Trifolirhizin relieves renal injury in a diabetic nephropathy model by inducing autophagy and inhibiting oxidative stress through the regulation of PI3K/AKT/mTOR pathway

Purpose: To evaluate the effects of trifolirhizin on diabetic nephropathy (DN), and the mechanism of action. Methods: Male db/db mice (8 weeks, n = 24) and age-matched control mice (n = 6) were obtained. The mice were further divided into four groups and administered increasing doses of trifolirhizin (0, 12.5, 25 and 50 mg/kg). Histological analysis of renal tissues were performed by H & E staining. Blood urea nitrogen (BUN) and creatinine were determined using enzyme-linked immunosorbent assay (ELISA). Immunoblot and TUNEL assay were performed to investigate the effect of trifolirhizin on autophagy and apoptosis, while ELISA and dihydroethidium (DHE) staining were conducted to evaluate reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) levels. The effect of trifolirhizin on PI3K/AKT/mTOR pathway was determined using Immunoblot assays. Results: Trifolirhizin alleviated renal injury in diabetic mice, and also activate autophagy and inhibited apoptosis in the renal tissues in diabetic mice (p < 0.001). In addition, trifolirhizin inhibited the oxidative stress response in the renal tissue in diabetic mice (p < 0.001). Trifolirhizin further inhibited PI3K/AKT/mTOR pathway and therefore relieved renal injury in the diabetic nephropathy model (p < 0.001). Conclusion: Trifolirhizin alleviates renal injury in diabetic mice, activates autophagy, and inhibits apoptosis in renal tissue of diabetic mice. Therefore, trifolirhizin is a promising a promising drug for the treatment of DN

What affects second language vocabulary learning? Evidence from multivariate analysis

IntroductionVocabulary acquisition is crucial in second language (L2) learning and can be affected by multi-variables. The fact that all these variables have typically been investigated separately (or, at best, in pairs) potentially obscures important interactions between them. This study comprehensively examines the intricate factors affecting vocabulary knowledge among Chinese learners studying English as a foreign language (EFL).MethodsWe conducted an investigation involving 200 Chinese EFL learners to identify the relationships between L2 proficiency, vocabulary learning strategies, age of acquisition (AoA), classroom exposure, and their relationships and predictive power on L2 vocabulary breadth and vocabulary depth.ResultsL2 proficiency emerged as the most robust predictor of vocabulary knowledge, closely trailed by vocabulary learning strategies, AoA, and classroom exposure. Notably, the use of metacognitive learning strategies such as self-regulated and self-aware learning, was found to be significant. Earlier L2 exposure resulted in a more sufficient vocabulary knowledge. However, the conventional belief that longer classroom sessions lead to enhanced vocabulary knowledge was challenged.DiscussionOur findings suggest the interconnectedness between L2 proficiency and L2 vocabulary knowledge. The investigation highlights the need for increased cognitive involvement and self-discipline in L2 vocabulary learning. This study also emphasizes the necessity to maximize the efficacy of classroom sessions, together with the benefits for an earlier age of L2 acquisition. Guidance for L2 researchers and instructors in second language vocabulary acquisition is offered

Increased co-expression of 4-1BB with PD-1 on CD8+ tumor-infiltrating lymphocytes is associated with improved prognosis and immunotherapy response in cervical cancer

BackgroundThe combination of agonistic antibodies with immune checkpoint inhibitors presents a promising avenue for cancer immunotherapy. Our objective is to explore the co-expression of 4-1BB, ICOS, CD28, with PD-1 on CD8+ T cells in the peripheral blood and tumor tissue of cervical cancer(CC) patients, with a specific focus on the association between the co-expression levels of 4-1BB with PD-1 and clinical features, prognosis as well as immunotherapy response. The goal is to offer valuable insights into cervical cancer immunotherapy.MethodsIn this study, 50 treatment-naive patients diagnosed with CC were enrolled. Flow cytometry was used to detect PD-1/4-1BB, PD-1/ICOS and PD-1/CD28 co-expression on CD8+ T cells. Subsequent analysis aimed to investigate the differential co-expression between peripheral blood and cancer tissue, and also the correlation between co-expression and clinical features in these patients. Gene Expression Omnibus (GEO) datasets, The Cancer Genome Atlas (TCGA) cohort, The IMvigor210 cohort, The BMS038cohort and Immunophenoscores were utilized to investigate the correlation between PD-1/4-1BB and the immune microenvironment, prognosis, immunotherapy, and drug sensitivity in cervical cancer.ResultsThe co-expression levels of PD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 on CD8+ tumor-infiltrating lymphocytes (TILs) were significantly higher in cervical cancer patients compared to those in peripheral blood. Clinical feature analysis reveals that on CD8+ TILs, the co-expression of PD-1/4-1BB is more closely correlated with clinical characteristics compared to PD-1/ICOS, PD-1/CD28, PD-1, and 4-1BB. Pseudo-time analysis and cell communication profiling reveal close associations between the subgroups harboring 4-1BB and PD-1. The prognosis, tumor mutation burden, immune landscape, and immunotherapy response exhibit statistically significant variations between the high and low co-expression groups of PD-1/4-1BB. The high co-expression group of PD-1/4-1BB is more likely to benefit from immunotherapy.ConclusionPD-1/4-1BB, PD-1/ICOS, and PD-1/CD28 exhibit elevated co-expression on CD8+TILs of cervical cancer, while demonstrating lower expression in circulating T cells. The co-expression patterns of PD-1/4-1BB significantly contributed to the prediction of immune cell infiltration characteristics, prognosis, and tailored immunotherapy tactics. PD-1/4-1BB exhibits potential as a target for combination immunotherapy in cervical cancer

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Danning Zhu, How to Improve China’s Approach to Parallel Imports of Goods Bearing Trademarks, 19 UIC Rev. Intell. Prop. L. 125 (2020)

Parallel import, also known as grey market goods, refers to the act of importing goods to a country and selling in the country without the permission of the domestic owner of IP vested in the imported goods. The importer can obtain profits through the price differences between parallel imported products and domestic products of the same variety. China and the United States have huge differences in parallel import policies, even though both countries have participated in major international IP treaties. The United States requires that parallel imported goods bearing a genuine trademark or trade name registered in the United States will be restricted from importing if the manufacturer or the owner of such goods has no relationship with or control of the owner of U.S. trademark or trade name. Different from the United States, China’s relevant laws and regulations do not explicitly limit parallel imports, including parallel imported goods that have no relationship with or control of the owner of the involved trademark registered in China. China’s approach encourages parallel imports. In practice, more and more international trademark holders have filed lawsuits in China, claiming that such parallel imports are trademark infringement which damage their benefits. These cases demonstrate China’s problem of the lack of regulations on restrictions of parallel imports even though such restrictions have been recognized by courts in practice. This Article recommends changes to China\u27s current parallel import policy by referring to the relevant U.S. parallel import statutes and precedents. In considering the differences between the two countries, the Article does not recommend the adoption of the “common control” requirement

Review on Facial-Recognition-Based Applications in Disease Diagnosis

Diseases not only manifest as internal structural and functional abnormalities, but also have facial characteristics and appearance deformities. Specific facial phenotypes are potential diagnostic markers, especially for endocrine and metabolic syndromes, genetic disorders, facial neuromuscular diseases, etc. The technology of facial recognition (FR) has been developed for more than a half century, but research in automated identification applied in clinical medicine has exploded only in the last decade. Artificial-intelligence-based FR has been found to have superior performance in diagnosis of diseases. This interdisciplinary field is promising for the optimization of the screening and diagnosis process and assisting in clinical evaluation and decision-making. However, only a few instances have been translated to practical use, and there is need of an overview for integration and future perspectives. This review mainly focuses on the leading edge of technology and applications in varieties of disease, and discusses implications for further exploration

Wake‐Riding Effect‐Inspired Opto‐Hydrodynamic Diatombot for Non‐Invasive Trapping and Removal of Nano‐Biothreats

Abstract Contamination of nano‐biothreats, such as viruses, mycoplasmas, and pathogenic bacteria, is widespread in cell cultures and greatly threatens many cell‐based bio‐analysis and biomanufacturing. However, non‐invasive trapping and removal of such biothreats during cell culturing, particularly many precious cells, is of great challenge. Here, inspired by the wake‐riding effect, a biocompatible opto‐hydrodynamic diatombot (OHD) based on optical trapping navigated rotational diatom (Phaeodactylum tricornutum Bohlin) for non‐invasive trapping and removal of nano‐biothreats is reported. Combining the opto‐hydrodynamic effect and optical trapping, this rotational OHD enables the trapping of bio‐targets down to sub‐100 nm. Different nano‐biothreats, such as adenoviruses, pathogenic bacteria, and mycoplasmas, are first demonstrated to be effectively trapped and removed by the OHD, without affecting culturing cells including precious cells such as hippocampal neurons. The removal efficiency is greatly enhanced via reconfigurable OHD array construction. Importantly, these OHDs show remarkable antibacterial capability, and further facilitate targeted gene delivery. This OHD serves as a smart micro‐robotic platform for effective trapping and active removal of nano‐biothreats in bio‐microenvironments, and especially for cell culturing of many precious cells, with great promises for benefiting cell‐based bio‐analysis and biomanufacturing