The relationship between low and asymmetric handgrip strength and low muscle mass: results of a cross-sectional study on health and aging trends in western China.

OBJECTIVE: The aim was to determine the relationship between low handgrip strength (HGS) only, asymmetric HGS only, and low HGS combined with asymmetric HGS and low muscle mass in the West China Health and Aging Trends Study (WCHAT) data. STUDY DESIGN: Individuals aged at least 50 years old were included in this cross-sectional study using WCHAT data. Demographic characteristics, such as age, marital status, education level, ethnicity, and drinking and smoking history, as well as chronic diseases, were recorded for all participants. The HGS of both hands was tested three times using a grip dynanometer with the participant in a standing position with arms extended, before recording the maximum value for both hands. The maximum value referred to values < 28 kg and < 18 kg for males and females, respectively. HGS ratios (non-dominant HGS/dominant HGS) of < 0.90 or > 1.10 suggest asymmetric HGS. The subjects were then allocated to the low HGS, asymmetrical HGS, and combined low and asymmetrical HGS (BOTH group) groups, and those with neither low nor asymmetric HGS (the normal group). The InBody 770 instrument was used for the analysis of muscle mass, with low muscle mass defined as a skeletal muscle mass index (SMI) of < 7.0 kg/m2 or < 5.7 kg/m2 for males and females, respectively. The associations between the different HGS groups and low muscle mass were assessed by logistic regression analysis. RESULTS: The study included 1748 subjects, of whom 1272 (72.77%) were over the age of 60 years. The numbers of Han, Tibetan, and Qiang were 885 (50.63%), 217 (12.41%), and 579 (33.12%), respectively. A total of 465 individuals (26.60%) were classified as having low muscle mass, while 228 (13.04%), 536 (30.66%), and 125 (7.15%) participants were allocated to the low HGS, asymmetric HGS, and BOTH groups, respectively. The average SMI differed significantly between the normal group and the other groups (normal group vs. asymmetric HGS group vs. low HGS group vs. BOTH group: 6.627 kg/m2 vs. 6.633 kg/m2 vs. 6.492 kg/m2 vs. 5.995 kg/m2, respectively, P < 0.05). In addition, the prevalence of low muscle mass in the normal, asymmetric HGS, low HGS, and BOTH groups increased sequentially, with significant differences (normal group vs. asymmetric HGS group vs. low HGS group vs. BOTH group: 21.5% vs. 22.4% vs. 39.5% vs. 56%, respectively, P = 0.001). Further logistic regression analysis showed that the presence of low HGS (OR = 1.7, 95%CI: 1.203-2.402) and both low and asymmetric HGS (OR = 3.378, 95%CI: 2.173-5.252) were predictive of low muscle mass, with the chance being higher for the latter condition. CONCLUSION: The findings suggest that although asymmetrical HGS itself does not increase the chances of low muscle mass. When low HGS and a combination of both features (low HGS combined with asymmetric HGS) is present in subjects, the chance of low muscle mass increases.

NDRG2 Deficiency Exacerbates UVB-Induced Skin Inflammation and Oxidative Stress Damage.

UVB radiation induces inflammatory and oxidative stress responses, contributing to skin damage, yet the underlying mechanisms are not fully understood. N-Myc downstream-regulated gene 2 (NDRG2), an emerging stress-associated gene, remains unexplored in UVB-induced skin injury. In this study, we detected skin NDRG2 expression after UVB irradiation for the first time and further used Ndrg2 knockout mice to clarify the role of NDRG2 in UVB-induced skin injury. Three-month-old male Ndrg2+/+ and Ndrg2-/- mice (16-18g) were exposed to UVB to induce acute skin damage, and then dorsal skin samples were collected for subsequent analyses. UVB-induced skin damage was scored. Western Blot Analysis, immunofluorescence (IF) double labeling, and immunohistochemistry (IHC) were employed to assess NDRG2 expression and/or distribution. The concentrations of TNF-α, IL-6, IL-1ß, MPO, MMP8, superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining were employed to determine pathological changes. RNA sequencing and analysis were performed to estimate transcript expression levels and analyze mRNA expression. DESeq2 software was employed to identify differentially expressed genes (DEGs). DEGs were visualized using volcanic and heat maps. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to identify primary biological functions, metabolic pathways, or signal transduction pathways associated with DEGs. UVB-challenged Ndrg2-/- mice exhibited significantly exacerbated skin damage (erythema, edema, and erosion), neutrophil infiltration, and apoptosis compared to Ndrg2+/+ mice. Furthermore, UVB-challenged Ndrg2-/- mice displayed significantly elevated pro-inflammatory cytokines, myeloperoxidase (MPO), matrix metalloproteinase-8 (MMP8), and reduced antioxidant expression. RNA sequencing identified 1091 significantly differentially expressed genes enriched in inflammation, immune response, and oxidative stress pathways. In conclusion, the deficiency of Ndrg2 markedly exacerbated UVB-induced skin damage by promoting inflammatory responses and inhibiting antioxidant responses. This suggests that stabilizing NDRG2 expression holds promise as a therapeutic strategy for protecting against UVB-induced skin damage.

SARC-F, SARC-CalF, and SARC-F+EBM as practical predictive tools for the risk of pneumonia in patients with stable schizophrenia-a prospective study.

Objectives: Individuals diagnosed with schizophrenia have a high incidence and fatality rates due to pneumonia. Sarcopenia is a contributing factor to the development of pneumonia in patients with schizophrenia. In this study, we examine the effectiveness of three simple screening questionnaires, namely SARC-F, SARC-CalF, and SARC-F + EBM, in predicting the occurrence of pneumonia in stable patients with schizophrenia who are experiencing sarcopenia. Design: A prospective study. Setting: Patients with stable schizophrenia patients aged ≥50 years in two psychiatric hospitals in western China. Methods: Medical data from patients were collected from September 1 to September 30, 2020. Data specifically from patients diagnosed with pneumonia were collected for a period of one year, from October 2020 to October 2021. Three hundred thirty-five stable schizophrenia patients, among whom 229 were males (68.36 %.), were enrolled in the prospective study. The risk of sarcopenia was evaluated using the SARC-F, SARC-CalF, and SARC-F + EBM scores, with values of ≥4, 11, and 12 indicating an elevated risk of sarcopenia. The collected data were analyzed using logistic regression analysis to establish the association between the scores of these screening tools and the risk of pneumonia in individuals with stable schizophrenia. Results: The rate of pneumonia in stable schizophrenia individuals was 24.48 %. Among the included stable schizophrenia patients, the incidence of pneumonia in individuals with SARC-CalF scores ≥11 was higher than in those with SARC-CalF scores less than 11 (29.91 % vs 14.88 %, P = 0.002). In individuals with SARC-F + EBM scores ≥12, the pneumonia occurrence was higher than that in those with SARC-F + EBM scores less than 12 (37.33 % vs 20.77 %, P = 0.003). However, this pattern was not found in patients with stable schizophrenia who had SARC-F scores of 4 or above and less than 4. Following the implementation of logistic regression data analysis, it has been discovered that persons with SARC-CalF scores greater than or equal to 11 were at a significantly increased risk of having pneumonia compared to patients with SARC-CalF scores less than 11 (OR = 2.441, 95 % CI: 1.367-4.36). After adjusting the possible confounders, patients with SARC-CalF scores ≥11 had a greater danger of pneumonia (OR = 2.518, 95%CI: 1.36-4.665). As a result, it was found that individuals with SACR-F+EBM scores ≥12 were more likely to acquire pneumonia (OR = 2.273, 95%CI: 1.304-3.961) when compared to those with scores <12 (OR = 2.273, 95%CI: 1.304-3.961). The results of this study, which controlled for potential confounders, indicated that patients with SARC-F + EBM scores ≥12 were more inclined to acquire pneumonia (OR = 2.181, 95%CI: 1.182-4.026). However, in stable schizophrenia patients with SARC-F scores ≥4 and < 4, this study has not yet observed a similar pattern for pneumonia risk. Conclusions and implications: These results demonstrate, in stable adults with schizophrenia, a relationship between pneumonia risk and SARC-F + EBM and SARC-CalF scores. It is, therefore, advised to use these scores to determine whether these patients have pneumonia, especially in hospitals that cannot diagnose sarcopenia.

Radiating blood flow signal: A new ultrasound feature of thyroid carcinoma.

OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.

Comparison of short-term outcomes of laparoscopic surgery, robot-assisted laparoscopic surgery, and open surgery for lateral lymph-node dissection for rectal cancer: a network meta-analysis.

This study attempted to compare short-term outcomes of laparoscopic surgery (LS), robot-assisted laparoscopic surgery (RS), and open surgery (OS) for lateral lymph-node dissection (LLND) in treatment of rectal cancer through network meta-analysis. Embase, Web of Science, PubMed, and The Cochrane Library databases were searched to collect cohort studies on outcomes of LS, RS, and OS for LLND for rectal cancer. Newcastle-Ottawa Scale (NOS) was utilized to evaluate the quality of cohort studies. Primary outcomes should at least include one of the following clinical outcome measures: operative time, blood loss, total lymph-node harvest, positive resection margin rate, postoperative complications, and postoperative hospital stay. A network meta-analysis was conducted using STATA software. Fourteen cohort studies including 8612 patients were eligible for inclusion. The network meta-analysis results showed that, in terms of intraoperative outcomes, the RS group had the longest operative time, while the OS group had the shortest; the LS and RS groups had significantly less blood loss than the OS group. In terms of histological outcomes, there were no significant differences in the total number of lymph nodes harvested and the positive margin rate among the LS, RS, and OS groups (P > 0.05). Regarding postoperative outcomes, the OS group had the highest probability of postoperative complications and the longest hospital stay, followed by the LS group, with the RS group being the lowest. RS was the best method in blood loss, postoperative complication rate, and postoperative hospital stay, followed by LS. OS had the shortest operative time and the highest blood loss.

Advancing skeletal health and disease research with single-cell RNA sequencing.

Orthopedic conditions have emerged as global health concerns, impacting approximately 1.7 billion individuals worldwide. However, the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders. The advent of single-cell RNA sequencing (scRNA-seq) technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity. Nevertheless, investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges. In this comprehensive review, we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines. By utilizing these methodologies, crucial insights into the developmental dynamics, maintenance of homeostasis, and pathological processes involved in spine, joint, bone, muscle, and tendon disorders have been uncovered. Specifically focusing on the joint diseases of degenerative disc disease, osteoarthritis, and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension. These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.

Quadrotors' double-loop controller design with tensor product model transformation and partial fully actuated method.

In the existing work of tensor product (TP) model transformation, the TP model transformation-based work on the quadrotor's control system design is scarce, the direct TP model transformation control strategy that applied to the quadrotor fails due to the calculation complexity, infeasibility of the huge amount of linear matrix inequalities, and the complexity of solving the linear matrix inequalities. To solve this problem, a partial TP model transformation-based double loop fuzzy controller has been studied in this work, the double-loop hybrid control scheme combines the fully actuated control method and the TP model transformation, while the fully actuated control method is used to the position subsystem control loop, and the TP model transformation based fuzzy controller is applied to the attitude control of the quadrotor. Moreover, for comparison purpose, a varying-input method based on TP model transformation is extended to the quadrotor's system control. The double-loop hybrid control scheme could also be extended with other TP model transformation based tensor sampling methods, such as, uniform sampling method and varying-input method. At last, the proposed algorithms are evaluated and compared on Parrot Mambo Minidrone, MFP450 and CUAV V5+ based hexarotor.

Assessment of sarcopenic obesity as a predictor of pneumonia in patients with stable schizophrenia-A prospective study.

OBJECTIVE: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) recently released the first international consensus on the diagnostic criteria for Sarcopenic obesity (SO). The present study aimed to explore the ability of SO to predict the risk of pneumonia in patients with stable schizophrenia. METHODS: This was a prospective study involving hospitalized patients with schizophrenia aged ≥50 years from two mental health centers in western China. Baseline patient data were collected from September 1 to September 30, 2020. Follow-up data on pneumonia were collected from October 2020 to October 2022. The diagnosis of SO was based on the ESPEN/EASO criteria. Patients were assessed for handgrip strength (HGS), skeletal muscle mass/weight (SMM/W), and fat mass percentage (FM%). Logistic regression analysis was used to explore the effect of SO on the risk of pneumonia in patients with stable schizophrenia. RESULTS: A total of 320 patients with stable schizophrenia were included. Of these, 74 (23.13%) were diagnosed with SO, while 117 (36.56%) developed pneumonia. Compared with patients in the non-low HGS, non-low HGS + non-low SMM/W (or non-low HGS + low SMM/W or low HGS + non-low SMM/W) and non-SO groups, the proportions of patients with pneumonia in the low HGS (42.3% vs. 25.9%, p = 0.004), low HGS + low SMM/W (45.3% vs. 33.3%, p = 0.048), and SO (47.3% vs. 33.3%, p = 0.029) groups, respectively, were higher. However, there was no difference in the proportion of patients with pneumonia in the low SMM/W group and the obese group compared with the non-low SMM/W and non-obese groups. Further logistic regression analysis after adjustment for potential influencing factors showed that compared with the non-low HGS group, patients in the low HGS group had a higher risk of pneumonia (OR = 1.892, 95%CI: 1.096-3.264). CONCLUSION: SO defined according to the ESPEN/EASO criteria was not found to be significantly associated with the development of pneumonia in patients with stable schizophrenia. Further verification of these results is needed with larger sample sizes and the establishment of a cutoff value for this population.

Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models.

Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co-culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF-ß. Additionally, a suspended co-culture multicellular spheroid model revealed molecular-level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro-angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF-ß, IL-17, Wnt, Notch, PI3K-Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts-endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases.

A prospective phase II single-arm study and predictive factor analysis of irinotecan as third-line treatment in patients with metastatic gastric cancer.

Background: Currently, there is no recommended standard third-line chemotherapy for metastatic gastric cancer. Objectives: In this study, we aimed to evaluate irinotecan's efficacy and safety in treating metastatic gastric cancer after the failure of first- and second-line chemotherapy. Design: Prospective single-arm, two-center, phase II trial. Methods: Patients were aged 18-70 years, with histologically confirmed gastric adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0-1, progressed during or within 3 months following the last administration of second-line chemotherapy and had no other severe hematologic, cardiac, pulmonary, hepatic, or renal functional abnormalities or immunodeficiency diseases. Eligible patients received 28-day cycles of irinotecan (180 mg/m2 intravenously, days 1 and 15) and were assessed according to the RECIST 1.1 criteria every two cycles. Patients who discontinued treatment for any reason were followed up every 2 months until death. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity. Results: A total of 98 eligible patients were enrolled in this study. In the intention-to-treat population, the median OS was 7.17 months, the median PFS was 3.47 months, and the ORR and DCR were 4.08% and 47.96%, respectively. In the per-protocol population, the median OS was 7.77 months, the median PFS was 3.47 months, and the ORR and DCR were 4.82% and 50.60%, respectively. The incidence of grade 3 or 4 hematological and non-hematological toxicities was 19.4%, and none of the patients died owing to adverse events. Cox regression analysis revealed neutropenia and baseline thrombocyte levels were independently correlated with PFS and OS. Conclusion: Irinotecan monotherapy is an efficient, well-tolerated, and economical third-line treatment for patients with metastatic gastric cancer as a third-line treatment. Trial registration: ClinicalTrials.gov identifier: NCT02662959.

Mitochondrial tRNASer(UCN) mutations associated non-syndromic sensorineural hearing loss in Chinese families.

Mitochondrial transfer RNA mutation is one of the most important causes of hereditary hearing loss in humans. Mitochondrial transfer RNASer (UCN) gene is another hot spot for mutations associated with non-syndromic hearing loss, besides the 12S ribosomal RNA gene. In this study, we assessed the clinical phenotype and the molecular characteristics of two Chinese families with non-syndromic hearing loss. Mutational analysis revealed that 7445A > G and 7510T > C mutations in the mitochondrial transfer RNASer (UCN) gene were the molecular etiology of Family 1 and Family 2, respectively. However, the clinical and genetic characteristics of the two families carrying the above mutations in the transfer RNASer (UCN) gene exhibited a variable expression of hearing loss and an incomplete penetrance. Sequencing analysis of the complete mitochondrial genome showed the presence of transfer RNATrp 5568A > G and NADH-ubiquinone oxidoreductase chain 4 11696G > A mutations in Family 1. The mitochondrial haplotype analysis showed that the two families belonged to Asian D4 and M80'D haplotypes, respectively, and no pathogenic variations were found in the nuclear genes. To our knowledge, our study is the first to report 7445A > G and 7510T > C mutations in the mitochondrial transfer RNASer (UCN) gene, in multi-generation non-syndromic hearing loss pedigrees from China. Our study suggests that 5568A > G and 11696G > A mutations may enhance the penetrance of hearing loss in Chinese Family 1, while mitochondrial haplotypes and known nuclear genes may not be modifiers for the phenotypic expression of 7445A > G and 7510T > C mutations in these Chinese families.

General Strategy to Prepare Nondoped Circularly Polarized Luminescent Liquid Crystal Materials with Tunable Performance.

Chiral luminescent liquid crystals have attracted widespread attention from researchers due to their unique advantages in constructing circularly polarized luminescent (CPL) materials with large luminescent asymmetry factor (glum) values. However, how to effectively prepare nondoped CPL chiral liquid crystals remains a challenge. In this article, we developed an effective and universal method to prepare nondoped CPL chiral liquid crystal materials. To achieve our strategy, we copolymerized chiral monomer M0Mt with α-cyanostilbene-based luminescent monomers MmPVPCN (m = 6, 8, 10) bearing different flexible spacer lengths to obtain a series of CPL chiral liquid crystal copolymers poly(MmPVPCN(x)-co-M0Mt(y)). Under the induction of the chiral component, the α-cyanostilbene component assembles to form chiral liquid crystals. Meanwhile, α-cyanostilbene also exhibits aggregation-induced emission enhancement characteristics. Therefore, with the help of the selective reflection effect of chiral liquid crystals, the copolymer films can emit efficient CPL. For poly(M8PVPCN(0.85)-co-M0Mt(0.15)), the glum and solid luminescence quantum yield can achieve -2.61 × 10-2 and 25.04%, respectively. In addition, by altering the chemical structure of the copolymers, the phase structure of the copolymers can be effectively controlled, thereby regulating their CPL properties.

Versatile dopamine-functionalized hyaluronic acid-recombinant human collagen hydrogel promoting diabetic wound healing via inflammation control and vascularization tissue regeneration.

The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing, delayed healing, susceptibility to infection, and elevated risk of reopening, highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels. Here, we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III (rhCol) by oxidative coupling of the catechol group using the H2O2/HRP catalytic system. The post-reactive hydrogel has a good porous structure, swelling rate, reasonable degradation, rheological and mechanical properties, and the catechol group and dopamine impart to the hydrogel tissue adhesiveness, antioxidant capacity, and excellent photothermal effects leading to superior in vitro antimicrobial activity. In addition, the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated. Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel. Wound closure, collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing. In summary, the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.

Water extract of moschus alleviates erastin-induced ferroptosis by regulating the Keap1/Nrf2 pathway in HT22 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Moschus, first described in the Shennong's Classic of the Materia medicine, is a scarce and precious animal medicine. Modern pharmacological researches have suggested that Moschus has neuroprotective actions, and its mechanism is related to anti-inflammatory, antioxidant, and anti-apoptosis effects. Ferroptosis is one of the major pathologies of Alzheimer's disease (AD) and is widely implicated in the pathogenesis and progression of AD. Although previous studies have suggested that Moschus possesses neuroprotective effect, whether Moschus could mitigate neuronal damages by inhibiting the onset of ferroptosis is unknown in model cells of AD. AIM OF THE STUDY: The aim of study was to explore the water extract of Moschus (WEM) on ferroptosis caused by erastin and the potential mechanism. MATERIALS AND METHODS: Erastin was used to stimulate HT22 cells to form ferroptosis model to evaluate the anti-ferroptosis effect of WEM by cell counting kit-8 and lactic dehydrogenase (LDH) tests. The malondialdehyde (MDA) and glutathione (GSH) kits are used for detection of MDA and GSH levels, and 2',7'-dichlorofluorescein diacetate and C11 BODIPY 581/591 fluorescence probe are used for evaluation of reactive oxygen species (ROS) and lipid peroxide (LOOH) levels. And Western blot was used to test nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), and ferroptosis associated proteins including glutathione peroxidase 4 (GPX4), cystine/glutamate antiporter subunit (SLC7A11), ferritin heavy chain 1 (FTH1), ferroportin1 (FPN1), transferrin receptor (TFRC). In addition, the Nrf2 inhibitor ML385 was applied to verify whether WEM prevents erastin-induced ferroptosis by activating the Keap1/Nrf2 pathway. RESULTS: After WEM treatment, erastin-induced HT22 cell survival was significantly elevated, the accumulation of intracellular MDA, ROS, and LOOH were significantly reduced, the level of GSH and expressions of ferroptosis inhibitors GPX4 and SLC7A11 were significantly increased, and iron metabolism-related proteins TFRC, FPN1, and FTH1 were regulated. These effects of WEM are implemented by activating the Keap1/Nrf2 pathway. CONCLUSIONS: This study demonstrated that WEM could perform neuroprotective effects by alleviating ferroptosis, verified that WEM treatment of AD can be mediated by the Keap1/Nrf2 pathway, and provided theoretical support for the application of WEM in the treatment of AD.

MPZL2-a common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population.

BACKGROUND: Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss. METHODS: In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing. RESULTS: Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency. CONCLUSIONS: We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2.

Better than being aPARt: S. aureus itches to get close to sensory neurons.

In a recent issue of Cell, Deng et al. show that S. aureus serine protease V8 triggers itch, independent of inflammation, by activating sensory neurons through PAR1. This study presents mechanistic insights into pruritogenic bacteria and their interactions with sensory neurons while providing a possible approach for treating itch-related diseases.

Relationship between neck vessel abnormalities and sarcopenia: results of a study examining trends in health and aging in western China.

OBJECTIVE: To elucidate the association between cervical vascular abnormalities (high Crouse score, high carotid intima-media thickness [CIMT], high plaque score [PS]) and sarcopenia and its diagnostic elements. STUDY DESIGN: This cross-sectional investigation selected patients from the Western China Health and Aging Trends Study (WCHAT) aged 60 years and older. High CIMT and high Crouse score was defined as values ≥ upper quartile cutoff. Moreover, PS ≥ 3 was set as an high PS. Sarcopenia diagnosis and the definition of sarcopenia diagnostic elements were based on the Asian Working Group on Sarcopenia (AWGS) 2019 consensus. Lastly, associations between high Crouse score, high PS, high CIMT, and sarcopenia and its diagnostic elements were assessed using logistic regression. RESULT: In all, we recruited 932 subjects in this study, among which, 138 people (14.81%) were diagnosed with sarcopenia. The rates of high Crouse score (sarcopenia vs. non-sarcopenia: 37.68% vs. 23.30%, P < 0.001) and high PS (sarcopenia vs. non-sarcopenia: 34.78% vs. 18.39%, P < 0.001) in subjects with sarcopenia were higher than those in subjects without sarcopenia. Logistic regression analysis and the correction of possible confounding factors showed that high Crouse score and high PS were related to sarcopenia (high Crouse score: OR = 1.573; 95%CI: 1.032-2.4; high PS: OR = 1.845; 95%CI: 1.195-2.851). Further analysis indicated that high Crouse score were associated with low muscle mass (OR = 1.403; 95%CI: 1.002-1.966) and low physical function (OR = 1.93; 95%CI: 1.3-2.866). High PS was found to be related to low physical function (OR = 1.83; 95%CI: 1.209-2.771). CONCLUSION: While both high Crouse score and high PS are related to sarcopenia, further analysis showed that high Crouse score were mainly associated with low muscle mass and low physical function while high PS was associated with low physical function.

[Clinical observation of virtual reality technology combined with isokinetic strength training for patients after anterior cruciate ligament reconstruction].

OBJECTIVE: To explore application value and effectiveness of virtual reality technology combined with isokinetic muscle strength training in the rehabilitation of patients after anterior cruciate ligament (ACL) reconstruction surgery. METHODS: Forty patients who underwent ACL reconstruction surgery from December 2021 to January 2023 were selected and divided into control group and observation group according to treatment methods, 20 patients in each group. Control group was received routine rehabilitation training combined with isokinetic muscle strength training, including 15 males and 5 females, aged from 17 to 44 years old, with an average of (29.10±8.60) years old. Observation group was performed virtual reality technology combined with isokinetic muscle strength training, including 16 males and 4 females, aged from 17 to 45 years old with an average of (30.95±9.11) years old. Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups at 12 (before training) and 16 weeks (after training) after surgery were compared. RESULTS: All patients were followed up for 1 to 6 months with an average of (3.30±1.42) months. There were no statistically significant difference in Lysholm knee joint score, peak knee extension peak torque, and peak knee flexion peak torque between two groups (P>0.05) before training. After training, Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque of both groups were improved compared to before training (P<0.05);there were significant difference in Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups(P<0.05). CONCLUSION: The application of virtual reality technology combined with isokinetic muscle strength training could promote recovery of knee joint function and enhance muscle strength in patients after ACL reconstruction surgery in further.

Shade-induced RTFL/DVL peptides negatively regulate the shade response by directly interacting with BSKs in Arabidopsis.

For shade-intolerant species, shade light indicates the close proximity of neighboring plants and triggers the shade avoidance syndrome (SAS), which causes exaggerated growth and reduced crop yield. Here, we report that non-secreted ROT FOUR LIKE (RTFL)/DEVIL (DVL) peptides negatively regulate SAS by interacting with BRASSINOSTEROID SIGNALING KINASEs (BSKs) and reducing the protein level of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) in Arabidopsis. The transcription of at least five RTFLs (RTFL13/16/17/18/21) is induced by low R:FR light. The RTFL18 (DVL1) protein is stabilized under low R:FR conditions and localized to the plasma membrane. A phenotype analysis reveals that RTFL18 negatively regulates low R:FR-promoted petiole elongation. BSK3 and BSK6 are identified as partners of RTFL18 through binding assays and structural modeling. The overexpression of RTFL18 or knockdown of BSK3/6 reduces BRASSINOSTEROID signaling and reduces low R:FR-stabilized PIF4 levels. Genetically, the overexpression of BSK3/6 and PIF4 restores the petiole phenotype acquired by RTFL18-overexpressing lines. Collectively, our work characterizes a signaling cascade (the RTFLs-BSK3/6-PIF4 pathway) that prevents the excessive activation of the shade avoidance response in Arabidopsis.

Event-related potentials reveal visual episodic memory deficits in patients with temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) patients usually suffer from impaired episodic memory (EM), but its underlying electrophysiologic mechanism and impacted cognitive performance are unclear. We aim to investigate the association between episodic memory reserve and physiological measures of memory workload in TLE patients using Event-related potentials (ERP). METHODS: A change detection task with image stimuli assesses visual episodic memory. During the memory encoding and decoding phases, the ERP signals were analyzed from twenty-nine TLE patients (twelve with left TLE patients, seventeen with TLE), and thirty healthy controls. Given that EM is a complex process involving many fundamental cognitive processes, the amplitudes and latencies of EM-related ERP (FN400, late positive potential (LPC), and late posterior negativity (LPN)), and the ERP reflecting the fundamental processes (P100, N100, P200, and P300) were calculated. Then we used a three-by-two factorial design on the ERP metrics for interaction and main effects. The correlation analysis among Wechsler Memory Scales-Chinese Revision (WMS-RC) results, behavioral data, and the ERPs was carried out. RESULTS: The TLE patients performed worse in WMS-RC and the memory task. The increased P200 and decreased P300 amplitudes were observed in the TLE patients, and LPN was abnormal in only LTLE patients. For EM-related components, differences were observed in both the LTLE and RTLE patients: the lack of the FN400 effect, the lack of the reversed LPC effect, and the reduced FN400. No significant inter-group difference was detected for the latencies of all the ERPs. Additionally, there were significant correlations among WMS-RC scores, behaviors, and some ERP amplitudes. CONCLUSIONS: The impaired EM is linked to the increased P200 and decreased P300 amplitudes. LPN seems to be sensitive to left temporal lobe dysfunction. More importantly, the abnormal old or new effects of the FN400 and LPC, and the reduced FN400 amplitude might be associated with the visual EM deficit in the TLE patients. These findings may assist in the deep understanding of the EM disorder and the evaluation of the side effects of antiepileptic drugs.