Detecting monogenic disorders in utero non-invasively based on fetal nucleated red blood cells highly-purified by multi-functional magnetic nanoparticles.

Background: Fetal monogenic disorders cause gestation anomalies, birth defects or infant mortality. Implementing non-invasive prenatal testing (NIPT) of these diseases benefits timely intervention while avoids high risk of inducing maternal complications and fetal injuries. However, fetal materials used for current NIPT (e.

Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response.

Non-Invasive Prenatal Diagnosis of Chromosomal and Monogenic Disease by a Novel Bioinspired Micro-Nanochip for Isolating Fetal Nucleated Red Blood Cells.

Purpose: Fetal nucleated red blood cells (fNRBCs) in the peripheral blood of pregnant women contain comprehensive fetal genetic information, making them an ideal target for non-invasive prenatal diagnosis (NIPD). However, challenges in identifying, enriching, and detecting fNRBCs limit their diagnostic potential.

Methods: To overcome these obstacles, we developed a novel biomimetic chip, replicating the micro-nano structure of red rose petals on polydimethylsiloxane (PDMS).

Topical administration of GLP-1 eyedrops improves retinal ganglion cell function by facilitating presynaptic GABA release in early experimental diabetes.

Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the brain, defects in y-aminobutyric acid (GABA) synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 (GLP-1) has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to RGCs and whether and how GLP-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to RGCs.

Compound heterozygous mutation of the gene causes autosomal recessive spinocerebellar ataxia 20.

The article aims to provide genetic counseling to a family with two children who were experiencing growth and developmental delays. Clinical information of the proband was collected. Peripheral blood was collected from core family members to identify the initial reason for growth and developmental delays by whole exome sequencing (WES) and Sanger sequencing.

Identification of chromosomal abnormalities in miscarriages by CNV-Seq.

Objective: The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies.

Methods: This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs).

Exendin-4 promotes retinal ganglion cell survival and function by inhibiting calcium channels in experimental diabetes.

Progressive damage of retinal ganglion cells (RGCs) is observed in early diabetic retinopathy. Intracellular Ca overload mediated by Ca influx through voltage-gated Ca channels (VGCCs) is involved in neurodegeneration, whereas glucagon-like peptide-1 (GLP-1) provides neuroprotection. However, whether GLP-1 plays a neuroprotective role in diabetic retinas by modulating VGCCs remains unknown.

Short-term acute bright light exposure induces a prolonged anxiogenic effect in mice via a retinal ipRGC-CeA circuit.

Light modulates mood through various retina-brain pathways. We showed that mice treated with short-term acute bright light exposure displayed anxiety-related phenotypes in a prolonged manner even after the termination of the exposure. Such a postexposure anxiogenic effect depended upon melanopsin-based intrinsically photosensitive retinal ganglion cell (ipRGC) activities rather than rod/cone photoreceptor inputs.

Characterization of the Glucan-Branching Enzyme GlgB Gene from Swine Intestinal Bacteria.

Starch hydrolysis by gut microbiota involves a diverse range of different enzymatic activities. Glucan-branching enzyme GlgB was identified as the most abundant glycosidase in Firmicutes in the swine intestine. GlgB converts α-(1→4)-linked amylose to form α-(1→4,6) branching points.

Secondary-Heteroatom-Doping-Derived Synthesis of N, S Co-Doped Graphene Nanoribbons for Enhanced Oxygen Reduction Activity.

The rareness and weak durability of Pt-based electrocatalysts for oxygen reduction reactions (ORRs) have hindered the large-scale application of fuel cells. Here, we developed an efficient metal-free catalyst consisting of N, S co-doped graphene nanoribbons (N, S-GNR-2s) for ORRs. GNRs were firstly synthesized via the chemical unzipping of carbon nanotubes, and then N, S co-doping was conducted using urea as the primary and sulfourea as the secondary heteroatom sources.

The role of ipRGCs in ocular growth and myopia development.

The increasing global prevalence of myopia calls for elaboration of the pathogenesis of this disease. Here, we show that selective ablation and activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in developing mice induced myopic and hyperopic refractive shifts by modulating the corneal radius of curvature (CRC) and axial length (AL) in an opposite way. Melanopsin- and rod/cone-driven signals of ipRGCs were found to influence refractive development by affecting the AL and CRC, respectively.

Signaling Mechanism for Modulation by GLP-1 and Exendin-4 of GABA Receptors on Rat Retinal Ganglion Cells.

Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (G) inhibitor NF 449 abolished the exendin-4 effect.

1,25-Dihydroxyvitamin D Inhibits Osteoarthritis by Modulating Interaction Between Vitamin D Receptor and NLRP3 in Macrophages.

Background: Osteoarthritis (OA) is the most prevalent chronic joint disease globally. Loss of extracellular matrix (ECM) by chondrocytes is a classic feature of OA. Inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), secreted mainly by macrophages, promote expression of matrix degrading proteins and further aggravate progression of OA.

Extracellular vesicles derived from LPS-preconditioned human synovial mesenchymal stem cells inhibit extracellular matrix degradation and prevent osteoarthritis of the knee in a mouse model.

Background: Previous studies report that lipopolysaccharide (LPS)-preconditioned mesenchymal stem cells have enhanced trophic support and improved regenerative and repair properties. Extracellular vesicles secreted by synovial mesenchymal stem cells (EVs) can reduce cartilage damage caused by osteoarthritis (OA). Previous studies show that extracellular vesicles secreted by LPS-preconditioned synovial mesenchymal stem cells (LPS-pre EVs) can improve the response to treatment of osteoarthritis (OA).

Orexin-A Intensifies Mouse Pupillary Light Response by Modulating Intrinsically Photosensitive Retinal Ganglion Cells.

We show for the first time that the neuropeptide orexin modulates pupillary light response, a non-image-forming visual function, in mice of either sex. Intravitreal injection of the orexin receptor (OXR) antagonist TCS1102 and orexin-A reduced and enhanced pupillary constriction in response to light, respectively. Orexin-A activated OXRs on M2-type intrinsically photosensitive retinal ganglion cells (M2 cells), and caused membrane depolarization of these cells by modulating inward rectifier potassium channels and nonselective cation channels, thus resulting in an increase in intrinsic excitability.

Egr-1 and RNA POL II facilitate glioma cell GDNF transcription induced by histone hyperacetylation in promoter II.

The specific mechanisms for epigenetic regulation of gene transcription remain to be elucidated. We previously demonstrated that hyperacetylation of histone H3K9 in promoter II of glioma cells promotes high transcription of the glial cell line-derived neurotrophic factor (GDNF) gene. This hyperacetylation significantly enhanced Egr-1 binding and increased the recruitment of RNA polymerase II (RNA POL II) to that region (P < 0.