Generation of induced pluripotent stem cell lines TRNDi037-A and TRNDi038-A from two patients with Alagille syndrome carrying heterozygous JAG1 mutations.

Human induced pluripotent stem cell (iPSC) lines TRNDi037-A and TRNDi038-A were generated from the lymphoblastoid cell lines (LCL) of two patients with different heterozygous JAG1 variants resulting in Alagille syndrome (ALGS). ALGS is a rare genetic disease of haploinsufficiency that affects the formation of the bile duct, in addition to other symptoms. These ALGS iPSC lines can be used to model ALGS and aid in the identification of therapeutics to treat patients with ALGS.

Generation of an induced pluripotent stem cell line (TRNDi042-A) from a Mucopolysaccharidosis type IIIB patient with homozygous p. R626X (c. 1876C > T) mutation in the NAGLU gene.

Mucopolysaccharidosis type IIIB (MPS IIIB), also known as Sanfilippo syndrome, is an autosomal recessive lysosomal storage disorder caused by mutations in the NAGLU gene. It is characterized by progressive neurodegeneration, behavioral problems, and motor function difficulties. A human induced pluripotent stem cell (iPSC) TRNDi042-A line was generated from fibroblasts of a male patient with a homozygous p.

The downregulation of tight junction proteins and pIgR in the colonic epithelium causes the susceptibility of EpCAM mice to colitis and gut microbiota dysbiosis.

Background: The genetic factors play important roles on the pathogenesis of inflammatory bowel disease (IBD). EpCAM is highly expressed in the intestinal epithelium. It is still unclear if the decrease or somatic mutation of EpCAM could cause IBD.

Protocol for differentiation of monocytes and macrophages from human induced pluripotent stem cells.

Study of disease-relevant immune cells, namely monocytes and macrophages, is limited based on availability of primary tissue, a limitation that can be remedied using human induced pluripotent stem cell (hiPSC) technology. Here, we present a protocol for differentiation of monocytes and macrophages from hiPSCs. We describe steps for hiPSC maintenance, mesoderm lineage induction, hematopoietic progenitor cells (HPCs) commitment and expansion, and myeloid lineage induction.

Exploring Abnormal Brain Functional Connectivity in Healthy Adults, Depressive Disorder, and Generalized Anxiety Disorder through EEG Signals: A Machine Learning Approach for Triple Classification.

Depressive disorder (DD) and generalized anxiety disorder (GAD), two prominent mental health conditions, are commonly diagnosed using subjective methods such as scales and interviews. Previous research indicated that machine learning (ML) can enhance our understanding of their underlying mechanisms. This study seeks to investigate the mechanisms of DD, GAD, and healthy controls (HC) while constructing a diagnostic framework for triple classifications.

Derived myeloid lineage induced pluripotent stem as a platform to study human C-C chemokine receptor type 5Δ32 homozygotes.

The C-C chemokine receptor type 5 (CCR5) expressed on immune cells supports inflammatory responses by directing cells to the inflammation site. CCR5 is also a major coreceptor for macrophage tropic human immunodeficiency viruses (R5-HIV-1) and its variants can confer protection from HIV infection, making it an ideal candidate to target for therapy. We developed a stepwise protocol that differentiates induced pluripotent stem cells (iPSCs) from individuals homozygous for the CCR5Δ32 variant and healthy volunteers into myeloid lineage induced monocytes (iMono) and macrophages (iMac).

Depressive Disorder Recognition Based on Frontal EEG Signals and Deep Learning.

Depressive disorder (DD) has become one of the most common mental diseases, seriously endangering both the affected person's psychological and physical health. Nowadays, a DD diagnosis mainly relies on the experience of clinical psychiatrists and subjective scales, lacking objective, accurate, practical, and automatic diagnosis technologies. Recently, electroencephalogram (EEG) signals have been widely applied for DD diagnosis, but mainly with high-density EEG, which can severely limit the efficiency of the EEG data acquisition and reduce the practicability of diagnostic techniques.

Hydration Mechanism and Its Effect on the Solubility of Aripiprazole.

Propose: The propose is to investigate the reasons for the insolubility of Form III in water and to explore the mechanism of the hydration process of Form III.

Methods: The conformational and cohesive energies of Form III and Form H1 were calculated using Gaussian 16 and Crystal Explorer 17. Gaussian 16 and Multiwfn 3.

A Protocol for Culture and Characterization of Human Induced Pluripotent Stem Cells After Induction.

Human induced pluripotent stem cells (hiPSCs) are characterized by unlimited self-renewal and the capability to differentiate into all three germ layers, with the potential to further differentiate into all types of cells and tissues. Human iPSCs retain all genetic information from their original donors and can be developed into disease models to study disease pathophysiology, identify disease phenotypes and biomarkers, and evaluate therapeutic efficacy and toxicity for drug development. Human iPSCs can also be used to develop cell therapies and regenerative medicine.

Mast cell activation and degranulation in acute artery injury: A target for post-operative therapy.

The increasing incidence of cardiovascular disease (CVD) has led to a significant ongoing need to address this surgically through coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI). From this, there continues to be a substantial burden of mortality and morbidity due to complications arising from endothelial damage, resulting in restenosis. Whilst mast cells (MC) have been shown to have a causative role in atherosclerosis and other vascular diseases, including restenosis due to vein engraftment; here, we demonstrate their rapid response to arterial wire injury, recapitulating the endothelial damage seen in PCI procedures.

Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome.

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases; pathomechanisms that regulate extravasation of damaging immune cells into surrounding tissues are poorly understood. Here we identified three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation. Two patients developed liver fibrosis in their first year of life.

3D printed biomimetic flexible blood vessels with iPS cell-laden hierarchical multilayers.

Successful recovery from vascular diseases has typically relied on the surgical repair of damaged blood vessels (BVs), with the majority of current approaches involving the implantation of autologous BVs, which is plagued by donor site tissue damage. Researchers have attempted to develop artificial vessels as an alternative solution to traditional approaches to BV repair. However, the manufacturing of small-diameter (< 6 mm) BVs is still considered one of the biggest challenges due to its difficulty in the precise fabrication and the replication of biomimetic architectures.

Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration.

Age-related macular degeneration (AMD), a leading cause of blindness, initiates in the outer-blood-retina-barrier (oBRB) formed by the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. The mechanisms of AMD initiation and progression remain poorly understood owing to the lack of physiologically relevant human oBRB models. To this end, we engineered a native-like three-dimensional (3D) oBRB tissue (3D-oBRB) by bioprinting endothelial cells, pericytes, and fibroblasts on the basal side of a biodegradable scaffold and establishing an RPE monolayer on top.

Human induced pluripotent stem cells generated from STING-associated vasculopathy with onset in infancy (SAVI) patients with a heterozygous mutation in the STING gene.

We have successfully created induced pluripotent stem cells (iPSC) from patients carrying a heterozygous mutation in the gene encoding STING. The gain-of-function mutation leads to constitutive activation of STING which leads to the development of the disease STING-associated vasculopathy with onset in infancy (SAVI). The iPSC lines derived from the SAVI patitents are shown to be morphologically and phenotypically normal and have the potential to self renew and differentiate into the three germ layers.

Human induced pluripotent stem cells generated from a patient with a homozygous mutation in the Lyn kinase gene.

We have successfully generated induced pluripotent stem cells (iPSC) from dermal fibroblasts of the patient with a germline mutation in the coding region of the LYN kinase gene. This gain of function (GOF) mutation eliminates the inhibitory tyrosine (Y) at the position p.Y508, with an unknown established disease etiology.

Human induced pluripotent stem cells generated from Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome patients with a homozygous mutation in the PSMB8 gene (NIHTVBi016-A, NIHTVBi017-A, NIHTVBi018-A).

We have successfully generated induced pluripotent stem cells (iPSC) from dermal fibroblasts and peripheral blood mononuclear cells from patients with a homozygous missense mutation in the gene encoding PSMB8. Biallelic loss of function mutations in this gene are responsible for the PSMB8 deficiency termed Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE). The iPSC carrying the homozygous PSMB8 gene mutation (c.

EpCAM Is Essential to Maintaining the Immune Homeostasis of Intestines Keeping the Expression of pIgR in the Intestinal Epithelium of Mice.

EpCAM deficiency causes congenital tufting enteropathy (CTE) which is considered as one kinds of very early onset inflammatory bowel disease (IBD). However, functions of EpCAM on regulating the immunity of intestines are still unclear. To study the mechanism of EpCAM on maintaining the intestinal immune homeostasis, the intestines of WT and EpCAM mice at E18.

High dose lithium chloride causes colitis through activating F4/80 positive macrophages and inhibiting expression of Pigr and Claudin-15 in the colon of mice.

Objective: Lithium chloride (LiCl) was a mood stabilizer for bipolar affective disorders and it could activate Wnt/β-catenin signaling pathway both in vivo and in vitro. Colon is one of a very susceptible tissues to Wnt signaling pathway, and so it would be very essential to explore the toxic effect of a high dose of LiCl on colon.

Methods: C57BL/6 mice were injected intraperitoneally with 200 mg/kg LiCl one dose a day for 5 days to activate Wnt signal pathway in intestines.

EpCAM is essential for maintenance of the small intestinal epithelium architecture via regulation of the expression and localization of proteins that compose adherens junctions.

Epithelial cell adhesion molecule (EpCAM) is highly expressed in mammalian intestines, and is essential for maintaining the homeostasis of the intestinal epithelium. EpCAM protein is localized at tight junctions and the basolateral membrane of the intestinal epithelium, where it interacts with many cell adhesion molecules. To explore the molecular functions of EpCAM in regulating adherens junctions in the intestinal epithelium, EpCAM knockout embryos and newborn pups were analyzed.

Supervised Learning Achieves Human-Level Performance in MOBA Games: A Case Study of Honor of Kings.

We present JueWu-SL, the first supervised-learning-based artificial intelligence (AI) program that achieves human-level performance in playing multiplayer online battle arena (MOBA) games. Unlike prior attempts, we integrate the macro-strategy and the micromanagement of MOBA-game-playing into neural networks in a supervised and end-to-end manner. Tested on Honor of Kings, the most popular MOBA at present, our AI performs competitively at the level of High King players in standard 5v5 games.

Human induced pluripotent stem cells generated from a patient with a homozygous L272P mutation in the OTULIN gene (NIHTVBi014-A).

We have successfully generated induced pluripotent stem cells (iPSC) from dermal fibroblasts of a patient with a homozygous p.Leu272Pro mutation in the gene encoding the linear deubiquitinase OTULIN. Biallelic loss of function mutations in this gene are responsible for the OTULIN deficiency termed Otulipenia or OTULIN-related autoinflammatory syndrome (ORAS).

STAT3 modulates reprogramming efficiency of human somatic cells; insights from autosomal dominant Hyper IgE syndrome caused by STAT3 mutations.

Human induced pluripotent stem cell (iPSC) technology has opened exciting opportunities for stem-cell-based therapy. However, its wide adoption is precluded by several challenges including low reprogramming efficiency and potential for malignant transformation. Better understanding of the molecular mechanisms of the changes that cells undergo during reprograming is needed to improve iPSCs generation efficiency and to increase confidence for their clinical use safety.

Variation on the Microstructure and Mechanical Properties of Ti-Al-N Films Induced by RF-ICP Ion Source Enhanced Reactive Nitrogen Plasma Atmosphere.

Acquiring the optimum growth conditions of Ti-Al-N films, the effects of gas atmosphere, especially the reactive plasma on the material microstructures, and mechanical properties are still a fundamental and important issue. In this study, Ti-Al-N films are reactively deposited by radio frequency inductively coupled plasma ion source (RF-ICPIS) enhanced sputtering system. Different nitrogen gas flow rates in letting into the ion source are adopted to obtain nitrogen plasma densities and alter deposition atmosphere.