Efficacy of repetitive transcranial magnetic stimulation in post-stroke cognitive impairment: an overview of systematic reviews.

Objective: The reliability of clinical evidence depends on high-quality meta-analyses/ systematic reviews (MAs/SRs). However, there has been no assessment of the quality of MAs/SRs for repetitive transcranial magnetic stimulation (rTMS) in post-stroke cognitive impairment (PSCI), both nationally and internationally. This article seeks to use radar plotting to visually present the quality of MAs/SRs on rTMS for improving cognitive function in PSCI, aiming to offer an intuitive foundation for clinical research. Methods: Eight Chinese or English databases were systematically searched to collect comprehensive literature, and the retrieval time ranged from inception to 26 March 2024. Literature ranking was calculated using six dimensions: publication year, design type, AMSTAR-2 score, PRISMA score, publication bias, and homogeneity. Finally, radar plots were drafted to present a multivariate literature evaluation. The GRADE tool assessed the strength of evidence for the outcome indicators included in the MAs/SRs. Results: The 17 articles included had average scores of 12.29, 17, 9.88, 9.71, 12.88, and 12.76 for each dimension. The radar plot showed that an article published in 2023 had the highest rank and a large radar plot area, while an article published in 2021 had the lowest rank and a small radar plot area. The GRADE tool evaluation revealed that 51 pieces of evidence were of very low quality, 67 were of low quality, 12 were of moderate quality, and only one was of high quality. Conclusion: The average rank score of literature ranged from 8.50 to 17, with higher rankings indicating greater significance in literature reference. Variations in literature quality were attributed to inadequate study planning, irregular literature search and screening, insufficient description of inclusion criteria for studies, and inadequate consideration of bias risk in the included studies. Most MAs/SRs indicated that rTMS was more effective than the control group in enhancing the global cognitive function and activities of daily living in PSCI patients. However, the overall quality of the literature was generally low and needs validation from future high-quality evidence.Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023491280.

Integrated Firefighting Textile with Temperature and Pressure Monitoring for Personal Defense.

Although electronic textiles that can detect external stimuli show great promise for fire rescue, existing firefighting clothing is still scarce for simultaneously integrating reliable early fire warning and real-time motion sensing, hardly providing intelligent personal protection under complex high-temperature conditions. Herein, we introduce an "all-in-one" hierarchically sandwiched fabric (HSF) sensor with a simultaneous temperature and pressure stimulus response for developing intelligent personal protection. A cross-arranged structure design has been proposed to tackle the serious mutual interference challenge during multimode sensing using two separate sets of core-sheath composite yarns and arrayed graphene-coated aerogels. The functional design of the HSF sensor not only possesses wide-range temperature sensing from 25 to 400 °C without pressure disturbance but also enables highly sensitive pressure response with good thermal adaptability (up to 400 °C) and wide pressure detection range (up to 120 kPa). As a proof of concept, we integrate large-scalable HSF sensors onto conventional firefighting clothing for passive/active fire warning and also detecting spatial pressure and temperature distribution when a firefighter is exposed to high-temperature flames, which may provide a useful design strategy for the application of intelligent firefighting protective clothing.

Clinical Performance of Immunonephelometric Assay and Chemiluminescent Immunoassay for Detection of IgG Subclasses in Chinese.

BACKGROUND: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc. METHODS: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820). CONCLUSIONS: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

The metabolic effects of habitual leg shaking: A randomized crossover trial.

AIMS: The adverse effects of sedentary behavior on obesity and chronic diseases are well established. However, the prevalence of sedentary behavior has increased, with only a minority of individuals meeting the recommended physical activity guidelines. This study aimed to investigate whether habitual leg shaking, a behavior traditionally considered unfavorable, could serve as an effective strategy to improve energy metabolism. MATERIALS AND METHODS: A randomized crossover study was conducted, involving 15 participants (mean [SD] age, 25.4 [3.6]; mean [SD] body mass index, 22 [3]; 7 women [46.7%]). The study design involved a randomized sequence of sitting and leg shaking conditions, with each condition lasting for 20 min. Energy expenditure, respiratory rate, oxygen saturation, and other relevant variables were measured during each condition. RESULTS: Compared to sitting, leg shaking significantly increased total energy expenditure [1.088 kj/min, 95% confidence interval, 0.69-1.487 kj/min], primarily through elevated carbohydrate oxidation. The average metabolic equivalent during leg shaking exhibited a significant increase from 1.5 to 1.8. Leg shaking also raised respiratory rate, minute ventilation, and blood oxygen saturation levels, while having no obvious impact on heart rate or blood pressure. Electromyography data confirmed predominant activation of lower leg muscles and without increased muscle fatigue. Intriguingly, a significant correlation was observed between the increased energy expenditure and both the frequency of leg shaking and the muscle mass of the legs. CONCLUSIONS: Our study provides evidence that habitual leg shaking can boost overall energy expenditure by approximately 16.3%. This simple and feasible approach offers a convenient way to enhance physical activity levels.

Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis.

Hexanucleotide repeat expansions in the C9orf72 gene are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Due to the lack of trunk neuromuscular organoids (NMOs) from ALS patients' induced pluripotent stem cells (iPSCs), an organoid system was missing to model the trunk spinal neuromuscular neurodegeneration. With the C9orf72 ALS patient-derived iPSCs and isogenic controls, we used an NMO system containing trunk spinal cord neural and peripheral muscular tissues to show that the ALS NMOs could model peripheral defects in ALS, including contraction weakness, neural denervation, and loss of Schwann cells. The neurons and astrocytes in ALS NMOs manifested the RNA foci and dipeptide repeat proteins. Acute treatment with the unfolded protein response inhibitor GSK2606414 increased the glutamatergic muscular contraction 2-fold and reduced the dipeptide repeat protein aggregation and autophagy. This study provides an organoid system for spinal neuromuscular pathologies in ALS and its application for drug testing.

IL-17A inhibitors alleviate Psoriasis with concomitant restoration of intestinal/skin microbiota homeostasis and altered microbiota function.

Background: Disturbed gut microbiota and associated metabolic dysfunction exist in Psoriasis. Despite the growing use of interleukin-17 inhibitor (anti-IL17) therapy, the effect of anti-IL17 on gut/skin microbiota function is not fully understood in patients with Psoriasis. Objective: Therefore, we explored whether Psoriasis is associated with alterations in selected gut/skin microbiota in a study cohort, and a longitudinal cohort study to reveal the effects of IL-17A inhibitor treatment on gut microbiota in Psoriasis. Methods: In a case-control study, 14 patients with Psoriasis and 10 age, sex and body mass index-matched Healthy Controls were recruited. Longitudinal mapping of the gut microbiome was performed using 16S rRNA gene sequencing. Mouse models were used to further study and validate the interrelationship between the skin microbiome and the gut microbiome in Psoriasis. PICRUST2 was applied to predict the function of the bacterial community. Results: In Psoriasis patients, gut microbiota dysbiosis was present with increased heterogeneity: decreased Bacteroidota and increased Firmicutes as well as Actinobacteriota predominating in Psoriasis. Escherichia-Shigella enrichment was associated with reduction in serum levels of total bile acid and markers in Apoptotic pathways. After IL-17A inhibitor treatment in Psoriasis patients, longitudinal studies observed a trend toward a normal distribution of the gut microbiome and modulation of apoptosis-related metabolic pathways. Results from a mouse model showed dysregulation of the skin microbiota in Psoriasis characterized by Staphylococcus colonization. Conclusion: The psoriatic gut/skin microbiota exhibits loss of community stability and pathogen enrichment. IL-17A inhibitors restore microbiota homeostasis and metabolic pathways, reduce pro-inflammatory cytokine expression, and alleviate symptoms in patients with Psoriasis.

Multi-Functional Integration of Phosphor, Initiator, and Crosslinker for the Photo-Polymerization of Flexible Phosphorescent Polymer Gels.

A general approach to constructing room temperature phosphorescence (RTP) materials involves the incorporation of a phosphorescent emitter into a rigid host or polymers with high glass transition temperature. However, these materials often suffer from poor processability and suboptimal mechanical properties, limiting their practical applications. In this work, we developed benzothiadiazole-based dialkene (BTD-HEA), a multifunctional phosphorescent emitter with a remarkable yield of intersystem crossing (ΦISC, 99.83 %). Its high triplet exciton generation ability and dialkene structure enable BTD-HEA to act as a photoinitiator and crosslinker, efficiently initiating the polymerization of various monomers within 120 seconds. A range of flexible phosphorescence gels, including hydrogels, organogels, ionogels, and aerogels were fabricated, which exhibit outstanding stretchability and recoverability. Furthermore, the unique fluorescent-phosphorescent colorimetric properties of the gels provide a more sensitive method for the visual determination of the polymerization process. Notably, the phosphorescent emission intensity of the hydrogel can be increased by the formation of ice, allowing for the precise detection of hydrogel freezing. The versatility of this emitter paves the way for fabricating various flexible phosphorescence gels with diverse morphologies using microfluidics, film-shearing, roll coating process, and two/three-dimensional printing, showcasing its potential applications in the fields of bioimaging and bioengineering.

Predicting the risk of interstitial lung disease in patients with primary Sjögren's syndrome: Novel nomogram and elevated Th2 cells.

OBJECTIVE: Interstitial lung disease (ILD) is one of the most common pulmonary complications in patients with primary Sjögren's syndrome (pSS). This study was performed to identify immunological risk factors of pSS-associated ILD (pSS-ILD) and to further establish and evaluate of nomograms predicting the risk of ILD in patients with pSS. METHODS: A total of 622 patients with pSS (117 with ILD and 505 without lung involvement) and 166 healthy control subjects (HCs) were ultimately recruited to this retrospective study. Routine examination indicators, tumour markers and lymphocyte (LYMP) subpopulations were extracted. Simple and multiple logistic regressions analyses were performed to screen for independent predictors. Restricted cubic splines were used to examine associations of independent predictors with ILD, and a risk assessment model was constructed. A nomogram prediction model was developed, and receiver operating characteristic (ROC) curve analysis was performed to assess its performance. RESULTS: Univariate and multivariate logistic regression analyses showed that the older age, white blood cell (WBC) count, haemoglobin (HB) level, albumin (ALB) level, CA242 level, and the C-reactive protein (CRP)/LYMP ratio (CLR) were independent predictors of pSS-ILD in a linear manner, these factors were integrated and used to construct a nomogram prediction model. The model had clinical predictive value. In addition, the elevated Th2 cells proportion in pSS patients was significantly positively correlated with lung involvement, while it was negatively correlated with HB and ALB levels. Remarkably, the numbers of Th2 cells were correlated with the CLR in both pSS patients and those with pSS-ILD. CONCLUSIONS: Our novel ILD nomogram could be used to assess the risk of ILD in pSS patients with good discrimination ability. As well as, elevated peripheral blood Th2 cell levels may be related to ILD in patients with pSS.

Scalable, Green, Flexible Photochromic Bacterial Cellulose for Multicolor Switching, Photo-patterning, and Daily Sunlight UV Monitoring.

Sustainable, durable, and diverse photochromic smart textiles based on bacterial cellulose (BC) have emerged as attractive candidates in UV-sensing applications due to the green and easy functionalization of BC. However, existing BC-based photochromic textiles lack photochromic efficiency and combining fastness. In this study, a green strategy for in situ fermentation is developed to achieve the directional distribution of functional particles and remarkable photochromism in photochromic bacterial cellulose (PBC). The unique functional design obtained by regulating the photochromic dye distribution in 3D nanonetworks of PBCs during in situ growth affords a more uniform distribution and high fastness. Benefiting from the uniform distribution of photochromic dyes and adequate utilization of the 3D network structure, more surface area is provided to receive and utilize the photon energy from the UV rays, making the photochromic process more effective. The as-prepared PBCs exhibited rapid (within 1 min) and stable (30 cycles) discoloration and multicolor selectivity. Their simple preparation process and exceptional wearability, e.g., their flexibility, lightweight, and air permeability, make them suitable for various applications, including tunable color switching systems, photopatterning, and daily sunlight UV monitoring. This study provides empirical value for the biofabrication of photochromic textiles and wearable flexible UV sensors.

Preparation, Characterization, and Bioactivity Evaluation of Lambda-Cyhalothrin Microcapsules for Slow-Controlled Release System.

The utilization of interfacial polymerization in the preparation of microcapsules with a slow-controlled release has been shown to effectively improve pesticide efficacy and reduce environmental pollution. In this study, polyurea microcapsules loaded with lambda-cyhalothrin were prepared by an interfacial polymerization method using modified isocyanate (MDI) as the wall material and GT-34 as the initiator. The microcapsules were fully characterized by optical microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, etc., and release behaviors were investigated. The results indicated that the microcapsules had a smooth surface and uniform distribution, the average particle size of the microcapsules was 1.97 µm, and the encapsulation efficiency of lambda-cyhalothrin microcapsules could reach 91.48%. Compared with other commercial formulations, the microcapsules exhibited an excellent sustained release property (>7 days) in a 50% acetonitrile aqueous solution (v/v). Subsequently, in vitro release studies showed that the lambda-cyhalothrin microcapsules could consistently control the release of the core materials at different pH, temperature, and MDI addition amount conditions. The release of lambda-cyhalothrin microcapsules was in accordance with the first-order model release, which was mainly by the Fickian diffusion mechanism. Furthermore, the biological activity on Myzus persicae showed that the microcapsules' persistence period was above 21 days, which was longer than that for the emulsifiable concentrate formulation.

Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway.

Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A. dahurica extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl4) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl4 injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-ß (TGF-ß) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl4-induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1ß, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl4-induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1ß expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1ß expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.

Effects of functional correction training on movement patterns and physical fitness in male college students.

The objective of this study is to investigate the effects of functional corrective training and static stretching on the quality of movement patterns and physical fitness in college students. The study was conducted with 30 male college students from a university in Guangzhou, China. The participants were randomly assigned to either the functional corrective training group (FCT, n = 15, age = 20.93 ± 0.85, BMI = 22.07 ± 2.33) or the static stretching group (SS, n = 13, age = 20.85 ± 0.86, BMI = 21.98 ± 1.80). Two participants from the SS group dropped out due to personal reasons, leaving 13 subjects in that group. Both groups underwent a 6-week training intervention, with sessions held twice a week. The FCT group participated in flexibility training, and/or static motor control training, and/or dynamic motor control training for 10-15 min. The SS group performed static stretching exercises targeting five specific muscles, with 30 s per side and two sets. The Functional Movement Screen (FMS), body composition, sit-and-reach, standing long jump, and pull-ups were assessed before and after the intervention. Differences in FMS outcomes were analyzed using two samples of the Mann-Whitney U test. Physical fitness outcomes were analyzed using a repeated measures analysis of variance (ANOVA) with a 2 (group) × 2 (time) design. After 6 weeks of intervention, the FCT group showed statistically significant improvements in the hurdle step (Z = -2.449, p = 0.014), inline lunge (Z = -2.000, p = 0.046), rotary stability (Z = -2.309, p = 0.021), and composite scores (Z = -3.316, p = 0.001). Comparisons between groups indicated that BMI (FCT, ES = 0.04; SS, ES = -0.11), 30-m sprint (FCT, ES = 0.12; SS, ES = 0.28), body fat percentage (BF%) (FCT, ES = -0.25; SS, ES = -0.07), and sit-and-reach (FCT, ES = 0.17; SS, ES = 0.06) were not statistically significant in both the pre- and post-tests. The effect sizes of all physical fitness indicators were greater in the FCT group than in the SS group. The FCT, consisting of two sessions per week for 6 weeks, has been proven to be effective in improving the quality of movement patterns by improved stability and advanced movements. However, the improvements in physical fitness did not reach statistical significance. FMS and FCT are generally affordable and accessible for college students. College students have the opportunity to employ the FMS tool to assess potential injury risks and address them, thereby reducing the risk of injuries.

Elevated serum IL-2 and Th17/Treg imbalance are associated with gout.

Gout is considered an auto-inflammatory disorder, and the immunological drivers have not been fully unraveled. This study compared the peripheral lymphocyte and CD4+T cell subsets, and cytokines in gout and healthy controls (HCs) to explore the contributions of T helper 17 (Th17) cells, T regulatory (Treg) cells and cytokines to the pathogenesis of gout. We enrolled 126 gout patients (53 early-onset gout with age of first presentation < 40 years, and 73 late-onset gout with age of first presentation ≥ 40 years) and 77 HCs. Percentage and absolute numbers of peripheral lymphocyte and CD4+T cell subpopulations in each group were detected by flow cytometry. The serum cytokine levels were determined by flow cytometric bead array. For circulating CD4+T cell subsets, Th17/Treg ratio was significantly higher in early-onset gout, late-onset gout and gout without tophus than HCs; Th17 cells were significantly elevated in early-onset gout and gout without tophus, while the percentage of Treg cells was significantly decreased in early-onset and late-onset gout. Additionally, gout patients had significantly higher cytokines levels (including IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α) than HCs; IL-2 levels were positively correlated with Treg cells and negatively correlated with ESR. ROC analysis showed that disease duration, CRP and fibrinogen, had moderate predictive performances for tophus in gout (the AUCs were 0.753, 0.703 and 0.701, respectively). Our study suggests that early-onset and late-onset gout differ in Th17/Treg imbalance, which in early-onset gout is due to elevated Th17 cells and in late-onset gout is due to decreased Treg cells. And increased serum cytokine levels, especially IL-2, may play an essential role in that. Restoring Th17/Treg balance may be a crucial way to improve the prognosis of gout patients.

Impaired immune tolerance mediated by reduced Tfr cells in rheumatoid arthritis linked to gut microbiota dysbiosis and altered metabolites.

BACKGROUND: Patients with rheumatoid arthritis (RA) showed impaired immune tolerance characterized by reduced follicular regulatory T (Tfr) cells, and they also exhibited altered gut microbiotas and their metabolites in RA. However, the association of gut microbiotas and their metabolites with the immune tolerance mediated by Tfr cells in RA remains unclear. METHODS: Peripheral blood and stool samples were collected from 32 new-onset RA patients and 17 healthy controls (HCs) in the Second Hospital of Shanxi Medical University between January 2022 and June 2022. The peripheral blood was used to detect the circulating regulatory T (Treg), helper T(Th)17, Tfr, and follicular helper T (Tfh) cells by modified flow cytometry. The stool samples were used to analyze the gut microbiotas and their metabolites via 16S rDNA sequencing and metabolomic profiling. We aimed to characterize the gut microbiotas and their metabolites in RA and identified their association with Tfr cell-mediated immune tolerance. RESULTS: The new-onset RA demonstrated reduced Treg and Tfr cells, associated with the disease activity and autoantibodies. There were significant differences in gut microbiotas between the two groups as the results of ß diversity analysis (P = 0.039) including 21 differential gut microbiotas from the phylum to genus levels. In which, Ruminococcus 2 was associated with the disease activity and autoantibodies of RA, and it was identified as the potential biomarker of RA [area under curve (AUC) = 0.782, 95% confidence interval (CI) = 0.636-0.929, P = 0.001]. Eleven differential metabolites were identified and participated in four main pathways related to RA. Arachidonic acid might be the potential biomarker of RA (AUC = 0.724, 95% CI = 0.595-0.909, P = 0.038), and it was the core metabolite as the positive association with six gut microbiotas enriched in RA. The reduced Tfr cells were associated with the altered gut microbiotas and their metabolites including the Ruminococcus 2, the arachidonic acid involved in the biosynthesis of unsaturated fatty acid pathway and the 3-methyldioxyindole involved in the tryptophan metabolism pathway. CONCLUSION: The breakdown of immune tolerance mediated by reduced Tfr cells was associated with the altered gut microbiotas and their metabolites implying the possible mechanism of RA pathogenesis from the perspective of microecology-metabolism-immune.

MicroRNA-193a Promotes Apoptosis in Retinal Neuronal Cells in Early-Stage Diabetic (DM) Rat via Wilms' Tumor Gene 1.

OBJECTIVE: This study aimed to investigate the role and mechanism of microRNA (miR)-193a in promoting apoptosis of retinal neuronal cells in early diabetic (DM) rats. METHODS: Seventy-two male SD-grade rats were selected to establish a DM model by intraperitoneal injection of streptozotocin (STZ), and randomly divided into a control group (blank control group), a DM group (diabetic model group), a DM+miR-NC inhibitor group (miR-193a inhibition negative control group), a DM+miR-193a inhibitor group (miR-193a inhibitor group), DM+miR-NC mimic group (miR-193a overexpression negative control group), DM+miR-193a mimic group (miR-193a overexpression group), with12 rats in each group. RESULTS: The miR-193a expression, apoptosis rate, and Bax, Caspase3, and Caspase9 protein expression levels were elevated, and Bcl-2 protein expression was decreased in the retinal tissues of DM rats and high glucose-induced rat retinal neuronal cells, while miR-193a inhibitors reversed these processes. These dual luciferase reporter assay showed that WT1CDS, and WT1Mut were lower in the miR-193a group than in the miR-NC group (P<0.05); WT1 protein expression was reduced in the retinal tissues of DM rat and high glucose-induced rat retinal neuronal cells, and miR-193a inhibitors increased WT1 protein expression. Compared with cells co-transfected with miR-193a and WT1vector, miR-193a and WT1 cotransfection inhibited high glucose-induced apoptosis in retinal neuronal cells and regulated apoptotic protein expression. miR-193a was highly expressed and WT1 was lowly expressed in retinal tissues of DM rats and high glucose-induced rat retinal neuronal cells. CONCLUSION: miR-193a could inhibit early retinal neuronal cell apoptosis in DM rats by targeting and negatively regulating WT1 expression.

Targeting transcription factors through an IMiD independent zinc finger domain.

Immunomodulatory imide drugs (IMiDs) degrade specific C2H2 zinc finger degrons in transcription factors, making them effective against certain cancers. SALL4, a cancer driver, contains seven C2H2 zinc fingers in four clusters, including an IMiD degron in zinc finger cluster two (ZFC2). Surprisingly, IMiDs do not inhibit growth of SALL4 expressing cancer cells. To overcome this limit, we focused on a non-IMiD degron, SALL4 zinc finger cluster four (ZFC4). By combining AlphaFold and the ZFC4-DNA crystal structure, we identified a potential ZFC4 drug pocket. Utilizing an in silico docking algorithm and cell viability assays, we screened chemical libraries and discovered SH6, which selectively targets SALL4-expressing cancer cells. Mechanistic studies revealed that SH6 degrades SALL4 protein through the CUL4A/CRBN pathway, while deletion of ZFC4 abolished this activity. Moreover, SH6 led to significant 62% tumor growth inhibition of SALL4+ xenografts in vivo and demonstrated good bioavailability in pharmacokinetic studies. In summary, these studies represent a new approach for IMiD independent drug discovery targeting C2H2 transcription factors in cancer.

Generation of two induced pluripotent stem cell lines from two sporadic amyotrophic lateral sclerosis patients.

Peripheral blood mononuclear cells were obtained from two patients diagnosed with amyotrophic lateral sclerosis (ALS), a 47-year-old female and a 45-year-old male. Induced pluripotent stem cells (iPSCs) were generated using a non-integrating SeV-based method, delivering the transcription factors OCT4, SOX2, c-MYC, and KLF4. These transgene-free iPSC lines exhibited typical pluripotent cell morphology, expressed pluripotency-associated markers, and had tri-lineage differentiation potential. Both iPSC lines were free of mycoplasma contamination and displayed normal karyotypes. The availability of these two cell lines provides a promising opportunity to use sporadic ALS models for investigating the intricate pathological mechanisms of ALS.

Bifunctional Smart Textiles with Simultaneous Motion Monitoring and Thermotherapy for Human Joint Injuries.

The motion detection and thermotherapy provides a convenient strategy for the diagnosis and rehabilitation assessment of joint injuries. However, it is still challenging to simultaneously achieve accurate joint motion monitoring and on-demand thermotherapy. Herein, core-sheath sensing yarns (CSSYs) is proposed and fabricated for excellent electrical and photothermal heating, which consists of carbon black (CB)-coated nylon (sheath layer), silver-plated nylon and elastic spandex yarns (core layer). The CSSYs demonstrates great joule heating performance, which reaches 75 °C at 2 V applied voltage. The good thermal management performance can be well maintained when weaving these yarns into bifunctional smart textile. Further, the optimized double-ply CSSYs (DPCSSYs) with helically twisted structure possess several appealing sensing performance, including preferable strain sensitivity (0.854), excellent linearity (0.962), and superior durability (over 5000 cycles). The as-woven bifunctional smart textile can provide instant and convenient thermotherapy to the injured joints, and simultaneously monitor the injury and recovery conditions of the joint. Therefore, the designed bifunctional smart textile can provide a promising route for developing next-generation healthcare smart textile.