Epilepsy therapy beyond neurons: unveiling astrocytes as cellular targets.

Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies.

Granules alleviate brain damage in spontaneously hypertensive rats by modulating the miR-124/STAT3 signaling axis.

Objectives: To explore the mechanism of Granules (QDG) for alleviating brain damage in spontaneously hypertensive rats (SHRs).

Methods: Twelve 5-week-old SHRs were randomized into SHR control group and SHR+QDG group treated with QDG by gavage at the daily dose of 0.9 g/kg for 12 weeks.

Factor structure and longitudinal measurement invariance of Edinburgh Postnatal Depression Scale during the whole perinatal period: a multicenter cohort study in China.

Background: Perinatal depression is common worldwide, which can cause many adverse effects on the physical and mental health of the mother and baby, as well as the whole family. The Edinburgh Postnatal Depression Scale (EPDS) is an efficient and effective instrument for perinatal depression. However, few studies have examined its longitudinal measurement invariance (LMI) during the whole perinatal period, which is particularly important in longitudinal studies, such as exploring developmental trajectories of perinatal depression and evaluating the effects of certain interventions.

MOF-derived intelligent arenobufagin nanocomposites with glucose metabolism inhibition for enhanced bioenergetic therapy and integrated photothermal-chemodynamic-chemotherapy.

Bioenergetic therapy based on tumor glucose metabolism is emerging as a promising therapeutic modality. To overcome the poor bioavailability and toxicity of arenobufagin (ArBu), a MOF-derived intelligent nanosystem, ZIAMH, was designed to facilitate energy deprivation by simultaneous interventions of glycolysis, OXPHOS and TCA cycle. Herein, zeolitic imidazolate framework-8 was loaded with ArBu and indocyanine green, encapsulated within metal-phenolic networks for chemodynamic therapy and hyaluronic acid modification for tumor targeting.

Transformative Gamified Binocular Therapy for Unilateral Amblyopia in Young Children: Pilot Prospective Efficacy and Safety Study.

Background: Amblyopia is a common cause of visual impairment in children. Compliance with traditional treatments for amblyopia is challenging due to negative psychosocial impacts. Recent shifts in amblyopia treatment have moved from suppressing the dominant eye to enhancing binocular visual function.

Ubiquitination-related Gene UBTD1 Mediates Poor Prognosis of Colorectal Cancer and Affects Colorectal Cancer Cell Proliferation and Ferroptosis.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, and its occurrence and progression are often regulated by genetic and hereditary factors. Ubiquitination and the associated ubiquitin-binding enzymes and ligases regulate the tumor microenvironment and antitumor immunity to mediate tumor pathogenesis and progression. In this study, we examined the molecular characteristics and immunomodulatory effects of ubiquitination-associated genes that mediate CRC prognosis.

High-throughput methylation sequencing reveals novel biomarkers for the early detection of renal cell carcinoma.

Purpose: Renal cell carcinoma (RCC) is a common malignancy, with patients frequently diagnosed at an advanced stage due to the absence of sufficiently sensitive detection technologies, significantly compromising patient survival and quality of life. Advances in cell-free DNA (cfDNA) methylation profiling using liquid biopsies offer a promising non-invasive diagnostic option, but robust biomarkers for early detection are current not available. This study aimed to identify methylation biomarkers for RCC and establish a DNA methylation signature-based prognostic model for this disease.

Pathways to usage intention of mobile health apps among hypertensive patients: A fuzzy-set qualitative comparative analysis.

The efficacy of mHealth apps in managing hypertension has been proven; however, low usage intention remains a significant challenge, warranting an in-depth exploration of the influencing factors. This study aimed to examine the factors influencing hypertensive new users' intention to use mobile health applications through a cross-sectional survey. Fuzzy-set qualitative comparative analysis (fsQCA) was employed to investigate the combinations of various determinants, including technology acceptance, adoption factors, compliance behavior initiation factors, and time motivation factors for decision making.

The impact of borneolum on Citalopram hydrobromide pharmacokinetics and serotonin levels in the hypothalamus of conscious rats.

Borneolum (BO) is an effectiveness adjuvant in facilitating the transportation of central nervous system drugs to the brain by opening the blood-brain barrier (BBB). Citalopram hydrobromide (CIT-HBr), a widely prescribed serotonin (5-HT) reuptake inhibitor, restricts the efficacy due to the BBB, resulting in slow onset and systemic side effects. Enhancing CIT-HBr's efficacy through BO appears to be a promising approach.

Crucial role of the cGAS N terminus in mediating flowable and functional cGAS-DNA condensate formation via DNA interactions.

The DNA-sensing protein cGAS plays a pivotal role in the innate immune response and pathogenesis of various diseases. DNA triggers liquid-liquid phase separation (LLPS) and enhances the enzymatic activity of cGAS. However, the regulatory mechanisms of the disordered N terminus remain unclear.

Discovery of Novel RNA Demethylase FTO Inhibitors Featuring an Acylhydrazone Scaffold with Potent Antileukemia Activity.

Fat mass obesity-associated protein (FTO) has been emerging as a potential therapeutic target for drug discovery in RNA epigenetics. In this work, a series of novel FTO inhibitors featuring an acylhydrazone scaffold were identified, and the optimized compounds - showed potent FTO inhibitory activities with IC values ranging from 7.1 to 9.

Neptunizhulides, Cryptic -AT Polyketide Synthase-Derived Metabolites from NBU2194.

Genome mining of NBU2194 resulted in the identification of a family of 17-membered macrolides, neptunizhulides A-F. Their structures were elucidated by comprehensive spectroscopic data analysis. Stereochemical assignments of the neptunizhulides were determined by -based configuration analysis, ROESY NMR, Mosher's ester derivatization, and bioinformatic predictions.

Nanopore Discriminates Watson-Crick and Hoogsteen Hydrogen Bonds in Multiple DNA Contexts.

Watson-Crick and Hoogsteen hydrogen bonds aid the formation of highly ordered structures in genomic DNA that dynamically govern genetic modes such as gene regulation and replication. Hence, measuring and distinguishing these two types of hydrogen bonds in different DNA contexts are essential for understanding DNA architectures. However, due to their transient nature and minimal structure differences at the sub-nanometer scale, differentiating Watson-Crick hydrogen bonds from Hoogsteen hydrogen bonds is difficult.

Selective Synthesis of Cyclopeptides with a 2-Oxindole or 3a-Hydroxy-hexahydropyrrolo-[2,3-]indole Structure by Cytochrome P450 Enzymes.

The structural groups of 2-oxindole and tricyclic 3a-hydroxy-hexahydropyrrolo-[2,3-]indole (HO-HPI) are important pharmacophores. Chemical synthesis of complex alkaloids containing a 2-oxindole or HO-HPI moiety, especially the latter one, has been a long-standing challenge. Herein, we characterized the P450 enzyme AfnD, and its homologue proteins, HmtT, ClpD, KtzM, and LtzR, as cyclopeptide 2-oxindole and HO-HPI monooxygenases (cpOPMOs) that could introduce a 2-oxindole or HO-HPI moiety into the tryptophan-containing cyclopeptides in a pH-dependent manner.

Insight into the Characteristic Components of Cigar Tobacco.

As an important agricultural product, cigar tobacco lacks reports on chemical compositions. The investigation on characteristic components of Yunnan local cigar tobacco revealed 15 Cembrane-type diterpenes including nine undescribed ones (-). Their structures were elucidated on the basis of extensive spectroscopic analysis, computational calculations, and X-ray diffraction.

Emergence of Chirality in an Optically Active Two-Dimensional Crystal with a Spiral Surface Pattern.

Some one-dimensional (1D) crystals containing a screw dislocation along their longer axis exhibit a helical twist due to lattice strain. These chiral structures have been thoroughly investigated by using transmission electron microscopy. However, whether two-dimensional (2D) crystals with a spiral surface pattern, presumably containing a screw dislocation, are structurally chiral remains unclear because their internal structures are not visible.

Molecular Mechanism for the Unprecedented Metal-Independent Hydroxyl Radical Production from Thioureas and HO.

The most well-known hydroxyl radical (OH)-generating system is the classic iron-mediated Fenton reaction. Thiourea has been considered as an efficient OH scavenger and is frequently used to study the role of OH in various biochemical and medical research studies. Here we found that the highly reactive OH can be produced from thiourea and HO through a metal-independent pathway, as measured by electron spin resonance (ESR) secondary radical spin-trapping and fluorescent methods.

Development and Validation of a Highly Sensitive Isotope-Coded Equivalent Reporter Ion Assay for the Semi-Quantification of Isocoumarins in Complex Matrices.

The accurate quantification of multicomponents using LC-MS is pivotal for ensuring the quality control of herbal medicine, as well as the investigation of their analysis of biological tissue distribution. However, two significant challenges persist: the scarcity of authentic standards and the selection of appropriate internal standards. In this study, we present a highly sensitive isotope-coded equivalent reporter ion assay (iERIA) that combines equivalently quantitative ion and isotope-coded derivatization strategies.

Can microbiota gut-brain axis reverse neurodegenerative disorders in human?

The trillions of microbial populations residing in the gut have recently shown that they can be used as a remedy for various diseases. The gut microbiota-brain-axis interface is one unique pathway that the microbiota demonstrates its medicinal value. This medicinal value is further seen when there is a decline in gut microbial diversity (dysbiosis).

Exosomal miR-302b rejuvenates aging mice by reversing the proliferative arrest of senescent cells.

Cellular senescence, a hallmark of aging, involves a stable exit from the cell cycle. Senescent cells (SnCs) are closely associated with aging and aging-related disorders, making them potential targets for anti-aging interventions. In this study, we demonstrated that human embryonic stem cell-derived exosomes (hESC-Exos) reversed senescence by restoring the proliferative capacity of SnCs in vitro.

Circulating tumour DNA in predicting and monitoring survival of patients with locally advanced rectal cancer undergoing multimodal treatment: long-term results from a prospective multicenter study.

Background: Neoadjuvant chemoradiotherapy (nCRT) is the standard for locally advanced rectal cancer (LARC). However, distant metastasis remains the primary cause of treatment failure. Early identification of high-risk individuals for personalized treatment may offer a solution.

Impact of leachate from boiled-water-treated plastic products on male reproductive health: Insights from transcriptomic and metabolomic profiling.

Given the extensive use of plastic materials in modern society, there is an escalating concern about the potential risks associated with exposure to plastic products. This study investigated the impact of plastic leachates from boiled-water-treated cups, including polypropylene (PP), high-density polyethylene (HDPE), low-density polyethylene (LDPE), polystyrene (PS), and polyethylene terephthalate (PET), on male reproductive health. Experimental mice were administered daily doses of the plastic leachates for 180 consecutive days.

Analysis of the efficacy of Langhans giant cells in controlling cutaneous Mycobacterium marinum infections.

Background: Cutaneous Mycobacterium marinum (M. marinum) infection can lead to the formation of infectious granulomas containing Langhans giant cells (LGCs). Due to concerns about prolonged antibiotic use and the development of drug resistance, its treatment poses challenges.

Discovery of CZY43 as a new small-molecule degrader of pseudokinase HER3.

The pseudokinase HER3 emerges as a promising anti-cancer target, especially for HER2-driven breast cancer and EGFR-mediated non-small cell lung cancer. However, it is challenging to target HER3 by ATP-competitive small molecules because HER3 is catalytically impaired. Herein, we report the discovery of a series of HER3 degraders by connecting a HER3 binder bosutinib with a hydrophobic tag adamantane.