High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1)

This study aimed at evaluating the effect of high glucose on the expression of extracellular matrix (ECM) protein Matrilin-2 and the mechanism underlying this effect by using a mouse mesangial cell line. Mouse mesangial cells (MMCs) were cultured in media containing normal (5 mM d-glucose) or high concentrations of glucose (30 mM d-glucose). The expression of Matrilin-2 was assessed by either RT-PCR or western blot. Additionally, transforming growth factor beta 1 (TGF-β1) inhibitors and TGF-β1 were used to determine whether glucose-regulated Matrilin-2 expression was mediated by the TGF-β1/Smad3 signaling pathway. Our data demonstrated that Matrilin-2 expression was markedly induced by high glucose and TGF-β1. High glucose-induced Matrilin-2 expression was inhibited by TGF-β1/Smad3 inhibitors, indicating that Matrilin-2 was markedly induced by high glucose and this induction was mediated by the TGF-β1/Smad3 pathway. Taken together, our results showed that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-β1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis and our finding provided a potential diagnostic and/or therapeutic target for DN

Progress in the Application and Scheme of the Ketogenic Diet in the Treatment of Metabolic Diseases

Ketogenic diets have been shown to play a role in some metabolic diseases and neurodegenerative diseases as a low-carbohydrate, high-fat diets supplemented with appropriate protein. Ketogenic diets have been proven effective, but the mechanisms of action are still unclear. Therefore, this paper summarizes the development of the ketogenic diet, its application in the treatment of metabolic diseases (type Ⅱ diabetes, obesity, non-alcoholic fatty liver disease, and gout), recommended diet plans and adverse reactions, and confirms that the ketogenic diet can be used as an adjunct therapy for metabolic diseases in terms of improving stress response and the intestinal microbiome. The classic ketogenic diet, medium-chain triglyceride, modified Atkins diet, and low glycemic index treatment are recommended as ketogenic diet programs. The adverse reactions of the ketogenic diet in metabolism, gastrointestinal tract, urinary system, and contraindications are summarized. This paper also summarizes the invention patents of ketogenic diet-related products, which paved the way and prospected for the subsequent product development and as an auxiliary treatment program

TOTA: Fully Homomorphic Encryption with Smaller Parameters and Stronger Security

We present fully homomorphic encryption schemes for fixed-point arithmetic with fixed precision. Our scheme achieves $\mathsf{IND}$-$\mathsf{CPA^D}$ security and uses $\mathsf{RLWE}$ ring with dimension ${2^{13}}$ or less. Our techniques could also be extended to construct fully homomorphic encryption schemes for approximate numbers with $\mathsf{IND}$-$\mathsf{CPA}$ security. The bootstrapping process of our $\mathsf{IND}$-$\mathsf{CPA}$ scheme preserves about 39-bit precision with ring dimension $2^{13}$, which is the first construction that preserves high precision while keeping the parameters small. The core technique in this paper is a new and efficient functional bootstrapping algorithm that avoids the negacyclicity constraint of the evaluated functions, which enables us to extract bits blocks homomorphically. This new functional bootstrapping algorithm could be applied to BFV and TFHE schemes as well, and is of independent interest

Hesperidin Protects against Acute Alcoholic Injury through Improving Lipid Metabolism and Cell Damage in Zebrafish Larvae

Alcoholic liver disease (ALD) is a series of abnormalities of liver function, including alcoholic steatosis, steatohepatitis, and cirrhosis. Hesperidin, the major constituent of flavanone in grapefruit, is proved to play a role in antioxidation, anti-inflammation, and reducing multiple organs damage in various animal experiments. However, the underlying mechanism of resistance to alcoholic liver injury is still unclear. Thus, we aimed to investigate the protective effects of hesperidin against ALD and its molecular mechanism in this study. We established an ALD zebrafish larvae model induced by 350 mM ethanol for 32 hours, using wild-type and transgenic line with liver-specific eGFP expression Tg (lfabp10α:eGFP) zebrafish larvae (4 dpf). The results revealed that hesperidin dramatically reduced the hepatic morphological damage and the expressions of alcohol and lipid metabolism related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, and fads2 compared with ALD model. Moreover, the findings demonstrated that hesperidin alleviated hepatic damage as well, which is reflected by the expressions of endoplasmic reticulum stress and DNA damage related genes (chop, gadd45αa, and edem1). In conclusion, this study revealed that hesperidin can inhibit alcoholic damage to liver of zebrafish larvae by reducing endoplasmic reticulum stress and DNA damage, regulating alcohol and lipid metabolism

Wild relatives of pigeonpea in China

Wild relatives play an important role in the genetic improvement of cultivated crops. Breeders turn their attention to the wild relatives of crops after unsuccessful search for some unique trait in the cultivated germplasm. According to van der Maesen (1986) the genus Cajanus has 32 species. Of these, the Indian subcontinent harbors 18 species. ICRISAT has the global responsibility of collection, maintenance, and evaluation of germplasm of the wild relatives of pigeonpea. At present a total of 213 accessions, representing 20 Cajanus species are conserved for use in the breeding programs

Accelerated structural evolution of galaxies in a starbursting cluster at z=2.51

Structural properties of cluster galaxies during their peak formation epoch, $z \sim 2-4$ provide key information on whether and how environment affects galaxy formation and evolution. Based on deep HST/WFC3 imaging towards the z=2.51 cluster, J1001, we explore environmental effects on the structure, color gradients, and stellar populations of a statistical sample of cluster SFGs. We find that the cluster SFGs are on average smaller than their field counterparts. This difference is most pronounced at the high-mass end ($M_{\star} > 10^{10.5} M_{\odot}$) with nearly all of them lying below the mass-size relation of field galaxies. The high-mass cluster SFGs are also generally old with a steep negative color gradient, indicating an early formation time likely associated with strong dissipative collapse. For low-mass cluster SFGs, we unveil a population of compact galaxies with steep positive color gradients that are not seen in the field. This suggests that the low-mass compact cluster SFGs may have already experienced strong environmental effects, e.g., tidal/ram pressure stripping, in this young cluster. These results provide evidence on the environmental effects at work in the earliest formed clusters with different roles in the formation of low and high-mass galaxies.Comment: 13 pages, 10 figures, 1 tabl

Machine-Learning-Enabled Virtual Screening for Inhibitors of Lysine-Specific Histone Demethylase 1

A machine learning approach has been applied to virtual screening for lysine specific demethylase 1 (LSD1) inhibitors. LSD1 is an important anti-cancer target. Machine learning models to predict activity were constructed using Morgan molecular fingerprints. The dataset, consisting of 931 molecules with LSD1 inhibition activity, was obtained from the ChEMBL database. An evaluation of several candidate algorithms on the main dataset revealed that the support vector regressor gave the best model, with a coefficient of determination (R2) of 0.703. Virtual screening, using this model, identified five predicted potent inhibitors from the ZINC database comprising more than 300,000 molecules. The virtual screening recovered a known inhibitor, RN1, as well as four compounds where activity against LSD1 had not previously been suggested. Thus, we performed a machine-learning-enabled virtual screening of LSD1 inhibitors using only the structural information of the molecules

Resident Immune Cells of the Liver in the Tumor Microenvironment

The liver is a central immunomodulator that ensures a homeostatic balance between protection and immunotolerance. A hallmark of hepatocellular carcinoma (HCC) is the deregulation of this tightly controlled immunological network. Immune response in the liver involves a complex interplay between resident innate, innate, and adaptive immune cells. The immune response in the liver is modulated by its continuous exposure to toxic molecules and microorganisms that requires a degree of immune tolerance to protect normal tissue from damage. In HCC pathogenesis, immune cells must balance a dual role that includes the elimination of malignant cells, as well as the repair of damaged liver tissue to maintain homeostasis. Immune response in the innate and adaptive immune systems extends to the cross-talk and interaction involving immune-regulating non-hematopoietic cells, myeloid immune cells, and lymphoid immune cells. In this review, we discuss the different immune responses of resident immune cells in the tumor microenvironment. Current FDA-approved targeted therapies, including immunotherapy options, have produced modest results to date for the treatment of advanced HCC. Although immunotherapy therapy to date has demonstrated its potential efficacy, immune cell pathways need to be better understood. In this review article, we summarize the roles of specific resident immune cell subsets and their cross-talk subversion in HCC pathogenesis, with a view to identifying potential new biomarkers and therapy options

Somatic SF3B1 hotspot mutation in prolactinomas.

The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1R625H) in 19.8% of prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1R625H mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics