USP10 promotes cell proliferation, migration, and invasion in NSCLC through deubiquitination and stabilization of EIF4G1.

Lung cancer is one of the most common types of malignant cancer worldwide, causing a serious social and economic burden. It is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for 80-85% of cases. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is highly expressed in NSCLC, playing an important role in regulating tumor growth, angiogenesis, malignant transformation, and phagocytosis. Ubiquitin-specific protease 10 (USP10) functions as a deubiquitinating enzyme to regulate substrate protein deubiquitination and reverse the ubiquitin proteasome degradation pathway. Our previous study identified an interaction between EIF4G1 and USP10; however, their regulatory mechanism remains unclear. Herein, we found that USP10 positively regulates EIF4G1 in NSCLC cells. An in vivo ubiquitination assay demonstrated deubiquitination of EIF4G1 by USP10, which reversed the ubiquitin proteasomal degradation of EIF4G1, thereby increasing its stability. Upregulation of EIF4G1 promoted cell proliferation, migration, and invasion in NSCLC cells. The current study not only reveals a novel mechanism through which USP10 positively regulates EIF4G1 in NSCLC, but also demonstrates the potential of USP10 as a therapeutic target to treat NSCLC.

Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion.

Non-small cell lung cancer (NSCLC) is the most common type of lung tumor; however, we lack effective early detection indicators and therapeutic targets. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is vital to initiate protein synthesis, acting as a scaffolding protein for the eukaryotic protein translation initiation factor complex, EIF4F, which regulates protein synthesis together with EIF4A, EIF4E, and other translation initiation factors. However, EIF4G1's function in NSCLC cancer is unclear. Herein, transcriptome sequencing showed that knockdown of EIF4G1 in H1299 NSCLC cells upregulated the expression of various inflammation-related factors. Inflammatory cytokines were also significantly overexpressed in NSCLC tumor tissues, among which CXCL8 (encoding C-X-C motif chemokine ligand 8) showed the most significant changes in both in the transcriptome sequencing data and tumor tissues. We revealed that EIF4G1 regulates the protein level of TNF receptor superfamily member 10a (TNFRSF10A) resulting in activation of the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) pathways, which induces CXCL8 secretion, leading to targeted chemotaxis of immune cells. We verified that H1299 cells with EIF4G1 knockdown showed increased chemotaxis compared with the control group and promoted increased chemotaxis of macrophages. These data suggested that EIF4G1 is an important molecule in the inflammatory response of cancer tissues in NSCLC.

Validation of a predictive model for coronary artery disease in patients with diabetes.

BACKGROUND: No reliable model can currently be used for predicting coronary artery disease (CAD) occurrence in patients with diabetes. We developed and validated a model predicting the occurrence of CAD in these patients. METHODS: We retrospectively enrolled patients with diabetes at Henan Provincial People's Hospital between 1 January 2020 and 10 June 2020, and collected data including demographics, physical examination results, laboratory test results, and diagnostic information from their medical records. The training set included patients ( n  = 1152) enrolled before 15 May 2020, and the validation set included the remaining patients ( n  = 238). Univariate and multivariate logistic regression analyses were performed in the training set to develop a predictive model, which were visualized using a nomogram. The model's performance was assessed by area under the receiver-operating characteristic curve (AUC) and Brier scores for both data sets. RESULTS: Sex, diabetes duration, low-density lipoprotein, creatinine, high-density lipoprotein, hypertension, and heart rate were CAD predictors in diabetes patients. The model's AUC and Brier score were 0.753 [95% confidence interval (CI) 0.727-0.778] and 0.152, respectively, and 0.738 (95% CI 0.678-0.793) and 0.172, respectively, in the training and validation sets, respectively. CONCLUSIONS: Our model demonstrated favourable performance; thus, it can effectively predict CAD occurrence in diabetes patients.

Transmissible Endoplasmic Reticulum Stress Mediated by Extracellular Vesicles from Adipocyte Promoting the Senescence of Adipose-Derived Mesenchymal Stem Cells in Hypertrophic Obesity.

Hypertrophic obesity, characterized by an excessive expansion of subcutaneous adipocytes, causes chronic inflammation and insulin resistance. It is the primary feature of obesity in middle-aged and elderly individuals. In the adipose microenvironment, a high level of endoplasmic reticulum (ER) stress and changes in the extracellular vesicle (EV) composition of adipocytes may cause the senescence and restrained differentiation of progenitor cells of adipose, including adipose-derived mesenchymal stem cells (ASCs). In this study, a hypertrophic obesity mouse model was established, and the effects of adipocytes on the ER stress and senescence of ASCs were observed in a coculture of control ASCs and hypertrophic obesity mouse adipocytes or their derived EVs. The adipocytes of hypertrophic obesity mice were treated with GW4869 or an iron chelation agent to observe the effects of EVs secreted by adipocytes and their iron contents on the ER stress and senescence of ASCs. Results showed higher ER stress level and senescence phenotypes in the ASCs from the hypertrophic obesity mice than in those from the control mice. The ER stress, senescence phenotypes, and ferritin level of ASCs can be aggravated by the coculture of ASCs with adipocytes or EVs released by them from the hypertrophic obesity mice. GW4869 or iron chelator treatment improved the ER stress and senescence of the ASCs cocultured with EVs released by the adipocytes of the hypertrophic obesity mice. Our findings suggest that EV-mediated transmissible ER stress is responsible for the senescence of ASCs in hypertrophic obesity mice.

Velocity clamping-assisted adaptive salp swarm algorithm: balance analysis and case studies.

Salp swarm algorithm (SSA) is a recently proposed, powerful swarm-intelligence based optimizer, which is inspired by the unique foraging style of salps in oceans. However, the original SSA suffers from some limitations including immature balance between exploitation and exploration operators, slow convergence and local optimal stagnation. To alleviate these deficiencies, a modified SSA (called VC-SSA) with velocity clamping strategy, reduction factor tactic, and adaptive weight mechanism is developed. Firstly, a novel velocity clamping mechanism is designed to boost the exploitation ability and the solution accuracy. Next, a reduction factor is arranged to bolster the exploration capability and accelerate the convergence speed. Finally, a novel position update equation is designed by injecting an inertia weight to catch a better balance between local and global search. 23 classical benchmark test problems, 30 complex optimization tasks from CEC 2017, and five engineering design problems are employed to authenticate the effectiveness of the developed VC-SSA. The experimental results of VC-SSA are compared with a series of cutting-edge metaheuristics. The comparisons reveal that VC-SSA provides better performance against the canonical SSA, SSA variants, and other well-established metaheuristic paradigms. In addition, VC-SSA is utilized to handle a mobile robot path planning task. The results show that VC-SSA can provide the best results compared to the competitors and it can serve as an auxiliary tool for mobile robot path planning.

The Prognostic Value and Immune Infiltration of USP10 in Pan-Cancer: A Potential Therapeutic Target.

Ubiquitin-specific peptidase 10 (USP10) can sustain cellular functions and regulate cellular processes. It plays an essential role in cancer inhibition or facilitation by reversing ubiquitin-proteasome degradation. Studies have identified USP10 to be involved in tumor progression in various cancers. However, the pan-cancer expression pattern of USP10, its prognostic value, and the association between tumor immune cell infiltration and USP10 expression remain to be discussed and thus comprised the aims of the present study. Based on clinical samples and bioinformatic analyses, high USP10 expression was observed in most cancer tissues except for ovarian cancer. High USP10 expression correlated with pathological stage and node metastasis and predicted poor patient prognosis. In addition, further analyses at the TIMER and GEPIA databases showed that USP10 is involved in the infiltration of multiple immune cells and regulated the infiltration levels of specific immune cell subpopulations, particularly in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). Importantly, USP10 might influence survival by modulating immune infiltration in patients with PAAD and LIHC. These results identified USP10 as a potential biomarker for pan-cancer prognosis, and in certain cancers, USP10 could identify clinical prognosis linked to tumor immune infiltration.

Undergraduate medical academic performance is improved by scientific training.

The effect of scientific training on course learning in undergraduates is still controversial. In this study, we investigated the academic performance of undergraduate students with and without scientific training. The results show that scientific training improves students' test scores in general medical courses, such as biochemistry and molecular biology, cell biology, physiology, and even English. We classified scientific training into four levels. We found that literature reading could significantly improve students' test scores in general courses. Students who received scientific training carried out experiments more effectively and published articles performed better than their untrained counterparts in biochemistry and molecular biology examinations. The questionnaire survey demonstrated that the trained students were more confident of their course learning, and displayed more interest, motivation and capability in course learning. In summary, undergraduate academic performance is improved by scientific training. Our findings shed light on the novel strategies in the management of undergraduate education in the medical school. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):379-384, 2017.

Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis.

Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin-1ß (IL-1ß), IL-6 (IL-6), and tumor necrosis factor-α (TNF-α) may be involved in the development of obesity. We conducted a systematic review of published evidence on the association between different adipokine genes and the risk of obesity. Librarian-designed searches of PubMed and HuGeNet, review of reference lists from published reviews and content expert advice identified potentially eligible studies. The genotyping information and polymorphisms of different adipokine genes, numbers of genotyped cases and controls and frequencies of genotypes were extracted from 48 eligible studies included in this review. Twenty-one polymorphisms each associated with obesity in at least one study were identified. Polymorphisms in the adipokine genes, LEP, LEPR, and RETN were not associated with obesity susceptibility, whereas ADIPOQ G276T (T vs. G: odds ratio (OR), 1.59; 95% confidence interval (CI), 1.39-1.81), IL-1ß C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-α G308A (GG vs. GA+AA: OR, 1.19; 95% CI, 1.02-1.39) polymorphisms were associated with an increased risk of obesity. The IL-6 G174C polymorphism was also associated obesity when using allelic comparisons, the recessive genetic model and the dominant genetic model with OR (95% CI) of 1.95 (1.37-2.77), 1.44 (1.15-1.80), and 1.36 (1.16-1.59), respectively. No significant evidence of publication bias was present. However, these "null" results were underpowered due to a small pooled sample size, and analysis of additional case-control studies with larger sample sizes should provide further clarifications.

[Construction of eukaryotic expression vector of LYRM1, a novel gene related with human obesity, and establishment of its stable transfected 3T3-L1 cell line].

OBJECTIVE: To construct the eukaryotic expression vector of LYRM1 and to transfect it to preadipocytes cell line 3T3-L1. METHODS: The complete coding sequence of LYRM1 gene was amplified by RT-PCR from human omental adipose tissue and was subcloned into eukaryotic expression vector pcDNA(TM)3.1/myc-His B. The recombinant plasmid was then transfected into 3T3-L1 preadipocytes by liposome. After screening culture by G418, stable transfected 3T3-L1 cell line was established. The expression of LYRM1 protein was identified by Western blot. RESULT: The recombinant plasmid was confirmed by PCR, restriction enzyme digestion and sequencing. The stable transfected 3T3-L1 cell line was established and the LYRM1 protein was expressed successfully. CONCLUSION: The eukaryotic expression vector of LYRM1 has been successfully established and the stably transfected 3T3-L1 cell line also established.

[Clinical characteristics and ultrastructural features of livers in children with Wilson disease manifested mainly as hepatic injuries].

OBJECTIVES: To study the feasibility and possibility to diagnose Wilson disease with electronmicroscopical examination of liver biopsies. METHODS: Clinical analysis, histological observation and ultrastructural examination were performed on 15 children with Wilson disease. RESULTS: All 15 subjects had symptoms of hepatic disorders, such as jaundice. Morphological signs of hepatocyte injury in three phase, namely steatosis, mitochondrion changes and cholestasis in bile canaliculi of the early phase, nucleus injury, dilation of endoplasmic reticulum, increase of lysosomes and appearance of residual bodies of the second phase, and massive autophagy and cirrhosis of the late phase were shown. A few inflammatory cells in the liver specimens were observed. Accumulation of copper in lysosomes and autophagosomes was found by energy-dispersion X-ray. CONCLUSION: The diagnostic signs for Wilson disease are autophagosomes in hepatocytes, cirrhosis accompanied with a few of inflammatory cells. A certain diagnosis of the disease depends on the finding of copper accumulation in hepatocytes.