Lipid droplet protein Perilipin 2 is critical for the regulation of insulin secretion through beta cell lipophagy and glucagon expression in pancreatic islets.

Knockdown (KD) of lipid droplet (LD) protein perilipin 2 (PLIN2) in beta cells impairs glucose-stimulated insulin secretion (GSIS) and mitochondrial function. Here, we addressed a pathway responsible for compromised mitochondrial integrity in PLIN2 KD beta cells. In PLIN2 KD human islets, mitochondria were fragmented in beta cells but not in alpha cells.

Perilipin 5 Phosphorylation is Dispensable for Upregulation of Hepatic Lipid Metabolism Genes upon Fasting but Required for Insulin Receptor Substrate 2 Expression in Male Mice.

Objective: Perilipin 5 (PLIN5) is a lipid droplet protein highly expressed in cells that actively oxidize fatty acids. Previous in vitro studies have revealed that PLIN5 phosphorylation (p-PLIN5) at serine 155 by PKA is critical for transcriptional regulation of PPARa target genes by which PLIN5 adapt cells for fatty acid oxidation. We aim to determine the extent of p-PLIN5 in vivo and the consequence of impaired PLIN5 phosphorylation in the liver by using a whole-body knock-in of phosphorylation resistant PLIN5 (SA/SA) in mice.

CD169 Skin Macrophages Function as a Specialized Subpopulation in Promoting Psoriasis-like Skin Disease in Mice.

Skin macrophages are critical to maintain and restore skin homeostasis. They serve as major producers of cytokines and chemokines in the skin, participating in diverse biological processes such as wound healing and psoriasis. The heterogeneity and functional diversity of macrophage subpopulations endow them with multifaceted roles in psoriasis development.

Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis.

Background: Lung cancer is the leading cause of cancer-related death worldwide. We previously found that Mediator complex subunit 23 (MED23) is important for the tumourigenicity of lung cancer cells with hyperactive Ras activity in vitro, although the in vivo function of MED23 in lung tumourigenesis remains to be explored.

Methods: In this study, we utilized well-characterized Kras-driven non-small cell lung cancer mouse model to investigate the role of MED23 in lung cancer.

Potential drug targets for asthma identified in the plasma and brain through Mendelian randomization analysis.

Background: Asthma is a heterogeneous disease, and the involvement of neurogenic inflammation is crucial in its development. The standardized treatments focus on alleviating symptoms. Despite the availability of medications for asthma, they have proven to be inadequate in controlling relapses and halting the progression of the disease.

Discovery of novel 2-aminopyridine derivatives as ROS1 and ALK dual inhibitors to combat drug-resistant mutants including ROS1 and ALK.

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test.

Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases.

Background: RNA N6-methyladenosine (m6A) regulators are considered post-transcriptional regulators that affect several biological functions, and their role in immunity, in particular, is emerging. However, the role of m6A regulators in respiratory allergic diseases remains unclear. Therefore, we aimed to investigate the role of key m6A regulators in mediating respiratory allergic diseases and immune microenvironment infiltration characteristics.

Utilization of commercial collagens for preparing well-differentiated human beta cells for confocal microscopy.

Introduction: With technical advances, confocal and super-resolution microscopy have become powerful tools to dissect cellular pathophysiology. Cell attachment to glass surfaces compatible with advanced imaging is critical prerequisite but remains a considerable challenge for human beta cells. Recently, Phelps et al.

A Novel and Highly Selective Epidermal Growth Factor Receptor Inhibitor, SMUZ106, for the Treatment of Glioblastoma.

Targeting the epidermal growth factor receptor (EGFR) is one of the potential ways to treat glioblastoma (GBM). In this study, we investigate the anti-GBM tumor effects of the EGFR inhibitor SMUZ106 in both in vitro and in vivo conditions. The effects of SMUZ106 on the growth and proliferation of GBM cells were explored through MTT and clone formation experiments.

Association of , and polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients.

To evaluate the association between , and polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation. High performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentrations. First-generation sequencing was performed to detect gene polymorphisms.

Losartan attenuates upstream vasculopathy in a modified piglet model of pulmonary vein stenosis: contribution of the Hippo pathway.

Background: Diffuse pulmonary vein stenosis (PVS) is an intractable congenital heart disease for which the underlying mechanism remains unclear. In this study, we investigated the effect of losartan and the role of the Hippo pathway in PVS.

Methods: A total of 19 neonatal piglets were divided into 3 groups: a sham group (n=7), a banded group (n=6) with the left upper pulmonary vein and common trunk of both lower pulmonary veins banded, and a losartan group (n=6) with losartan treatment (1 mg/kg/d) after the banding operation.

Deficiency of astrocyte CysLTR ameliorates depression-like behaviors in mice by modulating glutamate synaptic transmission.

Our previous study suggests that hippocampal cysteinyl leukotriene receptor 1 (CysLTR) could be involved in depression. Herein we hypothesize that CysLTR may regulate depression by affecting synaptic glutamate cycling based on existence of CysLTR in the astrocytes that participate in occurrence of depression. We found that CysLTR expression was significantly increased in the astrocyte of chronic unpredictable mild stress (CUMS)-induced depression-like mice, CysLTR astrocyte-specific conditional knockout (AcKO) significantly improved depression-like behaviors, as indicated by decreased immobility time in the forced swimming test and tail suspension test and increased sucrose preference in the sucrose preference test, and knockdown of CysLTR in the astrocyte of dentate gyrus (DG), the region with the most significant increase of CysLTR in the astrocyte of depression-like mice, produced similar effects.

CD169 subcapsular sinus macrophage-derived microvesicles are associated with light zone follicular dendritic cells.

Follicular dendritic cells (FDCs) are a specialized type of stromal cells that exclusively reside in B-cell follicles. When inflammation occurs, the FDC network is reorganized to support germinal center (GC) polarization into the light zone (LZ) and dark zone (DZ). Despite the indispensable role of FDCs in supporting humoral responses, the FDC regulatory requirements remain incompletely defined.

Orbits of charged particles trapped in a dipole magnetic field.

Motion of a test charged particle in a dipole magnetic field can be reduced to a two degree-of-freedom Hamiltonian system due to the axisymmetry of the dipole field. We carried out a systematic study of orbits of low-energy trapped charged particles in the dipole field via calculation of their Lyapunov characteristic exponents (LCEs) with random initial conditions in the four-dimensional phase space. Since there is at most one positive LCE, these orbits are classified as chaotic ones with one positive LCE and quasi-periodic ones with vanishing LCEs.

Lipid Droplets' Role in the Regulation of β-Cell Function and β-Cell Demise in Type 2 Diabetes.

During development of type 2 diabetes (T2D), excessive nutritional load is thought to expose pancreatic islets to toxic effects of lipids and reduce β-cell function and mass. However, lipids also play a positive role in cellular metabolism and function. Thus, proper trafficking of lipids is critical for β cells to maximize the beneficial effects of these molecules while preventing their toxic effects.

The Behavioral Role of Digital Economy Adaptation in Sustainable Financial Literacy and Financial Inclusion.

The basic aim of this research was to investigate the impact of the behavioral biases on financial inclusion in Pakistan while considering the moderating effect of financial literacy in this relation, in the context of behavioral perspective. This study focused on the significant behavioral phenomenon, including self-control, optimism, herding, and loss aversion with a perspective of the digital economy. To test the proposed hypothesis, the primary data collection method was used.

Modified Nuss procedure with a novel steel bar in patients with pectus excavatum post-congenital heart surgery.

Objectives: Pectus excavatum (PE) can be secondary in patients who underwent sternotomy for cardiac surgery. Retrosternal adhesions increase the complexity and risk of traditional Nuss repair. Thus, we summarized the outcomes of our modified Nuss procedure using a newly designed bar.

Oriented Localization of Surgical Tools by Location Encoding.

Surgical tool localization is the foundation to a series of advanced surgical functions e.g. image guided surgical navigation.

Yiqi Jiemin decoction alleviates allergic rhinitis in a guinea pig model by suppressing inflammation, restoring Th1/Th2 balance, and improving cellular metabolism.

We investigated the mechanisms underlying the therapeutic effects of Yiqi Jiemin decoction (YJD), a traditional Chinese medicine (TCM), in the ovalbumin (OVA)-induced allergic rhinitis (AR) model in guinea pigs. YJD significantly decreased infiltration of mast cells and eosinophils into the nasal mucosa of AR model guinea pigs. YJD also increased expression of TGF-β in the nasal mucosa, restored the balance of Th1/Th2 immune cell responses, and decreased serum levels of various pro-inflammatory mediators, including histamine (HA), neuropeptide Y (NPY), acetylcholine (ACH), norepinephrine and immunoglobulin E (IgE).

Mitochondrial Efflux of Citrate and Isocitrate Is Fully Dispensable for Glucose-Stimulated Insulin Secretion and Pancreatic Islet β-Cell Function.

The defining feature of pancreatic islet β-cell function is the precise coordination of changes in blood glucose levels with insulin secretion to regulate systemic glucose homeostasis. While ATP has long been heralded as a critical metabolic coupling factor to trigger insulin release, glucose-derived metabolites have been suggested to further amplify fuel-stimulated insulin secretion. The mitochondrial export of citrate and isocitrate through the citrate-isocitrate carrier (CIC) has been suggested to initiate a key pathway that amplifies glucose-stimulated insulin secretion, though the physiological significance of β-cell CIC-to-glucose homeostasis has not been established.

[Effect of intranasal acupuncture on neurogenic inflammation in allergic rhinitis rabbits].

Objective: To observe the effect of intranasal acupuncture on allergic rhinitis (AR), and expression of substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) proteins in the nasal mucosa and contents of serum immunoglobulin E (IgE), interleukin 4 (IL-4) and interferon-γ (IFN-γ) in AR rabbits, so as to explore its mechanisms underlying improvement of AR.

Methods: New Zealand rabbits were randomly divided into normal control, AR model, non-acupuoint acupuncture (NAA) and intranasal acupuncture (INA) groups, with 8 rabbits in each group. The AR model was established by intra-peritoneal injection of egg protein and nasal mucosal stimulation.

Perilipin 2 downregulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria.

Perilipin 2 (PLIN2) is a lipid droplet (LD) protein in β cells that increases under nutritional stress. Downregulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was downregulated in mouse β cells, INS1 cells, and human islet cells.