Chinese carrier of the p.Gln444fs variant exhibits enhanced response to sulfonylureas.

Background: We assessed the response to sulfonylureas and the functional characteristics of mutations in patients with maturity-onset diabetes of the young type 3 (MODY3).

Methods: We recruited a family with suspected MODY in this study, and gene sequencing (whole-exome sequencing) was used to screen germline mutations. Luciferase reporter assays were used to evaluate the activity of the mutated genes.

Association of a novel frameshift variant and a known deleterious variant in MMR genes with Lynch syndrome in Chinese families.

Background: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This condition is characterized by germline variants in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2. In this study, we analyzed the molecular defects and clinical manifestations of two families affected with CRC and proposed appropriate individual preventive strategies for all carriers of the variant.

AGEs promote atherosclerosis by increasing LDL transcytosis across endothelial cells via RAGE/NF-κB/Caveolin-1 pathway.

Objective: To elucidate the mechanism whereby advanced glycation end products (AGEs) accelerate atherosclerosis (AS) and to explore novel therapeutic strategies for atherosclerotic cardiovascular disease.

Methods And Results: The effect of AGEs on low-density lipoprotein (LDL) transcytosis across endothelial cells (ECs) was assessed using an in vitro model of LDL transcytosis. We observed that AGEs activated the receptor for advanced glycation end products (RAGE) on the surface of ECs and consequently upregulated Caveolin-1, which in turn increased caveolae-mediated LDL transcytosis and accelerated AS progression.

Identification of an variant in a Chinese familial hypercholesterolemia and its relation to ROS/NLRP3-Mediated pyroptosis in hepatic cells.

Background: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China.

Combination model of neutrophil to high-density lipoprotein ratio and system inflammation response index is more valuable for predicting peripheral arterial disease in type 2 diabetic patients: A cross-sectional study.

Background: Neutrophil/high-density lipoprotein (HDL) ratio (NHR), monocyte/HDL ratio (MHR), lymphocyte/HDL ratio (LHR), platelet/HDL ratio (PHR), systemic immune-inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) have been recently investigated as novel inflammatory markers. Herein, the correlation was investigated between these inflammatory biomarkers and peripheral arterial disease (PAD) in type 2 diabetes mellitus (T2DM) patients.

Methods: In this retrospective observational study, the hematological parameter data of 216 T2DM patients without PAD (T2DM-WPAD) and 218 T2DM patients with PAD (T2DM-PAD) at Fontaine stages II, III or IV stage had been collected.

Remnant cholesterol is independently asssociated with an increased risk of peripheral artery disease in type 2 diabetic patients.

Background: Remnant cholesterol (RC) has been correlated with a higher risk of atherosclerosis. It has been confirmed that in the general population, an elevated RC level is related to a 5-fold higher risk of peripheral arterial disease (PAD). Diabetes is one of the strongest risk factors for PAD development.

Scavenger receptor a mediates glycated LDL transcytosis across endothelial cells to promote atherosclerosis.

Glycated low-density lipoprotein (G-LDL) is an established proatherosclerotic factor, but the mechanism is not completely understood. In vitro, we evaluated the uptake and transcytosis rates of N-LDL and G-LDL in endothelial cells and the uptake and transcytosis rates of G-LDL were much higher than those of N-LDL. Then, using small interfering RNAs, the receptor mediating G-LDL uptake and transcytosis was screened among eight candidate receptors, and the mechanism of the receptor regulation was thoroughly examined.

C-band 100-GBaud/λ PAM-4 transmission enabled by hardware-efficient nonlinear equalizer with weight-sharing pruning.

A Volterra nonlinear equalizer (VNLE) can effectively mitigate both linear and nonlinear impairments arising in intensity-modulation direct-detection (IM-DD) transmission systems. However, the high computational complexity of the VNLE hinders its applications. Here, we propose a hardware-efficient Volterra equalizer with weight-sharing pruning (VE-WSP).

VCAM-1-binding peptide targeted cationic liposomes containing NLRP3 siRNA to modulate LDL transcytosis as a novel therapy for experimental atherosclerosis.

Background: Activation of NLRP3 inflammasome accelerates the formation of atherosclerotic plaques. Here, we evaluated the effects of inflammation on the expression of the NLRP3 inflammasome in endothelial cells (ECs).

Methods: The effect of TNF-α on transcytosis of LDL was measured.

Deacetylation of Caveolin-1 by Sirt6 induces autophagy and retards high glucose-stimulated LDL transcytosis and atherosclerosis formation.

Background: Atherosclerosis (AS) is the basis of diabetic macrovascular complications. The plasma low-density lipoprotein (LDL) particles transcytosis across endothelial cells (ECs) and deposition under the endothelium is the initiation step of AS. We previously reported that high glucose inhibits the autophagic degradation of Caveolin-1 and promote LDL transcytosis across ECs, which in turn accelerates atherosclerotic progression.

Age-related changes of human serum Sirtuin6 in adults.

Background: Aging is a natural life process and with an aging population, age-related diseases (e.g. type 2 diabetes mellitus (T2DM), atherosclerosis-based cardiovascular diseases) are the primary mortality cause in older adults.

Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system.

Gene therapy has become the most effective treatment for monogenic diseases. Congenital LEPTIN deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the Leptin gene. Ob/ob mouse is a monogenic obesity model, which carries a homozygous point mutation of C to T in Exon 2 of the Leptin gene.

Salidroside-Mediated Autophagic Targeting of Active Src and Caveolin-1 Suppresses Low-Density Lipoprotein Transcytosis across Endothelial Cells.

Subendothelial retention of apolipoprotein B100-containing lipoprotein, such as low-density lipoprotein (LDL), is the initial step of atherogenesis. Activation of autophagy exhibits beneficial effects for the treatment of atherosclerosis. In our previous study, we demonstrated that hyperglycemia suppressed autophagic degradation of caveolin-1, which in turn resulted in acceleration of caveolae-mediated LDL transcytosis across endothelial cells and lipid retention.

Wilson Disease With Novel Compound Heterozygote Mutations in the Gene Presenting With Severe Diabetes.

Objective: To determine the relationship between mutations and diabetes in Wilson disease (WD).

Research Design And Methods: A total of 21 exons and exon-intron boundaries of were identified by Sanger sequencing.

Results: Two novel compound heterozygous mutations (c.

Low density lipoprotein mimics insulin action on autophagy and glucose uptake in endothelial cells.

Elevated plasma low density lipoprotein (LDL) is an established risk factor for cardiovascular disease. In addition to being able to cross the endothelial barrier to become accumulated in subendothelial space and thereby initiate atherosclerosis, LDL may exert a direct effect on vascular endothelial cells through activation of LDL receptor and its downstream signaling. Whether LDL can modulate the signaling for autophagy in endothelial cells is not clear.