dCasMINI-mediated therapy rescues photoreceptors degeneration in a mouse model of retinitis pigmentosa.

Retinitis pigmentosa (RP) is characterized by degeneration of rod and cone photoreceptors that progresses to irreversible blindness. Now, there are no mutation-agnostic approaches to treat RP. Here, we utilized a single adeno-associated virus (AAV)-based CRISPR activation system to activate phosphodiesterase 6B (Pde6b) to mitigate the severe degeneration in mice.

Lipid-based nanoparticles for drug delivery in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that predominantly affects dopaminergic neurons in the substantia nigra and ventral tegmental area, resulting in symptoms such as tremors, muscle rigidity, bradykinesia, and potential cognitive and affective disturbances. The effective delivery of pharmacological agents to the central nervous system is hindered by various factors, including the restrictive properties of the blood‒brain barrier and blood‒spinal cord barrier, as well as the physicochemical characteristics of the drugs. Traditional drug delivery methods may not provide the therapeutic concentrations necessary for functional restoration in PD patients.

A pump-free microfluidic co-culture system for investigating NK cell-tumor spheroid interactions in flow conditions.

Natural killer (NK) cells are pivotal in immunotherapy due to their potent tumor-targeting capabilities. However, accessible in vitro 3D dynamic models for evaluating Tumor Infiltrating Natural Killer Cells (TINKs) remain scarce. This study addresses this gap by developing a novel pump-free microfluidic chip to investigate the interactions between NK-92 cells and prostate DU 145 tumor spheroids.

Myokines May Be the Answer to the Beneficial Immunomodulation of Tailored Exercise-A Narrative Review.

Exercise can regulate the immune function, activate the activity of immune cells, and promote the health of the organism, but the mechanism is not clear. Skeletal muscle is a secretory organ that secretes bioactive substances known as myokines. Exercise promotes skeletal muscle contraction and the expression of myokines including irisin, IL-6, BDNF, etc.

Unraveling the Mechanisms of S100A8/A9 in Myocardial Injury and Dysfunction.

S100A8 and S100A9, which are prominent members of the calcium-binding protein S100 family and recognized as calprotectin, form a robust heterodimer known as S100A8/A9, crucial for the manifestation of their diverse biological effects. Currently, there is a consensus that S100A8/A9 holds promise as a biomarker for cardiovascular diseases (CVDs), exerting an influence on cardiomyocytes or the cardiovascular system through multifaceted mechanisms that contribute to myocardial injury or dysfunction. In particular, the dualistic nature of S100A8/A9, which functions as both an inflammatory mediator and an anti-inflammatory agent, has garnered significantly increasing attention.

Internet use, dietary habits and adolescent obesity: evidence from China.

The widespread use of Internet has substantially influenced adolescents' lifestyles. This paper systematically explored the impact of Internet use on adolescent obesity and unveiled the underlying mechanism in China. We discussed the relationship among Internet use, dietary habits and obesity, and estimated the impact using panel data collected by the China Health and Nutrition Survey.

Co-application of biochars and improved the quality of coastal saline soil and promoted the growth of forage.

Soil quality is defined as the ability of soil to maintain the soil environment and the biosphere. Due to the limitation of salt and alkali stress, soil quality can be reduced, which in turn affects agricultural production. Biochar is widely used in saline-alkali land improvement because of its special pore structure and strong ion exchange ability, while is widely used in saline-alkali land improvement because it can symbiose with plants and improve plant stress resistance.

Study on the role of MYCN in retinoblastoma by inhibiting p53 and activating wnt/βcatenin/Fra-1 signaling pathway by reducing DKK3.

Retinoblastoma (RB) is a pediatric malignancy, typically diagnosed at birth or during early childhood. The pathogenesis of RB is marked by the amplification of the Basic Helix-Loop-Helix (BHLH) Transcription Factor MYCN, which serves as a transcriptional regulator capable of binding to Dickkopf 3 (DKK3). However, the precise role of DKK3 in the malignant progression of RB cells caused by MYCN remains elusive.

Primary cilia formation requires the Leigh syndrome-associated mitochondrial protein NDUFAF2.

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye.

M1/M2 macrophage-targeted nanotechnology and PROTAC for the treatment of atherosclerosis.

Macrophages play key roles in atherosclerosis progression, and an imbalance in M1/M2 macrophages leads to unstable plaques; therefore, M1/M2 macrophage polarization-targeted treatments may serve as a new approach in the treatment of atherosclerosis. At present, there is little research on M1/M2 macrophage polarization-targeted nanotechnology. Proteolysis-targeting chimera (PROTAC) technology, a targeted protein degradation technology, mediates the degradation of target proteins and has been widely promoted in preclinical and clinical applications as a novel therapeutic modality.

Individual differences in the discounting of combination outcomes in which immediate gains are followed by delayed losses.

The vast majority of studies on discounting have focused on simple delayed outcomes, but most everyday decisions are more complicated. The present experiment focused on one such scenario, an iconic self-control situation in which immediate gains are followed by delayed losses. The same participants were studied in all conditions to permit examination of individual differences in choice behavior using intercorrelations and factor analysis.

Sex differences in 3- to 5-year-old children's motor competence: A pooled cross-sectional analysis of 6241 children.

There is some, albeit inconsistent, evidence supporting sex differences in preschoolers' motor competence (MC), with these observations not uniform when analyzed by age, and cultural groups. Thus, this study examined sex differences across ages in 3- to 5-year-old children's MC. A cross-country pooled sample of 6241 children aged 3-5 years (49.

Social health and subsequent cognitive functioning in people aged 50 years and older: examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies.

Background: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition.

Post-traumatic stress, depression, and anxiety during the 2021 Myanmar conflict: a nationwide population-based survey.

Background: The UN warns that Myanmar faces the 'triple crises' of mass conflict, uncontrolled COVID-19, and economic collapse. Therefore, we aimed to assess the population mental health burden, healthcare needs, and the associated risk factors in Myanmar.

Methods: We established a nationwide random sample and recruited 1038 adults via random digit dialling from July 3-Aug 9, 2021, during the ongoing conflict since Feb 1, 2021, and surge in SARS-CoV-2 infections.

A comparative analysis of TCR immune repertoire in COVID-19 patients.

The coronavirus disease 2019 (COVID-19) has merged as a global health threat since its outbreak in December 2019. Despite widespread recognition, there has been a paucity of studies focusing on the T cell receptor (TCR) bias in adaptive immunity induced by SARS-CoV-2. This research conducted a comparative analysis of the TCR immune repertoire to identify notable αβ TCR bias sequences associated with the SARS-CoV-2 virus antigen.

Base editing correction of OCRL in Lowe syndrome: ABE-mediated functional rescue in patient-derived fibroblasts.

Lowe syndrome, a rare X-linked multisystem disorder presenting with major abnormalities in the eyes, kidneys, and central nervous system, is caused by mutations in OCRL gene (NG_008638.1). Encoding an inositol polyphosphate 5-phosphatase, OCRL catalyzes the hydrolysis of PI(4,5)P2 into PI4P.

KLF transcription factors in bone diseases.

Krüppel-like factors (KLFs) are crucial in the development of bone disease. They are a family of zinc finger transcription factors that are unusual in containing three highly conserved zinc finger structural domains interacting with DNA. It has been discovered that it engages in various cell functions, including proliferation, apoptosis, autophagy, stemness, invasion and migration, and is crucial for the development of human tissues.

Moderate mechanical stress suppresses chondrocyte ferroptosis in osteoarthritis by regulating NF-κB p65/GPX4 signaling pathway.

Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process of osteoarthritis (OA). Herein, we investigated the protective effect of moderate mechanical stress on chondrocyte ferroptosis and further revealed the internal molecular mechanism. Intra-articular injection of sodium iodoacetate (MIA) was conducted to induce the rat model of OA in vivo, meanwhile, interleukin-1 beta (IL-1β) was treated to chondrocytes to induce the OA cell model in vitro.

High throughput generating stable spheroids with tip-refill wafer.

Three-dimensional (3D) cell cultures have garnered significant attention in biomedical research due to their ability to mimic the in vivo cellular environment more accurately. The formation of 3D cell spheroids using hanging drops has emerged as a cost-effective and crucial method for generating uniformly-sized spheroids. This study aimed to validate the potential of a tip-refill wafer (TrW), a disposable laboratory item used to hold pipette tips, in facilitating 3D cell culture.