Synergy-based functional electrical stimulation and robotic-assisted for retraining reach-to-grasp in stroke: a study protocol for a randomized controlled trial.

BACKGROUND: Stroke survivors have long-term upper limb impairment, which impacts the quality of life (QOL) and social reintegration, but there is lack of effective therapeutic strategies and novel technologies. Customized multi-muscle functional electrical stimulation (FES) based on the muscle synergy of healthy adults and robotic-assisted therapy (RAT) have been proved efficacy respectively. Synergy-based FES combined with RAT can be a novel and more effective therapy for upper limb recovery of stroke survivors from the perspective of synergistic enhancement. However, few studies have examined the effectiveness of combined synergy-based FES and RAT, especially for motor control evaluated by reach-to-grasp (RTG) movements. The main objective of the following research protocol is to evaluate the effectiveness and efficacy, as well as adoptability, of FES-RAT and FES or RAT rehabilitation program for upper limb function improvement after stroke. METHODS: This will be an assessor-blinded randomized controlled trial involving a 12-week intervention and a 6-month follow-up. Stratified randomization will be used to equally and randomly assign 162 stroke patients into the FES + conventional rehabilitation program (CRP) group, RAT + CRP group and FES-RAT + CRP group. Interventions will be provided in 5 sessions per week, with a total of 60 sessions. The primary outcome measurements will include the Fugl-Meyer Assessment and Biomechanical Assessment of RTG movements. The secondary outcome measurements will include quality of life and brain neuroplasticity assessments by MRI. Evaluations will be performed at five time points, including at baseline, 6 weeks and 12 weeks from the start of treatment, and 3 months and 6 months following the end of treatment. A two-way analysis of variance with repeated measures will be applied to examine the main effects of the group, the time factor and group-time interaction effects. DISCUSSION: The results of the study protocol will provide high quality evidence for integrated synergy-based FES and RAT, and synergy-based FES alone and guide the design of more effective treatment methods for stroke rehabilitation. TRIAL REGISTRATION: ChiCTR2300071588.

Tetrahedral Imidazolate Frameworks with Auxiliary Ligands (TIF-Ax): Synthetic Strategies and Applications.

Zeolitic imidazolate frameworks (ZIFs) are an important subclass of metal-organic frameworks (MOFs). Recently, we reported a new kind of MOF, namely tetrahedral imidazolate frameworks with auxiliary ligands (TIF-Ax), by adding linear ligands (Hint) into the zinc-imidazolate system. Introducing linear ligands into the M2+-imidazolate system overcomes the limitation of imidazole derivatives. Thanks to the synergistic effect of two different types of ligands, a series of new TIF-Ax with interesting topologies and a special pore environment has been reported, and they have attracted extensive attention in gas adsorption, separation, catalysis, heavy metal ion capture, and so on. In this review, we give a comprehensive overview of TIF-Ax, including their synthesis methods, structural diversity, and multi-field applications. Finally, we also discuss the challenges and perspectives of the rational design and syntheses of new TIF-Ax from the aspects of their composition, solvent, and template. This review provides deep insight into TIF-Ax and a reference for scholars with backgrounds of porous materials, gas separation, and catalysis.

Taurine alleviated hepatic steatosis in oleic acid-treated-HepG2 cells and rats fed a high-fat diet.

Taurine has been proven in many trials to alleviate the symptoms of metabolic associated fatty liver disease. Here its protective effect for hepatic steatosis and modulation of AMP-activated protein kinase and insulin signaling pathway were investigated. Steatotic HepG2 cell established with oleic acid (0.05 mmol/L), treated with taurine (5 mmol/L), dorsomorphin (10 µmol/L) for 24 h. Sprague Dawley rats were divided into regular and high-fat diet (HFD) groups, and their corresponding taurine (70 or 350 mg/kg BW/d) groups, fed for 8 weeks. In steatotic cell, taurine reduced the TG concentration and SREBP-1c, PPARγ, FAS, ACC, SCD1 protein levels, decreased phosphorylation of mTOR, IRS1 (Ser302), increased phosphorylation of AMPKα, LKB1, PI3K, Akt, ACC. While dorsomorphin eliminated taurine's TG-lowering effect. In HFD-fed rats, taurine reduced liver TG, serum TG, ALT, AST, IL-1ß, IL-4, TNF-α. The effects of taurine on the main factors of fatty acid synthesis were mostly consistent with cell experiments, and the reduction of microRNAs (451, 33, 291b) was aligned with the improvement in LKB1 and AMPK expression in HFD rats. Taurine alleviated steatosis-induced inhibition of IRS1-PI3K-Akt pathway, but suppressed its positively regulated downstream factor mTOR. In parallel, taurine reduced steatosis by activating LKB1-AMPKα pathway via phosphorylation and no-phosphorylation manner, then inhibiting SREBP-1c directly or by suppressing mTOR phosphorylation.

Metal-Organic Framework with Structural Flexibility Responding Specifically to Acetylene and Its Adsorption Behavior.

Flexible metal-organic frameworks (MOFs) are one kind of stimuli-responsive materials that exhibit reversible structural transformations in response to external stimuli. Exploring and understanding the stimuli response behavior of flexible MOFs is challenging, as it involves weak host-guest interaction. We report here the unique flexibility of MOF Zn(int)(Ad) (TIF-A1, Hint = isonicotinic acid, Had = adenine) induced by acetylene adsorption. TIF-A1 is rigid toward most gas molecules, while only C2H2 can induce the flexibility of TIF-A1. C2H2-loaded TIF-A1 is characterized by single-crystal X-ray diffraction and molecular modeling. It is revealed that the flexibility of TIF-A1 originates from the strong interaction between acetylene and the framework, which pushes the rotation of the int ligand and the expansion of the framework simultaneously. This work is helpful in deeply understanding the flexibility of MOFs and guides exploring new flexible MOFs in the future.

Heterogenous Subtypes of Late-Life Depression and Their Cognitive Patterns: A Latent Class Analysis.

Background: Late-life depression (LLD), characterized by cognitive deficits, is considered heterogeneous across individuals. Previous studies have identified subtypes with diverse symptom profiles, but their cognitive patterns are unknown. This study aimed to investigate the subtypes of LLD and the cognitive profile of each group. Methods: In total, 109 depressed older adults were enrolled. We performed latent class analysis using Geriatric Depression Scale items as indicators to generate latent classes. We compared the sociodemographic and clinical characteristics with cognitive functions between groups and conducted regression analysis to investigate the association between class membership and variables with significant differences. Results: Two classes were identified: the "pessimistic" group was characterized by pessimistic thoughts and the "worried" group with a relatively high prevalence of worry symptoms. The two groups did not differ in sociodemographic characteristics. The "pessimistic" group showed a higher rate of past history of depression and lower age of onset. The "worried" group had more physical comorbidities and a higher rate of past history of anxiety. The "pessimistic" group was more impaired in general cognitive function, executive function, information processing speed, and attention. Lower general and executive functions were associated with the membership in the "pessimistic" group. Conclusions: Subjects with pessimistic symptoms and subjects with a propensity to worry may form two distinct subtypes of late-life depression with different cognitive profiles. Further, the cognitive evaluation of subjects with pessimistic symptoms is of utmost importance.

Caprylic Acid Improves Lipid Metabolism, Suppresses the Inflammatory Response and Activates the ABCA1/p-JAK2/p-STAT3 Signaling Pathway in C57BL/6J Mice and RAW264.7 Cells.

OBJECTIVE: This study aimed to investigate the effects of caprylic acid (C8:0) on lipid metabolism and inflammation, and examine the mechanisms underlying these effects in mice and cells. METHODS: Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a high-fat diet (HFD) without or with 2% C8:0, palmitic acid (C16:0) or eicosapentaenoic acid (EPA). RAW246.7 cells were randomly divided into five groups: normal, lipopolysaccharide (LPS), LPS+C8:0, LPS+EPA and LPS+cAMP. The serum lipid profiles, inflammatory biomolecules, and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured. RESULTS: C8:0 decreased TC and LDL-C, and increased the HDL-C/LDL-C ratio after injection of LPS. Without LPS, it decreased TC in mice ( P < 0.05). Moreover, C8:0 decreased the inflammatory response after LPS treatment in both mice and cells ( P < 0.05). Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD, C16:0 and EPA, and resulted in lower TNF-α, NF-κB mRNA expression than that with HFD ( P < 0.05). In RAW 264.7 cells, C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group, and higher protein expression of ABCA1, p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups ( P < 0.05). CONCLUSION: Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response, and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.

Diagnostic and therapeutic values of PMEPA1 and its correlation with tumor immunity in pan-cancer.

AIMS: The prostate transmembrane protein, androgen induced 1 (PMEPA1) is differentially expressed in pan-cancer. However, PMEPA1 specific role in cancers has not been fully clarified. This study aims to explore the potential role of Pmepa1 in pan-cancer and specific cancer, with a view to deepening the research on the pathological mechanism of cancer. MAIN METHODS: The Perl language and R language were used to identify the correlation between PMEPA1 expression level and clinical indicators, prognosis values, tumor microenvironment, immune cells' infiltration, immune checkpoint genes, TMB and MSI. The Therapeutic Target Database was used for identifying potential therapeutic drugs that target the pathways that are significantly affected by PMEPA1 expression. KEY FINDINGS: PMEPA1 differential expression significantly correlated with patients' age, race, tumors' stage and status. PMEPA1 high expression was closely correlated with poor prognosis in many cancer types, excluding prostate adenocarcinoma. PMEPA1 expression was closely related to tumor cells and the immune microenvironment in stromal and immune cells' level, immune cells' infiltration, immune checkpoint genes, tumor mutational burden and microsatellite instability. We also found that the activity of the olfactory transduction pathway was closely related to PMEPA1 expression. In pan-cancer, Trifluoperazine and Halofantrine have the potential to reduce PMEPA1 expression. SIGNIFICANCE: This study integrated existing data to explore PMEPA1 potential function in cancers, provided insights for the future cancer-related studies.

Overexpression of miR-10a-5p facilitates the progression of osteoarthritis.

The current study was aimed at exploring the potential roles and possible mechanisms of miR-10a-5p in osteoarthritis (OA). We performed RT-qPCR, Western blot, CCK8, EdU Assay, and flow cytometry assay to clarify the roles of miR-10a-5p in OA. Furthermore, the whole transcriptome sequencing together with integrated bioinformatics analyses were conducted to elucidate the underlying mechanisms of miR-10a-5p involving in OA. Our results demonstrated that miR-10a-5p was upregulated in OA and acted as a significant contributing factor for OA. A large number of circRNAs, lncRNAs, miRNAs, and mRNAs were identified by overexpressing miR-10a-5p. Functional enrichment analyses indicated that these differentially-expressed genes were enriched in some important terms including PPAR signaling pathway, PI3K-Akt signaling pathway, and p53 signaling pathway. A total of 42 hub genes were identified in the protein-protein interaction network including SERPINA1, TTR, APOA1, and A2M. Also, we constructed the network regulatory interactions across coding and noncoding RNAs triggered by miR-10a-5p, which revealed the powerful regulating effects of miR-10a-5p. Moreover, we found that HOXA3 acted as the targeted genes of miR-10a-5p and miR-10a-5p contributed to the progression of OA by suppressing HOXA3 expression. Our findings shed insight on regulatory mechanisms of miR-10a-5p, which might provide novel therapeutic targets for OA.

Is blood transfusion associated with an increased risk of infection among spine surgery patients?: A meta-analysis.

BACKGROUND: Blood transfusions are associated with many adverse outcomes among spine surgery patients, but it remains unclear whether perioperative blood transfusion during spine surgery and postoperative infection are related. Recently, many related cohort studies have been published on this topic. METHODS: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The PubMed, Embase, and Cochrane Library databases were searched for eligible published studies. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of the studies, and a random-effects model was used to calculate the odds ratios (ORs) with 95% CIs. Sensitivity analyses were conducted to explore the source of heterogeneity. RESULTS: The final analysis included 8 cohort studies with a total of 34,185 spine surgery patients. These studies were considered to be of high or moderate quality based on their NOS scores, which ranged from 5 to 9. Pooled estimates indicated that blood transfusion increased the infection rate (OR, 2.99; 95% CI, 1.95 to 4.59; I = 86%), which was consistent with the sensitivity analyses. CONCLUSIONS: Our results suggest that perioperative blood transfusion is a risk factor for postoperative infection among spine surgery patients. Further study is necessary to identify other influencing factors and to establish the mechanism underlying this relationship. Additional measures may be needed to reduce unnecessary blood transfusions during spine surgery.

Negative pressure wound therapy for surgical site infections: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Previous studies showed the effectiveness of negative pressure wound therapy (NPWT) in preventing surgical site infections (SSIs), but current guidelines do not recommend its routine use for surgical wounds. The aim was to compare the effectiveness and safety of NPWT with standard surgical dressing or conventional therapy for preventing SSIs. METHODS: Pubmed, Embase and the Cochrane Library were systematically searched on 10 April 2019. Also, we searched clinicaltrials.gov and references of relevant studies. Eligibility criteria were randomized controlled trials (RCTs) and adult surgical patients were included. The effectiveness of NPWT versus standard surgical dressing or conventional therapy was investigated. Relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were used to estimate the pooled effect of dichotomous outcomes and continuous outcomes respectively. The primary outcome was surgical site infections. The quality of included studies and the certainty of the evidence were assessed using the risk of bias tool and the GRADE approach. RESULTS: A total of 45 RCTs with 6624 surgical patients were included. NPWT reduced SSIs (RR 0.58; 95% CI 0.49-0.69) and wound dehiscence(17 RCTs; RR 0.80; 95% CI 0.65-1.00). NPWT did not increase the risk of hematoma (9 RCTs; RR 0.91; 95% CI 0.40-2.07) and hospital readmission(9 RCTs; RR 0.77; 95% CI 0.52-1.12) or prolong length of hospital stay(15 RCTs; MD -0.38; 95% CI, -0.78 to 0.02). NPWT significantly increased the risk of all adverse event-related outcomes (10 RCTs; RR 3.21; 95% CI, 1.17-8.78). The level of certainty was identified as low for the primary outcome and very low for all the secondary outcomes. CONCLUSIONS: Compared with standard wound care, NPWT may reduce the risk of SSIs. We are uncertain whether NPWT reduces or increases the risk of wound dehiscence, haematoma, hospital readmission and all adverse event-related outcomes or if it shortens or prolongs length of hospital stay.