Precise modelling of mitochondrial diseases using optimized mitoBEs.

The development of animal models is crucial for studying and treating mitochondrial diseases. Here we optimized adenine and cytosine deaminases to reduce off-target effects on the transcriptome and the mitochondrial genome, improving the accuracy and efficiency of our newly developed mitochondrial base editors (mitoBEs). Using these upgraded mitoBEs (version 2 (v2)), we targeted 70 mouse mitochondrial DNA mutations analogous to human pathogenic variants, establishing a foundation for mitochondrial disease mouse models.

Efficacy of radiotherapy in treating local recurrence concomitant with distant metastasis of nasopharyngeal carcinoma: a long-term retrospective multicenter study.

Purpose: Patients with nasopharyngeal carcinoma (NPC) experiencing locoregional recurrence concomitant with distant metastases (rmNPC) after initial treatment represent a unique subgroup with significant management challenges. This study aimed to evaluate overall survival (OS) in rmNPC patients treated with systemic therapies with or without radiotherapy.

Methods: This retrospective multicenter study included patients with locally recurrent and metastatic NPC from five hospitals.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Promoting in-situ stability of hydroxide exchange membranes by thermally conductive network for durable water electrolysis.

Hydroxide exchange membrane (HEM) water electrolysis is promising for green hydrogen production due to its low cost and excellent performance. However, HEM often has insufficient stability in strong alkaline solutions, particularly under in-situ electrolysis operation conditions, hindering its commercialization. In this study, we discover that the in-situ stability of HEM is primarily impaired by the locally accumulated heat in HEM due to its low thermal conductivity.

3D-printed sodium alginate/carbon nanotube/graphene porous scaffolds crosslinked with Ca for high-performance electromagnetic shielding and Joule heating.

High-performance green functional materials have garnered significant interest for electromagnetic interference (EMI) shielding applications, but creating customized, low-density, high-strength and high-efficiency biomass-based shielding materials remains challenging. In this study, lightweight Ca doped sodium alginate (SA) porous scaffolds with a carbon nanotube (CNT)/graphene (Gr) hybrid conductive network were fabricated via direct ink writing (DIW) 3D printing. The SA/CNT/Gr inks with unique rheological properties were formulated and architectures with arbitrarily customized structures could be freely constructed based on the printable inks.

Thermoresponsive dual-network chitosan-based hydrogels with demineralized bone matrix for controlled release of rhBMP9 in the treatment of femoral head osteonecrosis.

In an effort to mitigate or reverse the pathological progression of early-stage osteonecrosis of the femoral head (ONFH), this study employed a promising strategy that involves the sustained delivery of osteogenic factors to augment core decompression, facilitated by the use of composite hydrogels. Specifically, a hydrogel was synthesized by blending chitosan, Pluronic F-127, and tripolyphosphate, utilizing both ionic bonding and copolymer micelle cross-linking techniques. This hydrogel demonstrated exceptional biocompatibility, temperature responsiveness, pH-dependent biodegradation, and controlled release properties.

Gallic acid-grafted chitosan photothermal hydrogels functionalized with mineralized copper-sericin nanoparticles for MRSA-infected wound management.

The management of wounds infected with drug-resistant bacteria represents a significant challenge to public health globally. Nanotechnology-functionalized photothermal hydrogel with good thermal stability, biocompatibility and tissue adhesion exhibits great potential in treating these infected wounds. Herein, a novel photothermal hydrogel (mCS-Cu-Ser) was prepared through in situ mineralization in the hydrogel networks and ion cross-linking driven by copper ions (∼3 mM).

Engineered extracellular vesicles loaded in boronated cyclodextrin framework for pulmonary delivery.

Extracellular vesicles (EVs) are promising therapeutic carriers for their ideal nano-size and intrinsic biocompatibility, while rapid clearance and limited targeting ability are the major setbacks of EVs. With minimal absorption into the systemic circulation, inhalation for pulmonary disease therapy minimizes off-target toxicity to other organs and offers a safe and effective treatment for respiratory disorders. Herein, a nano-grid carrier made of boronated cyclodextrin framework (BCF) was prepared for pH/HO responsive release of EVs.

Higher serum Metrnl levels are associated with increased vascular calcification in hemodialysis patients.

Background: Meteorin-like (Metrnl) is a newly identified secreted protein that plays important roles in metabolic and inflammation-related diseases. Our study aimed to evaluate serum Metrnl levels and establish their relationship with vascular calcification (VC) in hemodialysis (HD) patients.

Methods: In total, 313 HD patients and 41 healthy individuals, as controls, were included.

Emotional Influences on Remembering and Forgetting Explained by Frontal and Parietal Dynamics.

Based on item-method directed forgetting (DF) task, sixty participants were recruited to explore the influence of emotion (negative, neutral, and positive) on memory encoding processing. Behavioral results showed that participants were more successful at remembering negative pictures that needed to be forgotten, with both higher recognition rates and Pr values compared to neutral pictures. In the brain, parietal activities reflected preferential processing during negative picture viewing through enhanced late parietal positive potentials (LPP) relative to neutral ones.

M2 macrophages regulate nucleus pulposus cell extracellular matrix synthesis through the OPN-CD44 axis in intervertebral disc degeneration.

Objective: Macrophages play a crucial role in various physiological processes. In intervertebral disc degeneration (IDD), macrophage infiltration has been observed in human intervertebral disc (IVD) specimens, but how macrophages influence IDD remains unclear.

Methods: According to the single-cell transcriptome expression profiles from GSE165722, we verified the infiltration of macrophages in IDD and the possible interaction between infiltrated macrophages and nucleus pulposus cells (NPCs).

Comparative study on the anti-alcoholic liver disease efficiency of the ethanol- and water-soluble polysaccharides from Baijiu vinasses.

Ethanol- and water-soluble polysaccharides were extracted from Baijiu vinasses (EP and WP), respectively. EP was dominantly composed by arabinose, glucose and xylose with molar ratio of 8.81: 76.

MCTASmRNA: A deep learning framework for alternative splicing events classification.

Alternative splicing (AS) plays crucial post-transcriptional gene function regulation roles in eukaryotic. Despite progress in studying AS at the RNA level, existing methods for AS event identification face challenges such as inefficiency, lengthy processing times, and limitations in capturing the complexity of RNA sequences. To overcome these challenges, we evaluated 10 AS detection tools and selected rMATS for dataset construction.

LCAT deficiency promotes hepatocellular carcinoma progression and lenvatinib resistance by promoting triglyceride catabolism and fatty acid oxidation.

Lecithin cholesterol acyltransferase (LCAT), a crucial enzyme in lipid metabolism, plays important yet poorly understood roles in tumours, especially in hepatocellular carcinoma (HCC). In this study, our investigation revealed that LCAT is a key downregulated metabolic gene and an independent risk factor for poor prognosis in patients with HCC. Functional experiments showed that LCAT inhibited HCC cell proliferation, migration and invasion.

Ultrasonic cavitation treatment of o-cresol wastewater and long-term pilot-scale study.

Acoustic cavitation is a cutting-edge and eco-friendly advanced oxidation technology with significant efficacy in removing organic pollutants from water. Despite its potential, research on the degradation of o-cresol, a common and challenging phenolic pollutant, is limited. This study systematically investigates the optimal conditions for degrading o-cresol via acoustic cavitation and evaluates its application potential through extensive pilot tests.

Prenatal PM exposure affects embryonic hematopoietic development through SOX2-regulated gene expression.

Fine particulate matter (PM) is one of the most concerning air pollutants, with emerging evidence indicating that it can negatively impact embryonic development and lead to adverse birth outcomes. Hematopoiesis is a critical process essential for the survival and normal development of the embryo, consisting of three temporally overlapping stages and involving multiple hematopoietic loci, including the yolk sac and fetal liver. Therefore, we hypothesized that abnormal embryonic hematopoietic development can significantly influence developmental outcomes.

Modulating the Oxygen Evolution Reaction of Single-Crystal Cobalt Carbonate Hydroxide via Surface Fe Doping and Facet Dependence.

The oxygen evolution reaction (OER) is a critical half-reaction in water splitting and metal-air cells. The sensitivity of the OER to the composition and structure of the electrocatalyst presents a significant challenge in elucidating the structure-property relationship. In this study, highly stable single-crystal cobalt carbonate hydroxide [Co(OH)CO, CoCH] was used as a model to investigate the correlations among structure, composition, and reactivity.

Prenatal Diagnosis of Berry Syndrome by Fetal Echocardiography.

Berry syndrome is a rare combination of cardiac malformations, which is characterized by the following malformations, including the aortopulmonary window, aortic right pulmonary origin, interrupted aortic arch or hypoplastic aortic arch or coarctation of the aorta, and an intact ventricular septum. There are few reviews on prenatal diagnosis of Berry syndrome by fetal echocardiography. We used sequential cross-sectional scanning from apex to bottom of the heart to find aortic right pulmonary origin, aortopulmonary window, and hypoplastic aortic arch.

An AI-Digital Pathology Algorithm Predicts Survival after Radical Prostatectomy from the PLCO Trial.

Purpose: Clinical variables alone have limited ability to determine which patients will have recurrence after radical prostatectomy (RP). We evaluated the ability of locked multimodal artificial intelligence (MMAI) algorithms trained on prostate biopsy specimens to predict prostate cancer specific mortality (PCSM) and overall survival (OS) among patients undergoing radical prostatectomy with digitized RP specimens.

Materials And Methods: The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Randomized Controlled Trial randomized subjects from 1993-2001 to cancer screening or control.

Digital channel-enabled distributed force decoding via small datasets for hand-centric interactions.

Tactile interfaces are essential for enhancing human-machine interactions, yet achieving large-scale, precise distributed force sensing remains challenging due to signal coupling and inefficient data processing. Inspired by the spiral structure of and the processing principles of neuronal systems, this study presents a digital channel-enabled distributed force decoding strategy, resulting in a phygital tactile sensing system named PhyTac. This innovative system effectively prevents marker overlap and accurately identifies multipoint stimuli up to 368 regions from coupled signals.

Ten Machine Learning Models for Predicting Preoperative and Postoperative Coagulopathy in Patients With Trauma: Multicenter Cohort Study.

Background: Recent research has revealed the potential value of machine learning (ML) models in improving prognostic prediction for patients with trauma. ML can enhance predictions and identify which factors contribute the most to posttraumatic mortality. However, no studies have explored the risk factors, complications, and risk prediction of preoperative and postoperative traumatic coagulopathy (PPTIC) in patients with trauma.

Nebulized Tranexamic Acid in the Management of Hemoptysis: An Integrative Review.

Objective: This integrative review aims to evaluate the efficacy and safety of nebulized tranexamic acid (TXA) in managing hemoptysis, assessing its potential as a non-invasive alternative to traditional invasive procedures.

Methods: An integrative review was conducted in accordance with PRISMA guidelines and was registered on PROSPERO (CRD42024584812). The search included databases such as PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials, encompassing studies published up to August 7, 2024.

Conventional and genetic association between migraine and stroke with druggable genome-wide Mendelian randomization.

The genetic relationship between migraine and stroke remains underexplored, particularly in the context of druggable targets. Previous studies have been limited by small sample sizes and a lack of focus on genetic-targeted therapies for these conditions. We analyzed the association and causality between migraine and stroke using multivariable logistic regression in the UK Biobank cohort and Mendelian randomization (MR) analyses based on genome-wide association study (GWAS) data.

Targeting EPHB2/ABL1 restores antitumor immunity in preclinical models of ependymoma.

Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.