Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk

Is More the Better? How Abundant Contents and Online Interaction Hinder the Learning Effectiveness of High-quality MOOCs

High dropout rates and low pass rates are prevalent problems encountered by online learning platforms. Drawing upon the theory of attention allocation, this study aims to investigate the factors influencing the effectiveness of Massive Open Online Courses (MOOCs), as well as the potential moderating effects. An empirical analysis of 8,609 courses on a Chinese MOOC platform (Zhihuishu) is conducted. The findings indicate that course quality, content richness and interactivity significantly influence course dropout rates and pass rates. Besides, content richness moderates the relationship between course quality and learning effectiveness. Frequent online interaction is associated with lower pass rates in high-quality courses, but the moderating effect of interactivity on dropout rates is insignificant. This study contributes to the extant literature by examining course-level factors that affect learning effectiveness. It also offers new theoretical insights and provides valuable suggestions for the design of MOOCs

In Vitro Induction of Interspecific Hybrid and Polyploidy Derived from <i>Oryza officinalis</i> Wall

Oryza officinalis Wall is a potential genetic resource for rice breeding; however, its distant genome limits its crossing ability with cultivated rice. The interspecific hybridization of O. officinalis and cultivated rice, establishment of its tissue culture, and induction of polyploidy are ways to improve O. officinalis’s poor crossability. We developed an interspecific hybrid and studied its reproductive pollen development process in this work, and the results showed that abortive pollens (81.94%) and embryo sac abnormalities (91.04%) were the key causes of its high sterility. In order to induce callus formation in interspecific hybrid explants, two different culture media, namely Chu’s N-6 medium (N6) and 1/2 Murashig and Skoog medium (1/2 MS), were employed. Additionally, two plant growth regulators (PGRs), namely 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BA), along with L-proline (Pro) and acid hydrolyzed casein, were utilized in the experiment. The optimal N6 medium, supplemented with 2.0 mg·L−1 2,4-D, produced the highest induction rate (80.56 ± 5.44)%. For callus differentiation and proliferation, the MS medium supplemented with 2.0 mg·L−1 BA + 0.2 mg·L−1 NAA produced the highest differentiation rate (75.00 ± 4.97)% and seedling emergence ratio (28.97 ± 4.67)%. The optimal combination for seedling rooting was the 1/2 MS medium supplemented with 2.0 mg L−1 NAA and 0.2 mg L−1 BA, which produced an average of 13.95 roots per plant. For polyploidy induction in the interspecific hybrid, the concentration of colchicine treatment at 400 mg·L−1 for three days is an ideal protocol. We devised tissue culture and interspecific hybrid polyploidy induction to overcome O. officinalis’ poor crossability and introduce its favorable features into cultivated rice

Fabrication of a Silicon-Based Microprobe for Neural Interface Applications

A two-dimensional (2D) multi-channel silicon-based microelectrode array is developed for recording neural signals. Three photolithographic masks are utilized in the fabrication process. SEM images show that the microprobe is 1. 2mm long,100μm wide,and 30μm thick, with recording sites spaced 200μm apart for good signal isolation. For the individual recording sites, the characteristics of impedance versus frequency are shown by in vitro testing. The impedance declines from 14MΩ to 1.9kv as the frequency changes from 0 to 10MHz. A compatible PCB (print circuit board) aids in the less troublesome implantation and stabilization of the microprobe

Research status of the effects of natural oligosaccharides on glucose metabolism

Abstract Diabetes is a common and frequently occurring endocrine and metabolic disease characterized by hyperglycemia with genetic tendency. At present, the drugs for diabetes include metformin, glimepiride, and acarbose. Although these drugs are effective, long‐term usage will produce secondary symptoms, such as Cushing's syndrome, limb hypertrophy, and even the risk of hypoglycemia. Many natural products have been found to treat diabetes, among which oligosaccharides are the most valuable. Oligosaccharides are low‐level oligosaccharides formed by the linkage of 2–10 monosaccharides through glycosidic bonds. Common oligosaccharides include chitosan oligosaccharides, xylooligosaccharides, konjac glucomannan, and brown algae oligosaccharides. It has the effects of reducing blood glucose, blood pressure, antioxidant, anti‐inflammatory, immune regulation, antiallergy, promoting the growth of bifidobacteria, and improving body health. With the continuous exploration of the medicinal value of natural oligosaccharides, more and more attention has been paid to their research. This review introduces some representative oligosaccharides with hypoglycemic effects, including their structural characteristics and hypoglycemic mechanism, as well as the application status and future development trend of oligosaccharides

Occurrence and Characterization of <i>Sclerotinia sclerotiorum</i> Causing Fruit Rot on Sweet Cherry in Southern China

Sweet cherry (Prunus avium L.) is widely planted in northern China due to its high economic value, and its cultivation has gradually spread south to warm regions. However, fruit rot, observed on the young fruits, poses a considerable threat to the development of sweet cherry. To determine the causal agent, morphological observation, molecular identification, and pathogenicity tests were performed on isolates obtained from diseased fruits. As a result, Sclerotinia sclerotiorum was identified as the pathogen. Pathogenicity tests on different sweet cherry cultivars indicated that ‘Summit’ was highly sensitive to S. sclerotiorum, whereas ‘Hongmi’ showed significant resistance. Besides sweet cherry, S. sclerotiorum could also infect other vegetable crops we tested, such as cowpea, soybean, tomato, and chili. Fungicide sensitivity and efficacy assays showed that both fludioxonil and pyraclostrobin can effectively inhibit the mycelial growth of S. sclerotiorum and decrease disease incidences on the young fruits of sweet cherry. Furthermore, genome sequencing resulted in a 37.8 Mb assembly of S. sclerotiorum strain ScSs1, showing abundant SNPs, InDels, and SVs with the genome of S. sclerotiorum reference strain 1980 UF-70. The above results provide an important basis for controlling the fruit rot of sweet cherry caused by S. sclerotiorum in China