Biliary atresia susceptibility gene EFEMP1 regulates extrahepatic bile duct elastic fiber formation and mechanics.

Background & Aims: EGF-containing fibulin extracellular matrix protein 1 (EFEMP1, also called fibulin-3) is an extracellular matrix protein linked in a genome-wide association study to biliary atresia, a fibrotic disease of the neonatal extrahepatic bile duct. Fibulin-3 is deposited in most tissues and null mice have decreased elastic fibers in visceral fascia; however, fibulin-3 does not have a role in the development of large elastic fibers and its overall function in the extrahepatic bile ducts remains unclear.

Methods: We used staining and histology to define the amount and organization of key extracellular matrix components in the extrahepatic bile ducts.

β-Cell Secretory Capacity Predicts Metabolic Outcomes over 6 Years following Human Islet Transplantation.

Transplanted islet functional β-cell mass is measured by the β-cell secretory capacity derived from the acute insulin response to glucose-potentiated arginine (AIRpot), however, data are limited beyond one-year post-transplant for individuals with type 1 diabetes. We evaluated changes in β-cell secretory capacity in a single-center longitudinal analysis and examined relationships with measures of islet cell hormone metabolism and clinical measures of graft function (mixed-meal tolerance test [MMTT] C-peptide, BETA-2 score, and continuous glucose monitoring [CGM]). Eleven individuals received purified human pancreatic islets over one or two intra-portal infusions to achieve insulin-independence and were followed over a median (IQR) 6 (5-7) years.

Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset.

Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. Studies of human T1D immunobiology have predominantly focused on circulating immune cells in the blood, while mouse models suggest diabetogenic lymphocytes primarily reside in pancreas-draining lymph nodes (pLN). A comprehensive study of immune cells in human T1D was conducted using pancreas draining lymphatic tissues, including pLN and mesenteric lymph nodes, and the spleen from non-diabetic control, β cell autoantibody positive non-diabetic (AAb+), and T1D organ donors using complementary approaches of high parameter flow cytometry and CITEseq.

Dopamine Regulates Its Own Synthesis via MdORG2 to Improve Low-Nitrogen Tolerance in Apple Plants.

Nitrogen (N) is crucial for plant growth and development. Exogenous dopamine has been shown to improve the N-deficiency tolerance of apple. However, the potential regulatory mechanisms by which dopamine mitigates low-N stress remain unclear.

Pyridine-Anchored Small Molecule Interlayer Enables Defect Passivation and Enhanced Carrier Transport for Perovskite Solar Cells.

Engineering of the interface between the perovskite and hole transport layer (HTL) has been crucial to achieving high performance. In this study, two interfacial materials, MN-CZ and CN-CZ, are designed by systematically regulating the group substitution site to study the relationship between spatial conformation and the passivation effect. The passivation groups of CN-CZ molecules exhibit a stronger "vector addition" effect, resulting in larger molecular dipoles and enhanced defect passivation and energy level regulation effects.

Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic β cell Pyroptosis upon Viral Infection.

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single cell RNA-seq analysis of human islets exposed to SARS-CoV-2 or Coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis.

Comparison of central corneal thickness measured in myopic eyes by Pentacam, Sirius and IOLMaster 700.

Purpose: The purpose of this study was to evaluate the correlations and consistency among the central corneal thickness (CCT) of healthy myopic patients measured with three different anterior segment analysis systems.

Design: This was a retrospective study. The study included myopia patients who had undergone preoperative examinations in the refractive surgery department of our hospital between January 2021 and December 2023.

Eco-friendly versatile shielding revolution: Tannin tailored bamboo waste composite with wave-absorbing, flame retardancy, and antibacterial abilities.

The swift evolution of fifth-generation technology has intensified the need for lightweight, high-efficiency, and low-reflection multifunctional electromagnetic interference shielding materials, crucial in combating escalating electromagnetic pollution in complex application environments. To tackle these challenges, an innovative solution has emerged: a biocomposite crafted from discarded bamboo materials. This innovation incorporates a meticulously engineered functional coating composed of tannic acid, boric acid, and polyvinyl alcohol.

Vitrified Metal-Organic Framework Composite Electrolyte Enabling Dendrite-Free and Long-Lifespan Solid-State Lithium Metal Batteries.

Solid-state lithium metal batteries (LMBs) are still plagued with low ionic conductivity and inferior interfacial contact, which hinder their practical implementation. Herein, a quasi-solid-state composite electrolyte, poly(1,3-dioxolane) (PDOL)/glassy ZIF-62 (PGZ) with fast ion transport and intimate interface contact, is fabricated via in situ polymerization. The in situ polymerization of DOL in an electrolyte matrix not only improves the exterior interface between electrolyte/electrode but also optimizes the inner interfaces among glassy particles, rendering PGZ as an uninterrupted ionic conductor.

Ionic Liquid Crystal-Polymer Composite Electromechanical Actuators: Design of Two-Dimensional Molecular Assemblies for Efficient Ion Transport and Effect of Electrodes on Actuator Performance.

We present the development of free-standing ionic liquid crystal-polymer composite electrolyte films aimed at achieving high-frequency response electromechanical actuators. Our approach entails designing novel layered ionic liquid-crystalline (LC) assemblies by complexing a mesomorphic dimethylphosphate with either a lithium salt or a room-temperature ionic liquid through the formation of ion-dipole interactions or hydrogen bonds. These electrolytes, exhibiting room-temperature ionic conductivities on the order of 10 S cm and wide LC temperature ranges up to 77 °C, were successfully integrated into porous polymer networks.

NKX2-2 based nuclei sorting on frozen human archival pancreas enables the enrichment of islet endocrine populations for single-nucleus RNA sequencing.

Background: Current approaches to profile the single-cell transcriptomics of human pancreatic endocrine cells almost exclusively rely on freshly isolated islets. However, human islets are limited in availability. Furthermore, the extensive processing steps during islet isolation and subsequent single cell dissolution might alter gene expressions.

Modeling type 1 diabetes progression using machine learning and single-cell transcriptomic measurements in human islets.

Type 1 diabetes (T1D) is a chronic condition in which beta cells are destroyed by immune cells. Despite progress in immunotherapies that could delay T1D onset, early detection of autoimmunity remains challenging. Here, we evaluate the utility of machine learning for early prediction of T1D using single-cell analysis of islets.

Layer-by-layer assembly of quercetin-loaded zein/γPGA/low-molecular-weight chitosan/fucoidan nanosystem for targeting inflamed blood vessels.

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells.

Development of PEG-mediated genetic transformation and gene editing system of Bryum argenteum as an abiotic stress tolerance model plant.

To establish a sterile culture system and protoplast regeneration system for Bryum argenteum, and to establish and apply CRISPR/Cas9 system in Bryum argenteum. Bryum argenteum is a fascinating, cosmopolitan, and versatile moss species that thrives in various disturbed environments. Because of its comprehensive tolerance to the desiccation, high UV and extreme temperatures, it is emerging as a model moss for studying the molecular mechanisms underlying plant responses to abiotic stresses.

Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies.

Pre-existing anti-human leukocyte antigen (HLA) allo-antibodies constitute a major barrier to transplantation. Current desensitization approaches fail due to ineffective depletion of allo-specific memory B cells (Bmems) and long-lived plasma cells (LLPCs). We evaluate the efficacy of chimeric antigen receptor (CAR) T cells targeting CD19 and B cell maturation antigen (BCMA) to eliminate allo-antibodies in a skin pre-sensitized murine model of islet allo-transplantation.

Serum CRP interacts with SPARC and regulate immune response in severe cases of COVID-19 infection.

Serum C-reactive protein (CRP) has been found elevated during COVID-19 infection, and associated with systematic inflammation as well as a poor clinical outcome. However, how did CRP participated in the COVID-19 pathogenesis remains poorly understood. Here, we report that serum C-reactive protein (CRP) levels are correlated with megakaryocyte marker genes and could regulate immune response through interaction with megakaryocytes.

Checkpoint kinase 2 controls insulin secretion and glucose homeostasis.

After the discovery of insulin, a century ago, extensive work has been done to unravel the molecular network regulating insulin secretion. Here we performed a chemical screen and identified AZD7762, a compound that potentiates glucose-stimulated insulin secretion (GSIS) of a human β cell line, healthy and type 2 diabetic (T2D) human islets and primary cynomolgus macaque islets. In vivo studies in diabetic mouse models and cynomolgus macaques demonstrated that AZD7762 enhances GSIS and improves glucose tolerance.

An integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D associated genes and regulatory signals.

Genome wide association studies (GWAS) have identified over 100 signals associated with type 1 diabetes (T1D). However, translating any given T1D GWAS signal into mechanistic insights, including putative causal variants and the context (cell type and cell state) in which they function, has been limited. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in healthy and autoantibody (AAB+) human islets, as well as islets under multiple T1D stimulatory conditions.

Adaptation of HLA testing to characterize the cynomolgus macaque MHC polymorphisms and alloantibody signatures.

Nonhuman primates are the closest animal models to humans with respect to genetics and physiology. Consequently, a critical component of immunogenetics research relies on drawing inferences from the cynomolgus macaque to inform human trials. Despite the conserved organization of the Major Histocompatibility Complex (MHC) between cynomolgus macaques and humans, MHC genotyping of cynomolgus macaques is challenging due to high rates of copy number variants, duplications, and rearrangements, particularly at the MHC class I loci.

ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through mA modification-mediated RNA stability control.

N-methyladenosine (mA) RNA modification controls numerous cellular processes. To what extent these post-transcriptional regulatory mechanisms play a role in hematopoiesis has not been fully elucidated. We here show that the mA demethylase alkB homolog 5 (ALKBH5) controls mitochondrial ATP production and modulates hematopoietic stem and progenitor cell (HSPC) fitness in an mA-dependent manner.

Observation of photonic Peierls transition for manipulating microwave in metallic diaphragm-array periodic structures.

Peierls transition that modifies electronic band structure has attracted intensive attention in solid state physics. In the present work, we report that a photonic analog of Peierls transition has been observed in a 1-D triangular metal diaphragm array, where the photonic bandgap structures have been designed at will by adjusting periodically metal diaphragm positions. It is shown by the numerical analysis that the transmission and radiation effect of the present periodic metal structure designed through the Peierls transition rule exhibits the behavior significantly different from an original periodic structure with each unit cell containing a metal diaphragm.