Drug Development.

Background: Pivotal Alzheimer's Disease (AD) trials typically require thousands of participants, resulting in long enrollment timelines and substantial costs. We leverage deep learning predictive models to create prognostic scores (forecasted control outcome) of trial participants and in combination with a linear statistical model to increase statistical power in randomized clinical trials (RCT). This is a straightforward extension of the traditional RCT analysis, allowing for ease of use in any clinical program.

Dementia Care Research and Psychosocial Factors.

Background: Loneliness has been linked to cognitive decline and an elevated risk of Alzheimer's disease (AD). Previous studies measured loneliness at a single point time, which may not accurately capture the longitudinal changes of different loneliness types (e.g.

Dementia Care Research and Psychosocial Factors.

Background: People living with dementia (PwD) experience progressive functional decline with increasing dependence on their caregivers. Advanced care planning (ACP) has the potential to promote quality of life, reduce iatrogenic harm, and minimize overutilization of healthcare resources, yet planning ahead in the context of dementia is challenging and requires consideration of numerous factors over an extended period of time. We examined caregivers' perceptions of current and end-stage medical care preferences in PwD and the impact of ACP-related discussions between caregivers and PwD.

New insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: molecular mechanisms, therapeutic targets, and natural products.

Anthracyclines (ANTs) are widely used in cancer therapy, particularly for lymphoma, sarcoma, breast cancer, and childhood leukemia, and have become the cornerstone of chemotherapy for various malignancies. However, it is associated with fatal and dose-dependent cardiovascular complications, especially cardiotoxicity. Mitochondrial quality control mechanisms, encompassing mitophagy, mitochondrial dynamics, and mitochondrial biogenesis, maintain mitochondrial homeostasis in the cardiovascular system.

HIF-2α/LPCAT1 orchestrates the reprogramming of lipid metabolism in ccRCC by modulating the FBXW7-mediated ubiquitination of ACLY.

The current research revealed a strong link between lipid reprogramming and dysregulated lipid metabolism to the genesis and development of clear cell renal cell carcinoma (ccRCC). Pathologically, ccRCC exhibits a high concentration of lipid droplets within the cytoplasm. HIF-2α expression has previously been demonstrated to be elevated in ccRCC caused by mutations in the von Hippel-Lindau (VHL) gene, which plays a vital role in the development of renal cell carcinoma.

Single-cell analysis unveils cell subtypes of acral melanoma cells at the early and late differentiation stages.

Background: Melanoma, a malignant neoplasm originating from melanocytes, is a form of skin cancer with rapidly increasing global incidence, often exacerbated by UV radiation[1]. Particularly, acral melanoma, characterized by its swift metastasis and poor prognosis, underscores the significance of further research into its heterogeneity. Single-cell sequencing has been widely utilized in the study of tumor heterogeneity; however, research related to melanoma remains to be further refined.

A Novel Oncolytic Virus Formulation Based on Mesenchymal Stem Cell-Derived Vesicles for Tumor Therapy.

Developing new drug delivery systems is crucial for enhancing the efficacy of oncolytic virus (OV) therapies in cancer treatment. In this study, mesenchymal stem cell (MSC)-derived vesicles and oncolytic viruses are exploited to construct a novel formulation. It has been hypothesized that vesicle-coated OVs could amplify cytotoxic effects through superior internalization by tumor cells.

Lasalocid inhibits melanoma by down-regulating FOXM1 through PI3K/AKT and JNK/P38 MAPK pathways.

Melanoma poses a significant challenge to patients due to its aggressive nature and limited treatment options. Recent studies have suggested that lasalocid, a feed additive ionophore antibiotic, may have potential as an anticancer agent. However, the mechanism of lasalocid in melanoma is unclear.

The Clinical Prediction Value of the Ubiquitination Model Reflecting the Microenvironment Infiltration and Drug Sensitivity in Breast Cancer.

The ubiquitin-proteasome system influences cancer progression through multiple mechanisms. Due to the extensive proteasomal modifications observed in cancer tissues, ubiquitination is closely related to various biological functions with cancer. However, the roles of ubiquitin-related genes (UbRGs) in breast cancer (BC) have not been thoroughly investigated.

Characteristics of the Bacterial Community in Alpine Meadows in Response to Altitude and Aspect in the Qilian Mountains, Northwest China.

As one of the most sensitive and fragile alpine ecosystems in the Qilian Mountains, the alpine meadow holds significant scientific importance in understanding the changes in the characteristics of soil bacterial community in response to altitude and aspect variations. In our study, we analyzed the composition, diversity, and function of soil bacterial communities in alpine meadows at different altitudes and aspects and their relationship with environmental factors. Our results indicate that altitude and aspect orientation significantly influences the diversity index and composition of soil bacterial communities.

Preclinical evaluation of a surgical assistant robot for use in minimally invasive abdominal surgeries.

In recent years, robotic assistance has become increasingly used and applied in minimally invasive surgeries. A new cooperative surgical robot system that includes a joystick-guided robotic scope holder was developed in this study, and its feasibility for use in minimally invasive abdominal surgery was evaluated in a preclinical setting. The cooperative surgical robot consists of a six-degree-of-freedom collaborative robot arm and a one-degree-of-freedom bidirectional telescopic end-effector specializing in surgical assistance.

Mangiferin Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the GAS6/Axl Signaling Pathway.

Ischemia reperfusion-induced myocardial injury is a prominent pathological feature in patients with coronary artery disease, contributing to significant mortality and morbidity rates. Mangiferin (MGF), the main active ingredient extracted from Anemarrhena asphodeloides Bge, has anti-inflammatory, anti-oxidation, anti-diabetes, and anti-tumor effects. The present study confirmed that the GAS6/Axl pathway was identified as a promising novel target for the treatment of myocardial ischemia reperfusion (IR) injury.

La Doped Nickel-Manganese Oxide as High-Capacity Cathode for Sodium-Ion Batteries Guided by Bayesian Optimization.

In sodium-ion batteries, the layered transition metal oxides used as cathode often experience interlayer sliding of interlayer spacing and lattice variations during charge/discharge, leading to structural damage and capacity degradation. To address this challenge, a La doping strategy guided by Bayesian optimization has been employed to prepare the high-performance O3-NaNiMnCuLaO (NMCL) cathode material. Density functional theory calculations reveal that the O 2p orbital overlaps with the t orbital of transition metals in NMCL, facilitating the formation of Na-O-La bonds and promoting the oxygen redox reaction kinetics.

ssDNA Capture Dynamics by Graphene Nanopores: The Role of Electrophoresis and Electro-osmotic Flow.

Efficient capture of single-stranded DNA (ssDNA) is crucial for high-throughput sequencing, which influences the speed and accuracy of genetic analysis. Electrophoresis (EP) and electro-osmotic flow (EOF) have a significant impact on the translocation behavior of ssDNA through the nanopore. Experimentally, dynamically tracking these two effects remains challenging, and conventional numerical methods also struggle to capture their dynamic properties in the presence of DNA.

Enhancing Tribo-Rehydration in Hydrogel by Brush-Like Surface and Its Modulation.

Synovial exudation, creeping, and lubrication failure in natural cartilage under a long-term normal loading can be counteracted by a tribo-rehydration (sliding-induced rehydration) phenomenon. Hydrogels, as porous materials, can also restore interfacial lubrication and overcome creep through this strategy. At appropriate sliding velocities, water molecules at the interface contact inlet are driven by hydrodynamic pressures into the porous network to resist creep extrusion.

Dual-Oxide Bridge-Trap Structure via Atomic Layer Infiltration for Enhanced Performance of Quantum Dot Photodetector.

Achieving high-performance lead sulfide quantum dot (PbS QD)-based photodetectors requires enhanced carrier transfer, which inevitably leads to an increased dark current. Balancing a high photocurrent and low dark current is crucial. In this work, a bridge-trap structure constructed by the atomic layer deposition of dual oxides is proposed to simultaneously enhance photoresponse performance and reduce dark current.

PHA Microplastic Aging Decreases NO Sink Capacity: Released γ-Butyrolactone Decouples Denitrifying Electron Transfer and Oxidative Phosphorylation.

Bacterial denitrification is a main pathway for soil NO sinks, which is crucial for assessing and controlling NO emissions. Biobased polyhydroxyalkanoate (PHA) microplastic particles (MPs) degrade slowly in conventional environments, remaining inert for extended periods. However, the impacts of PHA microplastic aging on the bacterial NO sink capacity before degradation remain poorly understood.

Association between renal mean perfusion pressure and prognosis in patients with sepsis-associated acute kidney injury: insights from the MIMIC IV database.

Objective: To investigate the association between renal mean perfusion pressure (MPP) and prognosis in sepsis-associated acute kidney injury (SA-AKI).

Methods: Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Group-based trajectory modeling (GBTM) was applied to identify dynamic MPP patterns, while restricted cubic spline (RCS) curves were utilized to confirm the non-linear relationship between MPP and mortality.

Dynamic Changes and Trends of SARS-CoV-2 Antibodies Induced by Infection and Vaccination Across Multiple Time Points.

As the COVID-19 pandemic continues, increasingly complex vaccination and infection histories have made it urgent to investigate the antibody dynamics in populations with hybrid immunity. This study aimed to explore the multi-time-point dynamics of SARS-CoV-2 IgG antibody levels in a community-based population in Jiangsu Province, China, following the Omicron BA.5 wave, as well as the long-term persistence of IgG antibodies nearly 2 years postinfection.

Design, Synthesis, and Antibacterial Activity of Novel Sulfone Derivatives Containing a 1,2,4-Triazolo[4,3-]Pyridine Moiety.

To develop antibacterial agents with a novel mechanism of action, a series of sulfone compounds containing a 1,2,4-triazolo[4,3-]pyridine were designed and synthesized by progressive molecular structure optimization. The antibacterial activities of some derivatives against the four plant pathogens (), (), (), and () were evaluated. Among them, compound demonstrated significant antibacterial activities against , , and , with EC values of 1.

Association of LDL-C/HDL-C Ratio With Hyperuricemia: A National Cohort Study.

Hyperuricemia (HUA) is a metabolic abnormality syndrome caused by disorders of purine metabolism. This study aimed to investigate the predictive value of the low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR) for the risk of developing HUA. We extracted data from the China Health and Retirement Longitudinal Study (CHARLS) database from 2011 to 2016.

Intermittent Fasting Enhances Motor Coordination Through Myelin Preservation in Aged Mice.

Integrating dietary interventions have been extensively studied for their health benefits, such as Alzheimer's disease, Huntington's disease, and aging. However, it is necessary to fully understand the mechanisms of long-term effects and practical applications of these dietary interventions for health. A 10-week intermittent fasting (IMF) regimen was implemented on the aging animals in the current study.

Optimizing Surface Maleimide/cRGD Ratios Enhances Targeting Efficiency of cRGD-Functionalized Nanomedicines.

Thiol-maleimide (MI) chemistry is a cornerstone of bioconjugation strategies, particularly in the development of drug delivery systems. The cyclic arginine-glycine-aspartic acid (cRGD) peptide, recognized for its ability to target the integrin αβ, is commonly employed to functionalize maleimide-bearing nanoparticles (NPs) for fabricating cRGD-functionalized nanomedicines. However, the impact of cRGD density on tumor targeting efficiency remains poorly understood.

Manipulating stomatal aperture by silencing StSLAC1 affects potato plant-herbivore-parasitoid tritrophic interactions under drought stress.

The effects of drought stress on stomatal opening dynamics, plant volatile organic compound (VOC) emissions and plant-insect interactions have been well-documented individually, but how they interact mechanistically remains poorly studied. Here, we studied how drought-triggered stomatal closure affects VOC emission and plant-trophic interactions by combining RNAi silencing, molecular biological and chemical analyses (GC-MS) of a potato-tuber moth-egg parasitoid tritrophic system. Drought stress attenuated stomatal apertures and VOC emissions, which made the potato (Solanum tuberosum L.