Thermogenic Adipocytes Promote M2 Macrophage Polarization through CNNM4-Mediated Mg Secretion.

M2 macrophages promote adipose tissue thermogenesis which dissipates energy in the form of heat to combat obesity. However, the regulation of M2 macrophages by thermogenic adipocytes is unclear. Here, it is identified magnesium (Mg) as a thermogenic adipocyte-secreted factor to promote M2 macrophage polarization.

The WFS1-ZnT3-Zn Axis Regulates the Vicious Cycle of Obesity and Depression.

Obesity, a growing global health concern, is closely linked to depression. However, the neural mechanism of association between obesity and depression remains poorly understood. In this study, neural-specific WFS1 deficiency exacerbates the vicious cycle of obesity and depression in mice fed a high-fat diet (HFD), positioning WFS1 as a crucial factor in this cycle.

Intermittent Fasting-Induced Orm2 Promotes Adipose Browning via the GP130/IL23R-p38 Cascade.

Intermittent fasting (IF) plays a critical role in mitigating obesity, yet the precise biological mechanisms require further elucidation. Here Orosomucoid 2 (Orm2) is identified as an IF-induced hepatokine that stimulates adipose browning. IF induced Orm2 expression and secretion from the liver through peroxisome proliferator-activated receptor alpha (PPARα).

Directly modulated deformed-square-FP coupled-cavity laser with intracavity-mode photon-photon resonance.

We propose and demonstrate a high-speed directly modulated laser based on a hybrid deformed-square-FP coupled cavity (DFC), aiming for a compact-size low-cost light source in next-generation optical communication systems. The deformed square microcavity is directly connected to the FP cavity and utilized as a wavelength-sensitive reflector with a comb-like and narrow-peak reflection spectrum for selecting the lasing mode, which can greatly improve the single-mode yield of the laser and the quality (Q) factor of the coupled mode. By optimizing the device design and operating condition, the modulation bandwidth of the DFC laser can be enhanced due to the intracavity-mode photon-photon resonance effect.

ISR inhibition reverses pancreatic β-cell failure in Wolfram syndrome models.

Pancreatic β-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of β cell specific Wfs1 knockout were applied to model β-cell failure in WS.

Self-pulsing and dual-mode lasing in a square microcavity semiconductor laser.

Self-pulsing and dual-mode lasing in a square microcavity semiconductor laser are studied experimentally. Self-sustained pulses originating from undamped relaxation oscillation induced by a two-mode interaction are obtained, as the injection current is slightly above the laser threshold. A repetition frequency of 4.

Charting a high-resolution roadmap for regeneration of pancreatic β cells by in vivo transdifferentiation from adult acinar cells.

Adult mammals have limited capacity to regenerate functional cells. Promisingly, in vivo transdifferentiation heralds the possibility of regeneration by lineage reprogramming from other fully differentiated cells. However, the process of regeneration by in vivo transdifferentiation in mammals is poorly understood.

Narrow linewidth optical frequency comb based on a directly modulated microcavity laser with optical feedback.

A narrow linewidth optical frequency comb (OFC) based on a directly modulated microcavity laser with external optical feedback is investigated numerically and demonstrated experimentally. Based on the numerical simulations with rate equations, the evolution of the optical and electrical spectra is presented for the direct-modulated microcavity laser with increased feedback strength, and the linewidth property is improved at suitable feedback conditions. The simulation results also show good robustness for the generated OFC in terms of feedback strength and phase.

Effects of TCPP and TCEP exposure on human corneal epithelial cells: Oxidative damage, cell cycle arrest, and pyroptosis.

Tris(2-chloroisopropyl) phosphate (TCPP) and Tris(2-chloroethyl) phosphate (TCEP) are the widely used organophosphorus flame retardants indoors and easily accessible to the eyes as the common adhesive components of dust and particle matter, however, hardly any evidence has demonstrated their corneal toxicity. In this study, the adverse effects of TCPP, TCEP, and TCPP + TCEP exposure on human corneal epithelial cells (HCECs) were investigated. The cell viability and morphology, intracellular reactive oxygen species (ROS), cell cycle, and the expressions of cell cycle and pyroptosis-related genes were assessed to explain the underlying mechanisms.

Thermogenic adipocyte-derived zinc promotes sympathetic innervation in male mice.

Sympathetic neurons activate thermogenic adipocytes through release of catecholamine; however, the regulation of sympathetic innervation by thermogenic adipocytes is unclear. Here, we identify primary zinc ion (Zn) as a thermogenic adipocyte-secreted factor that promotes sympathetic innervation and thermogenesis in brown adipose tissue and subcutaneous white adipose tissue in male mice. Depleting thermogenic adipocytes or antagonizing β-adrenergic receptor on adipocytes impairs sympathetic innervation.

Modeling disrupted synapse formation in wolfram syndrome using hESCs-derived neural cells and cerebral organoids identifies Riluzole as a therapeutic molecule.

Dysregulated neurite outgrowth and synapse formation underlie many psychiatric disorders, which are also manifested by wolfram syndrome (WS). Whether and how the causative gene WFS1 deficiency affects synapse formation remain elusive. By mirroring human brain development with cerebral organoids, WFS1-deficient cerebral organoids not only recapitulate the neuronal loss in WS patients, but also exhibit significantly impaired synapse formation and function associated with reduced astrocytes.

Nonlinear dynamics of a semiconductor microcavity laser subject to frequency comb injection.

The nonlinear dynamical behaviors of a semiconductor microcavity laser with frequency comb injection have been experimentally and numerically investigated. The microcavity laser is harmonically locked to a unit fraction of the comb spacing due to the undamped relaxation oscillation at certain conditions, creating additional comb lines with reduced frequency spacing. The stability maps indicating various locking states are obtained based on rate equations, which demonstrates that the locking regions are closely related to the relaxation oscillation.

Indoor air pollution and human ocular diseases: Associated contaminants and underlying pathological mechanisms.

People spend a long time indoors, especially young children. The risk of indoor pollution on human health is one of the current hotspots in environmental and public health. The human ocular surface is highly susceptible to indoor environment quality.

Hepatic ER stress suppresses adipose browning through ATF4-CIRP-ANGPTL3 cascade.

Hepatic endoplasmic reticulum (ER) stress is a hallmark of obesity-induced liver steatosis and contributes to the progress of steatosis and insulin resistance in liver. However, its influence on adipose function is still unclear. Here, we identify a hepatic ER stress-induced activating transcription factor 4 (ATF4)-cold-inducible RNA-binding protein (CIRP)-angiopoietin-related protein3 (ANGPTL3) cascade critical for the regulation of adipose browning.

Effects of Nickel at Environmentally Relevant Concentrations on Human Corneal Epithelial Cells: Oxidative Damage and Cellular Apoptosis.

Nickel (Ni) is ubiquitous in the environment and evidence has suggested that Ni can cause ocular surface inflammation, especially in fine particulate matter and personal products. Continuous daily exposure to Ni-containing dust may adversely impact the human cornea, whereas the underlying mechanism of this phenomenon remains not fully understood. Here, human corneal epithelial cells (HCEC) were employed to analyze the toxicity of Ni via detections of cell morphology, cell viability, reactive oxygen species production, cell apoptosis rate, and apoptotic gene expression levels after exposure for 24 h to uncover the damage of Ni to the cornea.

ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes.

Human embryonic stem cell-derived β cells (SC-β cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion.

[Chiropractic plus plum-blossom needling combined with flexibility training on attention deficit in mentally-retarded adolescents].

Objective: To observe the clinical efficacy of chiropractic plus plum-blossom needling combined with flexibility training for attention deficit in mentally-retarded adolescents.

Methods: Thirty adolescents with mild mental retardation were randomly divided into a medical rehabilitation plus flexibility training group (10 cases, 2 cases dropped off), a flexibility training group (10 cases, 1 case dropped off) and a control group (10 cases). The patients in the flexibility training group received flexibility training, once every other day, 3 times a week for 12 weeks.

Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice.

Exercise benefits M2 macrophage polarization, energy homeostasis and protects against obesity partially through exercise-induced circulating factors. Here, by unbiased quantitative proteomics on serum samples from sedentary and exercised mice, we identify parvalbumin as a circulating factor suppressed by exercise. Parvalbumin functions as a non-competitive CSF1R antagonist to inhibit M2 macrophage activation and energy expenditure in adipose tissue.

Manipulation of lasing modes in a circular-side octagonal microcavity laser with a spatially distributed current injection.

We propose and demonstrate a circular-side octagonal microcavity (COM) semiconductor laser with a spatially distributed current injection for manipulating the lasing modes. There are two types of high-quality-factor whispering-gallery (WG) modes with distinct field patterns in a COM: the four-bounced quadrilateral modes and the eight-bounced octagonal modes. By designing two separated p-electrodes, the COM laser is divided into two regions that are pumped independently to select specific modes for lasing.

[Abdominal acupoint thread embedding therapy based on "brain-intestinal connection" for mild-to-moderate Alzheimer's disease and its effects on serum levels of APP and Aβ].

Objective: To compare the clinical efficacy of abdominal acupoint thread embedding therapy based on "brain-intestinal connection" combined with donepezil hydrochloride tablets and oral donepezil hydrochloride tablets alone for mild-to-moderate Alzheimer's disease (AD) and observe its effects on amyloid precursor protein (APP) and β-amyloid protein (Aβ).

Methods: Sixty patients with AD were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 3 cases dropped off). The patients in the control group were treated with donepezil hydrochloride tablets (5 mg per day); based on the treatment in the control group, the patients in the observation group were treated with abdominal acupoint thread embedding therapy at Zhongwan (CV 12), Xiawan (CV 10), Huaroumen (ST 24), Wailing (ST 26), Daheng (SP 15), etc.

MiniCAFE, a CRISPR/Cas9-based compact and potent transcriptional activator, elicits gene expression in vivo.

CRISPR-mediated gene activation (CRISPRa) is a promising therapeutic gene editing strategy without inducing DNA double-strand breaks (DSBs). However, in vivo implementation of these CRISPRa systems remains a challenge. Here, we report a compact and robust miniCas9 activator (termed miniCAFE) for in vivo activation of endogenous target genes.

Sequential fate-switches in stem-like cells drive the tumorigenic trajectory from human neural stem cells to malignant glioma.

Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM.

Organophosphorus flame retardant TDCPP-induced cytotoxicity and associated mechanisms in normal human skin keratinocytes.

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), a widely used organophosphorus flame retardant, has been frequently detected in the environment including indoor dust. Long-term exposure to TDCPP-containing dust may adversely affect human skin, however, little is known about its potential cytotoxicity. In this study, human skin keratinocytes (HaCaT) were employed to study TDCPP-induced cytotoxicity and associated mechanisms.