Chondrocyte-targeted bilirubin/rapamycin carrier-free nanoparticles alleviate oxidative stress and modulate autophagy for osteoarthritis therapy.

Osteoarthritis (OA) is a prevalent chronic disease, characterized by the destruction of joint cartilage and synovitis, affects over 7 % of people worldwide. Disease-modifying treatments for OA still face significant challenges. Chondrocytes, as the exclusive cellular component of articular cartilage, play a pivotal role in synthesizing the intricate matrix of cartilage, thereby assuming a critical responsibility in facilitating its renewal and repair processes.

Guilu Erxian Jiao remodels dendritic spine morphology through activation of the hippocampal TRPC6-CaMKIV-CREB signaling pathway and suppresses fear memory generalization in rats with post-traumatic stress disorder.

Ethnopharmacological Relevance: Guilu Erxian Jiao (GLEXJ) is a renowned traditional Chinese herbal formula used to tonify the kidney. It is employed to treat psychiatric disorders, and alleviate memory impairment, cognitive dysfunction, and behavioral disorders. Modern pharmacological studies have demonstrated GLEXJ's ability to significantly inhibit the fear response in post-traumatic stress disorder (PTSD) and facilitate the extinction of fear memory.

Synthetic GPCRs for programmable sensing and control of cell behaviour.

Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery and basic research. However, established technologies such as chimeric antigen receptors can only detect immobilized antigens, have limited output scope and lack built-in drug control. Here we engineer synthetic G-protein-coupled receptors (GPCRs) that are capable of driving a wide range of native or non-native cellular processes in response to a user-defined antigen.

Construction of poly (styrene-divinylbenzene)@tris(4-aminophenyl)amine-p-phthalaldehyde-triethylenetetramine core-shell microspheres for the preparation of ion chromatography stationary phase.

Core-shell composite microspheres are increasingly favored for the development of stationary phases due to their ability to integrate the monodispersity of inner core with the functional versatility of outer shell. In this study, poly(styrene-divinylbenzene)@(tris(4-aminophenyl)amine-p-phthalaldehyde-triethylenetetramine) (PS-DVB@TAPA-PPA-TETA) core-shell composite microspheres were constructed via an amine-aldehyde condensation reaction. The resultant microspheres were subsequently quaternized using the residual amine groups of TETA in the shell to create an effective anion-exchange stationary phase.

A machine learning-based predictive model discriminates nonalcoholic steatohepatitis from nonalcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver-related morbidity and mortality. The diagnosis of non-alcoholic steatohepatitis (NASH) plays a crucial role in the management of NAFLD patients.

Objective: The aim of our observational study was to build a machine learning model to identify NASH in NAFLD patients.

Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system.

Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy.

Supramolecular nanoparticle loaded with bilirubin enhances cartilage protection and alleviates osteoarthritis via modulating oxidative stress and inflammatory responses.

Osteoarthritis (OA) is a chronic inflammation that gradually leads to cartilage degradation. Prolonged chondrocyte oxidative stress contributes to the development of diseases, including chondrocyte apoptosis, cartilage matrix degradation, and aggravation of articular cartilage damage. Bilirubin (BR) possesses strong antioxidant properties by scavenging reactive oxygen species (ROS) and potent protection effects against inflammation.

Construction of amine-rich coating utilizing amine curing reaction of triglycidyl isocyanate with triethylenetetramine on the surface of poly(styrene-divinylbenzene) microspheres for preparation of anion exchange stationary phase.

Epoxy resins, as important thermosetting polymers, exhibit excellent adhesion to various substrates. In view of this, reticulate coating of triglycidyl isocyanate with triethylenetetramine was introduced onto the surface of poly(styrene-divinylbenzene) utilizing amine curing reaction to obtain poly(styrene-divinylbenzene)@triglycidyl isocyanate-triethylenetetramine composite microspheres. The amino groups and epoxy groups of triglycidyl isocyanate-triethylenetetramine endowed poly(styrene-divinylbenzene) with good reactivity, which could be quaternized under mild conditions to obtain an anion exchange chromatographic stationary phase.

Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques.

In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable oocytes during IVM stands as a viable strategy.

Adverse childhood experiences and self-esteem among adolescents: The role of social capital and gender.

Introduction: Adverse childhood experiences have long-lasting effects on the self-esteem of adolescents. However, the extrinsic mechanism linking them to self-esteem, which is more modifiable, has rarely been examined. Therefore, this study examined the mediating roles of family, school, and peer social capital and the moderating role of gender in the association between adverse childhood experiences and adolescent self-esteem.

GABAergic interneurons in the hippocampal CA1 mediate contextual fear generalization in PTSD rats.

Fear overgeneralization is widely accepted as a pathogenic marker of post-traumatic stress disorder (PTSD). Recently, GABAergic interneurons have been regarded as key players in the regulation of fear memory. The role of hippocampal GABAergic interneurons in contextual fear generalization of PTSD remains incompletely understood.

Paeoniflorin exerts anti-PTSD effects in adult rats by modulating hippocampus and amygdala histone acetylation modifications in response to early life stress.

Early life stress (ELS) can cause long-term changes by epigenetic factors, especially histone acetylation modification, playing a crucial role, affect normal cognition, mood, and behavior, and increase susceptibility to post-traumatic stress disorder (PTSD) in adulthood. It has been found that paeoniflorin (PF) can cross the blood-brain barrier to exert anti-PTSD effects on adult PTSD rats. However, whether PF can alleviate the harmful effects caused by ELS in adulthood has not yet been reported.

Synthetic G protein-coupled receptors for programmable sensing and control of cell behavior.

Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery, and basic research. However, established technologies such as chimeric antigen receptors (CARs) can only detect immobilized antigens, have limited output scope, and lack built-in drug control. Here, we engineer synthetic G protein-coupled receptors (GPCRs) capable of driving a wide range of native or nonnative cellular processes in response to user-defined antigen.

Excitatory amino acid transporter supports inflammatory macrophage responses.

Excitatory amino acid transporters (EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues. However, the subcellular location and function of EAAT2 in macrophages are still obscure. In this study, we demonstrated that LPS stimulation increases expression of EAAT2 (coded by Slc1a2) via NF-κB signaling.

Quercetin reshapes gut microbiota homeostasis and modulates brain metabolic profile to regulate depression-like behaviors induced by CUMS in rats.

Quercetin, an abundant flavonoid compound in plants, is considered a novel antidepressant; however, its mechanisms of action are poorly understood. This study aimed to investigate the therapeutic effects of quercetin on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in rats and explore the underlying mechanisms by combining untargeted metabolomics and 16S rRNA sequencing analysis of brain tissue metabolites and gut microbiota. Gut microbiota analysis revealed that at the phylum level, quercetin reduced and the ratio and enhanced .

Targeting methionine metabolism in cancer: opportunities and challenges.

Reprogramming of methionine metabolism is a conserved hallmark of tumorigenesis. Recent studies have revealed mechanisms regulating methionine metabolism within the tumor microenvironment (TME) that drive both cancer development and antitumor immunity evasion. In this review article we summarize advancements in our understanding of tumor regulation of methionine metabolism and therapies in development that target tumor methionine metabolism.

Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo.

The serotonergic system plays important roles in both physiological and pathological processes, and is a therapeutic target for many psychiatric disorders. Although several genetically encoded GFP-based serotonin (5-HT) sensors were recently developed, their sensitivities and spectral profiles are relatively limited. To overcome these limitations, we optimized green fluorescent G-protein-coupled receptor (GPCR)-activation-based 5-HT (GRAB) sensors and developed a red fluorescent GRAB sensor.

Crosstalk of HDAC4, PP1, and GSDMD in controlling pyroptosis.

Gasdermin D (GSDMD) functions as a pivotal executor of pyroptosis, eliciting cytokine secretion following cleavage by inflammatory caspases. However, the role of posttranslational modifications (PTMs) in GSDMD-mediated pyroptosis remains largely unexplored. In this study, we demonstrate that GSDMD can undergo acetylation at the Lysine 248 residue, and this acetylation enhances pyroptosis.

Structural basis of DNA recognition of the CosR regulator.

Unlabelled: is a foodborne pathogen commonly found in the intestinal tracts of animals. This pathogen is a leading cause of gastroenteritis in humans. Besides its highly infectious nature, is increasingly resistant to a number of clinically administrated antibiotics.

Interguild fungal competition in litter and soil inversely modulate microbial necromass accumulation during Loess Plateau forest succession.

Microbial interactions determine ecosystem carbon (C) and nutrient cycling, yet it remains unclear how interguild fungal interactions modulate microbial residue contribution to soil C pools (SOC) during forest succession. Here, we present a region-wide investigation of the relative dominance of saprophytic versus symbiotic fungi in litter and soil compartments, exploring their linkages to soil microbial residue pools and potential drivers along a chronosequence of secondary Chinese pine (Pinus tabulaeformis) forests on the Loess Plateau. Despite minor changes in C and nitrogen (N) stocks in the litter or soil layers across successional stages, we found significantly lower soil phosphorus (P) stocks, higher ratios of soil C: N, soil N: P and soil C: P but lower ratios of litter C: N and litter C: P in old (>75 years) than young stands (<30 years).

Hippocampal parvalbumin and perineuronal nets: Possible involvement in anxiety-like behavior in rats.

The excitatory-inhibitory imbalance has been considered an important mechanism underlying stress-related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS-exposed rats exhibited increased anxiety-like behavior.