A randomized controlled trial of the Transdiagnostic Intervention for Sleep and Circadian dysfunction implemented via facilitation and delivered by community mental health providers: Improving the "fit" of psychological treatments by adapting to context.

To determine if the use of theory, data and end-user perspectives to guide an adaptation of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) yields better outcomes and improves the "fit" of TranS-C to community mental health centers (CMHCs), relative to the standard version. Ten counties in California were cluster-randomized by county to Adapted or Standard TranS-C. Within each county, adults who exhibited sleep and circadian dysfunction and serious mental illness (SMI) were randomized to immediate TranS-C or Usual Care followed by Delayed Treatment with TranS-C (UC-DT).

Secupyritines A‒C, Three Natural Propellane Securinega Alkaloids: Structure Elucidation and Total Synthesis Based on Biogenetic Building Blocks.

Secupyritines A‒C are unique polycyclic Securinega alkaloids isolated from medicinal plant Flueggea suffruticosa. They feature a distinctive 6/6/6/5/6 fused pentacyclic ring system with a highly strained 2-oxa-6-aza[4.4.

Development of a RIPK1 degrader to enhance antitumor immunity.

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo.

TRIM4 enhances small-molecule-induced neddylated-degradation of CORO1A for triple negative breast cancer therapy.

As a critical member of the Coronin family, Coronin 1A (CORO1A) plays a crucial role in the progression of triple-negative breast cancer (TNBC). However, CORO1A is typically considered "undruggable" due to its smooth surface and complex protein-protein interactions (PPIs). Molecular glues have emerged as one of the most effective strategies to rapidly degrade such "undruggable" targets.

Implementation facilitators and barriers of stress first aid to protect mental health of frontline health care workers during the COVID-19 pandemic: a qualitative study.

Background: The COVID-19 pandemic has taken a toll on frontline health care workers (HCWs), leading to poor mental and physical well-being. We conducted a large, cluster randomized controlled trial to implement an adapted Stress First Aid (SFA) intervention to support HCW well-being using a train-the-trainer (TTT) approach for rapid deployment in the United States and collected qualitative data through interviews to understand implementation. The goal of this study is to understand barriers and facilitators to deploying SFA using a TTT model, with particular emphasis on the acceptability, uptake, and barriers from the implementation.

A Qualitative Study of Black and Latine HIV Care Consumers' Perceptions of Providers' Behaviors, Medical Mistrust, and Experiences of Discrimination.

Black and Latine Americans face the highest HIV burden among U.S. racial and ethnic groups, exacerbated by intersectional stigma and medical mistrust.

Integrating habit science and learning theory to promote maintenance of behavior change: does adding text messages to a habit-based sleep health intervention (HABITs) improve outcomes for eveningness chronotype young adults? Study protocol for a randomized controlled trial.

Background: Eveningness chronotype-the tendency for later sleep and wake times-arises from a confluence of psychosocial, behavioral, and biological factors. With the onset and progression of puberty, many young people develop an eveningness chronotype, which remains prevalent through the transition into adulthood. Eveningness has been associated with increased risk for poorer health.

Demethylzeylasteral induces PD-L1 ubiquitin-proteasome degradation and promotes antitumor immunity targeting USP22.

Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells.

Short-Term Exposure to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Induces Colonic Energy Metabolism Disorders in Rats.

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic aromatic amines generated in thermally processed meat products, and the toxicities of its short-term exposure in the intestines remain unclear. This study aimed to elucidate the short-term PhIP toxicity in colons through administering PhIP orally to rats for 4 weeks. The results indicated that short-term PhIP exposure induced colonic oxidative stress, a significant decrease of serum triglyceride, and a disrupted colonic gene expression pattern associated with mitochondrial electron transport chain and energy metabolism.

Regulating the metabolic flux of pyruvate dehydrogenase bypass to enhance lipid production in Saccharomyces cerevisiae.

To achieve high efficiency in microbial cell factories, it is crucial to redesign central carbon fluxes to ensure an adequate supply of precursors for producing high-value compounds. In this study, we employed a multi-omics approach to rearrange the central carbon flux of the pyruvate dehydrogenase (PDH) bypass, thereby enhancing the supply of intermediate precursors, specifically acetyl-CoA. This enhancement aimed to improve the biosynthesis of acetyl-CoA-derived compounds, such as terpenoids and fatty acid-derived molecules, in Saccharomyces cerevisiae.

Effect of Acupuncture on Cognitive Function in Patients With Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

Aims And Objective: To investigate the impact of acupuncture on post-stroke cognitive impairment (PSCI).

Background: PSCI is a major barrier to stroke patients' rehabilitation, and acupuncture is one of the treatments. However, the benefit of acupuncture on PSCI is unclear.

Degradation of extracellular antibiotic resistance gene through singlet oxygen produced by carbon nanotubes-activated persulfate.

Extracellular antibiotic resistance gene (eARG) has emerged as a global crisis in recent years, yet commonly used disinfectants have proven ineffective for their elimination. Seeking to enhance the degradation efficiency of eARG, this study explored the potential of carbon nanotubes-activated persulfate (CNTs + PS) system as a novel method for eradicating eARG. Our findings demonstrated that CNTs + PS effectively disrupted the intact structure of eARG, inhibited their genetic replication and horizontal transfer capability, achieving remarkable degradation of eARG contamination.

Oligotrophic state reduces the time dependence of the observed survival fraction for heavy ion beam-irradiated and provides new insights into DNA repair.

Heavy ion beam (HIB) irradiation is widely utilized in studies of cosmic rays-induced cellular effects and microbial breeding. Establishing an accurate dose-survival relationship is crucial for selecting the optimal irradiation dose. Typically, after irradiating logarithmic-phase cell suspensions with HIB, the survival fraction (SF) is determined by the ratio of clonal-forming units in irradiated versus control groups.

Integrating the Memory Support Intervention into the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C): can improving memory for treatment in midlife and older adults improve patient outcomes? Study protocol for a randomized controlled trial.

Background: Poor memory for treatment is associated with poorer treatment adherence and poorer patient outcomes. The memory support intervention (MSI) was developed to improve patient memory for treatment with the goal of improving patient outcomes. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether a new, streamlined, and potent version of the MSI improves outcomes for midlife and older adults.

Impact of lipid oxidation products on the digestibility and structural integrity of Myofibrillar proteins during thermal processing.

This study explores the effects of lipid oxidation products (LOPs), specifically CHP, t,t-DDE, and MDA, on the digestibility and structural integrity of myofibrillar proteins (MP) during processing. LOPs were first assessed by heating at 180 °C for 15 min, showing a significant reduction in digestibility in MDA-treated samples (65.40 %), followed by t,t-DDE (45.

Efficacy of robot-assisted gait training on lower extremity function in subacute stroke patients: a systematic review and meta-analysis.

Background: Robot-Assisted Gait Training (RAGT) is a novel technology widely employed in the field of neurological rehabilitation for patients with subacute stroke. However, the effectiveness of RAGT compared to conventional gait training (CGT) in improving lower extremity function remains a topic of debate. This study aimed to investigate and compare the effects of RAGT and CGT on lower extremity movement in patients with subacute stroke.

Targeting senescence-associated secretory phenotypes to remodel the tumour microenvironment and modulate tumour outcomes.

Tumour cell senescence can be induced by various factors, including DNA damage, inflammatory signals, genetic toxins, ionising radiation and nutrient metabolism. The senescence-associated secretory phenotype (SASP), secreted by senescent tumour cells, possesses the capacity to modulate various immune cells, including macrophages, T cells, natural killer cells and myeloid-derived suppressor cells, as well as vascular endothelial cells and fibroblasts within the tumour microenvironment (TME), and this modulation can result in either the promotion or suppression of tumorigenesis and progression. Exploring the impact of SASP on the TME could identify potential therapeutic targets, yet limited studies have dissected its functions.

Improvement of Saccharomyces cerevisiae strain tolerance to vanillin through heavy ion radiation combined with adaptive laboratory evolution.

Vanillin is an inhibitor of lignocellulose hydrolysate, which can reduce the ability of Saccharomyces cerevisiae to utilize lignocellulose, which is an important factor limiting the development of the ethanol fermentation industry. In this study, mutants of vanillin-tolerant yeast named H6, H7, X3, and X8 were bred by heavy ion irradiation (HIR) combined with adaptive laboratory evolution (ALE). Phenotypic tests revealed that the mutants outperformed the original strain WT in tolerance, growth rate, genetic stability and fermentation ability.