CI431, an Aqueous Compound from Ciona intestinalis L., Induces Apoptosis through a Mitochondria-Mediated Pathway in Human Hepatocellular Carcinoma Cells

In the present studies, a novel compound with potent anti-tumor activity from Ciona intestinalis L. was purified by acetone fractionation, ultrafiltration, gel chromatography and High Performance Liquid Chromatography. The molecular weight of the highly purified compound, designated CI431, was 431Da as determined by HPLC-MS analysis. CI431 exhibited significant cytotoxicity to several cancer cell types. However, only a slight inhibitory effect was found when treating the benign human liver cell line BEL-7702 with the compound. To explore its mechanism against hepatocellular carcinoma, BEL-7402 cells were treated with CI431 in vitro. We found that CI431 induced apoptotic death in BEL-7402 cells in a dose- and time-dependent manner. Cell cycle analysis demonstrated that CI431 caused cell cycle arrest at the G2/M phase, and a sub-G1 peak appeared after 24 h. The mitochondrial-mediated pathway was implicated in this CI431-induced apoptosis as evidenced by the disruption of mitochondrial membrane potential. The results suggest that the CI431 induces apoptosis in BEL-7402 human hepatoma cells by intrinsic mitochondrial pathway

Analysis of congestion key parameters, dynamic discharge process, and capacity estimation at urban freeway bottlenecks: a case study in Beijing, China

Recurring bottlenecks significantly contribute to urban freeway congestion, making their analysis essential. This study examines six bottlenecks on Beijing’s Ring Road using multi-day data, identifying them via Dynamic Time Warping and Fuzzy C-Means Clustering (DTW+FCM). Key parameters—free-flow speed, critical speed, critical density, and jam density—are calibrated using fundamental diagram models. The Weibull distribution analyzes flow and speed patterns during congestion phases. The DTW+FCM method effectively identified bottlenecks and congestion levels. Severe congestion lasting over 10 hours on the West Second and Third Ring Roads averaged speeds of 15 km/h. The S3 model best fits data for the West Ring Roads, while the Van Aerde model suits the North Ring Roads. Different methods yield varying traffic capacity estimates, highlighting the need for nuanced approaches in urban expressway planning to maintain traffic quality and comfort. These findings offer valuable guidance for research and practical traffic management solutions

In Vitro Exploration of ACAT Contributions to Lipid Droplet Formation During Adipogenesis

As adipose tissue is the major cholesterol storage organ and most of the intracellular cholesterol is distributed to lipid droplets (LDs), cholesterol homeostasis may have a role in the regulation of adipocyte size and function. ACATs catalyze the formation of cholesteryl ester (CE) from free cholesterol to modulate the cholesterol balance. Despite the well-documented role of ACATs in hypercholesterolemia, their role in LD development during adipogenesis remains elusive. Here, we identify ACATs as regulators of de novo lipogenesis and LD formation in murine 3T3-L1 adipocytes. Pharmacological inhibition of ACAT activity suppressed intracellular cholesterol and CE levels, and reduced expression of genes involved in cholesterol uptake and efflux. ACAT inhibition resulted in decreased de novo lipogenesis, as demonstrated by reduced maturation of SREBP1 and SREBP1-downstream lipogenic gene expression. Consistent with this observation, knockdown of either ACAT isoform reduced total adipocyte lipid content by approximately 40%. These results demonstrate that ACATs are required for storage ability of lipids and cholesterol in adipocytes

AgRP Neurons Are Not Indispensable for Body Weight Maintenance in Adult Mice

In addition to their role in promoting feeding and obesity development, hypothalamic arcuate agouti-related protein/neuropeptide Y (AgRP/NPY) neurons are widely perceived to be indispensable for maintaining normal feeding and body weight in adults, and consistently, acute inhibition of AgRP neurons is known to reduce short-term food intake. Here, we adopted complementary methods to achieve nearly complete ablation of arcuate AgRP/NPY neurons in adult mice and report that lesioning arcuate AgRP/NPY neurons in adult mice causes no apparent alterations in ad libitum feeding or body weight. Consistent with previous studies, loss of AgRP/NPY neurons blunts fasting refeeding. Thus, our studies show that AgRP/NPY neurons are not required for maintaining ad libitum feeding or body weight homeostasis in adult mice

Endoscopy-assisted anterior cervical discectomy and fusion with internal fixation vs conventional surgery in the treatment of cervical disc herniation

Introduction: Cervical disc herniation (CDH) is a common condition, usually caused by excessive strain or trauma to the spine. Initially, it is treated conservatively; however, complex and resistant cases may require a surgical intervention. Aim: We aimed to compare the clinical effect of endoscopy-assisted anterior cervical discectomy and fusion (ACDF) with internal fixation and conventional surgery in the treatment of CDH. Materials and methods: Patients with CDH who underwent ACDF with fixation at the Zhoushan Dinghai Guanghua Hospital were enrolled. Of them, 10 individuals were treated with conventional ACDF (conventional surgery group), and the other 10 with endoscopy-assisted ACDF (endoscopy-assisted surgery group). The general characteristics, postoperative Japanese Orthopedic Association (JOA), visual analogue scale (VAS), 12-Item Short Form Survey Physical Component Summary (SF-12 PCS), and SF-12 Mental Component Summary (SF-12 MCS) scores, physiological stress response, rate of the improved JOA score (RIS), hemoglobin level, and bone graft fusion were compared between the groups. Results: Outcomes of the patients treated with endoscopy-assisted surgery were clearly superior to those observed in the conventional surgery group. The postoperative JOA, VAS, SF-12 PCS, and SF-12 MCS scores and RIS in the endoscopy-assisted surgery group were higher than in the conventional surgery group (P <⁠0.05). Following operation, there were significant differences between the 2 groups with respect to RIS at 1 week and 6 months postsurgery and hemoglobin levels on postoperative day 2. Changes in heart rate and diastolic blood pressure in the endoscopy-assisted surgery group were less pronounced than in the conventional surgery group (P <⁠0.05), and the fusion rate was significantly higher in the former group (90% vs 80%, respectively). Conclusions: Endoscopy-assisted ACDF with internal fixation has a greater clinical therapeutic effect than the conventional approach in the treatment of CDH. It is associated with a higher bone graft fusion rate and reduced intraoperative blood loss

Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis

Abstract Background Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation and altered keratinocyte differentiation and inflammation and is caused by the interplay of genetic and environmental factors. Previous studies have revealed that DNA methylation (DNAm) and genetic makers are closely associated with psoriasis, and strong evidences have shown that DNAm can be controlled by genetic factors, which attracted us to evaluate the relationship among DNAm, genetic makers, and disease status. Methods We utilized the genome-wide methylation data of psoriatic skin (PP, N = 114) and unaffected control skin (NN, N = 62) tissue samples in our previous study, and we performed whole-genome genotyping with peripheral blood of the same samples to evaluate the underlying genetic effect on skin DNA methylation. Causal inference test (CIT) was used to assess whether DNAm regulate genetic variation and gain a better understanding of the epigenetic basis of psoriasis susceptibility. Results We identified 129 SNP-CpG pairs achieving the significant association threshold, which constituted 28 unique methylation quantitative trait loci (MethQTL) and 34 unique CpGs. There are 18 SNPs were associated with psoriasis at a Bonferoni-corrected P < 0.05, and these 18 SNPs formed 93 SNP-CpG pairs with 17 unique CpG sites. We found that 11 of 93 SNP-CpG pairs, composed of 5 unique SNPs and 3 CpG sites, presented a methylation-mediated relationship between SNPs and psoriasis. The 3 CpG sites were located on the body of C1orf106, the TSS1500 promoter region of DMBX1 and the body of SIK3. Conclusions This study revealed that DNAm of some genes can be controlled by genetic factors and also mediate risk variation for psoriasis in Chinese Han population and provided novel molecular insights into the pathogenesis of psoriasis