Endothelial PHACTR1 Promotes Endothelial Activation and Atherosclerosis by Repressing PPARγ Activity Under Disturbed Flow in Mice.

BACKGROUND: Numerous genome-wide association studies revealed that SNPs (single nucleotide polymorphisms) at the PHACTR1 (phosphatase and actin regulator 1) locus strongly correlate with coronary artery disease. However, the biological function of PHACTR1 remains poorly understood. Here, we identified the proatherosclerotic effect of endothelial PHACTR1, contrary to macrophage PHACTR1. METHODS: We generated global (Phactr1-/-) and endothelial cell (EC)-specific (Phactr1ECKO) Phactr1 KO (knockout) mice and crossed these mice with apolipoprotein E-deficient (Apoe-/-) mice. Atherosclerosis was induced by feeding the high-fat/high-cholesterol diet for 12 weeks or partially ligating carotid arteries combined with a 2-week high-fat/high-cholesterol diet. PHACTR1 localization was identified by immunostaining of overexpressed PHACTR1 in human umbilical vein ECs exposed to different types of flow. The molecular function of endothelial PHACTR1 was explored by RNA sequencing using EC-enriched mRNA from global or EC-specific Phactr1 KO mice. Endothelial activation was evaluated in human umbilical vein ECs transfected with siRNA targeting PHACTR1 and in Phactr1ECKO mice after partial carotid ligation. RESULTS: Global or EC-specific Phactr1 deficiency significantly inhibited atherosclerosis in regions of disturbed flow. PHACTR1 was enriched in ECs and located in the nucleus of disturbed flow areas but shuttled to cytoplasm under laminar flow in vitro. RNA sequencing showed that endothelial Phactr1 depletion affected vascular function, and PPARγ (peroxisome proliferator-activated receptor gamma) was the top transcription factor regulating differentially expressed genes. PHACTR1 functioned as a PPARγ transcriptional corepressor by binding to PPARγ through the corepressor motifs. PPARγ activation protects against atherosclerosis by inhibiting endothelial activation. Consistently, PHACTR1 deficiency remarkably reduced endothelial activation induced by disturbed flow in vivo and in vitro. PPARγ antagonist GW9662 abolished the protective effects of Phactr1 KO on EC activation and atherosclerosis in vivo. CONCLUSIONS: Our results identified endothelial PHACTR1 as a novel PPARγ corepressor to promote atherosclerosis in disturbed flow regions. Endothelial PHACTR1 is a potential therapeutic target for atherosclerosis treatment.

One-Pot Facile Fabrication of Bioavailable Iron Nanoparticles with Good Biocompatibility for Anemia Therapy.

BACKGROUND Iron deficiency anemia (IDA) has been a major public health problem all over the world. Developing new iron (Fe) fortificants with both high bioavailability and negligible food sensory changes for IDA is in urgent demand. MATERIAL AND METHODS The Fe nanoparticles were fabricated through a one-pot reduction process under the protection of bovine serum albumin (BSA). The BSA-Fe nanoparticles were characterized systematically. The comparisons between BSA-Fe nanoparticles and FeSO4 in bioavailability were carried out through hemoglobin (Hb) repletion method. The biocompatibility of BSA-Fe nanoparticles was also investigated through in vitro and in vivo assays. RESULTS BSA-Fe nanoparticles have super-small size and good water solubility as well as water stability. The Hb repletion assay demonstrated that BSA-Fe nanoparticles have comparative bioavailability with FeSO4. The in vitro cell viability assay, in vivo histological analysis, and biochemical measurements proved the remarkable biocompatibility of BSA-Fe nanoparticles. CONCLUSIONS The BSA-Fe nanoparticles fabricated through a one-pot facile method have good water solubility, comparative bioavailability with FeSO4, and acceptable biocompatibility, exhibiting good potential for further clinical translations.

Can AI language models replace human participants?

Recent work suggests that language models such as GPT can make human-like judgments across a number of domains. We explore whether and when language models might replace human participants in psychological science. We review nascent research, provide a theoretical model, and outline caveats of using AI as a participant.

Prenatal diagnosis of congenital nephrotic syndrome of the Finnish type in a Chinese family.

OBJECTIVE: To explore the genetic bias in a Chinese family suspected of having congenital nephrotic syndrome of the Finnish type (CNF). CASE REPORT: We developed a prenatal genetic diagnosis in a Chinese family with CNF. A single heterozygous mutation (c.3213delG) was found in the foetus IId and we presumed that it was an asymptomatic carrier of the normal phenotype. Additionally, two compound heterozygous variants (c.3213delG and c.3478C > T) were discovered in the foetus IIe, which were inherited from the mother and father, respectively. We performed further pathological examinations after medical abortion. Kidney histopathology and immunofluorescence results were similar to those reported in previous studies. CONCLUSION: Prenatal genetic diagnosis of CNF still requires further research to explore the pathogenicity of suspected mutations.

Analysis of Vascular Mechanical Characteristics after Coronary Degradable Stent Implantation.

PURPOSE: To explore the effect of vascular stress changes on endothelial function recovery and vascular restenosis inhibition, under the condition of dynamic degradation process of the degradable stent. METHODS: Fitting the material parameters of the hyperelastic vascular constitutive relationship, the stress distribution of the intima of the blood vessel before the stent was implanted and during the dynamic degradation was calculated by numerical simulation. In vitro culture experiments were carried out, and the stretch ratios of the silicone chamber were set to 0%, 5%, 10%, and 15%, respectively, to simulate the effects of different degradation stages on the growth state of endothelial cells. RESULTS: After the stent was completely degraded, the circumferential intimal stress (strain) of the vessel was recovered to 0.137 MPa, 5.5%, which was close to the physiological parameters (0.122 MPa, 4.8%) before stent implantation. In vitro experiments showed that the endothelial cell survival rate was the highest under the condition of circumferential stress (strain) of 0.1 MPa, 5%, and all adhesion growth could be achieved. CONCLUSIONS: With the occurrence of degradation process of the stent, the circumferential stress (strain) of the intima was recovered to a range close to physiological parameters, which promotes the growth of endothelial cells. The recovery of intimal function can effectively inhibit the process of vascular restenosis. The results can provide a theoretical basis and experimental platform for the study of coronary intervention for the treatment of vascular restenosis.