Formaldehyde Exposure Induces Systemic Epigenetic Alterations in Histone Methylation and Acetylation.

Formaldehyde (FA) is a pervasive environmental organic pollutant and a Group 1 human carcinogen. While FA has been implicated in various cancers, its genotoxic effects, including DNA damage and DNA-protein cross-linking, have proven insufficient to fully explain its role in carcinogenesis, suggesting the involvement of epigenetic mechanisms. Histone post-translational modifications (PTMs) on H3 and H4, which are critical for regulating gene expression, may contribute to FA-induced pathogenesis, as lysine and arginine residues serve as targets for FA-protein adduct formation.

Animal models of developmental toxicity induced by early life electronic-cigarettes exposure.

The rising prevalence of electronic-cigarettes (E-cigs) use during pregnancy and lactation can be attributed, in part, to advertising campaigns promoting their safety. Nevertheless, the integrity of E-cigs as a secure substitute for conventional cigarettes necessitates further exploration. Some studies emphasize the toxic role of nicotine in E-cigs, while others underscore the significance of other distinct components whose toxicity cannot be disregarded.

Higher in-hospital proportion of breast milk intake improves brain functional connectivity and neurological assessment in preterm infants.

Objective: Preterm infants may face neurodevelopmental challenges linked to altered brain maturation processes. This study aimed to investigate the impact of in-hospital breast milk intake on brain resting-state functional connectivity (rs-FC) and neurological assessment at discharge in preterm infants.

Methods: We collected data on breast milk intake from 97 preterm infants, evaluated neurological outcomes using the Amiel-Tison Neurological Assessment (ATNAT), and assessed rs-FC via functional near-infrared spectroscopy (fNIRS).

Optimizing the compliance third-party supervision workflow of involved enterprises using artificial intelligence ant colony algorithm.

This article optimized the compliance third-party supervision workflow of the involved enterprises based on the artificial intelligence ant colony optimization (ACO) algorithm. The basic principles and application advantages of ACO were introduced, and a heuristic information matrix was defined using ACO to optimize the data collection and analysis stage of the compliance third-party supervision workflow. During the experimental phase, a feasibility analysis was conducted on the optimization of third-party supervision workflows for compliance by ACO involved enterprises through simulation experiments.

Formaldehyde induces and promotes Alzheimer's disease pathologies in a 3D human neural cell culture system.

Alzheimer's disease (AD) arises from complex multilevel interactions between genetic, epigenetic, and environmental factors. Recent studies suggest that exposure to the environmental and occupational toxicant formaldehyde (FA) may play a significant role in AD development. However, the effects of FA exposure on Aβ and tau pathologies in human neural cell 3D culture systems remain unexplored.

Formaldehyde Exposure Induces Systemic Epigenetic Alterations in Histone Methylation and Acetylation.

Formaldehyde (FA) is a pervasive environmental organic pollutant and a Group 1 human carcinogen. While FA has been implicated in various cancers, its genotoxic effects, including DNA damage and DNA-protein crosslinking, have proven insufficient to fully explain its role in carcinogenesis, suggesting the involvement of epigenetic mechanisms. Histone post-translational modifications (PTMs) on H3 and H4, critical for regulating gene expression, may contribute to FA-induced pathogenesis as lysine and arginine residues serve as targets for FA-protein adduct formation.

Assessment of in vitro assays and quantitative determination of selectivity and modality of inhibitors targeting the cell cycle regulating, oncogenic cyclin-dependent kinases.

At the heart of cancer pathology lies the dysregulated cell cycle, which is often driven by aberrant activities of the cell cycle regulating, cyclin-dependent kinases (CDKs). Efforts to harness the therapeutic potential of modulating CDK activities have led to the development of inhibitors with tailored CDK selectivity. However, uniformity in the methods used to evaluate CDK inhibitor selectivity has been lacking and consequently, direct comparison and interpretation of selectivity profiles determined under different assay conditions is difficult.

Optimizing the thermostability of triketone dioxygenase for engineering tolerance to mesotrione herbicide in soybean and cotton.

Optimized triketone dioxygenase (TDO) variants with enhanced temperature stability parameters were engineered to enable robust triketone tolerance in transgenic cotton and soybean crops. This herbicide tolerance trait, which can metabolize triketone herbicides such as mesotrione and tembotrione, could be useful for weed management systems and provide additional tools for farmers to control weeds. TDO has a low melting point (~39°C-40°C).

Design of Selective BRD4 Inhibitors for the Treatment of Autosomal Dominant Polycystic Kidney Disease.

Epigenetic modulation plays a pivotal role in restraining tumor progression by governing gene expression and protein function. Autosomal dominant polycystic kidney disease (ADPKD), characterized by neoplastic-like progression, can be managed by inhibiting cyst expansion. Of note, the epigenetic regulator BRD4 has been implicated in ADPKD's development.

Structure-Based Rational Design and Evaluation of BET-Aurora Kinase Dual-Inhibitors for Treatment of Cancers.

Simultaneous inhibition of the bromodomain and extra-terminal domain and Aurora kinases is a promising anticancer therapeutic strategy. Based on our previous study on BET-kinase dual inhibitors, we employed the molecular docking approach to design novel dual BET-Aurora kinase A inhibitors. Through several rounds of optimization and with the guidance of the solved cocrystal structure of BRD4 bound to inhibitor , we finally obtained a series of highly potent dual BET-Aurora kinase A inhibitors.

Clinical value of metagenomic sequencing in system evaluation of potential donors and donor-derived infection in kidney transplantation.

Objective: To explore the application and the clinical value of metagenomic sequencing in system evaluation of potential kidney donors, along with donor-derived infection in kidney transplantation.

Methods: A prospective study was conducted on 40 voluntary renal donors in Ningbo Urology and Kidney Disease hospital from January 2021 to August 2023. The results of donor pathogen fed back by metagenomic sequencing were analyzed to understand the clinical significance of metagenomic sequencing in donor evaluation.

Parental perceptions and experiences of kangaroo care for preterm infants in neonatal intensive care units in China: a qualitative study.

Background: kangaroo care (KC), endorsed by the World Health Organization, is an evidence-based intervention that plays a pivotal role in mitigating preterm infant mortality and morbidity. However, this intervention has not been fully integrated into healthcare systems in China. This study aimed to gain insight into parents' perceptions and experiences of KC for preterm infants to contribute to the KC implementation on a larger scale.

Healthcare providers' perceptions and experiences of kangaroo mother care for preterm infants in four neonatal intensive care units in China: a qualitative descriptive study.

Background: Kangaroo mother care (KMC) is an evidence-based intervention that can effectively reduce morbidity and mortality in preterm infants, but it has yet to be widely implemented in health systems in China. Most qualitative studies on KMC for preterm infants focused on the experiences and influencing factors from the perspective of preterm infant parents, while neglecting the perspective of healthcare providers, who played a critical role in guiding KMC practice. Therefore, this study aimed to explore the perceptions and experiences of healthcare providers regarding their involvement in KMC implementation for preterm infants to promote the contextualized implementation of KMC.

Remodeling tumor-associated macrophage for anti-cancer effects by rational design of irreversible inhibition of mitogen-activated protein kinase-activated protein kinase 2.

Mitogen-activated protein kinase-activated protein kinase 2 (MK2) emerges as a pivotal target in developing anti-cancer therapies. The limitations of ATP-competitive inhibitors, due to insufficient potency and selectivity, underscore the urgent need for a covalent irreversible MK2 inhibitor. Our initial analyses of The Cancer Genome Atlas database revealed MK2's overexpression across various cancer types, especially those characterized by inflammation, linking it to poor prognosis and highlighting its significance.

Efficacy and Safety of DPP-4 Inhibitors and Metformin Combinations in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis.

Objective: Several oral antidiabetic regimens are available for treating type 2 diabetes mellitus (T2DM), dipeptidyl peptidase-4 inhibitors (DPP4i) being one of them. We conducted a network meta-analysis (NMA) comparing DPP4i plus metformin (Met) combination with other Met-based oral antidiabetic drug (OAD) combinations used in treating patients with T2DM.

Methods: We searched PubMed and Embase from inception until 19th April, 2022 for phase II and phase III trials in patients with T2DM on Met-based traditional OADs.

The effect of in-hospital breast milk intake on the gut microbiota of preterm infants.

Objective: The aim of this study was to explore the effect of in-hospital breast milk intake on the development of early gut microbiota in preterm infants in two dimensions: longitudinal over time and cross-sectional between groups.

Methods: Researchers collected preterm infants' general data baseline characteristics, recorded their daily breast milk intake, probiotics, and antibiotics use, and collected their stool specimens at 1st week, 2 nd week, 3rd week and 4th week after birth. The researchers analyzed the effect of breast milk on gut microbiota of preterm infants by bioinformatics methods of intra-group longitudinal variation of gut microbiota structure and diversity in preterm infants and cross-sectional differences between >70 % in-hospital breast milk intake (BM) group and ≤70 % (PF) group.

NUPR1 packaged in extracellular vesicles promotes murine triple-negative breast cancer in a type 1 interferon-independent manner.

Aim: This study aims to elucidate the involvement of triple-negative breast cancer (TNBC)-derived extracellular vesicles in metastasis. The loss of components in the type 1 interferon (IFN1) signaling pathway has been linked to the promotion of metastasis. However, IFN1 signaling induces immunological dormancy and promotes tumorigenesis.

Structural and functional characterization of triketone dioxygenase from Oryza Sativa.

The transgenic expression of rice triketone dioxygenase (TDO; also known as HIS1) can provide protection from triketone herbicides to susceptible dicot crops such as soybean. Triketones are phytotoxic inhibitors of plant hydroxyphenylpyruvate dioxygenases (HPPD). The TDO gene codes for an iron/2-oxoglutarate-dependent oxidoreductase.

LOC102549726/miR-760-3p network is involved in the progression of ISO-induced pathological cardiomyocyte hypertrophy via endoplasmic reticulum stress.

Pathological cardiac hypertrophy (CH) is featured by myocyte enlargement and cardiac malfunction. Multiple signaling pathways have been implicated in diverse pathological and physiological processes in CH. However, the function of LOC102549726/miR-760-3p network in CH remains unclear.

Characterization of histone chaperone MCM2 as a key regulator in arsenic-induced depletion of H3.3 at genomic loci.

Arsenic exposure is associated with an increased risk of many cancers, and epigenetic mechanisms play a crucial role in arsenic-mediated carcinogenesis. Our previous studies have shown that arsenic exposure induces polyadenylation of H3.1 mRNA and inhibits the deposition of H3.

A Hybrid Scheme for Disaster-Monitoring Applications in Wireless Sensor Networks.

Disaster monitoring is a primary task for wireless sensor networks. Systems for the rapid reporting of earthquake information are a crucial aspect of disaster monitoring. Furthermore, during emergency rescue after a large earthquake, wireless sensor networks can provide pictures and sound information to save lives.

2,6-diazaspiro[3.4]octan-7-one derivatives as potent sigma-1 receptor antagonists that enhanced the antinociceptive effect of morphine and rescued morphine tolerance.

Opioids are efficacious analgesics for pain treatments. However, their repeated use in large doses often leads to analgesic tolerance, which limits the clinical application. Sigma-1 receptor (σ1R) antagonists were reported to synergistically enhance the analgesic effect of mu opioid receptor (MOR) agonists without amplifying the adverse effects.

Development of a series of quinazoline-2,5-diamine derivatives as potent hematopoietic progenitor kinase 1 (HPK1) inhibitors.

Hematopoietic progenitor kinase 1 (HPK1) is a serine/threonine kinase that serves as the negative regulator of multiple immune signaling pathways. Genetic studies using HPK1 knockout and kinase-dead mice suggested that inhibiting HPK1 either alone or in combination with immune checkpoint blockade could be a promising strategy in cancer immunotherapy. Herein, we report the design, synthesis and structure-activity relationship (SAR) study of a series of potent HPK1 inhibitors bearing quinazoline-2,5-diamine scaffold.