A Compact Base Editor Rescues AATD-associated Liver and Lung Disease in Mouse Models.

Alpha-1 antitrypsin deficiency (AATD) is commonly caused by a G-to-A mutation in the SERPINA1 gene (the PiZ mutation). The mutant PiZ AAT protein is sequestered in hepatocytes, causing lung emphysema due to insufficient AAT protein to inhibit neutrophil elastase in the lung. Here, we show that a compact adenine base editor (ABE) with an evolved Cas9 nickase derived from Neisseria meningitidis (eNme2.

An acoustic-optic confocal probe based photoacoustic and ultrasonic tracheal endoscopy for characterizing phantom and model of chronic obstructive pulmonary disease.

Integrated photoacoustic endoscopy and endoscopic ultrasound (PAE/EUS) are recognized as an effective method for detecting intestinal and intravascular diseases. Changes in the morphology and composition of the trachea are significant hallmarks of respiratory diseases. In this study, an acoustic-optic confocal probe was developed and integrated at the tip of a 2.

TCF25 serves as a nutrient sensor to orchestrate metabolic adaptation and cell death by enhancing lysosomal acidification under glucose starvation.

Cells adapt to nutrient limitation by activating catabolic and inhibiting anabolic pathways, yet prolonged stress may lead to cell death. How cells orchestrate metabolic adaptation and cell death to nutrient stress is poorly understood. We conduct a genome-wide CRISPR-Cas9 screen to identify regulators in glucose-starvation-induced cell death and find a group of genes in lysosomal pathway is enriched following glucose starvation.

High Oxidation State V-O-Co Structure Promotes the Role of V-O Intermediates in Efficient HMF Oxidation.

Designing heterometallic oxygen-bridge structure (M1-O-M2) to achieve the efficient and stable electrochemical conversion of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) has become an important approach to address the rapid consumption of fossil fuels and mitigate white pollution. However, designing effective M1-O-M2 structures and elucidating their catalytic mechanisms remains a key challenge in this field. In this study, a high oxidation state V-O-Co structure is constructed by doping V into reconstructed CoOOH, which promotes the formation of the active intermediate V-O.

ZIF-8-loaded decellularized porcine annulus fibrosus bioadhesive enhances rotator cuff tendon-to-bone healing in a rat model.

Introduction: The high rate of retear following rotator cuff repair is largely attributed to the absence of a fibrocartilage layer and limited bone regeneration capacity. We aim to evaluate a bioadhesive derived from decellularized porcine annulus fibrosus extracellular matrix, loaded with zeolitic imidazolate framework-8 (ZIF-8), and to promote rotator cuff tendon-bone healing.

Methods: Three adhesive formulations were developed: (1) silk fibroin/tannic acid (ST group), (2) ST combined with decellularized porcine annulus fibrosus extracellular matrix (ST/dECM group), and (3) ST/dECM supplemented with ZIF-8 (ST/dECM/ZIF-8 group).

Host deficiency aggravates acetaldehyde metabolism disturbance and gut microbiota dysbiosis in chronic alcohol exposure mice.

Alcohol is inextricably linked with intestinal microbiota as it was absorbed through gut. While mitochondrial aldehyde dehydrogenase 2 (ALDH2), as the major enzyme responsible for metabolizing toxic acetaldehyde to acetate, is important factor influencing alcohol metabolism. However, it is not yet known the relationship between knockout (KO) and gut microbiota profiles in mice under chronic alcohol exposure.

Genetic and neurobiological mechanisms underlying transition in self-injury thoughts and behaviours during adolescence.

Background: Adolescence is a pivotal stage for brain development and a critical window for the emergence and transition of self-injury thoughts and behaviours (SITBs). However, the genetic and neurobiological mechanisms underlying SITBs transition during this developmental period are poorly understood.

Aims: This study investigates associations among genetic predispositions, brain abnormalities and SITBs transition during adolescence, and identifies potential neurobiological and clinical mediators of genetic effects.

KRAS withdrawal in Cholangiocarcinoma leads to immune infiltration and tumor regression.

Background And Aims: Cholangiocarcinoma (CCA) is a liver cancer with poor survival rates. Current treatments, including targeted therapies for specific mutations, are limited and benefit only a small subset of patients. mutations are found in 15-40% of CCA, representing a new potential treatment target.

Prime assembly with linear DNA donors enables large genomic insertions.

Targeted insertion of large DNA fragments has promising applications for genome engineering and gene therapy. Twin prime editing (PE) guide RNAs (pegRNAs) have enabled relatively large insertions, but the efficiency remains low for insertions greater than 400 base pairs. Here we describe a Prime Assembly (PA) approach for the insertion of large DNA donor fragments, whose ends are designed to overlap with the flaps generated by twinPE.

Porous Decellularized Nerve Grafts Facilitate Recellularization and Nerve Regeneration in a Rat Model of Critical Long-Gap Peripheral Nerve Injury.

Severe peripheral nerve injury (PNI) requiring nerve graft remains a clinical challenge due to limitations associated with currently available grafts. While decellularized nerve grafts (DNGs) are commonly used, their efficacy is largely restricted to short-gap repairs due to their acellular and dense structure, which poses a persistent challenge in the treatment of critical long-gap nerve defects. It is hypothesized that making porous DNGs (PDNGs) can create a suitable microenvironment that would facilitate the cell infiltration, recellularization, and further axonal growth to enhance nerve regeneration.

A Compact Base Editor Rescues AATD-associated Liver and Lung Disease in Mouse Models.

Alpha-1 antitrypsin deficiency (AATD) is commonly caused by a G-to-A mutation in the gene (the PiZ mutation). The mutant PiZ AAT protein is sequestered in hepatocytes, causing lung emphysema due to insufficient AAT protein to inhibit neutrophil elastase in the lung. Here we show that a compact adenine base editor (ABE) with an evolved Cas9 nickase derived from (eNme2.

First-principles calculations of the photocatalytic performance of ZnO-MX (M = Mo, W; X = S, Se) heterojunctions.

In this work, we systematically investigate the stability, electronic structure, optical properties, and photocatalytic performance of four ZnO-MX (M = Mo, W; X = S, Se) heterojunctions. The results indicate that all four heterojunctions exhibit excellent structural stability. In each system, an internal electric field is formed from the ZnO layer to the MX layer, facilitating the effective transfer of electrons.

Huotan Jiedu Tongluo Decoction targets Nrf2-mediated macrophage autophagy to inhibit ferroptosis and reduce atherosclerotic lesions.

Background: Atherosclerosis (AS) serves as a fundamental pathological basis for cardiovascular diseases (CVDs), with its progression intimately linked to ferroptosis-mediated disruptions in intracellular iron homeostasis and lipid peroxidation. Huotan Jiedu Tongluo Decoction (HTJDTLD), an effective compound formulafor treating AS based on traditional Chinese medicine (TCM) theory, has exhibited remarkable efficacy in stabilizing plaques and delaying disease progression. However, its underlying mechanism remains unclear.

Ultrasound-based radiomic nomogram for predicting the invasive status of breast cancer: a multicenter study.

Purpose: This study aimed to develop a nomogram combining clinical, sonographic, and radiomic features to discriminate invasive breast cancer (IBC) from noninvasive breast cancer (non-IBC), and to evaluate the prognostic potential of conventional ultrasound (CUS)-based radiomic signatures in predicting breast cancer invasiveness.

Methods: A total of 403 IBCs and 221 non-IBCs were retrospectively collected from multiple institutes. The cases were divided into three subsets based on their institutional origin: a training set (n = 353), an internal test set (n = 153), and an external test set (n = 118).

Machine learning model and hemoglobin to red cell distribution width ratio evaluates all-cause mortality in pulmonary embolism.

The ratio of hemoglobin (Hb) to red blood cell distribution width (RDW), known as HRR, functions as an innovative indicator related to prognosis. However, whether HRR can predict the mortality for pulmonary embolism (PE) patients remains ambiguous. A retrospective cohort study was conducted using the MIMIC IV database (3.

CRISPR-based Shuttle Cloning: A High-throughput Cloning Method.

The development of genome-wide plasmid libraries using existing genomic repositories serves as a pivotal prerequisite for systematic functional characterization of genes across diverse biological processes. Current high-throughput methodologies for inter-vector DNA fragment transfer, however, necessitate PCR amplification of target sequences prior to cloning, rendering the generation of genome-scale plasmid collections technically demanding and time-intensive. By leveraging a CRISPRshuttle cassette, we developed a new high-throughput cloning method, CRISPR-based shuttle cloning (CRISPRshuttle cloning), which facilitates the transfer of many DNA fragments from donor plasmids sharing identical backbone sequences to a CRISPRshuttle-compatible vector without PCR amplification of the DNA fragments.

Altered fecal microbial and metabolic profiles reveal potential mechanisms underlying anemia in patients with chronic renal failure.

The gut microbiomes communicate with the kidney and may play a crucial role in the development of anemia in patients with chronic renal failure (CRF). However, the alterations in microbiota and their association with functional metabolites remain unclear. We performed metagenomics and untargeted metabolomics in a cohort of 30 patients with anemia of CRF and 20 healthy controls (HCs) to identify the characteristics of the gut microbiome and explore its potential interactions with the host.

Pathophysiologically relevant bisphenol S exposure accelerates aging by disrupting brown adipose tissue-regulated energy metabolism.

Bisphenol A (BPA) substitutes are widely used as food contact materials and consumer products, while the effects of pathophysiologically relevant concentrations of BPA substitutes on aging remain unclear. In this study, we used () to investigate the effects of five BPA substitutes [bisphenol S (BPS), bisphenol B, bisphenol F (BPF), tetramethyl BPF, and 4,4'-(Perfluoropropane-2,2-diyl)diphenol] at pathophysiologically relevant exposure levels during aging and examined the underlying mechanisms using a mouse model. Our results indicated that, among the five BPA substitutes, exposure to pathophysiologically relevant concentrations of BPS (300, 450, and 600 nM) accelerated aging in .

Absolute quantification of mammalian microRNAs for therapeutic RNA cleavage and detargeting.

MicroRNAs (miRNAs) are small regulatory RNAs that destabilize partially complementary transcripts and cleave perfectly paired targets. miRNAs are often expressed in a specific tissue, allowing miRNA-directed cleavage to be used to prevent genome editing or gene replacement therapy in unintended cell types, a strategy called detargeting. miRNA intracellular concentration influences the potency of gene silencing, yet the absolute steady-state levels of just a few miRNAs have been determined in mammalian tissues.

Active compounds of licorice ameliorate microplastics-induced intestinal damage by targeting FADD.

Microplastics (MPs), as a novel type of environmental pollutant, have the potential to impact human health. This study aims to investigate the protective efficacy of active compounds in licorice on microplastics-injured rats and reveal the underlying mechanisms. The MPs-injured rat model was established by orally administrated with MPs.

[Huotan Jiedu Tongluo Decoction inhibits ferroptosis by regulating Nrf2/GPX4 pathway to ameliorate atherosclerotic lesions in ApoE~(-/-) mice].

The purpose of this study was to clarify the effect of Huotan Jiedu Tongluo Decoction on atherosclerosis(AS) injury in ApoE~(-/-) mice by regulating the ferroptosis pathway. Seventy-five ApoE~(-/-) mice were randomly divided into model group, low-, medium-, and high-dose of Huotan Jiedu Tongluo Decoction groups, and evolocumab group(n=15), and 15 C57BL/6J mice were selected as the blank group. Mice in the blank group were fed with a normal diet, and those in the other groups were fed with a high-fat diet to induce AS.

Delineating circulating lymphocyte subsets in the transition from gout remission to recurrence.

Objectives: Lymphocytes and their subsets are implicated in both the onset and remission of gout. However, the specific roles in gout recurrence and complete remission remain unclear. This study aimed to characterize lymphocyte immunophenotypes across different stages of gout and developed a predictive model for remission and recurrence of gout.

Telangiectatic osteosarcoma of the thoracic vertebra: a case report and literature review.

Telangiectatic osteosarcoma (TOS) is a rare high-grade malignant tumour found primarily in the metaphysis of long bones, but can also occur in the pelvis, spine and skull. Characterized by extensive vascular dilatation and aggressive behavior, TOS often has a poor prognosis and may be misdiagnosed due to similarities with other lesions. This report presents a case of TOS of the thoracic vertebrae and reviews the relevant literature to enhance clinical awareness.