Effect of robot-assisted gait training on improving cardiopulmonary function in stroke patients: a meta-analysis.

OBJECTIVE: Understanding the characteristics related to cardiorespiratory fitness after stroke can provide reference values for patients in clinical rehabilitation exercise. This meta- analysis aimed to investigate the effect of robot-assisted gait training in improving cardiorespiratory fitness in post-stroke patients, compared to conventional rehabilitation training. METHODS: PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, CBM, CNKI and Wanfang databases were searched until March 18th, 2024. Randomized controlled trials (RCTs) comparing the effectiveness of robot-assisted gait training versus control group were included. The main outcome variable was peak oxygen uptake. 6-minute walking test, peak heart rate, peak inspiratory expiratory ratio as our secondary indicators. RevMan 5.3 software was used for statistical analysis. RESULTS: A total of 17 articles were included, involving 689 subjects. The results showed a significant effect for robot-assisted gait training to improve VO2peak (MD = 1.85; 95% CI: -0.13 to 3.57; p = 0.04) and 6WMT (MD = 19.26; 95% CI: 10.43 to 28.08; p < 0.0001). However, no significant difference favouring robot-assisted gait training were found in HRpeak (MD = 3.56; 95% CI: -1.90 to 9.02; p = 0.20) and RERpeak (MD = -0.01; 95% CI: -0.04 to 0.01; p = 0.34). CONCLUSION: These results showed that robot-assisted gait training may have a beneficial effect in improving VO2peak and 6WMT, with a moderate recommendation level according to the GRADE guidelines.

Healthcare center clustering for Cox's proportional hazards model by fusion penalty.

There has been growing research interest in developing methodology to evaluate healthcare centers' performance with respect to patient outcomes. Conventional assessments can be conducted using fixed or random effects models, as seen in provider profiling. We propose a new method, using fusion penalty to cluster healthcare centers with respect to a survival outcome. Without any prior knowledge of the grouping information, the new method provides a desirable data-driven approach for automatically clustering healthcare centers into distinct groups based on their performance. An efficient alternating direction method of multipliers algorithm is developed to implement the proposed method. The validity of our approach is demonstrated through simulation studies, and its practical application is illustrated by analyzing data from the national kidney transplant registry.

Effects of cortico-cortical paired associative stimulation based on multisensory integration to brain network connectivity in stroke patients: study protocol for a randomized doubled blind clinical trial.

INTRODUCTION: Brain has a spontaneous recovery after stroke, reflecting the plasticity of the brain. Currently, TMS is used for studies of single-target brain region modulation, which lacks consideration of brain networks and functional connectivity. Cortico-cortical paired associative stimulation (ccPAS) promotes recovery of motor function. Multisensory effects in primary visual cortex(V1) directly influence behavior and perception, which facilitate motor functional recovery in stroke patients. Therefore, in this study, dual-targeted precise stimulation of V1 and primary motor cortex(M1) on the affected hemisphere of stroke patients will be used for cortical visuomotor multisensory integration to improve motor function. METHOD: This study is a randomized, double-blind controlled clinical trial over a 14-week period. 69 stroke subjects will be enrolled and divided into sham stimulation group, ccPAS low frequency group, and ccPAS high frequency group. All groups will receive conventional rehabilitation. The intervention lasted for two weeks, five times a week. Assessments will be performed before the intervention, at the end of the intervention, and followed up at 6 and 14 weeks. The primary assessment indicator is the 'Fugl-Meyer Assessment of the Upper Extremity ', secondary outcomes were 'The line bisection test', 'Modified Taylor Complex Figure', 'NIHSS' and neuroimaging assessments. All adverse events will be recorded. DISCUSSION: Currently, ccPAS is used for the modulation of neural circuits. Based on spike-timing dependent plasticity theory, we can precisely intervene in the connections between different cortices to promote the recovery of functional connectivity on damaged brain networks after stroke. We hope to achieve the modulation of cortical visuomotor interaction by combining ccPAS with the concept of multisensory integration. We will further analyze the correlation between analyzing visual and motor circuits and explore the alteration of neuroplasticity by the interactions between different brain networks. This study will provide us with a new clinical treatment strategy to achieve precise rehabilitation for patient with motor dysfunction after stroke. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry with code ChiCTR2300067422 and was approved on January 16, 2023.

A Fluorescent Probe Based on the Hydrazone Schiff Base for the Detection of Zn2+ and its Application on Test Strips.

A novel fluorescent probe SHK for Zn2+ detection was designed based on the hydrazone Schiff base, successfully synthesized by Suzuki coupling and condensation reactions. The probe SHK in DMSO/H2O showed extremely weak fluorescence. However, the solution exhibited an intensive yellow-green emission with the introduction of Zn2+. In contrast, negligible fluorescence change was observed when other metal ions were added, suggesting a high selectivity of SHK for Zn2+ detection. The Job's Plot analysis revealed that a 1:1 stoichiometric adduct SHK-Zn2+ formed during the Zn2+ sensing. The binding constant of the complex was determined to be 184 M- 1, and the detection limit for Zn2+ was calculated to be 112 µM. Moreover, the probe SHK achieved selective fluorescence sensing for Zn2+ on test strips, which guaranteed its practical application prospect.

Natural product drupacine acting on a novel herbicidal target shikimate dehydrogenase.

Natural products are one of the important sources for the creation of new pesticides. Drupacine ((1R,11S,12S,13R,15S)-13-methoxy-5,7,21-trioxa-19-azahexacyclo[11.7.1.02,10.04,8.011,15.015,19]henicosa-2,4(8),9-trien-12-ol), isolated from Cephalotaxus sinensis (Chinese plum-yew), is a potent herbicidal compound containing an oxo-bridged oxygen bond structure. However, its molecular target still remains unknown. In this study, the targets of drupacine in Amaranthus retroflexus were identified by combining drug affinity responsive target stability (DARTS), cellular thermal shift assay coupled with mass spectrometry (CETSA MS), RNA-seq transcriptomic, and TMT proteomic analyses. Fifty-one and sixty-eight main binding proteins were identified by DARTS and CETSA MS, respectively, including nine co-existing binding proteins. In drupacine-treated A. retroflexus seedlings we identified 1389 up-regulated genes and 442 down-regulated genes, 34 up-regulated proteins, and 194 down-regulated proteins, respectively. Combining the symptoms and the biochemical profiles, Profilin, Shikimate dehydrogenase (SkDH), and Zeta-carotene desaturase were predicted to be the drupacine potential target proteins. At the same time, drupacine was found to bind SkDH stronger by molecular docking, and its inhibition on ArSkDH increased with the treatment concentration increase. Our results suggest that the molecular target of drupacine is SkDH, a new herbicide target, which lay a foundation for the rational design of herbicides based on new targets from natural products and enrich the target resources for developing green herbicides.

Amino Acid Mutations A286V and T437M in the Nucleoprotein Attenuate H7N9 Viruses in Mice.

The low-pathogenic H7N9 influenza viruses that emerged in 2013 acquired an insertion of four amino acids in their hemagglutinin cleavage site and thereby became highly pathogenic to chickens in 2017. Previous studies indicated that these highly pathogenic H7N9 viruses are virulent in chickens but have distinct pathotypes in mice. A/chicken/Guangdong/SD098/2017 (CK/SD098) is avirulent, with a 50% mouse lethal dose (MLD50) of >7.5 log10 50% egg infectious dose (EID50), whereas A/chicken/Hunan/S1220/2017 (CK/S1220) is virulent in mice, with an MLD50 of 3.2 log10 EID50 In this study, we explored the genetic determinants that contribute to the difference in virulence between these two H7N9 viruses by generating a series of reassortants and mutants in the CK/S1220 virus background and testing their virulence in mice. We found that the reassortant CK/1220-SD098-NP, carrying the nucleoprotein (NP) of CK/SD098, was avirulent in mice, with an MLD50 of >107.5 EID50 The NPs of these two viruses differ by two amino acids, at positions 286 and 437. We further demonstrated that the amino acid mutations A286V and T437M of NP independently slowed the process of NP import to and export from the nucleus and thus jointly impaired the viral life cycle and attenuated the virulence of these H7N9 viruses in mice. Our study identified new virulence determinants in NP and provided novel targets for the development of live attenuated vaccines and antiviral drugs against influenza viruses.IMPORTANCE The H7N9 influenza viruses that emerged in China in 2013 have caused over 1,500 human infections, with a mortality rate of nearly 40%. The viruses were initially low pathogenic but became highly pathogenic in chickens at the beginning of 2017 and caused severe disease outbreaks in poultry. Several studies suggested that the highly pathogenic H7N9 viruses have increased virulence in mammals; however, the genetic basis of the virulence of H7N9 viruses in mammals is not fully understood. Here, we found that two amino acids, 286A and 437T, in NP are prerequisites for the virulence of H7N9 viruses in mice and the mutations A286V and T437M collectively eliminate the virulence of H7N9 viruses in mice. Our study further demonstrated that the virulence of influenza viruses is a polygenic trait, and the newly identified virulence-related residues in NP may provide new targets for attenuated influenza vaccine and antiviral drug development.

Capturing heterogeneity in repeated measures data by fusion penalty.

In this article, we are interested in capturing heterogeneity in clustered or longitudinal data. Traditionally such heterogeneity is modeled by either fixed effects (FE) or random effects (RE). In FE models, the degree of freedom for the heterogeneity equals the number of clusters/subjects minus 1, which could result in less efficiency. In RE models, the heterogeneity across different clusters/subjects is described by, for example, a random intercept with 1 parameter (for the variance of the random intercept), which could lead to oversimplification and biases (for the estimates of subject-specific effects). Our "fused effects" model stands in between these two approaches: we assume that there are unknown number of distinct levels of heterogeneity, and use the fusion penalty approach for estimation and inference. We evaluate and compare the performance of our method to the FE and RE models by simulation studies. We apply our method to the Ocular Hypertension Treatment Study to capture the heterogeneity in the progression rate of primary open-angle glaucoma of left and right eyes of different subjects.

Insecticidal action of the botanical insecticide wilforine on Mythimna separata (Walker) related with the changes of ryanodine receptor expression.

The detailed molecular mechanism of wilforine, a novel botanical insecticidal component, remains unclear, except for the knowledge that it affects the calcium signaling pathway. The aim of the current study was to examine the underlying molecular mechanism of wilforine in Mythimna separata (Walker) by transcriptome and RNA interference (RNAi), with chlorantraniliprole as control. RNA sequencing showed that the relative expression of genes related to the calcium signaling pathway and muscle contraction in M. separata treated with wilforine significantly changed and was further validated by qRT-PCR. Interestingly, the expression level of the ryanodine receptor (MsRyR) gene was downregulated by wilforine at relatively high concentrations and long treatment time, contrary to that observed using chlorantraniliprole. Furthermore, a putative MsRyR was cloned using a 16,258-bp contiguous sequence containing a 308-bp 5'-untranslated region and 578-bp 3'-untranslated region by RT-PCR and RACE. The results of the RNAi experiment showed that injection of dsMsRyR significantly reduced MsRyR mRNA levels, and growth and development were inhibited. Importantly, silencing of the MsRyR gene resulted in decreased susceptibility to both wilforine and chlorantraniliprole. Together with the results of our previous studies on toxic symptoms and muscle tissue lesions between wilforine and chlorantraniliprole, we propose that RyR Ca2+ release channel dysfunction is closely related with significant lethal mechanisms of wilforine.

The adjuvant effects of rosin and coconut oil on nicosulfuron and mesotrione to control weeds.

Natural adjuvants are novel options to reduce the doses of chemical herbicides. The aim of the current study was to examine the compositions and adjuvant effects of rosin and coconut oil on herbicides using a combination of indoor experiment and field trial. The GC-MS results showed that the main component of rosin was abietic acid (40.02%), and the main components of coconut oil were 2-pentanone, 4-hydroxy-4-methyl- (21.45%) and dodecanoic acid (14.59%). In greenhouse experiment, rosin showed a significant adjuvant effect on nicosulfuron against Digitaria sanguinalis and Amaranthus retroflexus, with the GR50 ratios of 1.47 and 1.69, respectively. The GR50 values of nicosulfuron in the present of coconut oil were 3.99 and 10.13 g a.i./hm2 against D. sanguinalis and A. retroflexus, lower than that of individual application. The adjuvant effect of rosin and coconut oil on mesotrione was also found. In field trial, the fresh weight control efficiency of nicosulfuron (45 g a.i./hm2) and mesotrione (112.5 g a.i./hm2) was significantly improved after the addition of rosin and coconut oil, similar with that of recommended dose. Rosin and coconut oil could reduce the contact angle of nicosulfuron, with the results of 56.68° and 53.90°, respectively, lower than that of individual application. Furthermore, rosin and coconut oil could decrease the surface tension, wetting and penetration time; and increase the spreading diameter and maximum retention. Both rosin and coconut oil have adjuvant effects on herbicides in the lab & field with multiple mechanisms. Thus, they have the potential to be developed into natural adjuvants for herbicide formulation to control weeds.

Identification of Key Amino Acids in the PB2 and M1 Proteins of H7N9 Influenza Virus That Affect Its Transmission in Guinea Pigs.

Efficient human-to-human transmission is a prerequisite for a novel influenza virus to cause an influenza pandemic; however, the genetic determinants of influenza virus transmission are still not fully understood. In this study, we compared the respiratory droplet transmissibilities of four H7N9 viruses that are genetic closely related and found that these viruses have dissimilar transmissibilities in guinea pigs: A/Anhui/1/2013 (AH/1) transmitted efficiently, whereas the other three viruses did not transmit. The three nontransmissible viruses have one to eight amino acid differences compared with the AH/1 virus. To investigate which of these amino acids is important for transmission, we used reverse genetics to generate a series of reassortants and mutants in the AH/1 background and tested their transmissibility in guinea pigs. We found that the neuraminidase (NA) of the nontransmissible virus A/chicken/Shanghai/S1053/2013 had low enzymatic activity that impaired the transmission of AH/1 virus, and three amino acid mutations-V292I and K627E in PB2 and D156E in M1-independently abolished the transmission of the AH/1 virus. We further found that an NA reassortant and three single-amino-acid mutants replicated less efficiently than the AH/1 virus in A549 cells and that the amino acid at position 156 of M1 affected the morphology of H7N9 viruses. Our study identifies key amino acids in PB2 and M1 that play important roles in H7N9 influenza virus transmission and provides new insights into the transmissibility of influenza virus.IMPORTANCE Efficient transmission is a prerequisite for a novel influenza virus to cause an influenza pandemic; however, the genetic determinants of influenza virus transmission remain poorly understood. H7N9 influenza viruses, which emerged in 2013 in China, have caused over 1,560 human infection cases, showing clear pandemic potential. Previous studies have shown that the H7N9 viruses differ in their transmissibility in animal models. In this study, we found two amino acids in PB2 (292V and 627K) and one in M1 (156D) that are extremely important for H7N9 virus transmission. Of note, PB2 292V and M1 156D appear in most H7N9 viruses, and the PB2 627K mutation could easily occur when the H7N9 virus replicates in humans. Our study thus identifies new amino acids that are important for influenza virus transmission and suggests that just a few key amino acid changes can render the H7N9 virus transmissible in mammals.

Machine learning methods for leveraging baseline covariate information to improve the efficiency of clinical trials.

Clinical trials are widely considered the gold standard for treatment evaluation, and they can be highly expensive in terms of time and money. The efficiency of clinical trials can be improved by incorporating information from baseline covariates that are related to clinical outcomes. This can be done by modifying an unadjusted treatment effect estimator with an augmentation term that involves a function of covariates. The optimal augmentation is well characterized in theory but must be estimated in practice. In this article, we investigate the use of machine learning methods to estimate the optimal augmentation. We consider and compare an indirect approach based on an estimated regression function and a direct approach that aims directly to minimize the asymptotic variance of the treatment effect estimator. Theoretical considerations and simulation results indicate that the direct approach is generally preferable over the indirect approach. The direct approach can be implemented using any existing prediction algorithm that can minimize a weighted sum of squared prediction errors. Many such prediction algorithms are available, and the super learning principle can be used to combine multiple algorithms into a super learner under the direct approach. The resulting direct super learner has a desirable oracle property, is easy to implement, and performs well in realistic settings. The proposed methodology is illustrated with real data from a stroke trial.

A ROBUST AND EFFICIENT APPROACH TO CAUSAL INFERENCE BASED ON SPARSE SUFFICIENT DIMENSION REDUCTION.

A fundamental assumption used in causal inference with observational data is that treatment assignment is ignorable given measured confounding variables. This assumption of no missing confounders is plausible if a large number of baseline covariates are included in the analysis, as we often have no prior knowledge of which variables can be important confounders. Thus, estimation of treatment effects with a large number of covariates has received considerable attention in recent years. Most existing methods require specifying certain parametric models involving the outcome, treatment and confounding variables, and employ a variable selection procedure to identify confounders. However, selection of a proper set of confounders depends on correct specification of the working models. The bias due to model misspecification and incorrect selection of confounding variables can yield misleading results. We propose a robust and efficient approach for inference about the average treatment effect via a flexible modeling strategy incorporating penalized variable selection. Specifically, we consider an estimator constructed based on an efficient influence function that involves a propensity score and an outcome regression. We then propose a new sparse sufficient dimension reduction method to estimate these two functions without making restrictive parametric modeling assumptions. The proposed estimator of the average treatment effect is asymptotically normal and semiparametrically efficient without the need for variable selection consistency. The proposed methods are illustrated via simulation studies and a biomedical application.

A Single-Amino-Acid Substitution at Position 225 in Hemagglutinin Alters the Transmissibility of Eurasian Avian-Like H1N1 Swine Influenza Virus in Guinea Pigs.

Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model. We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs. We found that a single-amino-acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs. We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiencies. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza virus strains.IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus affinity for human-type receptors. In this study, we explored the genetic basis of the transmissibility difference between two Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses in guinea pigs and found that the amino acid glutamic acid at position 225 in the HA1 protein plays a critical role in the transmission of EAH1N1 virus by increasing the efficiency of viral assembly and budding.

Comprehensive chromosomal and mitochondrial copy number profiling in human IVF embryos.

Single cell whole genome sequencing helps to decipher the genome heterogeneity within a cell population and facilitates the analysis of trace amounts of genetic material, such as is found in human embryos. The mitochondrial genome, although an important part of the genetic composition of eukaryotic cells, is often neglected in single cell genome analysis. A recently developed single cell whole genome amplification method was used, known as multiple annealing and looping based amplification cycles (MALBAC-NGS), for simultaneous analysis of chromosomal and mitochondrial genomes at the single cell level. The platform was validated by a series of technical and biological replicates and used for chromosomal and mitochondrial copy number analysis in 399 in-vitro fertilized embryos from 81 couples. A positive correlation of maternal age with increased mitochondria quantity (ß = 0.176, P = 0.001) was observed after adjusting for the impact of cell type. Lower numbers of mitochondria were detected in successfully implanted embryos, although the difference was not significant. It is proposed that MALBAC-NGS could potentially be used for an advanced pre-implantation genetic screening procedure with both chromosomal constitution and mitochondrial copy number being evaluated.

Comparative studies on muscle microstructure and ultrastructure of Mythimna separata Walker treated with wilforgine and chlorantraniliprole.

We attempted to elucidate the comparative effects between wilforgine and chlorantraniliprole on the microstructure/ultrastructure of muscle tissue in Mythimna separate larvae. The typical toxicity symptoms of M. separata larvae upon wilforgine treatment was feeding cessation and flaccid paralysis, whereas feeding cessation and contraction paralysis were the main poisoning symptoms wrought by chlorantraniliprole. Light-microscopy observations showed that the microstructure of muscle tissue could be damaged by wilforgine and chlorantraniliprole, and the death of insects was associated with muscle lesions. Muscle tissue was loose after wilforgine treatment but constricted muscle tissue was observed upon chlorantraniliprole treatment. Transmission electron microscopy showed that wilforgine and chlorantraniliprole could disrupt endomembranes and plasma membranes. These results suggest that wilforgine can induce microstructural and ultrastructural changes in the muscles of M. separata larvae; the sites of action are proposed to be calcium receptors or channels in the muscular system.

Microstructural and ultrastructural changes in the muscle cells of the oriental armyworm Mythimna separata Walker (Lepidoptera: Noctuidae) on treatment with wilforine.

This study investigated the mode of action of wilforine, an alkaloid with insecticidal properties, extracted from Tripterygium wilfordii Hook f., on the microstructure and ultrastructure of the muscle cells of larvae and adults of the oriental armyworm Mythimna separata Walker. The bioassay results showed that wilforine had oral toxicity against both M. separata larvae (LC50=63µg/mL) and adults (LC50=36µg/mL). The typical toxicity sign was paralysis leading to death. Both light and electron microscope observations revealed that damage to the muscle cells increased with poisoning time in larvae and adults treated with the LC80 dose of wilforine. Histopathological examinations in the muscle cells of M. separata adults showed that there were large cytoplasmic spaces, disrupted Z-lines and swollen mitochondria in the muscle cells. Further, the sarcoplasmic reticulum was excessively dilated and fragmented; the nuclear membrane was ruptured; nuclear material was overflowing; and the myolemma was damaged. The similar pathological changes in the muscle cells of oriental armyworm larvae were observed, as above. In addition, a medullary sheath structure appeared and crystalline inclusion was also observed in the muscle cells of M. separata larvae. In conclusion, wilforine could induce pathological changes in the muscle cells of oriental armyworm larvae and adults, leading to their death; thus, the active site of action of wilforine maybe located in the muscle tissue of insects.

2,4-Di-tert-butylphenol and 7-hydroxy-3-(2-methylpropyl)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione: two natural products from Serratia marcescens Ha1 and their herbicidal activities.

BACKGROUND: Weeds are one of the critical factors that negatively affect crop yield and quality. Microbial herbicides are a research hotspot for novel herbicides owing to their environmental safety and lack of weed resistance. In the current study, the active ingredients of Serratia marcescens Ha1, a new microbial herbicide, were investigated for their effectiveness against agricultural weeds using bioassay-guided fractionation. RESULTS: The results revealed that petroleum ether and ethyl acetate extracts of S. marcescens Ha1 had high herbicidal activity. Forty-nine compounds were identified from the petroleum ether extract, including 2,4-di-tert-butylphenol (DB; C14 H22 O, 38.82%), ethyl 14-methyl-hexadecanoate, 1-nonadecene, and [1,1'-biphenyl]-2,3'-diol, 3,4',5,6'-tetrakis. Of these, DB showed significant inhibitory effects on root and shoot growth in Amaranthus retroflexus, with half-maximal inhibitory concentration (IC50 ) values of 389.17 and 832.44 mg L-1 , respectively. In addition, 7-hydroxy-3-(2-methylpropyl)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione (HPD) was identified as the major active ingredient in the ethyl acetate extract of S. marcescens Ha1 using bioassay-guided fractionation, with IC50 values of 439.86 and 476.95 mg L-1 against A. retroflexus shoot and root growth, respectively. Scanning electron microscopy indicated that DB and HPD exert destructive effects on A. retroflexus root, and the damage is gradually aggravated with increasing treatment time and concentration. CONCLUSION: The S. marcescens Ha1 extract and its active compounds DB and HPD exhibit significant herbicidal activity, which could be utilized further for the development of microbial herbicides. © 2023 Society of Chemical Industry.

Effectiveness of Yijinjing on cognitive and motor functions in patients with Parkinson's disease: study protocol for a randomized controlled trial.

Background: Parkinson's disease (PD) is a common neurodegenerative disorder that affects motor and non-motor functions, significantly reducing patients' quality of life. No effective drug-based treatments are known to solve this problem. Non-drug therapies such as Yijinjing exercise have shown potential in improving cognitive and motor functions in PD patients. However, solid evidence must still be provided to support their clinical efficacy. This study aims to evaluate the clinical efficacy of Yijinjing exercise interventions in PD patients and explore the underlying mechanisms between the cognitive and motor functions in PD. Methods: This is a single-center randomized controlled trial in which 96 eligible PD patients will be randomly assigned to receive either Yijinjing exercise group or brisk walking group or control group in a ratio of 1:1:1. Interventions (Yijinjing exercise or brisk walking training, 40 min per session) will be provided in 3 sessions per week (Monday, Wednesday, Friday) for 12 weeks, with a total of 36 sessions. After the treatment, there will be a 1-month follow-up period. The primary outcomes will be measured using the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale motor section (UPDRS-III). Secondary outcomes include balance function, executive function, walking function, sleep quality, and quality of life. Additionally, the prefrontal cerebral and sensorimotor cortex blood oxygen signal level will be collected to explore the underlying mechanisms. All outcomes will be assessed at baseline, at the end of 12 weeks of treatment and after an additional 1-month follow-up period. Discussion: The results of the study protocol will provide high-quality evidence for the potential of intervention measures based on the Yijinjing exercise to improve the cognitive and activity levels of Parkinson's disease patients. We envision the Yijinjing exercise as a non-pharmacological family activity that can provide a new and more effective method for the treatment of Parkinson's disease patients or those at risk. Clinical trial registration: This study was approved by the Ethics Committee of the Second Rehabilitation Hospital of Shanghai (2020-05-01). The trial has been registered in the China Clinical Trials Registry (ChiCTR2200055636).

Advances in novel biomaterials combined with traditional Chinese medicine rehabilitation technology in treatment of peripheral nerve injury.

Peripheral nerve injuries (PNI) represent one of the primary neuropathies leading to lifelong disability. Nerve regeneration and targeted muscle atrophy stand as the two most crucial factors influencing functional rehabilitation post peripheral nerve injury. Over time, traditional Chinese medicine (TCM) rehabilitation approaches such as acupuncture, Tuina, and microneedles serve as pivot means to activate the regeneration of injured nerve Schwann cells. By promoting axon regeneration, these approaches can accomplish nerve repair, reconstruction, and functional rehabilitation. Although TCM rehabilitation approaches have clinically demonstrated effectiveness in promoting the repair and regeneration of PNI, the related molecular mechanisms remain unclear. This significantly hampers the application and promotion of TCM rehabilitation in PNI recovery. Therefore, deeply delving into the cellular and molecular mechanisms of TCM rehabilitation technologies to foster nerve regeneration stands as the most pressing issue. On the other hand, in recent years, novel biomaterials represented by hydrogels, microfluidic platforms, and new chitosan scaffolds have showed their unique roles in treating various degrees of nerve injury. These methods exhibit immense potential in conducting high-throughput cell and organoid culture in vitro and synthesizing diverse tissue engineering scaffolds and drug carriers. We believe that the combination of TCM rehabilitation technology and novel biomaterials can more effectively address precise treatment issues such as identification of treatment target and dosage control. Therefore, this paper not only summarizes the molecular mechanisms of TCM rehabilitation technology and novel biomaterials in treating peripheral nerve injury individually, but also explores the research direction of precise treatment by integrating the two at both macro and micro levels. Such integration may facilitate the exploration of cellular and molecular mechanisms related to neurodegeneration and regeneration, providing a scientific and theoretical foundation for the precise functional rehabilitation of PNI in the future.

A fusion learning method to subgroup analysis of Alzheimer's disease.

Uncovering the heterogeneity in the disease progression of Alzheimer's is a key factor to disease understanding and treatment development, so that interventions can be tailored to target the subgroups that will benefit most from the treatment, which is an important goal of precision medicine. However, in practice, one top methodological challenge hindering the heterogeneity investigation is that the true subgroup membership of each individual is often unknown. In this article, we aim to identify latent subgroups of individuals who share a common disorder progress over time, to predict latent subgroup memberships, and to estimate and infer the heterogeneous trajectories among the subgroups. To achieve these goals, we apply a concave fusion learning method to conduct subgroup analysis for longitudinal trajectories of the Alzheimer's disease data. The heterogeneous trajectories are represented by subject-specific unknown functions which are approximated by B-splines. The concave fusion method can simultaneously estimate the spline coefficients and merge them together for the subjects belonging to the same subgroup to automatically identify subgroups and recover the heterogeneous trajectories. The resulting estimator of the disease trajectory of each subgroup is supported by an asymptotic distribution. It provides a sound theoretical basis for further conducting statistical inference in subgroup analysis.