Quantifying constraint in the human mitochondrial genome.

Mitochondrial DNA (mtDNA) has an important yet often overlooked role in health and disease. Constraint models quantify the removal of deleterious variation from the population by selection and represent powerful tools for identifying genetic variation that underlies human phenotypes. However, nuclear constraint models are not applicable to mtDNA, owing to its distinct features.

Potential mechanisms underlying podophyllotoxin-induced cardiotoxicity in male rats: toxicological evidence chain (TEC) concept.

Introduction: Podophyllotoxin (PPT) is a high-content and high-activity compound extracted from the traditional Chinese medicinal plant () which exhibits various biological activities. However, its severe toxicity limits its use. In clinical settings, patients with poisoning often experience adverse reactions when taking large doses in a short period.

Saturation mutagenesis-reinforced functional assays for disease-related genes.

Interpretation of disease-causing genetic variants remains a challenge in human genetics. Current costs and complexity of deep mutational scanning methods are obstacles for achieving genome-wide resolution of variants in disease-related genes. Our framework, saturation mutagenesis-reinforced functional assays (SMuRF), offers simple and cost-effective saturation mutagenesis paired with streamlined functional assays to enhance the interpretation of unresolved variants.

Efficient selective adsorption of Cr(VI) by S-doped porous carbon prepared from industrial lignin: Waste increment and wastewater treatment.

Industrial lignin is a waste product of the paper industry, which contains a large amount of oxygen group structure, and can be used to treat industrial wastewater containing Cr(VI). However, lignin has very low reactivity, so how to enhance its adsorption performance is a major challenge at present. In this study, a two-stage hydrothermal and activation strategy was used to activate the lignin activity and doping S element to prepare high-performance S-doped lignin-based polyporous carbon (S-LPC).

High-throughput assays to assess variant effects on disease.

Interpreting the wealth of rare genetic variants discovered in population-scale sequencing efforts and deciphering their associations with human health and disease present a critical challenge due to the lack of sufficient clinical case reports. One promising avenue to overcome this problem is deep mutational scanning (DMS), a method of introducing and evaluating large-scale genetic variants in model cell lines. DMS allows unbiased investigation of variants, including those that are not found in clinical reports, thus improving rare disease diagnostics.

Lama1 upregulation prolongs the lifespan of the dy/dy mouse model of LAMA2-related congenital muscular dystrophy.

LAMA2-related congenital muscular dystrophy (LAMA2-CMD), characterized by laminin-α2 deficiency, is debilitating and ultimately fatal. To date, no effective therapy has been clinically available. Laminin-α1, which shares significant similarities with laminin-α2, has been proven as a viable compensatory modifier.

Two-stage hydrothermal oxygenation for efficient removal of Cr(VI) by starch-based polyporous carbon: Wastewater application and removal mechanism.

Cr(VI) is of concern because of its high mobility and toxicity. In this work, a two-stage hydrothermal strategy was used to activate the O sites of starch, and by inserting K-ion into the pores, starch-based polyporous carbon (S-PC) adsorption sites was synthesized for removal of Cr(VI). Physicochemical characterization revealed that the O content of the S-PC reached 20.

CLMP is a tumor suppressor that determines all-trans retinoic acid response in colorectal cancer.

CAR-like membrane protein (CLMP) is a tight junction-associated protein whose mutation is associated with congenital short bowel syndrome (CSBS), but its functions in colorectal cancer (CRC) remain unknown. Here, we demonstrate that CLMP is rarely mutated but significantly decreased in CRC patients, and its deficiency accelerates CRC tumorigenesis, growth, and resistance to all-trans retinoic acid (ATRA). Mechanistically, CLMP recruits β-catenin to cell membrane, independent of cadherin proteins.

Deep Mutational Scanning in Disease-related Genes with Saturation Mutagenesis-Reinforced Functional Assays (SMuRF).

Interpretation of disease-causing genetic variants remains a challenge in human genetics. Current costs and complexity of deep mutational scanning methods hamper crowd-sourcing approaches toward genome-wide resolution of variants in disease-related genes. Our framework, Saturation Mutagenesis-Reinforced Functional assays (SMuRF), addresses these issues by offering simple and cost-effective saturation mutagenesis, as well as streamlining functional assays to enhance the interpretation of unresolved variants.

The effects of physiotherapeutic scoliosis-specific exercise on idiopathic scoliosis in children and adolescents: a systematic review and meta-analysis.

Background: Physiotherapeutic scoliosis-specific exercise (PSSE) is recommended by SOSORT as the first step in the treatment of adolescent idiopathic scoliosis (AIS). However, a thorough summary and meta-analysis of the evidence for the effectiveness of PSSE is lacking.

Objective: To summarise the up-to-date evidence on the efficacy of PSSE in AIS compared with the other non-surgical therapies.

Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy.

We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) with recombinant adeno-associated virus (rAAV) serotype 9 containing dCas9 (i.e., "dead" Cas9, in which the Cas9 nuclease activity has been inactivated) fused to VP64; this transgene was designed to up-regulate cortical dystrophin as a custom CRISPR-transactivator therapy.

Enhancement of Cr(VI) adsorption on lignin-based carbon materials by a two-step hydrothermal strategy: Performance and mechanism.

Cr(VI) is a carcinogenic heavy metal that forms an oxygen-containing anion, which is difficult to remove from water by adsorbents. Here, industrial alkali lignin was transformed into a Cr(VI) adsorbent (N-LC) by using a two-step hydrothermal strategy. The characterization results of the adsorbent showed that O and N were uniformly distributed on the surface of the adsorbent, resulting in a favorable morphology and structure.

Trinuclear Fe Clusters for Highly Efficient CO Photoreduction.

Photocatalytic reduction of CO into valuable chemicals or fuels is considered a promising solution to mitigate the energy crisis. In this work, efficient CO to CO conversion was achieved, accompanied by a class of trinuclear Fe clusters as photocatalysts. Under optimal conditions, the highest catalytic rate could be up to 140.

Study on the Process Characteristics Based on Joule Heat of Sliding-Pressure Additive Manufacturing.

This study developed an experimental system based on Joule heat of sliding-pressure additive manufacturing (SP-JHAM), and Joule heat was used for the first time to accomplish high-quality single-layer printing. The roller wire substrate is short-circuited, and Joule heat is generated to melt the wire when the current passes through. Through the self-lapping experimental platform, single-factor experiments were designed to study the effects of power supply current, electrode pressure, contact length on the surface morphology and cross-section geometric characteristics of the single-pass printing layer.

Preschool Children's Physical Activity and Community Environment: A Cross-Sectional Study of Two Cities in China.

Research on the relationship between preschool children's physical activity (PA) and community environment is limited and inconclusive, yet understanding this relationship is important to acquire sufficient information to guide the development of intervention programs. This study aims to objectively measure preschool children's PA and examine associations between PA and the community environments. A total of 471 preschool children aged 3-6 years old were recruited from eight kindergartens in Beijing and Zhengzhou.

Nuclease-Deficient Clustered Regularly Interspaced Short Palindromic Repeat-Based Approaches for and Gene Activation.

Clustered regularly interspaced short palindromic repeat (CRISPR)-based technology has been adapted to achieve a wide range of genome modifications, including transcription regulation. The focus of this review is on the application of CRISPR-based platforms such as nuclease-deficient Cas9 and Cas12a, to achieve targeted gene activation. We review studies to date that have used CRISPR-based activation technology for the elucidation of biological mechanism and disease correction, as well as its application in genetic screens as a powerful tool for high-throughput genotype-phenotype mapping.

Barley C-Hordein as the Calibrant for Wheat Gluten Quantification.

The lack of certified reference materials has been one major challenge for gluten quantification in gluten-free products. In this study, the feasibility of using barley C-hordein as the calibrant for wheat gluten in R5 sandwich enzyme-linked immunosorbent assay (ELISA) was investigated. The gluten composition and total gluten R5 reactivity ranged largely depending on the genotypes and the growing environment.

Study on the mechanisms of "Xiaoerhuashi Pill, XP" in intervening the health status of high-calorie diet animals.

Ethnopharmacological Relevance: "Xiaoerhuashi Pill, XP", with a history of 30 years in China, was included in the first part of the 2015 edition of the Chinese Pharmacopoeia and is widely used in the treatment for pediatric diseases in clinical application. Its main indications include the accumulation of heat caused by food stagnation in children, which has the effect of digestive stagnation and purge heat to relax the bowels.

Aim Of The Study: High-calorie diet, closely related to the occurrence and development of multiple diseases, is an unhealthy status of life.

Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.

Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries.

Preparing the key metabolite of Z-ligustilide in vivo by a specific electrochemical reaction.

The key in vivo metabolites of a drug play an important role in its efficacy and toxicity. However, due to the low content and instability of these metabolites, they are hard to obtain through in vivo methods. Electrochemical reactions can be an efficient alternative to biotransformation in vivo for the preparation of metabolites.