High-risk screening for late-onset Pompe disease in China: An expanded multicenter study.

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population.

Integrating single-cell and spatial analysis reveals MUC1-mediated cellular crosstalk in mucinous colorectal adenocarcinoma.

Background: Mucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in-depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies.

Methods: We integrated single-cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells.

Integrative analysis of bioinformatics and machine learning to identify cuprotosis-related biomarkers and immunological characteristics in heart failure.

Backgrounds: Cuprotosis is a newly discovered programmed cell death by modulating tricarboxylic acid cycle. Emerging evidence showed that cuprotosis-related genes (CRGs) are implicated in the occurrence and progression of multiple diseases. However, the mechanism of cuprotosis in heart failure (HF) has not been investigated yet.

Glenohumeral joint trajectory tracking for improving the shoulder compliance of the upper limb rehabilitation robot.

Background: Exoskeletons have become an important tool to help patients with upper extremity motor dysfunction in rehabilitation training and life assistance. In the study of the upper limb exoskeleton, the human glenohumeral joint will produce accompanying movement during the movement of the shoulder joint. This phenomenon causes a positional deviation between the shoulder joint and the exoskeleton, which affects the accuracy of exoskeleton-assisted human movement and the wearing comfort.

Independent and joint associations of body mass index, waist circumference, waist-height ratio and their changes with risks of hyperuricemia in middle-aged and older Chinese individuals: a population-based nationwide cohort study.

Background: Previous reports regarding the predictive power of adiposity indices remain inconsistent, and longitudinal studies on this top are limited. The associations of hyperuricemia risk with changes in obesity status, as well as the joint effects of baseline adiposity indices and body adiposity change on hyperuricemia risk are not fully elucidated. This study aimed to explore the independent and joint associations of baseline adiposity indicators and body adiposity change with hyperuricemia risk among middle-aged and older population in China.

Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment.

The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance.

Targeting the autophagy promoted antitumor effect of T-DM1 on HER2-positive gastric cancer.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate consisted of the HER2-targeted monoclonal antibody trastuzumab and the tubulin inhibitor emtansine, has shown potent therapeutic value in HER2-positive breast cancer (BC). However, a clinical trial indicated that T-DM1 exerts a limited effect on HER2-positive gastric cancer (GC), but the underlying mechanism is inconclusive. Our research attempted to reveal the probable mechanism and role of autophagy in T-DM1-treated HER2-positive GC.

IL-22-mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury.

Kidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end-stage renal disease (ESTD). Interleukin-22 (IL-22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here, we first provide evidence that IL-22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs).

Freeze substitution Hi-C, a convenient and cost-effective method for capturing the natural 3D chromatin conformation from frozen samples.

Chromatin interactions functionally affect genome architecture and gene regulation, but to date, only fresh samples must be used in High-through chromosome conformation capture (Hi-C) to keep natural chromatin conformation intact. This requirement has impeded the advancement of 3D genome research by limiting sample collection and storage options for researchers and severely limiting the number of samples that can be processed in a short time. Here, we develop a freeze substitution Hi-C (FS-Hi-C) technique that overcomes the need for fresh samples.

Effects of music-based movement therapy on motor function, balance, gait, mental health, and quality of life for patients with Parkinson's disease: A systematic review and meta-analysis.

Objective: To conduct a systematic review evaluating the effects of music-based movement therapy on motor function, balance, gait, mental health, and quality of life among individuals with Parkinson's disease.

Data Sources: A systematic search of PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CINAHL, and Physiotherapy Evidence Database was carried out to identify eligible papers published up to December 10, 2020.

Review Methods: Literature selection, data extraction, and methodological quality assessment were independently performed by two investigators.

Associations between sleep duration, midday napping, depression, and falls among postmenopausal women in China: a population-based nationwide study.

Objective: To explore the independent and joint associations of sleep duration, midday napping, and depression with fall accidents in Chinese postmenopausal women.

Methods: A total of 2,378 postmenopausal women aged ≥ 45 years from the baseline survey of the China Health and Retirement Longitudinal Study were enrolled in the study. Each participant provided data on falls, sleep duration, midday napping by a self-reporting approach.

Interleukin-22 drives a metabolic adaptive reprogramming to maintain mitochondrial fitness and treat liver injury.

: Interleukin 22 (IL-22) is an epithelial survival cytokine that is at present being explored as therapeutic agents for acute and chronic liver injury. However, its molecular basis of protective activities remains poorly understood. : Here we demonstrate that IL-22 inhibits the deteriorating metabolic states induced by stimuli in hepatocytes.

Interleukin-22 ameliorated acetaminophen-induced kidney injury by inhibiting mitochondrial dysfunction and inflammatory responses.

Acetaminophen (APAP) overdose can lead to acute, severe kidney injury, which has recently attracted considerable attention among researchers and clinicians. Unfortunately, there are no well-established treatments for APAP-induced renal injury, and the molecular mechanism of APAP-induced kidney injury is still unclear. Herein, we explored the protective effects of interleukin (IL)-22 on APAP-induced renal injury and the underlying molecular basis.

Blocking CD47 efficiently potentiated therapeutic effects of anti-angiogenic therapy in non-small cell lung cancer.

Background: Inhibitors targeting VEGF and VEGFR are commonly used in the clinic, but only a subset of patients could benefit from these inhibitors and the efficacy was limited by multiple relapse mechanisms. In this work, we aimed to investigate the role of innate immune response in anti-angiogenic therapy and explore efficient therapeutic strategies to enhance efficacy of anti-angiogenic therapy against non-small cell lung cancer (NSCLC).

Methods: Three NSCLC tumor models with responses to VEGF inhibitors were designed to determine innate immune-related underpinnings of resistance to anti-angiogenic therapy.

GSDMD membrane pore is critical for IL-1β release and antagonizing IL-1β by hepatocyte-specific nanobiologics is a promising therapeutics for murine alcoholic steatohepatitis.

Excessive release of interleukin-1β (IL-1β) is well-known to provoke cascades of inflammatory responses thus contributing to the pathogenesis of alcohol-induced steatohepatitis (ASH), but the cellular mechanism that regulates IL-1β release during ASH remains unclear. Herein, we identified that gasdermin D (GSDMD) membrane pore is critical in mediating IL-1β hypersecretion from chronic ethanol or acetaldehyde-stimulated macrophages. Deletion of GSDMD reduced IL-1β release and ameliorated alcoholic steatohepatitis in vivo.

Interleukin-22 Attenuated Renal Tubular Injury in Aristolochic Acid Nephropathy via Suppressing Activation of NLRP3 Inflammasome.

Aristolochic acid nephropathy (AAN), as a rapidly progressive interstitial nephropathy due to excessive ingestion of aristolochia herbal medications, has recently raised considerable concerns among clinicians and researchers as its underlying pathogenic mechanisms are largely unclear. In the current study, we identified NLRP3 inflammasome activation as a novel pathological mechanism of AAN. We found that NLRP3 inflammasome was aberrantly activated both and after AA exposure.

Targeting PARP and autophagy evoked synergistic lethality in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), one of the most lethal malignancies worldwide, has limited efficient therapeutic options. Here, we first demonstrated that simultaneously targeting poly (ADP-ribose) polymerase (PARP) and autophagy could evoke striking synergistic lethality in HCC cells. Specifically, we found that the PARP inhibitor Niraparib induced cytotoxicity accompanied by significant autophagy formation and autophagic flux in HCC cells.

The Association between Toxoplasma gondii Infection and Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis.

Background: Several studies have investigated the association between Toxoplasma gondii (T. gondii) infection and risk of Parkinson's disease (PD) with inconsistent results. Clarifying this relation might be useful for better understanding of the risk factors and the relevant mechanisms of PD, thus a meta-analysis was conducted to explore whether exposure to T.

Targeted Interleukin-22 Gene Delivery in the Liver by Polymetformin and Penetratin-Based Hybrid Nanoparticles to Treat Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is now a leading cause of chronic liver disease, and there is currently no available treatment strategy. Interleukin-22 (IL-22) has been recognized as a promising agent for alleviating NAFLD, but the efficacy of IL-22 is far from satisfactory because safe dose of IL-22 elicited limited improvement, whereas higher concentration might induce serious side effects and off-target toxicities. Thus, targeted and sustained expression of IL-22 in the liver is necessary.

Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017).

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011.

Kidney protection effects of dihydroquercetin on diabetic nephropathy through suppressing ROS and NLRP3 inflammasome.

Background: Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is acknowledged as an independent risk factor for cardiovascular disease, which underlines the urgent need for new medications to DN. Dihydroquercetin (DHQ), an important natural dihydroflavone, exerts significant antioxidant, anti-inflammatory, and antifibrotic properties, but its effects on DN have not been investigated yet.

Purpose: We aimed to explore the kidney protection effects of DHQ on DN rats induced by high-fat diet/streptozotocin in vivo and the underlying mechanisms of DHQ on renal cells including HBZY-1 and HK2 exposed to high glucose in vitro.

Targeting the MYCN-PARP-DNA Damage Response Pathway in Neuroendocrine Prostate Cancer.

We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphologic criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for neuroendocrine prostate cancer (NEPC). Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public data sets and a panel of 28 PDX models, we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro. ChIP-PCR assay revealed that N-MYC transcriptionally activates PARP1, PARP2, BRCA1, RMI2, and TOPBP1 through binding to the promoters of these genes.

Interleukin-22 ameliorated renal injury and fibrosis in diabetic nephropathy through inhibition of NLRP3 inflammasome activation.

Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with metabolic disorders and chronic inflammation. Although the cytokine IL-22 was initially implicated in the pathogenesis of chronic inflammatory diseases, recent studies suggested that IL-22 could suppress inflammatory responses and alleviate tissue injury. Herein, we examined the role of IL-22 in DN.