% and F1 score of 0.8000 had the best generalization ability. Conclusion Changes in dynamic plantar pressure are promising mechanical biomarkers that distinguish between non-ROA and ROA. Combining a wearable in-shoe system with machine learning enables dynamic monitoring of KOA, which could help guide treatment plans.

BackgroundHypertension (HT) is a common chronic disease in older adults. It not only leads to dizziness and other symptoms affecting balance in older adults with HT but also affects the hemodynamics of the cerebral cortex. At present, potential neural mechanisms of balance control in older adults with HT are still unclear. Therefore, this study aimed to explore the differences in the center of pressure (COP) and cerebral cortex activation between older adults with HT and normotension (NT) during standing balance tasks. This study May provide guidance for the early detection of the risk of falls among older adults with HT and the development of clinical rehabilitation strategies.MethodsIn this cross-sectional study, 30 older adults with NT (NT group) and 27 older adults with HT (HT group) were subjected to three conditions: task 1, standing with eyes open on a stable surface; task 2, standing with eyes closed on a stable surface; and task 3, standing with eyes open on the surface of the foam pad. Cortical hemodynamic reactions were measured using functional near-infrared spectroscopy, and COP parameters were measured using a force plate.ResultsThe mean velocity of the COP in the medial–lateral direction in the NT group was significantly higher than that in the HT group (F = 5.955, p = 0.018) during task 3. When proprioception was disturbed, the activation of the left premotor cortex and supplementary motor cortex in the HT group was significantly lower than that in the NT group (F = 14.381, p

Abstract Background Hypertension increases the risk of cognitive impairment and related dementia, causing impaired executive function and unusual gait parameters. However, the mechanism of neural function illustrating this is unclear. Our research aimed to explore the differences of cerebral cortex activation, gait parameters, and working memory performance between healthy older adults (HA) and older hypertensive (HT) patients when performing cognitive and walking tasks. Method A total of 36 subjects, including 12 healthy older adults and 24 older hypertensive patients were asked to perform series conditions including single cognitive task (SC), single walking task (SW), and dual‐task (DT), wearing functional near‐infrared spectroscopy (fNIRS) equipment and Intelligent Device for Energy Expenditure and Activity equipment to record cortical hemodynamic reactions and various gait parameters. Results The left somatosensory cortex (L‐S1) and bilateral supplementary motor area (SMA) showed higher cortical activation (p

Low back pain (LBP) is one of the most prevalent and disabling disease worldwide. However, the specific biomechanical changes due to LBP are still controversial. The purpose of this study was to estimate the lumbar and lower limb kinematics, lumbar moments and loads, muscle forces and activation during walking in healthy adults and LBP. A total of 18 healthy controls and 19 patients with chronic LBP were tested for walking at a comfortable speed. The kinematic and dynamic data of the subjects were collected by 3D motion capture system and force plates respectively, and then the motion simulation was performed by OpenSim. The OpenSim musculoskeletal model was used to calculate lumbar, hip, knee and ankle joint angle variations, lumbar moments and loads, muscle forces and activation of eight major lumbar muscles. In our results, significant lower lumbar axial rotation angle, lumbar flexion/extension and axial rotation moments, as well as the muscle forces of the four muscles and muscle activation of two muscles were found in patients with LBP than those of the healthy controls (p < 0.05). This study may help providing theoretical support for the evaluation and rehabilitation treatment intervention of patients with LBP.

BackgroundPrevious evidence suggests a link between gut microbiota and chronic pain, but the causal relationship is not yet fully understood.MethodsWe categorized gut microbiota based on phylum, class, order, family, and genus levels and gathered pain-related information from the UKB and FinnGen GWAS project. Then, we conducted MR analysis to explore the potential causal relationship between gut microbiota and chronic pain at 12 specific locations.ResultsWe have discovered a direct connection between genetic susceptibility in the gut microbiota (gut metabolites) and pain experienced at 12 specific locations. Notably, Serotonin (5-HT) and Glycine were found to be associated with a higher risk of pain in the extremities. On the other hand, certain microbial families and orders were found to have a protective effect against migraines. Specifically, the family Bifidobacteriaceae (IVW, FDR p = 0.013) was associated with a lower risk of migraines. Furthermore, the genus Oxalobacter (IVW, FDR p = 0.044) was found to be linked to an increased risk of low back pain. Importantly, these associations remained significant even after applying the Benjamini-Hochberg correction test. Our analysis did not find any heterogeneity in the data (p > 0.05), as confirmed by the Cochrane’s Q-test. Additionally, both the MR-Egger and MR-PRESSO tests indicated no significant evidence of horizontal pleiotropy (p > 0.05).ConclusionOur MR analysis demonstrated a causal relationship between the gut microbiota and pain, highlighting its potential significance in advancing our understanding of the underlying mechanisms and clinical implications of microbiota-mediated pain.

Background: Single-cell sequencing (SCS) is a technique used to analyze the genome, transcriptome, epigenome, and other genetic data at the level of a single cell. The procedure is commonly utilized in multiple fields, including neurobiology, immunology, and microbiology, and has emerged as a key focus of life science research. However, a thorough and impartial analysis of the existing state and trends of SCS-related research is lacking. The current study aimed to map the development trends of studies on SCS during the years 2010–2022 through bibliometric software.Methods: Pertinent papers on SCS from 2010 to 2022 were obtained using the Web of Science Core Collection. Research categories, nations/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords were analyzed using VOSviewer, the R package “bibliometric”, and CiteSpace.Results: The bibliometric analysis included 9,929 papers published between 2010 and 2022, and showed a consistent increase in the quantity of papers each year. The United States was the source of the highest quantity of articles and citations in this field. The majority of articles were published in the periodical Nature Communications. Butler A was the most frequently quoted author on this topic, and his article “Integrating single-cell transcriptome data across diverse conditions, technologies, and species” has received numerous citations to date. The literature and keyword analysis showed that studies involving single-cell RNA sequencing (scRNA-seq) were prominent in this discipline during the study period.Conclusion: This study utilized bibliometric techniques to visualize research in SCS-related domains, which facilitated the identification of emerging patterns and future directions in the field. Current hot topics in SCS research include COVID-19, tumor microenvironment, scRNA-seq, and neuroscience. Our results are significant for scholars seeking to identify key issues and generate new research ideas.

Introduction: Gait, as a fundamental human movement, necessitates the coordination of muscles across swing and stance phases. Functional electrical stimulation (FES) of the tibialis anterior (TA) has been widely applied to foot drop correction for patients with post-stroke during the swing phase. Although the gastrocnemius (GAS) during the stance phase is also affected, the Functional electrical stimulation of the gastrocnemius received less attention.Methods: To address this limitation, a timing- and intensity-adaptive Functional electrical stimulation control strategy was developed for both the TA and GAS. Each channel incorporates a speed-adaptive (SA) module to control stimulation timing and an iterative learning control (ILC) module to regulate the stimulation intensity. These modules rely on real-time kinematic or kinetic data during the swing or stance phase, respectively. The orthotic effects of the system were evaluated on eight patients with post-stroke foot drop. Gait kinematics and kinetics were assessed under three conditions: no stimulation (NS), Functional electrical stimulation to the ankle dorsiflexor tibialis anterior (SA-ILC DS) and FES to the tibialis anterior and the ankle plantarflexor gastrocnemius (SA-ILC DPS).Results: The ankle plantarflexion angle, the knee flexion angle, and the anterior ground reaction force (AGRF) in the SA-ILC DPS condition were significantly larger than those in the NS and SA-ILC DS conditions (p < 0.05). The maximum dorsiflexion angle during the swing phase in the SA-ILC DPS condition was similar to that in the SA-ILC DS condition, with both being significantly larger than the angle observed in the NS condition (p < 0.05). Furthermore, the angle error and force error relative to the set targets were minimized in the SA-ILC DPS condition.Discussion: The observed improvements can be ascribed to the appropriate stimulation timing and intensity provided by the SA-ILC DPS strategy. This study demonstrates that the hybrid and adaptive control strategy of functional electrical stimulation system offers a significant orthotic effect, and has considerable potential for future clinical application.

Abstract Objective The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA). Methods This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45–79. Quadriceps strength was measured by isometric knee extension testing at baseline. Knee joint structural abnormalities, including cartilage damage, bone marrow lesions (BMLs), effusion-synovitis and Hoffa-synovitis, were evaluated by Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) at baseline and 1-year follow-up. Generalized estimating equations were employed to examine the associations between quadriceps strength and knee structural abnormalities. All analyses were stratified by sex. Results One thousand three hundred thirty-eight participants (523 men and 815 women) with a mean age of 61.8 years and a mean BMI of 29.4 kg/m2 were included in this study. For men, no significantly longitudinal association of quadriceps strength with structural abnormalities was detected. In contrast, quadriceps strength was significantly and negatively associated with changes in cartilage damage and BMLs in lateral patellofemoral joint (PFJ) (cartilage damage: OR: 0.91, 95% CI 0.84 to 0.99, P = 0.023; BMLs: OR: 0.85, 95% CI 0.74 to 0.96, P = 0.011) and effusion-synovitis (OR = 0.88, 95% CI 0.78 to 0.99, P = 0.045) among females longitudinally. Higher quadriceps strength was significantly associated with less progression of lateral PFJ cartilage damage, BMLs and effusion-synovitis in females. Conclusions Higher quadriceps strength was associated with changes in cartilage damage and BMLs within the lateral PFJ and effusion-synovitis among females, suggesting the potential protective role of quadriceps strength on joint structures in women.

Background: Stroke is one of the leading causes of mortality and permanent disability worldwide. However, the current stroke treatment has a limited effect. Therefore, a new treatment is urgently needed. Stem cell therapy is a cutting-edge treatment for stroke patients. This study aimed to gain better understanding of global stem cell trends in stroke via a bibliometric analysis.Methods: We used the Web of Science Core Collection to search pertinent articles about stem cells in stroke published between 2004 and 2022. Analysis was conducted using CiteSpace, VOSviewer, and the R package “bibliometrix” to identify publication outputs, countries/regions, institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords.Results: A total of 6,703 publications were included in the bibliometric analysis. The total number of citations significantly and rapidly increased between 2004 and 2022, with the most pronounced growth pattern observed in the period of 2008–2009. In terms of authoritarian countries, the USA had the most publications among the countries. As for institutions and authors, the most prolific institution was the University of South Florida, followed by Oakland University and then Shanghai Jiao Tong University, and Chopp, M. and Borlongan, Cesario V, had the most output among the authors. Regarding the journals, Cell Transplantation had the highest publication, followed by Brain Research. As for references, “Mesenchymal stem cells as trophic mediators” was the most frequently cited (2,082), and the article entitled Neuronal replacement from endogenous precursors in the adult brain after stroke had the strongest burstiness (strength = 81.35). Emerging hot words in the past decade included “adhesion molecule,” “mesenchymal stromal cell,” “extracellular vesicle,” “pluripotent stem cells,” “signaling pathway,” “plasticity,” and “exosomes.”Conclusion: Between 2004 and 2022, the terms “neurogenesis,” “angiogenesis,” “mesenchymal stem cells,” “extracellular vesicle,” “exosomes,” “inflammation,” and “oxidative stress” have emerged as the hot research areas for research on stem cells in stroke. Although stem cells exert a number of positive effects, the main mechanisms for mitigating the damage caused by stroke are still unknown. Clinical challenges may include complicating factors that can affect the efficacy of stem cell therapy, which are worth a deep exploration.

Background and aimsThe mortality rate of stroke has been increasing worldwide. Poststroke somatic dysfunctions are common. Motor function rehabilitation of patients with such somatic dysfunctions enhances the quality of life and has long been the primary practice to achieve functional recovery. In this regard, we aimed to delineate the new trends and frontiers in stroke motor function rehabilitation literature published from 2004 to 2022 using a bibliometric software.MethodsAll documents related to stroke rehabilitation and published from 2004 to 2022 were retrieved from the Web of Science Core Collection. Publication output, research categories, countries/institutions, authors/cocited authors, journals/cocited journals, cocited references, and keywords were assessed using VOSviewer v.1.6.15.0 and CiteSpace version 5.8. The cocitation map was plotted according to the analysis results to intuitively observe the research hotspots.ResultsOverall, 3,302 articles were retrieved from 78 countries or regions and 564 institutions. Over time, the publication outputs increased annually. In terms of national contribution, the United States published the most papers, followed by China, Japan, South Korea, and Canada. Yeungnam University had the most articles among all institutions, followed by Emory University, Fudan University, and National Taiwan University. Jang Sung Ho and Wolf S.L. were the most productive (56 published articles) and influential (cited 1,121 times) authors, respectively. “Effect of constraint-induced movement therapy on upper extremity function 3–9 months after stroke: the Extremity Constraint Induced Therapy Evaluation randomized clinical trial” was the most frequently cited reference. Analysis of keywords showed that upper limbs, Fugl–Meyer assessment, electromyography, virtual reality, telerehabilitation, exoskeleton, and brain–computer interface were the research development trends and focus areas for this topic.ConclusionPublications regarding motor function rehabilitation following stroke are likely to continuously increase. Research on virtual reality, telemedicine, electroacupuncture, the brain–computer interface, and rehabilitation robots has attracted increasing attention, with these topics becoming the hotspots of present research and the trends of future research.

Background: Ischemic stroke, the most common stroke type, has threatened human life and health. Currently, intravenous thrombolysis and endovascular thrombectomy are the mainstream treatment methods, but they may cause cerebral ischemia-reperfusion injury (CIRI), which aggravates brain injury. Consequently, it is worthwhile to start with a study of CIRI mechanism to identify better prevention and treatment methods. Applying single-cell RNA sequencing (scRNA-seq) technology to further understand the biological functions of various cell types in CIRI will facilitate the intervention of CIRI. Methods: This study aimed to establish a rat middle cerebral artery occlusion (MCAO) model to simulate cerebral ischemia-reperfusion, perform enzymatic hydrolysis, and suspend cerebral cortex tissue edema. Single-cell transcriptome sequencing was used, combined with cluster analysis, t-distributed stochastic neighbor embedding (t-SNE) visualization, and other bioinformatics methods to distinguish cell subgroups while using gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment to reveal the biological function of each cell subgroup. Results: We identified 21 brain clusters with cell type-specific gene expression patterns and cell subpopulations, as well as 42 marker genes representing different cell subpopulations. The number of cells in clusters 0–3 increased significantly in MCAO group compared to that in the sham group, and nine-cell subpopulations exhibited remarkable differences in the number of genes. Subsequently, GO and KEGG analyses were performed on the top 40 differentially expressed genes (DEGs) in the six cell subpopulations with significant differences. These results indicate that biological processes and signaling pathways are involved in different cell subpopulations. Conclusions: ScRNA-seq revealed the diversity of cell differentiation and the unique information of cell subpopulations in the cortex of rats with acute ischemic stroke, providing novel insight into the pathological process and drug discovery in stroke.

The manufacturing of flexible strain sensors for wearable electronics usually requires different conductive materials for the sensing part and the connection part. This increases the complexity, cost, and performance issues due to the mismatch of the thermo-electro-mechanical properties of the materials. Herein, a new design scheme using a single conductive material is presented for a low-cost mass-producible fabric strain sensor, where a carbon/silicone nanocomposite is screen-printed to make both parts. By exploring the dimension effect and modelling of the conductive tracks, and adopting a large difference of over 100 times in aspect ratio, this research makes the electrical response of the fabric strain sensor depend almost exclusively on the sensing part, while its connection part has a low resistance. The sensor exhibits outstanding performance with a wide working range (60% strain), adequate linearity, long fatigue life (∼50,000 cycles), and mechanical robustness, rendering it suitable for human body movement detection. Moreover, the manufacturing process is simple and low-cost ($11 per m2). Thus, the new design scheme overcomes the mismatch issue and provides an important reference value for the design of flexible resistive sensors working in a high resistance range, from ∼ 100 KΩ to several MΩ.

With the development of Internet of things, the healthcare service is getting intelligent and wearable devices have become the focus of healthcare. In the field of healthcare, wearable devices are mainly applied in health monitoring, motion sensing, big health analysis, and so on. All these applications make wearable devices a good tool to achieve the ultimate goal of rehabilitation medicine, which is function recovery and health promotion, thus wearable devices are meant to play an important role in rehabilitation medicine. The users will have a high demand for the comforts and designs of the wearable devices because the wearable devices need to be worn for a long period in the skin; however, traditional devices are unable to satisfy the demand so that novel materials are needed. Nowadays, the wearable devices sold in the market such as smart watches and smart glasses are made of rigid materials, which have poor ductility and high density, thus they are difficult to satisfy the demand of users for comforts and convenience. Flexible materials are novel materials with good portability, high ductility, and could keep stable physicochemical properties even if in the process of extension. The wearable devices made of flexible materials inherit the advantages of flexible materials so that they might make up for the shortcomings of traditional wearable devices and then be widely applied in the field of rehabilitation medicine. As is shown in the domestic and foreign literature, flexible wearable devices have the potential for clinical application. Compared with traditional devices, flexible wearable devices not only improve user experience but also offer more powerful functions to meet a variety of clinical demands. In this review, we briefly introduce the principle and classification of flexible wearable devices and review the research progress of the application of flexible wearable devices in the field of rehabilitation medicine from six aspects: health monitoring, motion monitoring, swallow-speech monitoring, home rehabilitation, fall warning, and intelligent rehabilitation. Finally, we summarize current challenges and recent development trends of flexible wearable devices to provide a theoretical basis for future clinical applications

Pre-frailty is a transitional stage between health and frailty. Previous studies have demonstrated that individuals with pre-frailty experience declines in cognitive and gait performances compared with healthy individuals. However, the basic neural mechanism underlying this needs to be clarified. In this cross-sectional study, twenty-one healthy older adults and fifteen with pre-frailty underwent three conditions, including a single cognitive task (SC), single walking task (SW), and dual-task (DT), while cortical hemodynamic reactions were measured using functional near-infrared spectroscopy (fNIRS). The prefrail group (PG) showed a significantly lower activation of the left dorsolateral prefrontal cortex (L-DLPFC) than the healthy group (HG) when performing SC (p < 0.05). The PG showed a significantly lower Timed Up and Go test and step speed than the HG during SW (p < 0.05). The coefficient of variation (CV) of the step length of the PG was significantly higher than that of the HG when performing DT (p < 0.05). No significant correlation in cerebral cortex activation and gait parameters in the HG when performing SW and DT was noted (p > 0.05). Participants of the PG with a higher oxygenated area in the left anterior prefrontal cortex (L-APFC) had a lower step frequency during SW (r = −0.533, p = 0.041), and so did the following indicators of the PG during DT: L-APFC and step speed (r = −0.557, p = 0.031); right anterior prefrontal cortex and step speed (r = −0.610, p = 0.016); left motor cortex and step speed (r = −0.674, p = 0.006); step frequency (r = −0.656, p = 0.008); and step length (r = −0.535, p = 0.040). The negative correlations between the cerebral cortex and gait parameters of the PG indicated a neural compensatory effect of pre-frailty. Therefore, older adults with pre-frailty promote prefrontal activation to compensate for the impaired sensorimotor systems.

Abstract Background Real-time ultrasound imaging (RUSI) has been increasingly used as a form of biofeedback when instructing and re-training muscle contraction. However, the effectiveness of the RUSI on a single sustained contraction of the lumbar multifidus (LM) and transversus abdominis (TrA) has rarely been reported. This preliminary study aimed to determine if the use of RUSI, as visual biofeedback, could enhance the ability of activation and continuous contraction of the trunk muscles including LM and TrA. Methods Forty healthy individuals were included and randomly assigned into the experimental group and control group. All subjects performed a preferential activation of the LM and/or TrA (maintained the constraction of LM and/or TrA for 30 s and then relaxed for 2 min), while those in the experimental group also received visual feedback provided by RUSI. The thickness of LM and/or TrA at rest and during contraction (Tc-max, T15s, and T30s) were extracted and recorded. The experiment was repeated three times. Results No significant differences were found in the thickness of LM at rest (P > 0.999), Tc-max (P > 0.999), and T15s (P = 0.414) between the two groups. However, the ability to recruit LM muscle contraction differed between groups at T30s (P = 0.006), with subjects in the experimental group that received visual ultrasound biofeedback maintaining a relative maximum contraction. Besides, no significant differences were found in the TrA muscle thickness at rest (P > 0.999) and Tc-max (P > 0.999) between the two groups. However, significant differences of contraction thickness were found at T15s (P = 0.031) and T30s (P = 0.010) between the two groups during the Abdominal Drawing-in Maneuver (ADIM), with greater TrA muscle contraction thickness in the experimental group. Conclusions RUSI can be used to provide visual biofeedback, which can promote continuous contraction, and improve the ability to activate the LM and TrA muscles in healthy subjects.

Cerebral ischemia and the subsequent cerebral ischemia-reperfusion (I/R) injury usually result in neuronal impairment with serious disabilities. Although neural stem cell (NSC) transplantation can help with functional recovery after stroke, due to the improper cellular milieu after brain injury, direct NSC transplantation will result low cell survival rates and differentiation efficiency into neurons. Here a conductive hybrid hydrogel based on gelatin methacryloyl (GelMA) and poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT:PSS) was created as a NSC niche for the treatment of cerebral I/R injury. GelMA/PEDOT:PSS hybrid hydrogel promoted the development of NSCs into neurons. GelMA/PEDOT:PSS hydrogel along with NSCs could enhance neuronal activity and minimize apoptosis when co-cultured with oxygen-glucose deprivation/reperfusion (OGD/R) neurons. Furthermore, after 7 days of implantation, GelMA/PEDOT:PSS/NSCs on the infarcted brain of rats subjected to reperfusion injury after middle cerebral artery occlusion (MCAO) was verified to attenuate inflammatory responses. These findings show that the conductive GelMA/PEDOT:PSS hybrid hydrogel could regulate NSC development and act as promising cell niches for the treatment of cerebral I/R injury.

Background and Objective. Intervertebral disc degeneration (IDD) is closely related to back pain. Finding biomarkers of IDD is very helpful for maintaining the function of the intervertebral disc and reducing the occurrence of back pain. This study is to explore the biomarkers in IDD and to explore the role of immune cell infiltration in IDD. Methods. The data sets of GSE56081 and GSE63492 in the Gene Expression Omnibus (GEO) database were used for screening and analysis, and the key gene markers were verified by GSE34095 and GSE126883. Finally, the infiltration of immune cells in the data were analyzed by MCPcounter analysis package. Results. In this study, a ceRNA containing 15 lncRNAs, 9 miRNAs, and 103 mRNAs was constructed. After multimodel screening and verification, key gene marker was found, namely, ATF2. The lncRNA/miRNA/mRNA axis closely related to ATF2 have also been found, namely, SNHG5/miR-299-5p/ATF2. In the analysis of immune infiltration, ATF2 was negatively correlated with T cells but positively correlated with neutrophils and endothelial cells. Conclusion. The SNHG5/miR-299-5p/ATF2 can be used as biomarker of IDD, and infiltration of immune cells plays an important role in the pathological development of IDD. In addition, as a marker of IDD, the involvement of the above-mentioned axis in the pathological development of IDD remains to be further explored.

Background: Flexor spasticity of the upper limb is common in poststroke patients and seriously affects the recovery of upper limb function. However, there are no standard management protocols for this condition. Radial extracorporeal shock wave therapy (rESWT) is widely used for various diseases, some studies reported the effects of ESWT on reducing spasticity, but the mechanism of ESWT to reduce spasticity by affecting the excitability of stretch reflex or non-neural rheological components in spastic muscles or both is not yet clear. A large randomized controlled trial with comprehensive evaluation indicators is still needed. The study is to observe the effect of rESWT on flexor spasticity of the upper limb after stroke and explore its mechanism.Methods: A prospective, randomized, double-blind controlled trial is to be performed. One hundred participants will be recruited from the Inpatient Department of Zhujiang Hospital. Eligible patients will be randomly allocated to either receive three sessions of active rESWT (group A) or sham-placebo rESWT (group B) with 3-day intervals between each session. Assessment will be performed at baseline and at 24 h after each rESWT (t1, t2, and t3). The primary assessment outcome will be the Modified Ashworth Scale, and other assessments include surface electromyography, MyotonPRO digital muscle function evaluation, and infrared thermal imaging. All data will be analyzed using intention-to-treat principles. Multiple imputation by chained equations will be used to address missing data caused by loss to follow-up and nonresponses. Per protocol, analyses will also be performed on the participants who complete other assessments. Statistical analysis will be performed using SPSS software (version 20.0) and the significance level set at p < 0.05.Discussion: This trial aims to analyze the application of rESWT for the management of spasticity after stroke via appropriate assessments. We hypothesized that after receiving active rESWT, patients would show greater improvement of upper limb muscles compared with patients within the sham-placebo group. The rESWT would be an alternative to traditional methods, and the results of this study may provide support for the further study of potential mechanisms.Clinical Trial Registration:www.chictr.org.cn, identifier: ChiCTR1800016144.

Objective: To investigate the efficacy and safety of a novel lower-limb exoskeletal robot, BEAR-H1 (Shenzhen Milebot Robot Technology), in the locomotor function of subacute stroke patients.Methods: The present study was approved by the ethical committee of the First Affiliated Hospital of Nanjing Medical University (No. 2019-MD-43), and registration was recorded on the Chinese Clinical Trial Registry with a unique identifier: ChiCTR2100044475. A total of 130 patients within 6 months of stroke were randomly divided into two groups: the robot group and the control group. The control group received routine training for walking, while in the robot group, BEAR-H1 lower-limb exoskeletal robot was used for locomotor training. Both groups received two sessions daily, 5 days a week for 4 weeks consecutively. Each session lasted 30 min. Before treatment, after treatment for 2 weeks, and 4 weeks, the patients were assessed based on the 6-minute walking test (6MWT), functional ambulation scale (FAC), Fugl-Meyer assessment lower-limb subscale (FMA-LE), and Vicon gait analysis.Results: After a 4-week intervention, the results of 6MWT, FMA-LE, FAC, cadence, and gait cycle in the two groups significantly improved (P < 0.05), but there was no significant difference between the two groups (P > 0.05). The ratio of stance phase to that of swing phase, swing phase symmetry ratio (SPSR), and step length symmetry ratio (SLSR) was not significantly improved after 4 weeks of training in both the groups. Further analyses revealed that the robot group exhibited potential benefits, as the point estimates of 6MWT and Δ6MWT (post-pre) at 4 weeks were higher than those in the control group. Additionally, within-group comparison showed that patients in the robot group had a significant improvement in 6MWT earlier than their counterparts in the control group.Conclusions: The rehabilitation robot in this study could improve the locomotor function of stroke patients; however, its effect was no better than conventional locomotor training.

Objective:To observe the clinical efficacy of the wearable back trainer combined with massage on chronic nonspecific low back pain patients.Methods:A total of 56 chronic nonspecific low back pain patients were randomly assigned to three groups. The treatment group (n=19) was treated with wearable device treatments based on massage for two weeks, once a day, eight minutes each time, five times a week, while the control group (n=19) received massage only for two weeks, once a day, 20 minutes each time, and the blank group (n=18) rest only with closely observation. The therapeutic effect of three groups were evaluated by VAS and ODI scores before the treatment, one week after treatment and two weeks after treatment respectively.Results:There was no statistical difference among the three groups in VAS score before treatment (P> 0.05). There were statistical differences among the three groups in VAS score one week after treatment and two weeks after treatment respectively (P< 0.05); the score showed a downward trend with time, the decreasing amplitude of VAS score in the treatment group was higher than that of control group two weeks after treatment (P< 0.05), and the decreasing amplitude of VAS score in the treatment group and the control group was higher respectively than that of blank group one week after treatment and two weeks after treatment (P< 0.05). There was no statistical difference among the three groups in ODI score before treatment and one week after treatment (P> 0.05). There were statistical differences among the three groups in ODI score two weeks after treatment respectively (P< 0.05); the score showed a downward trend with time in the treatment group and the control group, the decreasing amplitude of ODI score in the treatment group was higher than that of control group two weeks after treatment (P< 0.05), and the ODI value in the blank group was decreased one week after treatment and increased two weeks after treatment.Conclusion:The clinical efficacy of the wearable back trainer combined with massage has good effect on patients of chronic nonspecific low back pain, and the effect of the combined therapy is better than simple massage therapy especially in pain relief.

Background: Cerebral ischemia–reperfusion (I/R) injury can lead to severe dysfunction, and its treatment is difficult. It is reported that nucleotide-binding domain and leucine-rich repeat family protein 3 (NLRP3) inflammasome-mediated cell pyroptosis is an important part of cerebral I/R injury and the activation of autophagy can inhibit pyroptosis in some tissue injury. Our previous study found that the protective effects of bone marrow mesenchymal stem cells (BMSCs) in cerebral I/R injury may be associated with the regulation of autophagy. Recent studies have demonstrated that exosomes secreted from BMSCs (BMSC-Exos) may play an essential role in the effective biological performance of BMSCs and the protective mechanism of BMSC-Exos is associated with the activation of autophagy and the remission of inflammation, but it has not been reported in studies of cerebral I/R injury. We aimed to investigate the effects of BMSC-Exos on cerebral I/R injury and determine if the mechanism is associated with the regulation of pyroptosis and autophagic flux.Method: PC12 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cerebral I/R in vitro and were cocultured with BMSC-Exos. Cell viability was determined with CCK-8 and lactate dehydrogenase (LDH) detection kits. Scanning electron microscopy (SEM), Hoechst 33342/propidium iodide (PI) double staining, 2′,7′-dichlorodihydrofluorescein diacetate assay, immunofluorescence, Western blot, and Enzyme-linked immunosorbent assay (ELISA) were used to detect cell pyroptosis. Furthermore, transmission electron microscopy (TEM), GFP-RFP-LC3 adenovirus transfection, and Western blot were used to detect autophagic flux and its influence on pyroptosis. Finally, coimmunoprecipitation was used to detect the binding interaction between NLRP3 and LC3.Results: BMSC-Exos increased cell viability in OGD/R. The inhibitory effect of BMSC-Exos on pyroptosis was comparable to the NLRP3 inhibitor MCC950 and was reversed by NLRP3 overexpression. Furthermore, BMSC-Exos promoted autophagic flux through the AMP-activated kinase (AMPK)/mammalian target of the rapamycin pathway, whereas chloroquine, AMPK silencing, and compound C blocked the inhibitory effect on pyroptosis.Conclusions: BMSC-Exos can protect PC12 cells against OGD/R injury via attenuation of NLRP3 inflammasome-mediated pyroptosis by promoting AMPK-dependent autophagic flux.

The in vitro expansion of endothelial progenitor cells (EPCs) is necessary for obtaining sufficient amounts of cells for clinical applications. However, EPC expansion is conventionally carried out under non-physiologic oxygen concentrations (normoxia, ~20% O2). We compared the effects of normoxic and hypoxic culture on the stemness of expanded EPCs. Human EPCs were cultured under hypoxia (1% O2) or normoxia (~20% O2), respectively. Cell proliferation, colony formation, in vitro angiogenesis, and the migration ability of the expanded EPCs were compared. To explore the underlying mechanism, whole transcriptome RNA sequencing (RNA-seq) was also performed to select differentially expressed genes (DEGs), which were then partially validated by western blotting. EPCs cultured under normoxia showed reduced proliferation, colony formation, in vitro angiogenesis, and migration abilities and a higher proportion of senescent cells compared with those cultured under hypoxia. A total of 48 DEGs were identified by transcriptome RNA-seq. Further bioinformatics analysis revealed that six pathways were enriched, among which the p53 signaling pathway. Finally, we confirmed the differential expression of the p53 pathway by Western blot analysis. Compared with hypoxia, normoxia is not favorable for maintaining the stemness of human EPCs. Several signaling pathways, including the p53 signaling pathway implicate in reducing stemness of EPCs under normoxia. Keywords: Endothelial progenitor cells, Stemness, Normoxia, Hypoxia, Expansion

MCM-41 was prepared through the sol–gel method and encapsulated by polydopamine (PDA) before being coordinated with metal ions to form a highly efficient sustained release system (M-PDA–MCM-41) for triazolone delivery. The characterization results confirmed the existence of the coordination bond between the PDA layer and triazolone through the bridge effect from metal ions, which enhanced the interaction between PDA–MCM-41 and triazolone. The adsorption capacity of Fe-PDA–MCM-41 increased up to 173 mg g–1, which was 160% more than that of MCM-41. The sustained release performance of M-PDA–MCM-41 in different pH values was investigated. Under the conditions of pH ≤7, the release speed of triazolone increased with pH decreasing, whereas its release speed in the weak base condition was slower than in the neutral condition. Therefore, the as-synthesized system showed significant pH-sensitivity in the sustained release process, indicating that the sustained release system can be well stored in the neutral or basic environment and activated in the acid environment. Their sustained release curves described by the Korsmeyer–Peppas equation at pH 7 showed the same behaviour, indicating that PDA decoration or metal ion coordination only increases the steric hindrance and the interaction between carrier and triazolone instead of changing the original structure of the pure MCM material in accordance with X-ray diffraction and Brunauer-Emmett-Teller analysis results.

ObjectiveTo determine whether robot-assisted gait training (RAGT) is more effective in improving mobility, endurance, gait performance, and balance in patients with multiple sclerosis (MS) compared with conventional walking rehabilitation treatment (CWT).Data sourcesSources included the Cochrane Library, PubMed, Embase, and Science Direct databases.Review methodAll possible articles were retrieved by two independent investigators and relevant articles were gathered. Studies on adult patients (older than 19 years old) suffering from MS were included, regardless the subtype of MS diagnosis. Finally, we identified seven studies that comprised 205 patients with MS.ResultsWe identified seven studies comprising 205 patients with MS in our meta-analysis. The pooled mean difference (MD) for the six-minute walk test (6MWT) was 14.25 [95% confidence interval (CI) 3.19 to 25.32, Z = 2.53, P = 0.01, I2 = 54%], which indicates that RAGT is superior to CWT on improving endurance. No significant improvement on using RAGT was found regarding the Berg Balance Scale (MD = −0.59, 95% CI: −2.7 to 1.52, Z = 0.55, P = 0.58, I2 = 51%), 10-meter walk test [standard mean difference (SMD) = 0.03, 95% CI: −0.26 to 0.31, Z = 0.18, P = 0.86, I2 = 48%] timed up and go (TUG) test (MD = −1.04, 95% CI: −8.68 to 6.60, Z = 0.27, P = 0.79), or stride length (SMD = 0.36, 95% CI: −0.13 to 0.85, Z = 0.73, P = 0.15).ConclusionWe can conclude that RAGT can bring more benefits on improving 6MWT among MS patients, but it is not enough to make a clinically significance conclusion. Considering the limitation of our study, it takes reservations about recommending all MS patients to take RAGT as primary rehabilitation intervention. Unless patients with progressive MS can take conventional rehabilitation in early time, RAGT would be a suitable substitute.