Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK.

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

Gate-tunable subband degeneracy in semiconductor nanowires.

Degeneracy and symmetry have a profound relation in quantum systems. Here, we report gate-tunable subband degeneracy in PbTe nanowires with a nearly symmetric cross-sectional shape. The degeneracy is revealed in electron transport by the absence of a quantized plateau. Utilizing a dual gate design, we can apply an electric field to lift the degeneracy, reflected as emergence of the plateau. This degeneracy and its tunable lifting were challenging to observe in previous nanowire experiments, possibly due to disorder. Numerical simulations can qualitatively capture our observation, shedding light on device parameters for future applications.

Post-stroke cognitive impairment: exploring molecular mechanisms and omics biomarkers for early identification and intervention.

Post-stroke cognitive impairment (PSCI) is a major stroke consequence that has a severe impact on patients' quality of life and survival rate. For this reason, it is especially crucial to identify and intervene early in high-risk groups during the acute phase of stroke. Currently, there are no reliable and efficient techniques for the early diagnosis, appropriate evaluation, or prognostication of PSCI. Instead, plenty of biomarkers in stroke patients have progressively been linked to cognitive impairment in recent years. High-throughput omics techniques that generate large amounts of data and process it to a high quality have been used to screen and identify biomarkers of PSCI in order to investigate the molecular mechanisms of the disease. These techniques include metabolomics, which explores dynamic changes in the organism, gut microbiomics, which studies host-microbe interactions, genomics, which elucidates deeper disease mechanisms, transcriptomics and proteomics, which describe gene expression and regulation. We looked through electronic databases like PubMed, the Cochrane Library, Embase, Web of Science, and common databases for each omics to find biomarkers that might be connected to the pathophysiology of PSCI. As all, we found 34 studies: 14 in the field of metabolomics, 5 in the field of gut microbiomics, 5 in the field of genomics, 4 in the field of transcriptomics, and 7 in the field of proteomics. We discovered that neuroinflammation, oxidative stress, and atherosclerosis may be the primary causes of PSCI development, and that metabolomics may play a role in the molecular mechanisms of PSCI. In this study, we summarized the existing issues across omics technologies and discuss the latest discoveries of PSCI biomarkers in the context of omics, with the goal of investigating the molecular causes of post-stroke cognitive impairment. We also discuss the potential therapeutic utility of omics platforms for PSCI mechanisms, diagnosis, and intervention in order to promote the area's advancement towards precision PSCI treatment.

Selective-Area-Grown PbTe-Pb Planar Josephson Junctions for Quantum Devices.

Planar Josephson junctions are predicted to host Majorana zero modes. The material platforms in previous studies are two-dimensional electron gases (InAs, InSb, InAsSb, and HgTe) coupled to a superconductor such as Al or Nb. Here, we introduce a new material platform for planar JJs, the PbTe-Pb hybrid. The semiconductor, PbTe, was grown as a thin film via selective area epitaxy. The Josephson junction was defined by a shadow wall during the deposition of superconductor Pb. Scanning transmission electron microscopy reveals a sharp semiconductor-superconductor interface. Gate-tunable supercurrents and multiple Andreev reflections are observed. A perpendicular magnetic field causes interference patterns of the switching current, exhibiting Fraunhofer-like and SQUID-like behaviors. We further demonstrate a prototype device for Majorana detection wherein phase bias and tunneling spectroscopy are applicable.

Paint sludge derived activated carbon encapsulating with cobalt nanoparticles for non-radical activation of peroxymonosulfate.

Industrial solid waste management and recycling are important to environmental sustainability. In this study, cobalt (Co) nanoparticles encapsulated in paint sludge-derived activated carbon (AC) were fabricated. The Co-AC possessed high conductivity, magnetic properties and abundant metal oxide impurities (TiAlSiOx), which was applied as multifunctional catalyst for peroxymonosulfate (PMS) activation. Compared to pure AC, the Co-AC exhibited significant enhanced performance for degradation of tetracycline hydrochloride (TCH) via PMS activation. Mechanism studies by in situ Raman spectroscopy, Fourier infrared spectroscopy, electrochemical analysis and electron paramagnetic resonance suggested that surface-bonded PMS (PMS*) and singlet oxygen (1O2) are the dominant reactive species for TCH oxidation. The non-radical species can efficiently oxidize electron-rich pollutants with high efficiency, which minimized the consumption of PMS and the catalyst. The removal percentages of TCH reached 97 % within 5 min and âˆ¼ 99 % within 15 min in the Co-AC/PMS system. The Co active sites facilitated PMS adsorption to form the PMS* and the TiAlSiOx impurities provided abundant oxygen vacancy for generation of the 1O2. In addition, the Co-AC/PMS system achieved high efficiency and stability for oxidation of the target pollutants over a long-term continuous operation. This work not only offers a cost-effective approach for recycling industrial waste but also provides new insights into the application of waste-derived catalyst for environmental remediation.

Ballistic PbTe Nanowire Devices.

Disorder is the primary obstacle in the current Majorana nanowire experiments. Reducing disorder or achieving ballistic transport is thus of paramount importance. In clean and ballistic nanowire devices, quantized conductance is expected, with plateau quality serving as a benchmark for disorder assessment. Here, we introduce ballistic PbTe nanowire devices grown by using the selective-area-growth (SAG) technique. Quantized conductance plateaus in units of 2e2/h are observed at zero magnetic field. This observation represents an advancement in diminishing disorder within SAG nanowires as most of the previously studied SAG nanowires (InSb or InAs) have not exhibited zero-field ballistic transport. Notably, the plateau values indicate that the ubiquitous valley degeneracy in PbTe is lifted in nanowire devices. This degeneracy lifting addresses an additional concern in the pursuit of Majorana realization. Moreover, these ballistic PbTe nanowires may enable the search for clean signatures of the spin-orbit helical gap in future devices.

Effectiveness and feasibility of continuous positive airway pressure in patients with stroke and sleep apnea: a meta-analysis of randomized trials.

STUDY OBJECTIVES: This meta-analysis aimed to investigate the feasibility and effectiveness of continuous positive airway pressure (CPAP) treatment in stroke patients with sleep apnea. METHODS: PubMed, EMBASE, and the Cochrane Library were searched from inception until July 28, 2022, for randomized controlled trials comparing the use of CPAP and usual treatment in patients with stroke or transient ischemic attack and sleep apnea. The primary outcome measures were the feasibility of CPAP therapy, neurological function, and functional status. RESULTS: After screening 5,747 studies, 14 studies with 1,065 patients were included in this meta-analysis. Overall, 8 of the 14 studies recorded CPAP use, and the mean CPAP use was 4.47 hours per night (95% confidence interval [CI]: 3.85-5.09). The risk ratio of discontinuing CPAP was 1.50 (95% CI: 0.76-2.94; P = .24). Analysis of the neurofunctional scales showed that CPAP treatment improved neurological function (standardized mean difference: 0.28; 95% CI: 0.02-0.53), but there was substantial heterogeneity (I2 = 57%, P = .03) across the studies. CPAP treatment had no significant effect on functional status vs the control (standardized mean difference: 0.25; 95% CI: -0.01 to 0.51), but the studies also had substantial heterogeneity (I2 = 55%, P = .06). CONCLUSIONS: CPAP treatment is feasible in patients with stroke and sleep apnea and may improve neurological outcomes in these patients. However, this finding should be interpreted with caution because of the substantial heterogeneity of current trials. CITATION: Fu S, Peng X, Li Y, Yang L, Yu H. Effectiveness and feasibility of continuous positive airway pressure in patients with stroke and sleep apnea: a meta-analysis of randomized trials. J Clin Sleep Med. 2023;19(9):1685-1696.

C-Reactive Protein Levels and Cognitive Decline following Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Cognitive decline (CD) is devastating with a high incidence in patients after stroke. Although some studies have explored underlying associations between C-reactive protein (CRP) levels and cognitive decline after stroke, consistent results have not been obtained. Therefore, this meta-analysis aimed to explore whether or not higher levels of C-reactive proteins were associated with an increased risk of cognitive decline after stroke. To this end, PubMed, Embase, the Cochrane Library, and Web of Science were searched for eligible studies, and pooled effect sizes from eligible studies were calculated using random effect models. Furthermore, subgroups were established and meta-regression analyses were performed to explain the causes of heterogeneity. Eventually, nine studies with 3893 participants were included. Our statistical results suggested that the concentrations of peripheral CRP may be significantly increased for CD patients after stroke, compared to those of non-CD patients. Subgroup analyses showed that CRP was higher in CD than that in non-CD patients when the mini-mental state examination was used. A higher level of CRP in the acute phase of ischemic stroke may suggest an increased risk of CD after stroke. However, these results should be cautiously interpreted because of the limited sample sizes and the diversity of potential confounders in the studies included in this meta-analysis.

The sensitivity of mechanical properties and pore structures of Beishan granite to large variation of temperature in nuclear waste storage sites.

Granite is the host rock of the Beishan Underground Research Laboratory (URL) for geological disposal of high-level radioactive waste in China. The mechanical behavior of Beishan granite is the key in determining whether the repository can serve safely for a long time. The surrounding rock of the repository will be exposed to thermal environment induced by radionuclide decay, resulting in significant changes in the physical and mechanical properties of the Beishan granite. This study investigated the pore structure and mechanical properties of Beishan granite after thermal treatment. The T2 spectrum distribution, pore size distribution, porosity, and magnetic resonance imaging (MRI) were obtained through nuclear magnetic resonance (NMR); uniaxial compressive strength (UCS) and acoustic emission (AE) signal characteristic of granite were investigated through uniaxial compression tests. The results showed that high temperature significantly affected the T2 spectrum distribution, pore size distribution, porosity, compressive strength, and elastic modulus of granite, and porosity gradually increases, whereas the strength and elastic modulus gradually decline with increasing temperature. The porosity of granite has a linear relationship with UCS and elastic modulus, indicating that the essential mechanism for the deterioration of macroscopic mechanical properties lies in changes of microstructure. In addition, the thermal damage mechanism of granite was revealed, and a damage variable was defined based on porosity and uniaxial compressive strength.

Real-life experience of accepting assistive device services for Tibetans with dysfunction: A qualitative study.

Objective: This study aimed to understand the real-life experiences of Tibetans in China with dysfunction in the process of accepting assistive device services and to provide a reference for service quality improvement and policy formulation. Methods: Semi-structured personal interviews were used to collect data. Ten Tibetans with dysfunction representing three categories of different economic level areas in Lhasa, Tibet were selected to participate in the study by purposive sampling method from September to December 2021. The data were analyzed using Colaizzi's seven-step method. Results: The results present three themes and seven sub-themes: identification of tangible benefits from assistive devices (enhancing self-care ability for persons with dysfunction, assisting family members with caregiving and promoting harmonious family relationships), problems and burdens (difficulty in accessing professional services and cumbersome processes, not knowing how to use it correctly, psychological burden: fear of falling and stigmatization), and needs and expectations (providing social support to reduce the cost of use, enhancing the accessibility of barrier-free facilities at the grassroots level and improving the environment for the use of assistive devices). Conclusion: A proper understanding of the problems and challenges faced by Tibetans with dysfunction in the process of accepting assistive device services, focusing on the real-life experiences of people with functional impairment, and proposing targeted suggestions for improving and optimizing the user experience can provide reference and basis for future intervention studies and related policy formulation.

Factors Influencing Utilization of Assistive Devices by Tibetan Seniors on the Qinghai-Tibet Plateau: Based on Research Strategy of Triangulation.

Purpose: To investigate the current situation of assistive device (AD) usage among seniors in Tibet, China, and explore its influencing factors. Methods: A mixed-methods design was used. Cognition, attitude, behavior, and preference toward ADs were assessed by a self-designed questionnaire. Additionally, participants responded to the open-ended questions. Anderson's behavior model analyzed the impacts of the prerequisite factors, enabling factors, and demand factors influencing the utilization of ADs by Tibetan seniors. Results: Of the 211 Tibetan seniors, 149 (70.6%) Tibetan seniors expressed the willingness to utilize ADs. Binary Logistic regression analysis showed that one prerequisite factor: age; one enabling factor: care situation, and one demand factor: dysfunctional condition were factors influencing the utilization of ADs. Qualitative comments described: psychological, physical environment, and social support factors were the main influencing factors. Conclusion: This study presents the current situation to utilize ADs by Tibetan seniors on the Qinghai-Tibet Plateau, incorporates Anderson's behavioral model for quantitative analysis, and combines qualitative research to explore the facilitating and hindering factors, to provide reference and basis for the development of ADs for seniors and policy formulation. The sample size of this study is relatively small and limited to ethnic groups, and we plan to increase the sample size and include more ethnic groups in the future study.

Non-invasive brain stimulation for limb motor function and daily living activity improvement in acute stroke: A meta-analysis.

OBJECTIVE: To evaluate the effect of non-invasive brain stimulation (NIBS) in improving limb motor dysfunction and daily living activity during at the phase of acute stroke. MATERIALS AND METHODS: Randomized controlled trials about the effect of NIBS on hemiparesis in acute stroke were retrieved from databases of China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, CBM, PubMed, Embase, Cochrane Library, and Web of Science from inception until January 3rd 2022. The quality of the trials was assessed, and the data were extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. A statistical analysis was carried out using Review Manager 5.3 and STATA 14. The effect size was evaluated by using the weighed mean difference (WMD) and a 95% confidence interval (CI). The stability and sensitivity of the results and sources of heterogeneity were also analyzed. RESULTS: 12 studies involving 639 patients were included. Our meta-analysis showed that NIBS could improve the Fugl-Meyer Assessment (weighed mean difference = 3.96, 95% confidence interval = 3.45 to 4.48) and Barthel Index (weighed mean difference = 12.29, 95% confidence interval = 4.93 to 19.66), while reducing the National Institutes of Health Stroke Scale (weighed mean difference = -2.37, 95% confidence interval = -3.43 to -1.31). CONCLUSION: NIBS is effective in improving paretic limb motor function and activities of daily living in patients during at the phase of acute stroke.

Effect of Manual Lymphatic Drainage on Breast Cancer-Related Postmastectomy Lymphedema: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Manual lymphatic drainage (MLD) is widely used in the treatment of breast cancer-related postmastectomy lymphedema (BCRL). However, the therapeutic benefit of MLD on BCRL remains controversial. OBJECTIVE: The aim of this study was to analyze the efficacy of MLD for BCRL. METHOD: Four electronic databases were systematically searched for trials comparing MLD and no MLD treatment as options for BCRL. Comparative treatment results included reduction of upper extremity limb volume with subgroup analysis by the number and duration of treatments. RESULTS: A total of 457 patients were included in the analysis. There was no significant difference in the amount of upper extremity edema between the MLD treatment and control or no MLD groups ( P = .11). However, when the treatment course was ≥20 sessions, there was a significant reduction in the upper extremity volume ( P = .03). There was also a significant reduction in the upper extremity volume when treatment duration was >2 weeks ( P = .03). CONCLUSION: Manual lymphatic drainage treatment statistically did not reduce the upper extremity limb volume of BCRL, but upper extremity volume was reduced at statistically significant levels when treatment number were ≥20 sessions or the duration of treatment was >2 weeks. IMPLICATION FOR PRACTICE: Reduction in upper limb volume is dependent on the number and duration of treatments. When treatment number were ≥20 sessions, or the duration of treatment was >2 weeks, reduction of upper limb volume was statistically achieved. Manual lymphatic drainage treatment can be clinically recommended to treat BCRL according to these parameters.

Efficient oil-water emulsion treatment via novel composite membranes fabricated by CaCO3-based biomineralization and TA-Ti(IV) coating strategy.

Continuous increasing discharge of industrial oily wastewater and frequent occurrence of oil spill accidents have taken heavy tolls on global environment and human health. Organic-inorganic modifications can fabricate superhydrophilic/submerged superoleophobic membranes for efficient oil-water separation/treatment though they still suffer from complex operation, non-environmental friendliness, expensive cost or uneven distribution. Herein, a new strategy regarding tannic acid (TA)-Ti(IV) coating and CaCO3-based biomineralization through simple inkjet printing processes was proposed to modify polyvinylidene fluoride (PVDF) membrane, endowing the membrane with high hydrophilicity (water contact angle (WCA) decreased from 86.01° to 14.94°) and underwater superoleophobicity (underwater contact angle (UOCA) > 155°). The optimized TA-Ti(IV)-CaCO3 modified membrane possessed perfect water permeation to various oil/water emulsions (e.g., 355.7 L·m-2·h-1 for gasoline emulsion) under gravity with superior separation efficiency (>98.8 %), leading the way in oil/water emulsion separation performance of PVDF membranes modified with polyphenolic surfaces to our knowledge. Moreover, the modified membrane displayed rather high flux recovery after eight cycles of filtration while maintaining the original excellent separation efficiency. The modification process proposed in this study is almost independent of the nature of the substrate, and meets the demand for simple, inexpensive, rapid preparation of highly hydrophilic antifouling membranes, showing abroad application prospect for oil-water emulsion separation/treatment.

Social participation of community-dwelling older adults in western China: A latent profile analysis.

Objective: Social participation has become a policy framework to address population aging. However, little is known about the social participation of older adults in western China, and extensive, multicenter, regional research is lacking. This research investigated the profiles of social participation of older adults in western China and explored the characteristics and factors influencing social participation. Method: This cross-sectional study was conducted in 3 provinces (Chongqing, Sichuan, and Inner Mongolia) in western China from March 2021 to December 2021 and included 3,456 participants aged 60 years or older. Social participation was assessed using the Chinese version of the Impact on Participation and Autonomy Questionnaire (IPA). Latent profile analysis (LPA) was performed to extract latent classes of social participation among older adults in western China. The chi-square test and multinomial regression analyses were used to identify differences between these classes. Results: Three social participation classes were identified by LPA: high social participation (25.2%), moderate social participation (55.1%), and low social participation (19.7%). Being older, having a primary school education level, having mobility or speaking impairment, using assistive devices, and having a chronic disease were highly associated with the low social participation class (P < 0.05). Furthermore, older adults with no dependence (OR = 0.018, 95% CI = 0.005-0.062) or mild dependence (OR = 0.039, 95% CI = 0.011-0.139) in activities of daily living (ADLs) were less likely to be in the low social participation class. Older adults who were cared for by non-spouse primary caregivers were more likely to be assigned to the moderate social participation group (OR = 2.097, 95% CI = 1.501-2.930) than to the high social participation group. Conclusions: Most older adults in western China have a moderate level of social participation. Advanced age, reduced ADL ability, reduced speech ability, reduced mobility, and non-spouse care are related to the level of social participation. Healthcare professionals should pay attention to the predictors for different classes, identifying high-risk groups as early as possible.

Molecular insights into impacts of EDTMPA on membrane fouling caused by transparent exopolymer particles (TEP).

While ethylenediamine tetramethylenephosphonic acid (EDTMPA) has been emerged as a stronger chelating agent than ethylene diamine tetraacetic acid (EDTA) for fouling mitigation, and transparent exopolymer particles (TEP) is a major foulant in membrane-based water treatment process, effects of EDTMPA on TEP fouling and the underlying mechanism have been not yet studied. In this study, Flory-Huggins lattice theory was combined with density functional theory (DFT) technology to explore this subject at molecular level. Filtration experiments showed a unimodal pattern of specific filtration resistance (SFR) of TEP sample with Ca2+ concentration in range of 0-3 mM. For the TEP sample with the peak SFR value at 1.5 mM Ca2+, continuous addition of EDTMPA (from 0 to 100 mg·L-1) resulted in a sustained decrease in SFR. Energy dispersive spectroscopy (EDS) mapping characterization showed the continuing decline of calcium content in the TEP layer with increase of EDTMPA addition, indicating that EDTMPA successfully captured Ca2+ from alginate­calcium ligation (TEP), and then disintegrated the TEP structure. DFT simulation showed that Ca2+ preferentially coordinated with the terminal carboxyl groups of alginate chains to form a coordination configuration that is conducive to stretch the three-dimensional polymer network. Such a network corresponded to an extremely high SFR according to Flory-Huggins theory. EDTMPA addition caused disintegration of the coordination configuration of Ca2+ binding to terminal carboxyl groups, which further resulted in collapse and flocculation of TEP gel network structure, thus leading to a continuous SFR decrease. This work provided deep thermodynamic insights into effects of EDTMPA on TEP-associated fouling at molecular level, facilitating to better understanding and mitigation of membrane fouling.

Mechanistic insights into Ca-alginate gel-associated membrane fouling affected by ethylene diamine tetraacetic acid (EDTA).

While transparent exopolymer particles (TEP) is a major foulant, and ethylene diamine tetraacetic acid (EDTA) is a strong chelating agent frequently used for fouling mitigation in membrane-based water treatment processes, little has been known about TEP-associated membrane fouling affected by EDTA. This work was performed to investigate roles of EDTA addition in TEP (Ca-alginate gel was used as a TEP model) associated fouling. It was interestingly found that, TEP had rather high specific filtration resistance (SFR) of 2.49 × 1015 m-1·kg-1, and SFR of TEP solution firstly decreased and then increased rapidly with EDTA concentration increase (0-1 mM). A series of characterizations suggested that EDTA took roles in SFR of TEP solution by means of changing TEP microstructure. The rather high SFR of TEP layer can be attributed to the big chemical potential gap during filtration described by the extended Flory-Huggins lattice theory. Initial EDTA addition disintegrated TEP structure by EDTA chelating calcium in TEP, inducing reduced SFR. Continuous EDTA addition decreased solution pH, resulting into no effective chelating and accumulation of EDTA on membrane surface, increasing SFR. It was suggested that factors increasing homogeneity of TEP gel will increase SFR, and vice versa. This study revealed the thermodynamic mechanism of TEP fouling behaviors affected by EDTA, and also demonstrated the importance of EDTA dosage and pH adjustment for TEP-associated fouling control.

Peripheral blood and urine metabolites and biological functions in post-stroke depression.

Post-stroke depression (PSD) is the most common and severe neuropsychiatric complication after stroke. However, the molecular mechanism of PSD is still unclear. Previous studies have identified peripheral blood and urine metabolites associated with PSD using metabolomics techniques. We searched and systematically summarized metabolites that may be involved in metabolic changes in peripheral blood and urine of patients with PSD from the Metabolite Network of Depression Database (MENDA) and other biomedical databases. MetaboAnalyst5.0 software was used for pathway analysis and enrichment analysis of differential metabolites, and subgroup analyses were performed according to tissue types and metabolomics techniques. We identified 47 metabolites that were differentially expressed between patients with and without PSD. Five differential metabolites were found in both plasma and urine, including L-glutamic acid, pyroglutamic acid, palmitic acid, L-phenylalanine, and L-tyrosine. We integrated these metabolites into metabolic pathways, and six pathways were significantly altered. These pathways could be roughly divided into three modules including amino acid metabolism, nucleotide metabolism, and glucose metabolism. Among them, the most significantly altered pathway was "phenylalanine metabolism" and the pathway containing the most associated metabolites was "aminoacyl-tRNA biosynthesis", which deserve further study to elucidate their role in the molecular mechanism of PSD. In summary, metabolic changes in peripheral blood and urine are associated with PSD, especially the disruption of "phenylalanine metabolism" and "aminoacyl-tRNA biosynthesis" pathways. This study provides clues to the metabolic characteristics of patients with PSD, which may help to elucidate the molecular pathogenesis of PSD.

Effect of Time-Dose-Matched Virtual Reality Therapy on Upper Limb Dysfunction in Patients Poststroke: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To investigate the efficacy and acceptability of virtual reality (VR) with time-dose-matched conventional therapy (CT) in patients poststroke with upper limb dysfunction. DATA SOURCES: Cochrane, PubMed, Web of Science, Embase, and ProQuest were systematically searched up to May 24, 2021. STUDY SELECTION: Randomized controlled trials comparing VR with time-dose-matched CT in patients poststroke with upper limb dysfunction were included. DATA EXTRACTION: The extracted data included efficacy (mean change in structure/function, activity, and participation scores), acceptability (dropouts for all reasons), adverse events, and characteristics of the included studies. The Cochrane risk of bias assessment tool was used to assess the risk of bias. DATA SYNTHESIS: Thirty-one randomized controlled trails were included. VR was superior to time-dose-matched CT in terms of the World Health Organization's International Classification of Functioning, Disability and Health structure/function, with a standardized mean difference (SMD) of 0.35, but not activity and participation. Subgroup analyses demonstrated that virtual environment was superior to CT in structure/function (SMD=0.38) and activity (SMD=0.27), whereas there were no significant differences between commercial gaming and CT in any World Health Organization International Classification of Functioning, Disability and Health domain. VR mixed with CT was more effective than time-dose-matched CT in structure/function (SMD=0.56), whereas VR only was not significantly different from CT. There were no significant differences in the incidence of adverse events and dropout rates between VR and CT. CONCLUSIONS: The results suggest that VR is superior to time-dose-matched CT in terms of recovery of upper extremity motor function, especially when a virtual environment is used or VR is mixed with CT. However, VR (VR only or mixed with CT) does not improve patients' daily activity performance and participation compared with CT. Overall, VR appears to be safe and acceptable as CT. Large-scale definitive trials are needed to verify or refute these findings.

Proteomic and metabolomic characterization of amygdala in chronic social defeat stress rats.

BACKGROUND: Depression is a leading cause of disability worldwide. There is increasing evidence showing that depression is associated with the pathophysiology in amygdala; however, the underlying mechanism remains poorly understood. METHOD: We established a rat model of chronic social defeat stress (CSDS) and conducted a series of behavior tests to observe behavioral changes. Then liquid chromatography mass spectrometry (LC-MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed to detect metabolomes and proteomes in the amygdala, respectively. Ingenuity pathway analysis (IPA) and other bioinformatic analyses were used to analyze differentially expressed metabolites and proteins. RESULTS: The significantly lower sucrose preference index in the sucrose preference test and longer immobile time in the forced swim test were observed in the CSDS rats compared with control rats. In the multi-omics analysis, thirty-seven significantly differentially expressed metabolites and 123 significant proteins were identified. Integrated analysis of differentially expressed metabolites and proteins by IPA revealed molecular changes mainly associated with synaptic plasticity, phospholipase c signaling, and glutamine degradation I. We compared the metabolites in the amygdala with those in the hippocampus and prefrontal cortex from our previous studies and found two common metabolites: arachidonic acid and N-acetyl-l-aspartic acid among these three brain regions. CONCLUSION: Our study revealed the presence of depressive-like behaviors and molecular changes of amygdala in the CSDS rat model, which may provide further insights into the pathogenesis of depression, and help to identify potential targets for antidepressants.