Effects of folic acid and folic acid plus zinc supplements on the sperm characteristics and pregnancy outcomes of infertile men: A systematic review and meta-analysis.

Background: Folic acid and zinc supplements have been used to treat male infertility, but their efficacy is still debated. Objective: To systematically evaluate the effects of folic acid and folic acid plus zinc supplements on sperm characteristics and pregnancy outcomes of infertile men. Methods: An online systematic search was performed using PubMed, Cochrane Library, and EMBASE databases from inception to August 1, 2022. The goal was to identify randomized controlled trials (RCTs) that used folic acid or folic acid plus zinc to improve sperm characteristics of infertile men. Data were extracted by two investigators who independently screened the literature and assessed for quality according to the criteria. The meta-analysis was performed using RevMan 5.4 software. Results: A total of 8 RCT studies involving 2168 patients were included. The results showed that compared with the controls, folic acid significantly increased sperm motility (MD, 3.63; 95% CI, -1.22 to 6.05; P = 0.003), but did not affect the sperm concentration (MD, 2.53; 95% CI, -1.68 to 6.73; P = 0.24) and sperm morphology (MD, -0.02; 95% CI, -0.29 to 0.24; P = 0.86) in infertile men. Folic acid plus zinc did not affect sperm concentration (MD, 1.87; 95% CI, -1.39 to 5.13; P = 0.26), motility (MD, 1.67; 95% CI, -1.29 to 4.63; P = 0.27), and morphology (MD, -0.05; 95% CI, -0.27 to 0.18; P = 0.69) in infertile men. Secondary results showed that compared with a placebo, folic acid alone had a higher rate of pregnancy in transferred embryos (35.6% vs. 20.4%, P = 0.082), but the difference was not significant. Folic acid plus zinc did not affect pregnancy outcomes. Conclusions: Based on the meta-analysis, no significant improvements in sperm characteristics with folic acid plus zinc supplements were seen. However, folic acid alone has demonstrated the potential to improve sperm motility and in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) outcomes. This indicates that folic acid supplements alone may be a viable treatment option for male infertility.

Exoskeleton-Assisted Sit-to-Stand Training Improves Lower-Limb Function Through Modifications of Muscle Synergies in Subacute Stroke Survivors.

Abnormal muscle synergies during sit-to-stand (STS) transitions have been observed post-stroke, which are associated with deteriorated lower-limb function and mobility. Although exoskeletons have been used in restoring lower-limb function, their effects on muscle synergies and lower-limb motor recovery remain unclear. Here, we characterized normal muscle synergy patterns during STS activity in ten healthy adults as a reference, comparing with pathological muscle synergy patterns in ten participants with subacute stroke. Moreover, we assessed the effects of a 3-week exoskeleton-assisted STS training intervention on muscle synergies and clinical scores in seven stroke survivors. We also investigated correlations between neuromuscular complexity of muscle synergies and clinical scores. Our results showed that the STS task involved three motor modules representing distinct biomechanical functions among healthy subjects. In contrast, stroke participants showed 3 abnormal modules for the paretic leg and 2 modules for the non-paretic leg. After the intervention, muscle synergies partially shifted towards the normal pattern observed in healthy subjects on the paretic side. On the non-paretic side, the synergy modules increased to three and neuromuscular coordination improved. Furthermore, the significant intervention-induced increases in Fugl-Meyer Assessment of Lower Extremity and Berg Balance Scale scores were associated with improved muscle synergies on the non-paretic side. These results indicate that the paretic side demonstrates abnormal changes in muscle synergies post-stroke, while the non-paretic side can synergistically adapt to post-stroke biomechanical deviations. Our data show that exoskeleton-based training improved lower-limb function post-stroke by inducing modifications in muscle synergies.

Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors: A Phase I Trial.

BACKGROUND: Senaparib, a novel poly(ADP-ribose) polymerase 1/2 inhibitor, demonstrated antitumor activity in preclinical studies. This phase I, first-in-human, dose-escalation/-expansion study explored the pharmacokinetics, safety and tolerability, and preliminary antitumor activity of senaparib in Chinese patients with advanced solid tumors. PATIENTS AND METHODS: Adults with advanced solid tumors who had failed ³1 line of prior systemic treatment were enrolled. Senaparib (once daily [QD]) dose was escalated from 2 mg until the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) using a modified 3 + 3 design. Dose expansion included: dose groups with ≥1 objective response and one dose higher, as well as those at the MTD/RP2D. Primary objectives were to evaluate the safety and tolerability, and determine the MTD and/or RP2D of senaparib. RESULTS: Fifty-seven patients were enrolled across 10 dose groups (2-120 mg QD, and 50 mg twice daily). No dose-limiting toxicities were observed. The most common senaparib-related adverse events were anemia (80.9%), white blood cell count decreased (43.9%), platelet count decreased (28.1%), and asthenia (26.3%). Senaparib exposure increased dose proportionately at 2-80 mg; absorption saturated at 80-120 mg. Senaparib accumulation was minimal after repeated QD administration (accumulation ratio=1.1-1.5). The objective response rate was 22.7% (n=10/44) overall (all partial responses) and 26.9% (n=7/26) for patients harboring BRCA1/BRCA2 mutations. Disease control rates were 63.6% and 73.1%, respectively. CONCLUSIONS: Senaparib was well tolerated and demonstrated promising antitumor activity in Chinese patients with advanced solid tumors. The RP2D for this clinical study in China was identified as 100 mg QD. CLINICALTRIALS.GOV IDENTIFIER: NCT03508011.

Exoskeleton-Assisted Anthropomorphic Movement Training for the Upper Limb After Stroke: The EAMT Randomized Trial.

BACKGROUND: Robot-assisted arm training is generally delivered in the robot-like manner of planar or mechanical 3-dimensional movements. It remains unclear whether integrating upper extremity (UE) natural coordinated patterns into a robotic exoskeleton can improve outcomes. The study aimed to compare conventional therapist-mediated training to the practice of human-like gross movements derived from 5 typical UE functional activities managed with exoskeletal assistance as needed for patients after stroke. METHODS: In this randomized, single-blind, noninferiority trial, patients with moderate-to-severe UE motor impairment due to subacute stroke were randomly assigned (1:1) to receive 20 sessions of 45-minute exoskeleton-assisted anthropomorphic movement training or conventional therapy. Treatment allocation was masked from independent assessors, but not from patients or investigators. The primary outcome was the change in the Fugl-Meyer Assessment for Upper Extremity from baseline to 4 weeks against a prespecified noninferiority margin of 4 points. Superiority would be tested if noninferiority was demonstrated. Post hoc subgroup analyses of baseline characteristics were performed for the primary outcome. RESULTS: Between June 2020 and August 2021, totally 80 inpatients (67 [83.8%] males; age, 51.9±9.9 years; days since stroke onset, 54.6±38.0) were enrolled, randomly assigned to the intervention, and included in the intention-to-treat analysis. The mean Fugl-Meyer Assessment for Upper Extremity change in exoskeleton-assisted anthropomorphic movement training (14.73 points; [95% CI, 11.43-18.02]) was higher than that of conventional therapy (9.90 points; [95% CI, 8.15-11.65]) at 4 weeks (adjusted difference, 4.51 points [95% CI, 1.13-7.90]). Moreover, post hoc analysis favored the patient subgroup (Fugl-Meyer Assessment for Upper Extremity score, 23-38 points) with moderately severe motor impairment. CONCLUSIONS: Exoskeleton-assisted anthropomorphic movement training appears to be effective for patients with subacute stroke through repetitive practice of human-like movements. Although the results indicate a positive sign for exoskeleton-assisted anthropomorphic movement training, further investigations into the long-term effects and paradigm optimization are warranted. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100044078.

Exploring the effects of skeletal architecture and muscle properties on bipedal standing in the common chimpanzee (Pan troglodytes) from the perspective of biomechanics.

Introduction: It is well known that the common chimpanzee, as both the closest living relative to humans and a facultative bipedal, has the capability of bipedal standing but cannot do so fully upright. Accordingly, they have been of exceeding significance in elucidating the evolution of human bipedalism. There are many reasons why the common chimpanzee can only stand with its hips-knees bent, such as the distally oriented long ischial tubercle and the almost absent lumbar lordosis. However, it is unknown how the relative positions of their shoulder-hip-knee-ankle joints are coordinated. Similarly, the distribution of the biomechanical characteristics of the lower-limb muscles and the factors that affect the erectness of standing as well as the muscle fatigue of the lower limbs remain a mystery. The answers are bound to light up the evolutional mechanism of hominin bipedality, but these conundrums have not been shed much light upon, because few studies have comprehensively explored the effects of skeletal architecture and muscle properties on bipedal standing in common chimpanzees. Methods: Thus, we first built a musculoskeletal model comprising the head-arms-trunk (HAT), thighs, shanks, and feet segments of the common chimpanzee, and then, the mechanical relationships of the Hill-type muscle-tendon units (MTUs) in bipedal standing were deduced. Thereafter, the equilibrium constraints were established, and a constrained optimization problem was formulated where the optimization objective was defined. Finally, thousands of simulations of bipedal standing experiments were performed to determine the optimal posture and its corresponding MTU parameters including muscle lengths, muscle activation, and muscle forces. Moreover, to quantify the relationship between each pair of the parameters from all the experimental simulation outcomes, the Pearson correlation analysis was employed. Results: Our results demonstrate that in the pursuit of the optimal bipedal standing posture, the common chimpanzee cannot simultaneously achieve maximum erectness and minimum muscle fatigue of the lower limbs. For uni-articular MTUs, the relationship between muscle activation, relative muscle lengths, together with relative muscle forces, and the corresponding joint angle is generally negatively correlated for extensors and positively correlated for flexors. For bi-articular MTUs, the relationship between muscle activation, coupled with relative muscle forces, and the corresponding joint angles does not show the same pattern as in the uni-articular MTUs. Discussion: The results of this study bridge the gap between skeletal architecture, along with muscle properties, and biomechanical performance of the common chimpanzee during bipedal standing, which enhances existing biomechanical theories and advances the comprehension of bipedal evolution in humans.

In pursuit of reconstructing missing human hands.

Exploring bio-intelligence of human limbs could provide a new perspective for reconstructing missing limbs.

Weighted gene co-expression network analysis revealed the key pathways and hub genes of potassium regulating cotton root adaptation to salt stress.

Soil salinization is one of the main abiotic stresses affecting cotton yield and planting area. Potassium application has been proven to be an important strategy to reduce salt damage in agricultural production. However, the mechanism of potassium regulating the salt adaptability of cotton has not been fully elucidated. In the present research, the appropriate potassium application rate for alleviating salt damage of cotton based on different K+/Na+ ratios we screened, and a gene co-expression network based on weighted gene co-expression network analysis (WGCNA) using the transcriptome data sets treated with CK (0 mM NaCl), S (150 mM NaCl), and SK8 (150 mM NaCl + 9.38 mM K2SO4) was constructed. In this study, four key modules that are highly related to potassium regulation of cotton salt tolerance were identified, and the mitogen-activated protein kinase (MAPK) signaling pathway, tricarboxylic acid (TCA) cycle and glutathione metabolism pathway were identified as the key biological processes and metabolic pathways for potassium to improve cotton root salt adaptability. In addition, 21 hub genes and 120 key candidate genes were identified in this study, suggesting that they may play an important role in the enhancement of salt adaptability of cotton by potassium. The key modules, key biological pathways and hub genes discovered in this study will provide a new understanding of the molecular mechanism of potassium enhancing salinity adaptability in cotton, and lay a theoretical foundation for the improvement and innovation of high-quality cotton germplasm.

p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer's disease.

BACKGROUND: Ribosomal protein S6 kinase 1 (S6K1) is a serine-threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer's disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown. METHODS: We fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice. RESULTS: p85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice. CONCLUSIONS: These results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.

Research Progress and Application Prospect of Facial Micro-Expression Analysis in Forensic Psychiatry / 法医学杂志

Research on facial micro-expression analysis has been going on for decades. Micro-expression can reflect the true emotions of individuals, and it has important application value in assisting auxiliary diagnosis and disease monitoring of mental disorders. In recent years, the development of artificial intelligence and big data technology has made the automatic recognition of micro-expressions possible, which will make micro-expression analysis more convenient and more widely used. This paper reviews the development of facial micro-expression analysis and its application in forensic psychiatry, to look into further application prospects and development direction.

Use of chemical labeling-assisted liquid chromatography-mass spectrometry for discovering derivatives of brassinosteroids.

Brassinosteroids (BRs) are plant steroid hormones that are involved in the regulation of plant growth and development as well as environmental adaptation. The discovery of new BR derivatives is beneficial to their biosynthesis and regulation mechanisms research. However, there are few reports on the methods for exploring new BRs, and the existing methods tend to lack coverage. In this work, we established a comprehensive, highly sensitive and selective structure-oriented method for the screening and structural identification of potential BRs in plants using chemical isotope labeling-assisted liquid chromatography-high resolution mass spectrometry (CL-LC-HRMS). The potential BRs were speculated according to the structural features of the reported BRs, and those speculated BRs containing cis-diol groups were labeled by isotope reagents of 2-methyl-4-phenylaminomethylphenylboronic acid (2-methyl-4-PAMBA) and 2-methyl-4-PAMBA-d5 to improve the sensitivity and selectivity of MS detection. In addition, the fragmentation of 2-methyl-4-PAMBA-labeled BRs via collision-induced dissociation (CID) led to the generation of reporter ions, which contributed to specific screening of potential BRs. In-depth structure of potential BRs was elucidated by analyzing multistage MS (MSn) fragmentation patterns. Using our proposed method, a total of 16 potential BRs were detected from plant samples including 5 new ones, of which one new BR derivative was identified as 2-deoxy-3-epi-6-deoxy-dolichosterone, and this new BR may be involved in the biosynthesis of BRs as precursor of 6-deoxo-dolichosterone. The method developed in this work is promising for screening and identifying new BR derivatives in plants, thereby supplementing the biosynthesis pathway of BRs.

Screening and Identification of Potential Abscisic Acid Catabolites by Chemical Labeling-Assisted Ultrahigh-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry.

In this study, a screening strategy was established based on ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry assisted by chemical isotope labeling (CIL-UPLC-HRMS) for screening and identifying abscisic acid (ABA) catabolites. Based on the structures of known ABA catabolites, this strategy first proposed the structures of catabolites to be discovered. Afterward, a pair of isotope reagents N,N-2-dimethylaminoethylamine (DMED) and d4-DMED were used as labeling reagents to label the carboxyl groups in ABA and its catabolites. Then, the mass-to-charge ratio (m/z) of DMED- and d4-DMED-labeled ABA catabolites was calculated based on the labeling schema. In light of the characteristic fragmentation patterns of the DMED-labeled standards of ABA and its catabolites, screening criteria were formulated. Using our strategy, ABA, t-ABA, and 18 ABA catabolites were identified from seven plant samples. Of the identified catabolites, 16 were known, and to our knowledge, 2 were previously unidentified. Our findings contribute to ABA catabolic network improvement.

Neophaseic acid catabolism in the 9'-hydroxylation pathway of abscisic acid in Arabidopsis thaliana.

Abscisic acid (ABA) hydroxylation is an important pathway for ABA inactivation and homeostasis maintenance. Here, we discover a new downstream catabolite of neophaseic acid (neoPA) in the ABA 9'-hydroxyl pathway and identify it as epi-neodihydrophaseic acid (epi-neoDPA) by comparing its accurate mass, retention time, and MSn spectra with those of our chemically synthesized epi-neoDPA. Analyses of Arabidopsis seed germination and ABA-related gene expression reveal that neoPA rather than epi-neoDPA possesses ABA-like hormonal activity. In vitro enzyme activity tests of prokaryotic recombinant protein reveal that NeoPAR1 (neoPA reductase 1) identified from Arabidopsis converts neoPA into epi-neoDPA. Site-directed mutation at Tyr163 in the conserved motif of NeoPAR1 abolishes the catalytic activity of NeoPAR1. Accelerated seed germination was observed in NeoPAR1 knockdown and knockout mutants, whereas retarded seed germination and the accumulation of epi-neoDPA and ABA were observed in NeoPAR1 overexpression lines, suggesting that NeoPAR1 is involved in seed germination and maintenance of ABA homeostasis.

Carboxylic submetabolome-driven signature characterization of COVID-19 asymptomatic infection.

Asymptomatic infection of COVID-19 is a global threat for public health. Unfortunately, the study about metabolic dysregulation of asymptomatic infection is barely investigated. Here, we performed carboxylic submetabolome profiling of serum from 62 asymptomatic and 122 control individuals, by a highly sensitive chemical isotope labelling method. Twenty-one discriminative carboxylic features, including 12-hydroxyeicosatetraenoic acid, cholic acid, glycoursodeoxycholic acid and 15,16-dihydroxyoctadeca-9,12-dienoic acid were discovered to be dysregulated in asymptomatic patients. This panel containing 21 carboxylic features could accurately identify asymptomatic patients based on a random forest model, providing an accuracy of 85.7% with only 3.6% false positive rate and 7.1% false negative rate. The dysregulated metabolites found in asymptomatic patients covered several important pathways, such as arachidonic acid metabolism, synthesis of bile acid, ß-oxidation of fatty acids, activation of macrophage and platelet aggregation. This work provided valuable knowledge about serum biomarkers and molecular clues associated with asymptomatic COVID-19 patients.

Anthropomorphic Reaching Movement Generating Method for Human-Like Upper Limb Robot.

How to generate anthropomorphic reaching movement remains a challenging problem in service robots and human motor function repair/reconstruction equipment. However, there is no universally accepted computational model in the literature for reproducing the motion of the human upper limb. In response to the problem, this article presents a computational framework for generating reaching movement endowed with human motion characteristics that imitated the mechanism in the control and realization of human upper limb motions. This article first establishes the experimental paradigm of human upper limb functional movements and proposes the characterization of human upper limb movement characteristics and feature movement clustering methods in the joint space. Then, according to the specific task requirements of the upper limb, combined with the human sensorimotor model, the estimation method of the human upper limb natural postures was established. Next, a continuous task parametric model matching the characteristic motion class is established by using the Gaussian mixture regression method. The anthropomorphic motion generation method with the characteristics of the smooth trajectory and the ability of natural obstacle avoidance is proposed. Finally, the anthropomorphic motion generation method proposed in this article is verified by a human-like robot. The measurement index of the human-likeness degree of the trajectory is given. The experimental results show that for all four tested tasks, the human-likeness degrees were greater than 90.8%, and the trajectories' jerk generated by this method is very similar to the trajectories' jerk of humans, which validates the proposed method.

Integration of Chemical Derivatization and in-Source Fragmentation Mass Spectrometry for High-Coverage Profiling of Submetabolomes.

In-source fragmentation-based high-resolution mass spectrometry (ISF-HRMS) is a potential analytical technique, which is usually used to profile some specific compounds that can generate diagnostic neutral loss (NL) or fragment ion (FI) in ion source inherently. However, the ISF-HRMS method does not work for those compounds that cannot inherently produce diagnostic NL or FI in ion source. In this study, a derivatization-based in-source fragmentation-information-dependent acquisition (DISF-IDA) strategy was proposed for profiling the metabolites with easily labeled functional groups (submetabolomes) by liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-Q-TOF MS). As a proof-of-concept study, 36 carboxylated compounds labeled with N,N-dimethylethylenediamine (DMED) were selected as model compounds to examine performance of DISF-IDA strategy in screening the carboxylated metabolites and acquiring their MSn spectra. In ESI source, the DEMD-derived carboxylated compounds were fragmented to produce characteristic neutral losses of 45.0578, 63.0684, and/or 88.1000 Da that were further used as diagnostic features for screening the carboxylated metabolites by DISF-IDA-based LC-Q-TOF MS. Furthermore, high-resolution MSn spectra of the model compounds were also obtained within a single run of DISF-IDA-based LC-Q-TOF MS analysis, which contributed to the improvement of the annotation confidence. To further verify its applicability, DISF-IDA strategy was used for profiling carboxylated submetabolome in mice feces. Using this strategy, a total of 351 carboxylated metabolites were detected from mice feces, of which 178 metabolites (51% of the total) were positively or putatively identified. Moreover, DISF-IDA strategy was also demonstrated to be applicable for profiling other submetabolomes with easily labeled functional groups such as amino, carbonyl, and cis-diol groups. Overall, our proposed DISF-IDA strategy is a promising technique for high-coverage profiling of submetabolomes with easily labeled functional groups in biological samples.

Preliminary Assessment of a Postural Synergy-Based Exoskeleton for Post-Stroke Upper Limb Rehabilitation.

Upper limb exoskeletons have drawn significant attention in neurorehabilitation because of the anthropomorphic mechanical structure analogous to human anatomy. Whereas, the training movements are typically unorganized because most exoskeletons ignore the natural movement characteristic of human upper limbs, particularly inter-joint postural synergy. This paper introduces a newly developed exoskeleton (Armule) for upper limb rehabilitation with a postural synergy design concept, which can reproduce activities of daily living (ADL) motion with the characteristics of human natural movements. The semitransparent active control strategy with the interactive force guidance and visual feedback ensured the active participation of users. Eight participants with hemiplegia due to a first-ever, unilateral stroke were recruited and included. They participated in exoskeleton therapy sessions for 4 weeks, with passive/active training under trajectories and postures with the characteristics of human natural movements. The primary outcome was the Fugl-Meyer Assessment for Upper Extremities (FMA-UE). The secondary outcomes were the Action Research Arm Test(ARAT), modified Barthel Index (mBI), and metric measured with the exoskeleton After the 4-weeks intervention, all subjects showed significant improvements in the following clinical measures: the FMA-UE (difference, 11.50 points, p = 0.002), the ARAT (difference, 7.75 points ), and the mBI (difference, 17.50 points, p = 0.003 ) score. Besides, all subjects showed significant improvements in kinematic and interaction force metrics measured with the exoskeleton. These preliminary results demonstrate that the Armule exoskeleton could improve individuals' motor control and ADL function after stroke, which might be associated with kinematic and interaction force optimization and postural synergy modification during functional tasks.

Robot-Assisted Arm Training in Stroke Individuals With Unilateral Spatial Neglect: A Pilot Study.

Background: Robot-assisted arm training (RAT) is an innovative exercise-based therapy that provides highly intensive, adaptive, and task-specific training, yet its effects for stroke individuals with unilateral spatial neglect remain to be explored. The study was aimed to investigate the effects of RAT on unilateral spatial neglect, arm motor function, activities of daily living, and social participation after stroke. Methods: In a pilot randomized controlled trial, individuals with unilateral spatial neglect after right hemisphere stroke were equally allocated to intervention group and control group, 45-min training daily, 5 days/week, for 4 weeks. Outcome measures included the Behavioral Inattention Test-conventional section (BIT-C), Catherine Bergego Scale (CBS), Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Modified Barthel Index (MBI), and World Health Organization Disability Assessment Schedule Version 2.0 (WHODAS 2.0). Results: From November 2018 to February 2021, 20 stroke patients (mean age 47.40 ± 8.47) were enrolled in the study. Robot-assisted arm training was feasible and safe for individuals with unilateral spatial neglect. Both groups had significant improvements in all outcome measures. Participants assigned to RAT therapy had significantly greater improvements in BIT-C (difference, 7.70; 95% CI, 0.55-14.85, P = 0.04), FMA-UE (difference, 5.10; 95% CI, 1.52-8.68, P = 0.01), and WHODAS 2.0 (difference, -7.30; 95% CI, -12.50 to -2.10, P = 0.01). However, the change scores on CBS and MBI demonstrated no significance between the groups. Conclusion: Our findings provide preliminary support for introducing robot-assisted arm training to remediate unilateral spatial neglect after stroke. The training program focusing on neglect of contralateral space and affected upper extremity may be effective in neglect symptoms, motor function recovery, and social participation, while not generalizing into improvements in activities of daily living. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) on 17 October 2019, identifier: ChiCTR1900026656.

Comparative Transcriptome Analysis Reveals Regulatory Networks during the Maize Ear Shank Elongation Process.

In maize, the ear shank is a short branch that connects the ear to the stalk. The length of the ear shank mainly affects the transportation of photosynthetic products to the ear, and also influences the dehydration of the grain by adjusting the tightness of the husks. However, the molecular mechanisms of maize shank elongation have rarely been described. It has been reported that the maize ear shank length is a quantitative trait, but its genetic basis is still unclear. In this study, RNA-seq was performed to explore the transcriptional dynamics and determine the key genes involved in maize shank elongation at four different developmental stages. A total of 8145 differentially expressed genes (DEGs) were identified, including 729 transcription factors (TFs). Some important genes which participate in shank elongation were detected via function annotation and temporal expression pattern analyses, including genes related to signal transduction hormones (auxin, brassinosteroids, gibberellin, etc.), xyloglucan and xyloglucan xyloglucosyl transferase, and transcription factor families. The results provide insights into the genetic architecture of maize ear shanks and developing new varieties with ideal ear shank lengths, enabling adjustments for mechanized harvesting in the future.

Screening and Identification of Epoxy/Dihydroxy-Oxylipins by Chemical Labeling-Assisted Ultrahigh-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry.

Epoxy/dihydroxy-oxylipins are important biologically active compounds that are mainly formed from polyunsaturated fatty acids (PUFAs) in the reactions catalyzed by the cytochrome P450 (CYP 450) enzyme. The analysis of epoxy/dihydroxy-oxylipins would be helpful to gain insights into their landscape in living organisms and provide a reference for the biological studies of these compounds. In this work, we employed chemical labeling-assisted liquid chromatography (LC) coupled with high-resolution mass spectrometry (CL-LC-HRMS) to establish a highly sensitive and specific method for screening and annotating epoxy/dihydroxy-oxylipins in biological samples. The isotope reagents 2-dimethylaminoethylamine (DMED) and DMED-d4 were employed to label epoxy/dihydroxy-oxylipins containing carboxyl groups so as to improve the analysis selectivity and MS detection sensitivity of epoxy/dihydroxy-oxylipins. Based on a pair of diagnostic ions with a mass-to-charge ratio (m/z) difference of 15.995 originating from the fragmentation of derivatives via high-energy collision dissociation (HCD), the potential epoxy/dihydroxy-oxylipins were rapidly screened from the complex matrix. Furthermore, the epoxy/dihydroxy groups could be readily localized by the diagnostic ion pairs, which enabled us to accurately annotate the epoxy/dihydroxy-oxylipins detected in biological samples. The applicability of our method was demonstrated by profiling epoxy/dihydroxy-oxylipins in human serum and heart samples from mice with high-fat diet (HFD). By the proposed method, a total of 32 and 62 potential epoxy/dihydroxy-oxylipins including 42 unreported ones were detected from human serum and the mice heart sample, respectively. Moreover, the relative quantitative results showed that most of the potential epoxy/dihydroxy-oxylipins, especially the oxidation products of linoleic acid (LA) or α-linolenic acid (ALA), were significantly decreased in the heart of mice with HFD. Our developed method is of high specificity and sensitivity and thus is a promising tool for the identification of novel epoxy/dihydroxy-oxylipins in biological samples.

Exoskeleton-Assisted Anthropomorphic Movement Training (EAMT) for Poststroke Upper Limb Rehabilitation: A Pilot Randomized Controlled Trial.

OBJECTIVE: To investigate the feasibility of exoskeleton-assisted anthropomorphic movement training (EAMT) and its effects on upper extremity motor impairment, function, and kinematics after stroke. DESIGN: A single-blind pilot randomized controlled trial. SETTING: Stroke rehabilitation inpatient unit. PARTICIPANTS: Participants with a hemiplegia (N=20) due to a first-ever, unilateral, subacute stroke who had a score of 8-47 on the Fugl-Meyer Assessment for Upper Extremity (FMA-UE). INTERVENTIONS: The exoskeleton group received EAMT therapy that provided task-specific training under anthropomorphic trajectories and postures. The control group received conventional upper limb therapy. For both groups, therapy was delivered at the same intensity, frequency, and duration: 45 minutes daily, 5 days per week, for 4 weeks. MAIN OUTCOME MEASURES: Primary outcome: feasibility analysis. SECONDARY OUTCOMES: FMA-UE, Action Research Arm Test (ARAT), modified Barthel Index (MBI), and kinematic metrics during exoskeleton therapy. RESULTS: Twenty participants with subacute stroke were recruited and completed all therapy sessions. EAMT therapy was feasible and acceptable for the participants. The recruitment rate, retention rate, and number of therapists required for EAMT therapy were acceptable compared with other robotic trials. EAMT was determined to be safe, as no adverse event occurred except tolerable muscle fatigue in 2 participants. There were significant between-group differences in the change scores of FMA-UE (difference, 4.30 points; P=.04) and MBI (difference, 8.70 points; P=.03) in favor of EAMT therapy. No significant between-group difference was demonstrated for the change scores of ARAT (P=.18). Participants receiving EAMT showed significant improvements in kinematic metrics after treatment (P<.01). CONCLUSIONS: Our results indicate that EAMT is a feasible approach and may improve upper extremity motor impairment, activities of daily living, and kinematics after stroke. However, fully powered randomized controlled trials are warranted to confirm the results of this pilot study and explore the underlying mechanisms by which EAMT therapy might work.