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Background Autophagy, a process of self-digestion, is closely related to multiple biological processes of colon cancer. This study aimed to construct and evaluate prognostic signature of autophagy-related genes (ARGs) to predict overall survival (OS) in colon cancer patients. Materials and methods First, a total of 234 ARGs were downloaded via The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, differentially expressed ARGs were identified in colon cancer. The univariate and multivariate Cox regression analysis was performed to screen prognostic ARGs to construct the prognostic model. The feasibility of the prognostic model was evaluated using receiver operating characteristic curves and Kaplan-Meier curves. A prognostic model integrating the gene signature with clinical parameters was established with a nomogram. Results We developed an autophagy risk signature based on the 6 ARGs (ULK3, ATG101, MAP1LC3C, TSC1, DAPK1, and SERPINA1). The risk score was positively correlated with poor outcome and could independently predict prognosis. Furthermore, the autophagy-related signature could effectively reflect the levels of immune cell type fractions and indicate an immunosuppressive microenvironment. Conclusion We innovatively identified and validated 6 autophagy-related gene signature that can independently predict prognosis and reflect overall immune response intensity in the colon cancer microenvironment.

We investigate the chiroptical responses of the hybrid systems consisting of metal-insulator-metal (MIM) gammadion arrays on top of a dielectric slab waveguide. We demonstrate that both the transverse magnetic (TM) and transverse electric (TE) waveguide modes could be coupled to the antisymmetric localized surface plasmon resonances (LSPRs) of the individual MIM-gammadions, leading to the formation of narrow hybrid waveguide-plasmon resonances (WPRs), of which the TM-WPR is less dependent while the TE-WPR is highly dependent on the handedness of the incident light. Associated with the excitation of the TE-WPRs, strong negative and positive circular dichroism (CD) peaks with high quality factors could be obtained on the short-wavelength and long-wavelength side of the LSPRs of the MIM-gammadion, respectively. Moreover, we show that the variation on either the lattice period or slab waveguide thickness allows for easily tuning the TE-WPRs based CD peaks over a relative wide spectral range. Our proposed hybrid system provides tunable and strong CD responses with narrow linewidth, which may have applications in chiral selective imaging, chiral plasmonic bio-sensing and spectroscopy.

Objective: Immunotherapy has improved the prognosis of cancer patients who did not benefit from conventional treatment and decreased mortality, which has become an effective treatment for multiple carcinomas in their advanced stages. Patients with colorectal cancer (CRC) were mostly in the state of mismatch repair-proficient or microsatellite stability, with limited benefit in immunotherapy. Hence, immunotherapy strategies for CRC still need to be explored continuously. Methods: Based on comprehensive analysis of the immune infiltration associated genes in the Cancer Genome Atlas (TCGA) database and differential genes for the progression and metastasis of CRC in the Gene Expression Omnibus (GEO) database, as well as validation analysis on several online databases, we obtained two genes (KCNE4 and DNASE1L3) as novel immune-related molecules for CRC. Results: High expression of KCNE4 and DNASE1L3 were significantly correlated with CRC progression and prognosis, and were strongly associated with the infiltration of different types of macrophages in the CRC tumor microenvironment. In addition, we analysed the guidance value of KCNE4 and DNASE1L3 in anti-PD-1 therapy using data from the IMvigor210 group, and predicted the significant value of KCNE4 and DNASE1L3 in CRC immunotherapy by analyzing the correlation of KCNE4 and DNASE1L3 with the expression of CRC immune checkpoint markers. Conclusions: We hypothesized that DNASE1L3 and KCNE4 would be potential prognostic biomarkers and predictors of immunotherapy in CRC. Our results may serve as an indication of survival prognosis and provide a new assessment indicator for the choice of immunotherapy for CRC patients.

Background Cervical cancer stem cells (CCSCs), a small part of tumor population, are one of the important reasons for metastasis and recurrence of cervical cancer. Targeting CCSCs may be an effective way to eliminate tumors. Salinomycin (Sal) has been proved to be an effective anticancer drug in many studies, especially for cancer stem cells (CSCs). However, the cytotoxicity of salinomycin limits its further research as an anticancer drug. High-density lipoprotein (HDL) nanoparticles are an excellent drug carrier, which can reduce the toxicity of Sal, have a certain targeting effect and improve the clinical benefit of Sal. Methods Salinomycin-loaded high-density lipoprotein (S-HDL) was synthesized and characterized by various analytical techniques. CD44highCD24low CCSCs were isolated from HeLa cells by magnetic separation. The uptake of HDL nanoparticles was observed by laser confocal microscopy, and the effect of S-HDL on the proliferation of CCCs and CCSCs was detected by cell viability analysis. Genome-wide analysis was used to analyze the effects of S-HDL on the biological processes of CCCs and then cell apoptosis, cell cycle and cell migration were selected for verification. Results S-HDL had a particle size of 38.98 ± 1.78 nm and an encapsulation efficiency of 50.73 ± 4.29%. Cell uptake analysis showed that HDL nanoparticles could enhance the drug uptake of CCCs and CCSCs and may target CCCs and CCSCs. In cell viability analysis, CCCs and CCSCs showed high sensitivity to S-HDL. S-HDL can more efficiently prevent CCSCs from developing tumorspheres than Sal in tumorsphere formation study. S-HDL had stronger ability to induce cell cycle arrest, promote cell apoptosis and inhibit cell migration compared with free Sal, which was consistent with the results of Genome Wide analysis. Conclusion S-HDL can effectively target and eliminate CCCs and CCSCs, which is a potential drug for the treatment of cervical cancer., Graphical Abstract

Coronavirus disease 2019 (COVID-19) pandemic is caused by the novel coronavirus that has spread rapidly around the world, leading to high mortality because of multiple organ dysfunction; however, its underlying molecular mechanism is unknown. To determine the molecular mechanism of multiple organ dysfunction, a bioinformatics analysis method based on a time-order gene co-expression network (TO-GCN) was performed. First, gene expression profiles were downloaded from the gene expression omnibus database (GSE161200), and a TO-GCN was constructed using the breadth-first search (BFS) algorithm to infer the pattern of changes in the different organs over time. Second, Gene Ontology enrichment analysis was used to analyze the main biological processes related to COVID-19. The initial gene modules for the immune response of different organs were defined as the research object. The STRING database was used to construct a protein–protein interaction network of immune genes in different organs. The PageRank algorithm was used to identify five hub genes in each organ. Finally, the Comparative Toxicogenomics Database played an important role in exploring the potential compounds that target the hub genes. The results showed that there were two types of biological processes: the body’s stress response and cell-mediated immune response involving the lung, trachea, and olfactory bulb (olf) after being infected by COVID-19. However, a unique biological process related to the stress response is the regulation of neuronal signals in the brain. The stress response was heterogeneous among different organs. In the lung, the regulation of DNA morphology, angiogenesis, and mitochondrial-related energy metabolism are specific biological processes related to the stress response. In particular, an effect on tracheal stress response was made by the regulation of protein metabolism and rRNA metabolism-related biological processes, as biological processes. In the olf, the distinctive stress responses consist of neural signal transmission and brain behavior. In addition, myeloid leukocyte activation and myeloid leukocyte-mediated immunity in response to COVID-19 can lead to a cytokine storm. Immune genes such asSRC,RHOA,CD40LG,CSF1,TNFRSF1A,FCER1G,ICAM1,LAT,LCN2,PLAU,CXCL10,ICAM1,CD40,IRF7, andB2Mwere predicted to be the hub genes in the cytokine storm. Furthermore, we inferred that resveratrol, acetaminophen, dexamethasone, estradiol, statins, curcumin, and other compounds are potential target drugs in the treatment of COVID-19.

The aim of this study was to compare the safety and effectiveness of robotic hysterectomy (RH) with conventional laparoscopic hysterectomy (LH) for the treatment of cervical cancer using multivariate regressions. We designed a retrospective single-center study and consecutively collected patients with cervical cancer from February 2014 to October 2017. Data extraction was performed by two independent researchers. The surgical outcomes include operative time, estimated blood loss, number of lymph nodes, time to first flatus, time to a full diet, time to remove drainage tube, length of hospital stay, and postoperative complication. A total of 152 patients with cervical cancer were collected in our study including 92 patients who underwent RH and 60 patients who underwent LH. Both groups have similar characteristics. The RH group showed shorter operative time (Coe − 42.89; 95% CI − 74.39 to 11.39; P = 0.008) and more number of lymph nodes (Coe 6.06; 95% CI 2.46–9.66; p = 0.001) than the LH group. As for the postoperative parameters, the RH group showed shorter time to remove drainage tube (Coe − 0.89; 95% CI –1.62 to –0.15; p = 0.019) and length of hospital stay (Coe − 6.40; 95% CI − 10.19 to − 2.95; p = 0.001). No significant difference was found between the groups in estimated blood loss (Coe 34.64; 95% CI − 33.08 to 102.37; p = 0.314), time to first flatus (Coe 0.11; 95% CI − 0.38 to 0.61; p = 0.652), time to a full diet (Coe − 0.24; 95% CI − 0.54 to 0.06, p = 0.118), and postoperative complication (OR 0.84; 95% CI 0.35–1.98; p = 0.685). The results from this study suggest that RH is safe and effective as LH but robotic surgery significantly contributed to the feasibility of alternative treatment options for cervical cancer patients.

Background Long non-coding RNAs (lncRNAs) have been demonstrated to play important roles in human diseases. Yet, the functions of lncRNAs in neurodegenerative disorders, such as Parkinson's disease (PD) are poorly understood. In this study, we used human neuroblastoma SH-SY5Y cell line as a cell-basedin vitro PD model, and investigated the role of lncRNA, Non-Coding RNA Activated By DNA Damage (NORAD) in 1-methyl-4-phenylpyridinium (MPP+)-induced PD-like cytotoxicity. Methods SH-SY5Y cells were culturedin vitro, and treated with MPP + at various concentrations, or of various durations of times to induce PD-like cytotoxic events. qRT-PCR was used to measure MPP+-induced NORAD expression changes. Lentiviral transduction was applied to stably upregulate or downregulate NORAD in SH-SY5Y cells. The effects of NORAD upregulation or downregulation on MPP+-induced cytotoxic events, including dose-dependent and time-dependent cell death, apoptosis, caspase 3/7, reactive Oxygen Species (ROS) and lactate dehydrogenase (LDH) activities, were quantitatively investigated. Results MPP + induced cytotoxicity, and downregulated NORAD in both dose- and time- dependent manners in SH-SY5Y cells. Lentiviral-induced NORAD upregulation was found to protect against MPP+-induced cytotoxicity in SH-SY5Y cells, as it rescued MPP+-induced cellular destruction and apoptosis, as well as decreased MPP+-induced caspase 3/7, ROS and LDH activities. Alternatively, NORAD downregulation was found to significantly deteriorate MPP+-induced cytotoxicity in SH-SY5Y cells. Conclusion We presented a novel functional role of lncRNA NORAD in regulating human Parkinson’s disease.

Summary: Objective: To compare robot-assisted surgery and conventional laparoscopy for gynecologic oncology regarding intra- and post-operative outcomes. Methods: A retrospective study was performed on consecutive patients with gynecologic oncology from February 2014 to October 2017 at Gansu Provincial Hospital, China. Multivariable linear and logistic regression models were performed to explore the difference between two surgeries in the surgical outcomes after adjusting for potential confounders. Results: 276 women were included in this study: 153 robot-assisted surgeries and 123 conventional laparoscopies. The multivariable linear regression model showed that robot-assisted surgery was longer operative time [coefficient (coef), 33.76; 95% CI, 12.47, 55.05; P = 0.002) ], higher lymph node yield (coef, 10.41; 95% CI, 7.47, 13.35; P 0.05). The multivariable logistic regression model showed that post-operative complications were similar between robot-assisted surgery and conventional laparoscopy (P > 0.05). Conclusion: Robot-assisted surgery was superior to conventional laparoscopy regarding intra- and post-operative outcomes for gynecologic oncology. Keywords: Early feeding, Gynecologic oncology, Laparoscopy, Minimally invasive surgery, Robotic-assisted surgery

The effect of aluminum on microstructure and properties of martensitic wear-resistant and heat-resistant steels was investigated. The results indicate that as-cast microstructure of the specimens is composed of ferrite, pearlite and carbides. After quenching at 1,000 °C and tempering at 600 °C, the microstructure of the specimens consists of tempered sorbite and Fe–Cr–Al intermetallic compounds which distribute directionally in the matrix and increase with increase in Al content. The additions of Al enhance the ambient tensile strength which reaches the peak at 1,230 MPa when the specimens contain 1.97 % Al. Oxidation notably decreases with the increase of Al and the average oxidation rates reduce to 0.0095 g m−2 h−1 at 650 °C and 0.0285 g m−2 h−1 at 800 °C, respectively. Wear resistance of the specimens containing Al obviously increased when compared to the Al-free specimens.