Dwarf Open Reading Frame (DWORF) Gene Therapy Ameliorated Duchenne Muscular Dystrophy Cardiomyopathy in Aged mdx Mice.

Background Cardiomyopathy is a leading health threat in Duchenne muscular dystrophy (DMD). Cytosolic calcium upregulation is implicated in DMD cardiomyopathy. Calcium is primarily removed from the cytosol by the sarcoendoplasmic reticulum calcium ATPase (SERCA).

Microdystrophin Expression as a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials.

Duchenne muscular dystrophy (DMD) is a serious, rare genetic disease, affecting primarily boys. It is caused by mutations in the gene and is characterized by progressive muscle degeneration that results in loss of function and early death due to respiratory and/or cardiac failure. Although limited treatment options are available, some for only small subsets of the patient population, DMD remains a disease with large unmet medical needs.

Single Posterior Surgery Versus Combined Posterior-Anterior Surgery for Lumbar Tuberculosis Patients.

Objective: Posterior approach of debridement, interbody graft, and instrumentation, and combined posterior-anterior approach of posterior instrumentation and anterior debridement and interbody graft are two essential surgeries for the surgical treatment of spinal tuberculosis (TB), and, until now, which one should be chosen is still controversial. This study aimed to compare the therapeutic efficacy between the single posterior surgery and combined posterior-anterior surgery for lumbar tuberculosis (LTB) patients to elucidate the role of debridement and the effects that result from posterior structure resection.

Methods: One hundred and nineteen LTB patients managed with single posterior debridement, interbody graft, and instrumentation surgery (Group P, 73 cases), or combined posterior-anterior surgery of posterior instrumentation and anterior debridement and interbody graft (Group P-A, 46 cases) from January 2008 to December 2016 were retrospectively analyzed.

Lymphoid enhancer binding factor 1 is associated with nose color in Yunong black pigs.

Yunong black pig is an indigenous black pig breed being cultivated that has a pure black whole body. However, some individuals appear with a white spot on the nose. We performed case-control association studies and F approaches in 76 animals with nose color records (26 white-nosed pigs vs.

Organelle-Specific Mechanisms in Crosstalk between Apoptosis and Ferroptosis.

Apoptosis has been extensively studied, whereas ferroptosis is a newly discovered form of regulated cell death that involves iron-dependent accumulations of lipid hydroperoxides. While these two cell death mechanisms were initially believed to be mutually exclusive, recent studies have revealed cellular contexts requiring a balanced interaction between them. Numerous subcellular sites and signaling molecules within these sites are involved in both processes, either as modules or switches that allow cells to choose on how to proceed.

An integrative investigation of developmental toxicities induced by triphenyltin in a larval coral reef fish, Amphiprion ocellaris.

Triphenyltin (TPT) is widely distributed on coastlines, which makes coral reef fish a potential target of TPT pollution. However, the negative effects of TPT on coral reef fish remain poorly understood. Therefore, in the present study, the larval coral reef fish Amphiprion ocellaris was used to investigate the developmental toxicities of TPT at environmentally relevant concentrations (0, 1, 10 and 100 ng/L).

Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)-microdystrophin (μDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 10 vector genomes per kilogram (vg/kg), 1 × 10 vg/kg, and 2 × 10 vg/kg; = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing.

Proteomic analysis of radioiodine-refractory differentiated thyroid cancer identifies CHI3L1 upregulation in association with dysfunction of the sodium-iodine symporter.

Radioiodine refractory differentiated thyroid cancer (RR-DTC) is the main factor adversely affecting the overall survival rate of patients with thyroid cancer. The aim of the present study was to investigate the underlying molecular mechanism of pathogenesis of RR-DTC and to explore novel therapeutic targets for clinical treatment. A proteomic analysis was performed using the tumor tissues of patients with RR-DTC.

Comparative safety of multiple doses of erythropoietin for the treatment of traumatic brain injury: A systematic review and network meta-analysis.

Introduction: Over the past few decades, advances in traumatic brain injury (TBI) pathology research have dynamically enriched our knowledge. Therefore, we aimed to systematically elucidate the safety and efficacy of erythropoietin (EPO) dosing regimens in patients with TBI.

Methods: Data search included PubMed, the Cochrane Library, Embase, Web of Science, and ClinicalTrials.

Cellular and Intravital Imaging of NAD(P)H by a Red-Emitting Quinolinium-Based Fluorescent Probe that Features a Shift of Its Product from Mitochondria to the Nucleus.

NAD(P)H is a vital hydrogen donor and electron carrier involved in numerous biological processes. The development of small-molecule tools for intravital imaging of NAD(P)H is significant for further exploring their pathophysiological roles. Herein, we rationally designed a fluorescent probe NADH-R by a simple graft of pyridiniumylbutenenitrile on a 1-methylquinolinium moiety in the 3-position.

High-performance atomic Co/N co-doped porous carbon catalysts derived from Co-doped metal-organic frameworks for oxygen reduction.

Improving the activity and durability of carbon-based catalysts is a key challenge for their application in fuel cells. Herein, we report a highly active and durable Co/N co-doped carbon (CoNC) catalyst prepared via pyrolysis of Co-doped zeolitic-imidazolate framework-8 (ZIF-8), which was synthesized by controlling the feeding sequence to enable Co to replace Zn in the metal-organic framework (MOF). The catalyst exhibited excellent oxygen reduction reaction (ORR) performance, while the half-wave potential decreased by only 8 mV after 5,000 accelerated stress test (AST) cycles in an acidic solution.

Ternary superconducting hydrides stabilized via Th and Ce elements at mild pressures.

The discovery of covalent HS and clathrate structure LaH with excellent superconducting critical temperatures at high pressures has facilitated a multitude of research on compressed hydrides. However, their superconducting pressures are too high (generally above 150 GPa), thereby hindering their application. In addition, making room-temperature superconductivity close to ambient pressure in hydrogen-based superconductors is challenging.

Highly efficient overall urea electrolysis via single-atomically active centers on layered double hydroxide.

Anodic urea oxidation reaction (UOR) is an intriguing half reaction that can replace oxygen evolution reaction (OER) and work together with hydrogen evolution reaction (HER) toward simultaneous hydrogen fuel generation and urea-rich wastewater purification; however, it remains a challenge to achieve overall urea electrolysis with high efficiency. Herein, we report a multifunctional electrocatalyst termed as Rh/NiV-LDH, through integration of nickel-vanadium layered double hydroxide (LDH) with rhodium single-atom catalyst (SAC), to achieve this goal. The electrocatalyst delivers high HER mass activity of 0.

pH dependence of arsenic speciation in paddy soils: The role of distinct methanotrophs.

Arsenic (As) is a priority environmental pollutant in paddy field. The coupling of arsenate (As(V)) reduction with anaerobic methane (CH) oxidation was recently demonstrated in paddy soils and has been suggested to serve as a critical driver for As transformation and mobilization. However, whether As(V)-dependent CH oxidation is driven by distinct methanotrophs under different pH conditions remains unclear.

Fabrication of the high-precision micro-structure array using a phase shift modulation of superimposed oscillation in ultra-precision grinding.

Various micro-structure surface texturing methods have been used to produce optical functional surface in the grinding, such as the textured grinding wheel, wheel path control and off-spindle-axis grinding. However, those grinding technologies are inherently challenged to employ in large-scale surface grinding due to the extremely high requirement for wheel cutting profile dressing. In this study, a novel phase shift modulation based on wheel oscillation motion was proposed to generate the micro-structure array in ultra-precision grinding.

Lifelong Outcomes of Systemic Adeno-Associated Virus Micro-Dystrophin Gene Therapy in a Murine Duchenne Muscular Dystrophy Model.

Adeno-associated virus (AAV)-mediated systemic micro-dystrophin (μDys) therapy is currently in clinical trials. The hope is to permanently improve the life quality of Duchenne muscular dystrophy (DMD) patients. Numerous preclinical studies have been conducted to support these trials.

TLR7 agonist RO7020531 versus placebo in healthy volunteers and patients with chronic hepatitis B virus infection: a randomised, observer-blind, placebo-controlled, phase 1 trial.

Background: Toll-like receptor 7 (TLR7) agonists augment immune activity and have potential for the treatment of chronic hepatitis B virus (HBV) infection. We aimed to assess the safety and tolerability of RO7020531 (also called RG7854), a prodrug of the TLR7 agonist RO7011785, in healthy volunteers and patients with chronic HBV infection.

Methods: This randomised, observer-blind, placebo-controlled, phase 1 study was done in two parts.

Deciphering the active constituents of Dabushen decoction of ameliorating osteoarthritis PPARγ preservation by targeting DNMT1.

Osteoarthritis (OA) is a multifactorial and chronic degenerative joint disease. Due to the adverse effects of currently used drugs, a safer and more effective therapy for treating OA is needed. Peroxisome proliferator-activated receptor-γ (PPARγ) is a key protein protecting cartilage.

Identifying an Interfacial Stabilizer for Regeneration-Free 300 h Electrochemical CO Reduction to C Products.

The electrochemical CO reduction reaction (CORR) to produce high value-added hydrocarbons and oxygenates presents a sustainable and compelling approach toward a carbon-neutral society. However, uncontrollable migration of active sites during the electrochemical CORR limits its catalytic ability to simultaneously achieve high C selectivity and ultradurability. Here, we demonstrate that the generated interfacial CuAlO species can efficiently stabilize the highly active sites over the Cu-CuAlO-AlO catalyst under harsh electrochemical conditions without active sites regeneration for a long-term test.

Non-communicable Disease-Related Sustainable Development Goals for 66 Belt and Road Initiative Countries.

Background: Since 2015, the Global Burden of Disease Study (GBD) has measured progress in achieving health-related Sustainable Development Goals (SDGs) annually worldwide. Little is known about the status and attainment of indicators of non-communicable diseases (NCDs) by 65 countries from the Belt and Road Initiative (BRI) proposed by China in 2013.

Methods: Data from GBDs were used to estimate 24 NCD-related SDG indicators in BRI countries from 1990 to 2017.

Assessment of the Gene Therapy Immune Response in the Canine Muscular Dystrophy Model.

The immune response is a primary hurdle in the development of gene therapy for neuromuscular diseases. Both innate and adaptive immune responses have been observed in human trials. The canine model is an excellent platform to understand immunological consequences of gene therapy.

MRI Evaluation of Gene Therapy in the Canine Model of Duchenne Muscular Dystrophy.

Magnetic resonance imaging (MRI) is a well-established and widely used technique to characterize and quantify skeletal and cardiac muscle changes in Duchenne muscular dystrophy (DMD). Recently, MRI has been explored to study disease progression and response to gene therapy in the canine DMD model. Using traditional sequences, delayed gadolinium enhancement, novel sequences, and spectroscopy, investigators have begun to (i) establish the baseline MRI characteristics of the muscles in normal and affected dogs and (ii) evaluate gene therapy outcomes in treated dogs.

Histological Assessment of Gene Therapy in the Canine DMD Model.

Assessing histological changes is essential for characterizing muscle disease progression and for studying the response to therapies in Duchenne muscular dystrophy (DMD), an X-linked progressive muscle-wasting disease caused by the loss of the dystrophin protein. Canine models are by far the best-characterized large animal models for DMD. In this chapter, we describe methods for muscle tissue collection and storage, hematoxylin and eosin staining for studying general muscle morphology, and special staining protocols for evaluating fibrosis, calcification, and neuronal nitric oxide synthase (nNOS) activity.

Molecular and Biochemical Assessment of Gene Therapy in the Canine Model of Duchenne Muscular Dystrophy.

Mutations in the dystrophin gene result in Duchenne muscular dystrophy (DMD), a progressive muscle-wasting disease. Adeno-associated virus (AAV) mediated gene replacement, and CRISPR/Cas9-mediated genome editing hold the potential to treat DMD. Molecular and biochemical analyses are essential to determine gene transfer efficiency and therapeutic efficacy.