A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion.

The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes.

Mechanistic insights into SIRT7 and EZH2 regulation of cisplatin resistance in bladder cancer cells.

Cisplatin (CDDP) resistance has been established to significantly impact Bladder Cancer (BCa) therapy. On the other hand, the crucial regulatory involvement of SIRT7 and EZH2 in bladder cancer development is well known. Herein, the collaborative regulatory roles and underlying mechanisms of SIRT7 and EZH2 in CDDP resistance in bladder cancer were explored.

An AI-Cyborg System for Adaptive Intelligent Modulation of Organoid Maturation.

Recent advancements in flexible bioelectronics have enabled continuous, long-term stable interrogation and intervention of biological systems. However, effectively utilizing the interrogated data to modulate biological systems to achieve specific biomedical and biological goals remains a challenge. In this study, we introduce an AI-driven bioelectronics system that integrates tissue-like, flexible bioelectronics with cyber learning algorithms to create a long-term, real-time bidirectional b ioelectronic interface with o ptimized a daptive intelligent m odulation (BIO-AIM).

Correlation and mediation analysis between plasmapheresis donation behavior and bone mineral density and bone metabolism biomarkers: a cross-sectional study based on plasmapheresis donors at high risk of osteoporosis in China.

Background: As a group of more than 3.67 million people, the bone health of Chinese plasmapheresis donors, which the main population is also a risk group of osteoporosis (OP), has raised concerns. Therefore, this article investigates the relationship between bone mineral density (BMD), bone metabolism indicators, and plasmapheresis donation behavior among some high-risk plasmapheresis donors for OP in China, and further explores the mediating factors through reasonable statistical methods.

A new human autologous hepatocyte/macrophage co-culture system that mimics drug-induced liver injury-like inflammation.

The development of in vitro hepatocyte cell culture systems is crucial for investigating drug-induced liver injury (DILI). One prerequisite for monitoring DILI related immunologic reactions is the extension of primary human hepatocyte (PHH) cultures towards the inclusion of macrophages. Therefore, we developed and characterized an autologous co-culture system of PHH and primary human hepatic macrophages (hepM) (CoC1).

Effects of prolonged NaHCO exposure on the serum immune function, antioxidant capacity, intestinal tight junctions, microbiota, mitochondria, and autophagy in crucian carp (Carassius auratus).

This study investigated the effects of long-term NaHCO stress on serum immunity, antioxidant capacity, intestinal tight junction, intestinal microbiota, mitochondrial function and autophagy in crucian carp. A total of 240 fish (31.19 ± 1.

Comparative Efficacy and Safety of Different Low-Dose Platelet Inhibitors in Patients With Coronary Heart Disease: A Bayesian Network Meta-Analysis.

Objective: The optimal low-dose antiplatelet agents in patients with coronary heart disease (CHD) had not been determined. The objective of this study was to compare the impact of different low-dose antiplatelet agents on cardiovascular outcomes and bleeding risks in patients with CHD.

Methods: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, VIP, WanFang Data, and China Biology Medicine.

Air pollution is linked to cognitive decline independent of hypersensitive C-reactive protein: insights from middle-aged and older Chinese.

Background: Long-term air pollution exposure and inflammation are considered to be associated with cognitive decline. However, whether air pollution exposure related cognitive decline is dependent on inflammation remains uncertain.

Materials And Methods: The present study collected data from China Health and Retirement Longitudinal Study (CHARLS) at baseline in 2011, with a follow up period in 2015.

Advances in theories and models of cardiac rehabilitation after acute myocardial infarction: A narrative review.

Acute myocardial infarction (AMI) remains a leading cause of mortality and disability worldwide, with its high mortality and recurrence rates significantly impacting patients' quality of life and prognosis. Cardiac rehabilitation, as a comprehensive intervention strategy, plays a crucial role in improving outcomes for AMI patients. The aims to comprehensively analyze and evaluate the theoretical foundations and practical models of cardiac rehabilitation following AMI, providing healthcare professionals with up-to-date research advances and practical guidance.

Diazonium-based derivatization for enhanced detection of phosphorylated metabolites by LC-MS in cells.

Phosphorylated small molecule metabolites play crucial roles in physiological processes such as glycogen metabolism and inflammation regulation. However, their high polarity, structural similarity, poor chromatographic separation, and weak mass spectrometric signals make their accurate quantification challenging, thereby hindering the study of related metabolic mechanisms and diseases. To address these challenges, we developed a novel derivatization reagent, DMQX (5-diazomethane quinoxaline), and combined it with liquid chromatography-mass spectrometry (LC-MS).

Dynamic changes in the skin transcriptome for the melanin pigmentation in embryonic chickens.

Dermal hyperpigmentation stands out among the various skin pigmentation phenotypes in chickens, where most other pigmentation variants affect feather color and patterning predominantly. Despite numerous black chicken breeds worldwide, only a select few exhibit comprehensive black pigmentation, which encompasses the skin, meat, flesh, and bones. The process of skin melanin pigmentation is intricate and develops successively.

DNA nanotechnology-based strategies for minimising hybridisation-dependent off-target effects in oligonucleotide therapies.

Targeted therapy has emerged as a transformative breakthrough in modern medicine. Oligonucleotide drugs, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), have made significant advancements in targeted therapy. Other oligonucleotide-based therapeutics like clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems are also leading a revolution in targeted gene therapy.

Autophagy promotes p72 degradation and capsid disassembly during the early phase of African swine fever virus infection.

During viral infections, autophagy functions as a cell-intrinsic defense mechanism by facilitating the delivery of virions or viral components to the endosomal/lysosomal pathway for degradation. In this study, we report that internalized African swine fever virus (ASFV) virions enter autolysosomes during the early phase of viral infection. Autophagy selectively targets the major capsid protein p72 within the ASFV virion.

Assessment of transglutaminase catalyzed cross-linking on the potential allergenicity and conformation of heterologous protein polymers.

Transglutaminase (TGase)-mediated cross-linking has gained significant attention due to its potential to reduce the allergenicity of food proteins. This study investigates the effects of TGase cross-linking on allergenicity and conformational modifications in a dual-protein system comprising soy protein isolate (SPI) and β-lactoglobulin (β-LG). The results showed that TGase cross-linking effectively decreased the allergenic potential of both SPI and β-LG, with a more pronounced reduction observed in the allergenicity of soy protein in the dual-protein system.

Advanced PROTAC and Quantitative Proteomics Strategy Reveals Bax Inhibitor-1 as a Critical Target of Icaritin in Burkitt Lymphoma.

Understanding the molecular targets of natural products is crucial for elucidating their mechanisms of action, mitigating toxicity, and uncovering potential therapeutic pathways. Icaritin (ICT), a bioactive flavonoid, demonstrates significant anti-tumor activity but lacks defined molecular targets. This study employs an advanced strategy integrating proteolysis targeting chimera (PROTAC) technology with quantitative proteomics to identify ICT's key targets.

Zuojin Pill Alleviates Precancerous Lesions of Gastric Cancer by Modulating the MEK/ERK/c-Myc Pathway: An Integrated Approach of Network Pharmacology, Molecular Dynamics Simulation, and Experimental Validation.

Background: Precancerous lesions of gastric cancer (PLGC) represent critical stages in gastric cancer progression, with a high risk of malignancy. Current treatments, such as Helicobacter pylori eradication, show limited efficacy in reversing precancerous molecular changes. Zuojin Pill (ZJP), a traditional Chinese medicine, has demonstrated potential for treating digestive disorders and may offer a promising approach for PLGC intervention.

Experimental study of the effects of pirfenidone and nintedanib on joint inflammation and pulmonary fibrosis in a rheumatoid arthritis-associated interstitial lung disease mouse model.

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious pulmonary complication in rheumatoid arthritis (RA) patients, is one of the leading causes of death in RA patients. This study was designed to determine whether pirfenidone and nintedanib can alleviate joint inflammation and pulmonary fibrosis in a mouse model of RA-ILD.

Methods: Male DBA/1 mice were injected with bovine type II collagen (bCII) to establish the RA-ILD model.

Piceatannol-3'-O-β-D-glucopyranoside inhibits neuroexcitotoxicity and ferroptosis through NMDAR/NRF2/BACH1/ACSL4 pathway in acute ischemic stroke.

Background: Neuronal protection is a well-established method of acute ischemic stroke (AIS) treatment. The pharmacodynamic effect of Piceatannol-3'-O-β-D-glucopyranoside (Chinese name: Quzhazhigan, QZZG) on AIS has been reported, but the molecular mechanism of this effect remains unknown.

Purpose: The purpose of this study is to elucidate the pharmacodynamic effects and mechanisms of QZZG in the treatment of AIS.

hPSCs-derived brain organoids for disease modeling, toxicity testing and drug evaluation.

Due to the differences and variances in genetic background, in vitro and animal models cannot meet the modern medical exploration of real human brain structure and function. Recently, brain organoids generated by human pluripotent stem cells (hPSCs) can mimic the structure and physiological function of human brain, being widely used in medical research. Brain organoids generated from normal hPSCs or patient-derived induced pluripotent stem cells offer a more promising approach for the study of diverse human brain diseases.

Herbal Multiomics Provide Insights into Gene Discovery and Bioproduction of Triterpenoids by Engineered Microbes.

Triterpenoids are natural products found in plants that exhibit industrial and agricultural importance. Triterpenoids are typically synthesized through two main pathways: the mevalonate (MVA) and methylerythritol 4-phosphate (MEP) pathways. They then undergo structural diversification with the help of squalene cyclases (OSCs), cytochrome P450 monooxygenases (P450s), UDP glycosyltransferases (UGTs), and acyltransferases (ATs).

Similar outcomes between HLA-haploid and matched sibling donor hematopoietic stem cell transplantation: a multicenter, retrospective study and severe aplastic anemia transplant-specific prognostic scoring system.

In recent years, great progress has been made in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) treatment for hematological malignant diseases because of the advent of novel conditioning regimens, optimized graft manipulation, improved graft-versus-host disease (GVHD) prophylaxis, and advances in supportive care. Recent studies have shown very favorable outcomes in severe aplastic anemia (SAA) patients, with comparable outcomes to those of patients receiving immune suppressive therapy (IST) and allogeneic HSCT from a matched sibling donor (MSD) or matched unrelated donor (MUD). However, most of the previous studies relied on single-center data analyses, and the conditioning regimen, GVHD prophylaxis and supportive care used were relatively singular.

Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells.

Introduction: Cannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.

Methods: Herein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells.

Association between genetic polymorphisms and gestational diabetes mellitus susceptibility in a Chinese population.

Background: Although the association between HHEX, IGF2BP2, and FTO polymorphisms and the risk of GDM has been investigated in several studies, the findings have been inconsistent across different populations. The study aimed to investigate the association between genetic polymorphisms and GDM risk in a Chinese population.

Methods: 502 control volunteers and 500 GDM patients were enrolled.