De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast.

Protoberberine alkaloids and benzophenanthridine alkaloids (BZDAs) are subgroups of benzylisoquinoline alkaloids (BIAs), which represent a diverse class of plant-specialized natural metabolites with many pharmacological properties. Microbial biosynthesis has been allowed for accessibility and scalable production of high-value BIAs. Here, we engineer Saccharomyces cerevisiae to de novo produce a series of protoberberines and BZDAs, including palmatine, berberine, chelerythrine, sanguinarine and chelirubine.

All-Arthroscopic Treatment of Combined Off-Track Hill-Sachs Lesions Using Interference Screw and Shoulder Glenoid Bone Defects Using Bone Grafting With Soft Fixation.

Bony changes such as glenoid bone defects and Hill-Sachs lesions are responsible for recurrent anterior shoulder dislocations. With the development of arthroscopic techniques as well as arthroscopic surgical instruments, arthroscopic repair of bony structures has become an important surgical procedure for the treatment of recurrent shoulder dislocation. In this Technical Note, we used screws to fill Hill-Sachs lesions and autologous iliac bone grafts combined with soft tissue to repair the glenoid bone defects.

Agonist antibody to guanylate cyclase receptor NPR1 regulates vascular tone.

Heart failure is a leading cause of morbidity and mortality. Elevated intracardiac pressures and myocyte stretch in heart failure trigger the release of counter-regulatory natriuretic peptides, which act through their receptor (NPR1) to affect vasodilation, diuresis and natriuresis, lowering venous pressures and relieving venous congestion. Recombinant natriuretic peptide infusions were developed to treat heart failure but have been limited by a short duration of effect.

PharmaBench: Enhancing ADMET benchmarks with large language models.

Accurately predicting ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties early in drug development is essential for selecting compounds with optimal pharmacokinetics and minimal toxicity. Existing ADMET-related benchmark sets are limited in utility due to their small dataset sizes and the lack of representation of compounds used in drug discovery projects. These shortcomings hinder their application in model building for drug discovery.

Heritability and Genetic Factors of Astigmatism and Corneal Curvature: A Systematic Review and Meta-analysis.

Purpose: To systematically review and meta-analyze all reported heritability studies of refractive astigmatism (RA), corneal astigmatism (CA) and corneal curvature (CC), and evaluate the existing genetic associations of RA, CA and CC.

Design: Systematic review and meta-analysis (PROSPERO ID: CRD42023447370).

Methods: Studies that reported the heritability and genetic associations of RA, CA and/or CC were identified from PubMed, Web of Science and EMBASE (from inception to October 1, 2023).

Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria.

CelTOS is a malaria vaccine antigen that is conserved in Plasmodium and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes.

Engineered minimal type I CRISPR-Cas system for transcriptional activation and base editing in human cells.

Type I CRISPR-Cas systems are widespread and have exhibited high versatility and efficiency in genome editing and gene regulation in prokaryotes. However, due to the multi-subunit composition and large size, their application in eukaryotes has not been thoroughly investigated. Here, we demonstrate that the type I-F2 Cascade, the most compact among type I systems, with a total gene size smaller than that of SpCas9, can be developed for transcriptional activation in human cells.

A Systematic Review on Conditions Before and After Training of Teamwork Competencies and the Effect on Transfer of Skills to the Clinical Workplace.

We conducted a systematic review to assess if any condition before- or after simulation-based training of teamwork competencies for healthcare professionals affects learning or transfer of skills to the clinical environment.We searched CINAHL, Medline, and Embase for studies published between January 1, 2011, and July 10, 2023. We screened 13,149 abstracts and 335 full texts, of which 5 studies were included.

Hypertensive Disorders of Pregnancy and Brain Health in Midlife: The CARDIA Study.

Background: To understand the role of hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension (GH), in brain health earlier in life, we investigated the association of HDP with midlife cognition and brain health.

Methods: We studied a prospective cohort of women, baseline age 18 to 30 years, who were assessed at study years 25 and 30 with a cognitive battery and a subset with brain magnetic resonance imaging. A history of HDP was defined based on self-report.

Simulations of classical three-body thermalization in one dimension.

One-dimensional systems, such as nanowires or electrons moving along strong magnetic field lines, have peculiar thermalization physics. The binary collision of pointlike particles, typically the dominant process for reaching thermal equilibrium in higher-dimensional systems, cannot thermalize a 1D system. We study how dilute classical 1D gases thermalize through three-body collisions.

An Accurate and Rapidly Calibrating Speech Neuroprosthesis.

Background: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy.

Methods: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes.

Genotype Associated With Visual Prognosis in Patients With Congenital Ectopia Lentis Following Lens Surgery: A Prospective Cohort Study.

Purpose: To investigate the relationship between visual prognosis and genotype in patients undergoing lens surgery for congenital ectopia lentis (EL).

Design: Prospective clinical cohort study.

Methods: Patients with congenital EL who underwent lens removal and intraocular lens implantation received panel-based next-generation sequencing.

Textbook anastomotic success in patients with low rectal cancer treated by intersphincteric resection: reappraising surgical, oncological, and functional outcomes.

Previous studies on successful anastomosis after intersphincteric resection (ISR) for low rectal cancer (LRC) primarily focused on anastomotic complications rather than functional outcomes. Here, we improved the anastomotic success criteria by considering surgical, oncological, and functional outcomes and proposed a new composite outcome, "textbook anastomotic success" (TASS). This retrospective single-center study included patients with LRC treated with ISR from January 2014 to April 2020.

AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery.

Ionizable lipid nanoparticles (LNPs) are seeing widespread use in mRNA delivery, notably in SARS-CoV-2 mRNA vaccines. However, the expansion of mRNA therapies beyond COVID-19 is impeded by the absence of LNPs tailored for diverse cell types. In this study, we present the AI-Guided Ionizable Lipid Engineering (AGILE) platform, a synergistic combination of deep learning and combinatorial chemistry.