Drug Development.

Background: The DL-3-n-butylphthalide (NBP), a multi-target neuroprotective drug, improving cognitive impairment in patient with vascular cognitive impairment has been confirmed. The efficacy of NBP in patients with cognitive impairment due to Alzheimer's disease (AD) remains unknown. This study aimed to evaluate the efficacy and safety of NBP in patients with mild cognitive impairment (MCI) due to AD though a clinical randomized controlled trail.

Drug Development.

Background: Effective early intervention of mild cognitive impairment (MCI) is the key for preventing dementia. However, there is currently no drug for MCI. As a multi-targeted neuroprotective agent, butylphthalide has been demonstrated to repair cognition in patients with vascular cognitive impairment, and has the potential to treat MCI due to Alzheimer's disease (AD).

Drug Development.

Background: Pyroptosis is a type of inflammasome-dependent cell death, in which gasdermin D (GSDMD) plays key roles as the executor. Neuroinflammation and pyroptosis have been indicated critical roles in neurodegenerative disorders including Alzheimer's disease (AD). Therefore, novel GSDMD inhibitors represent valuable probes to understand and validate GSDMD as a viable drug target for AD.

Drug Development.

Background: Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS.

Method: We compared scores on the Research Attitudes Questionnaire (RAQ) of individuals enrolled in two recruitment registries: the UCI Consent to Contact [C2C (N = 4818)] and DS-Connect (N = 976).

Drug Development.

Background: Apolipoprotein E4 (apoE4) has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Our lab has demonstrated that chronic administration of Aβ12-28P, a synthetic peptide that blocks apoE4/Aβ binding, in middle-aged transgenic AD mice significantly ameliorates pathology progression, resulting in reduced Aβ plaques deposition and cerebral amyloid angiopathy (CAA) along with improved memory and cognition. However, whether blocking apoE4/Aβ interaction by Aβ12-28P also has an ameliorating effect on the neuronal and cognitive function of old AD mice where Aβ pathology has been extensively developed remains unknown.

Dementia Care Research and Psychosocial Factors.

Background: Dementia is strongly linked to increased care use, but the use of formal and informal care throughout dementia journey remains unclear.

Method: Within a population-based cohort study, we identified 240 older adults (aged ≥78 years) with who developed CIND and 155 with incident dementia. These participants were matched to 480 and 310 cognitively intact participants, respectively, and their formal and informal care use and care hours were compared with a control groups before and after diagnosis of cognitive disorders.

Electrocatalytic Mapping of Metal Fatigue with Persistent Slip Bands.

Metal fatigue, characterized by the accumulation of dislocation defects, is a prevalent failure mode in structural materials. Nondestructive early-stage detection of metal fatigue is extremely important to prevent disastrous events and protect human life. However, the lack of a precise quantitative method to visualize fatigue with spatiotemporal resolution poses a significant obstacle to timely detection.

Dementia Care Research and Psychosocial Factors.

Background: It has been validated that dementia can be alleviated by talk therapy. While general large language models (LLMs) have the potential for talk therapy and dementia treatment, customized LLMs resembling a mental-health therapist can be more professional and powerful. We introduced an LLM solution designed for tailored mental health support for future dementia care.

A Neural-Network-Based Mapping and Optimization Framework for High-Precision Coarse-Grained Simulation.

The accuracy and efficiency of a coarse-grained (CG) force field are pivotal for high-precision molecular simulations of large systems with complex molecules. We present an automated mapping and optimization framework for molecular simulation (AMOFMS), which is designed to streamline and improve the force field optimization process. It features a neural-network-based mapping function, DSGPM-TP (deep supervised graph partitioning model with type prediction).

Modified Taohong Siwu Decoction Improved Cardiac Function after Myocardial Infarction by Activating PI3K/Akt Signaling Pathway.

Introduction: Taohong Siwu decoction (THSWD), a traditional prescription for enhancing blood circulation and eliminating blood stasis, primarily comprises peach kernel, safflower, angelica, chuanxiong, and rehmannia. Modified Taohong Siwu decoction (MTHSWD), an advanced version of THSWD, incorporates additional ingredients such as epimedium, cinnamon, and salvia miltiorrhiza. This addition serves to augment its efficacy in warming yang and promoting blood circulation.

Establishment of a Prognostic Necroptosis-Related lncRNA Signature in Ovarian Cancer.

Introduction: Ovarian Cancer (OC) was known for its high mortality rate among gynecological malignancies, often resulting in a poor prognosis. This study sought to identify prognostic necroptosis-related long non-coding RNAs (lncRNAs) (NRlncRNAs) with prognostic potential and to construct a reliable risk prediction model for OC patients.

Method: The transcriptome and clinic data were sourced from TCGA and GTEx databases.

Circadian rhythm disruptions exacerbate inner ear damage in a murine endolymphatic hydrops model.

Meniere's disease (MD) is an inner ear disease characterized by endolymphatic hydrops (EH). Maintaining a regular daily routine is crucial for MD patients. However, the relationship between circadian rhythms and MD remains unclear.

Lipoprotein(a) and Atrial Fibrillation: Mechanistic Insights and Therapeutic Approaches.

Elevated lipoprotein(a) [Lp(a)] levels are increasingly recognized as a significant risk factor for cardiovascular diseases and may also contribute to atrial fibrillation (AF). This review investigated the indirect mechanisms through which Lp(a) may influence AF, including proatherogenic, prothrombotic, and proinflammatory pathways. Traditional lipid-lowering therapies, such as lifestyle modifications and statins, have limited effects on Lp(a) levels.

The positive feedback loop between SP1 and MAP2K2 significantly drives resistance to VEGFR inhibitors in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common and aggressive malignancies of the urinary system. Despite being the first-line treatment for advanced ccRCC, vascular endothelial growth factor receptor inhibitors (VEGFRis) face significant limitations due to both initial and acquired resistance, which impede complete tumor eradication. Using a CRISPR/Cas9 library screening approach, was identified as a resistance-associated gene for three prevalent VEGFRis (Sunitinib, Axitinib, and Sorafenib).

Downregulated CCND3 Is a Key Event Driving Lung Adenocarcinoma Metastasis during Acquired Cisplatin Resistance.

Cyclin D3 (CCND3), a member of the cyclin D family, is known to promote cell cycle transition. In this study, we found that CCND3 was downregulated in cisplatin-resistant (-diamminedichloroplatinum, DDP) lung adenocarcinoma (LUAD) cells. The loss of CCND3 indeed impeded cell cycle transition.

Tubulointerstitial nephritis antigen-like 1 promotes the progression of liver fibrosis after HCV eradication with direct-acting antivirals.

Although therapies based on direct-acting antivirals (DAAs) effectively eradicate hepatitis C virus (HCV) in patients, there is still a high risk of liver fibrosis even after a sustained virological response. Therefore, it is of great clinical importance to understand the mechanism of potential factors that promote liver fibrosis after virological cure by treatment with DAAs. Here, we found that tubulointerstitial nephritis antigen-like 1 (TINAGL1) is significantly increased in HCV-infected hepatocytes and in the liver of patients with liver fibrosis, and that higher TINAGL1 expression persists in HCV-eradicated hepatocytes after treatment with DAAs.

Caveolin-1 mitigates the advancement of metabolic dysfunction-associated steatotic liver disease by reducing endoplasmic reticulum stress and pyroptosis through the restoration of cholesterol homeostasis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, which has the potential to advance to fibrosis. CAV1 has the effects of improving liver lipid deposition in MASLD, however, the potential mechanism is largely unknown. Here, we establish a MASLD mouse model in CAV1 knockout (KO) mice and perform transcriptome analysis on livers from mice to investigate the effects of CAV1 in MASLD progression.

Cold atmospheric plasma potentiates ferroptosis via EGFR(Y1068)-mediated dual axes on GPX4 among triple negative breast cancer cells.

Cold atmospheric plasma (CAP) has been proposed as an emerging onco-therapeutics that can specifically kill cancer cells without harming healthy cells. Here we explore its potency in triggering ferroptosis in transformed cells using triple negative breast cancer as the disease model. Through the whole transcriptome sequencing, mass spectrometry analysis, point mutation, and a series of and molecular assays, we identified two signaling axes centered at EGFR(Y1068), i.

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.

Deficiency of Epithelial PIEZO1 Alleviates Liver Steatosis Induced by High-Fat Diet in Mice.

PIEZO1 has been found to play a vital role in regulating intestinal epithelial cells (IEC) function and maintaining intestinal barrier in recent years. Therefore, IEC PIEZO1 might exert a significant impact on liver metabolism through the gut-liver axis, but there is no research on this topic currently. Classic high-fat diet (HFD) model and mice with IEC-specific deficiency of PIEZO1 ( ) were used to explore the problem.

USP25 stabilizes STAT6 to promote IL-4-induced macrophage M2 polarization and fibrosis.

As a leading cause of morbidity and mortality, fibrosis is the common pathway of various chronic inflammatory diseases in organs and causes death in a large number of patients. It can destroy the structure and function of organs and ultimately lead to organ failure, which is a major cause of disability and death in many diseases. However, the regulatory mechanism of organ fibrosis is not well clear and the lack of effective drugs and treatments, which seriously endangers human health and safety.

Efficacy and Safety of Ciprofol for Anesthesia in Painless Colonoscopy with Varying Body Mass Indices Patients: A Prospective, Single-Center, Observational Study.

Background: Ciprofol, a novel intravenous anesthetic derived from propofol, exhibits high lipophilicity. Its pharmacokinetics and pharmacodynamics may vary across different body mass indices (BMI) categories, but data on its optimal dosing as well as its safety and efficacy during colonoscopy anesthesia in varying BMI groups are lacking.

Objective: To evaluate the efficacy and safety of ciprofol during anesthesia for painless colonoscopy in patients with varying BMI, and to explore the correlation between BMI and induction dose.

Pharmacokinetics and Bioequivalence of Two Fixed-Dose Combination Tablets of Valsartan/Amlodipine (80/5 Mg) in Healthy Chinese Subjects.

Purpose: The study aimed to investigate the pharmacokinetics and bioequivalence of coformulations of valsartan and amlodipine in healthy Chinese subjects under both fasting and fed conditions.

Methods: The research was conducted under both fasting and fed studies and employed a single-center, randomized, open-label, single-dose, three-period design with partial-repeat and crossover elements. A total of 71 healthy Chinese adult participants were included under fasting (n = 36) and fed (n = 35) conditions.

Copper homeostasis; A rapier between mycobacteria and macrophages.

Copper is a vital trace element crucial for mediating interactions between and macrophages. Within these immune cells, copper modulates oxidative stress responses and signaling pathways, enhancing macrophage immune functions and facilitating clearance. Conversely, copper may promote escape from macrophages through various mechanisms: inhibiting macrophage activity, diminishing phagocytic and bactericidal capacities, and supporting survival and proliferation.