High-efficiency base editing in the retina in primates and human tissues.

Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.

Aqueous Proteomic and Metabolomic Profiles in Low-Energy vs High-Energy Femtosecond Laser-Assisted Cataract Surgery.

Purpose: To investigate the aqueous proteomics and metabolomics in low-energy and high-energy femtosecond laser-assisted cataract surgery (FLACS).

Methods: In this prospective observational study, 72 patients were randomized to 3 groups: low-energy FLACS, high-energy FLACS, and conventional phacoemulsification (controls). Aqueous was collected after femtosecond laser treatment or at the beginning of surgery (controls).

NPA7: A Dual Receptor Activating Peptide That Inhibits Cardiac Oxidative Stress.

Background: Cardiomyocyte oxidative stress significantly contributes to the progression of hypertension-induced heart failure, highlighting the need for targeted therapies. We developed a novel peptide, NPA7, that coactivates the GC-A (guanylyl cyclase A)/cGMP and MasR (Mas receptor)/cAMP pathway. This study aimed to test NPA7's ability to inhibit oxidative stress by modulating the p62-KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2-related factor 2) pathway in human cardiomyocytes (HCMs) and a rat model of hypertension.

Investigating the Impact of Glycogen-Depleting Exercise Combined with Prolonged Fasting on Autophagy and Cellular Health in Humans: A Randomised Controlled Crossover Trial.

Importance: Although prolonged fasting has become increasingly popular, the favourable biological adaptations and possible adverse effects in humans have yet to be fully elucidated.

Objective: To investigate the effects of a three-day water-only fasting, with or without exercise-induced glycogen depletion, on autophagy activation and the molecular pathways involved in cellular damage accumulation and repair in healthy humans.

Design: A randomised, single-centre, two-period, two-sequence crossover trial.

Corrigendum to: Investigation of the Expression and Regulation of SCG5 in the Context of the Chromogranin-Secretogranin Family in Malignant Tumors.

An error was found in the affiliations of the author in the article titled 'Investigation of the Expression and Regulation of SCG5 in the Context of the Chromogranin-Secretogranin Family in Malignant Tumors'', published in Protein and Peptide Letters, 2024, 31(9), 657-666 [1]. Details of the error and a correction are provided here. Original: *Address correspondence to these authors at the Department of Thoracic Surgery, The Sixth Affiliated Hospital of Nantong University, Yancheng Third People's Hospital, Yancheng 224000, P.

Performance and stability analysis of all-perovskite tandem photovoltaics in light-driven electrochemical water splitting.

All-perovskite tandem photovoltaics are a potentially cost-effective technology to power chemical fuel production, such as green hydrogen. However, their application is limited by deficits in open-circuit voltage and, more challengingly, poor operational stability of the photovoltaic cell. Here we report a laboratory-scale solar-assisted water-splitting system using an electrochemical flow cell and an all-perovskite tandem solar cell.

Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation.

Reversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives diverse diseases, kinases and phosphatases have been targets for drug discovery, with some achieving remarkable clinical success. Most protein kinases are activated by phosphorylation of their activation loops, which shifts the conformational equilibrium of the kinase toward the active state.

Pseudo-linkage or real-linkage of rust resistance genes in a wheat-Thinopyrum intermedium translocation line.

We analysed the chromosomal structures of two wheat-Thinopyrum intermedium addition lines Z4 and Z5 and resolved the linkage relationship between the leaf rust and stripe rust resistance genes in Z4. Wheat addition lines Z4 and Z5 carrying rust resistance genes from Thinopyrum intermedium (JJJJStSt, 2n = 6x = 42) together with three wheat lines involved in the production of these addition lines were analysed by rust response, 90K SNP genotyping, and molecular cytogenetic analysis. Seedling leaf rust (LR) responses to five diverse pathotypes indicated that the LR resistance gene(s) was located in translocation chromosome T3DS-3AS.

Mechanisms of Low Temperature Thickening of Different Materials for Deepwater Water-Based Drilling Fluids.

During deepwater drilling, the low mudline temperatures and narrow safe density window pose serious challenges to the safe and efficient performance of deepwater water-based drilling fluids. Low temperatures can lead to physical and chemical changes in the components of water-based drilling fluids and the behavior of low temperature gelation. As a coarse dispersion system, water-based drilling fluid has a complex composition of dispersed phase and dispersing medium.

A Systematic Method to Detect Next-Generation Sequencing-Based Microsatellite Instability in Plasma Cell-Free DNA: plasmaMSI.

Microsatellite instability (MSI) detection using tumor tissue is a well-established prognostic and predictive biomarker for certain types of cancers. However, tumor tissue samples are less convenient to obtain than blood plasma samples. The main challenge facing next-generation sequencing-based MSI detection in blood plasma samples is the ultralow signal/noise ratio in plasma cell-free DNA (cfDNA).

Long-term Comparative Outcomes of All-Inside Versus Inside-Out Repair of Bucket-Handle Meniscal Tears: A Cohort Study.

Background: Bucket-handle meniscal tears (BHMTs) are a common subtype of meniscal tears that represent a clinical challenge. Arthroscopic inside-out repair has been considered the gold standard in treatment; however, an all-inside approach has gained widespread popularity, with limited long-term evidence.

Purpose/hypothesis: The purpose of this study was to (1) compare long-term clinical outcomes and rates of failure after surgical repair of BHMTs using the all-inside versus inside-out technique, and 2) identify risk factors for failure at long-term follow-up.

COVID-19 Diagnosis Within 6 Weeks of Arthroscopic Knee Surgery Leads to Higher Risk for Postoperative Venous Thromboembolism.

Purpose: To determine if preoperative infection with COVID-19 increased risk for postoperative venous thromboembolism (VTE) in patients undergoing arthroscopic knee surgery.

Methods: PearlDiver Mariner 165 database was queried for patients undergoing knee arthroscopy between 2010 and October 2022. Patients were categorized by history of COVID-19 diagnosis and timing in relation to surgery.

Engineering and structures of Crimean-Congo hemorrhagic fever virus glycoprotein complexes.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tickborne virus that can cause severe disease in humans with case fatality rates of 10%-40%. Although structures of CCHFV glycoproteins GP38 and Gc have provided insights into viral entry and defined epitopes of neutralizing and protective antibodies, the structure of glycoprotein Gn and its interactions with GP38 and Gc have remained elusive. Here, we use structure-guided protein engineering to produce a stabilized GP38-Gn-Gc heterotrimeric glycoprotein complex (GP38-Gn-Gc).

Multiancestry Genome-Wide Association Study of Early Childhood Caries.

Early childhood caries (ECC) is the most common noncommunicable childhood disease-an important health problem with known environmental and social/behavioral influences lacking consensus genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multiancestry population of U.S.

How to build the virtual cell with artificial intelligence: Priorities and opportunities.

Cells are essential to understanding health and disease, yet traditional models fall short of modeling and simulating their function and behavior. Advances in AI and omics offer groundbreaking opportunities to create an AI virtual cell (AIVC), a multi-scale, multi-modal large-neural-network-based model that can represent and simulate the behavior of molecules, cells, and tissues across diverse states. This Perspective provides a vision on their design and how collaborative efforts to build AIVCs will transform biological research by allowing high-fidelity simulations, accelerating discoveries, and guiding experimental studies, offering new opportunities for understanding cellular functions and fostering interdisciplinary collaborations in open science.

Evaluating the Use of Environmental and Polygenic Risk Scores to Inform Colorectal Cancer Risk-Based Surveillance Intervals.

Introduction: United States Multi-Society Task Force colonoscopy surveillance intervals are based solely on adenoma characteristics, without accounting for other risk factors. We investigated whether a risk model including demographic, environmental, and genetic risk factors could individualize surveillance intervals under an "equal management of equal risks" framework.

Methods: Using 14,069 individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnostic colonoscopy following an abnormal flexible sigmoidoscopy, we modeled the risk of colorectal cancer, considering the diagnostic colonoscopy finding, baseline risk factors (e.

Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration.

The use of adeno-associated viruses (AAVs) as donors for homology-directed repair (HDR)-mediated genome engineering is limited by safety issues, manufacturing constraints and restricted packaging limits. Non-viral targeted genetic knock-ins rely primarily on double-stranded DNA (dsDNA) and linear single-stranded DNA (lssDNA) donors. dsDNA is known to have low efficiency and high cytotoxicity, while lssDNA is challenging for scaled manufacture.

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Endothelial FUNDC1 Deficiency Drives Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression.

Neuroimaging Correlates of 3 Distinct Physical-Cognitive Phenotypes in Cognitively Normal Older Adults: The Gothenburg H70 Cohort Study.

Background And Objectives: Individuals aged 70 and older frequently experience an increased risk of deficits in both physical and cognitive functions. However, the natural progression and interrelationship of these deficits, as well as their neurologic correlates, remain unclear. We aimed to classify the data-driven physical-cognitive phenotypes and then investigate their associations with neuroimaging markers.

Autofluorescence Virtual Staining System for H&E Histology and Multiplex Immunofluorescence Applied to Immuno-Oncology Biomarkers in Lung Cancer.

We extend the capabilities of virtual staining from AF to a different disease and stain modality. Our work includes newly developed virtual stains for H&E and a multiplex immunofluorescence panel (DAPI, PanCK, PD-L1, CD3, and CD8) for non-small cell lung cancer, which reproduce the key features of real stains.

Cis-regulatory elements driving motor neuron-selective viral payload expression within the mammalian spinal cord.

Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin accessibility profiling of genetically defined mouse MNs was used to identify candidate cis-regulatory elements (CREs) capable of driving MN-selective gene expression.

Direct electrochemical N oxidation to nitrate on supportive Pt/CeO.

Here, we present the development of an efficient Pt/CeO catalyst for electrocatalytic N oxidation to nitrate. Characterization results indicate that highly dispersed Pt and oxygen vacancies from CeO nanocubes (NCs) exhibit strong interactions, which promote the N adsorption on the catalyst surface and suppress the competitive OER activity on oxygen vacancies, resulting in significantly enhanced e-NOR performance.