Pan-cancer analyses of immunogenic cell death-derived gene signatures: Potential biomarkers for prognosis and immunotherapy.

BACKGROUND: Immunogenic cell death (ICD) is a type of regulated cell death that is capable of initiating an adaptive immune response. Induction of ICD may be a potential treatment strategy, as it has been demonstrated to activate the tumor-specific immune response. AIMS: The biomarkers of ICD and their relationships with the tumor microenvironment, clinical features, and immunotherapy response are not fully understood in a clinical context. Therefore, we conducted pan-cancer analyses of ICD gene signatures across 33 cancer types from The Cancer Genome Atlas database. METHODS AND RESULTS: We identified key genes that had strong relationships with survival and the tumor microenvironment, contributing to a better understanding of the role of ICD genes in cancer therapy. In addition, we predicted therapeutic agents that target ICD genes and explored the potential mechanisms by which gemcitabine induce ICD. Moreover, we developed an ICD score based on the ICD genes and found it to be associated with patient prognosis, clinical features, tumor microenvironment, radiotherapy access, and immunotherapy response. A high ICD score was linked to the immune-hot phenotype, while a low ICD score was linked to the immune-cold phenotype. CONCLUSION: We uncovered the potential of ICD gene signatures as comprehensive biomarkers for ICD in pan-cancer. Our research provides novel insights into immuno-phenotypic assessment and cancer therapeutic strategies, which could help to broaden the application of immunotherapy to benefit more patients.

Opioid-free anesthesia reduces the severity of acute postoperative motion-induced pain and patient-controlled epidural analgesia-related adverse events in lung surgery: randomized clinical trial.

Background: Opioids have been used as pain relievers for thousands of years. However, they may also cause undesirable side effects. We therefore performed this study to compare the effect of opioid-free anesthesia (OFA) versus opioid-sparing anesthesia (OSA) on postoperative pain and patient-controlled epidural analgesia (PCEA)-related events. Methods: This is a single center randomized clinical trial that was recruited patients aged from 18 to 70 years who received video-assisted lung surgery between October 2021 and February 2022. Participants were 1:1 randomly assigned to OFA or OSA. Patients in the OFA group received propofol, rocuronium, esmolol, lidocaine, and magnesium sulfate intravenously with epidural ropivacaine. Patients in the OSA group received propofol, rocuronium, remifentanil, and sufentanil intravenously with epidural hydromorphone and ropivacaine. Results: A total number of 124 patients were randomly allocated to the OFA or OSA group. In the OFA group, the severity of pain during coughs on the first postoperative days (PODs; VAS score 1.88 ± 0.88 vs. 2.16 ± 1.1, p = 0.044) was significantly lower than that in the OSA group. The total ratio of PCEA-related adverse events in the OFA group [11 (19.6%) vs. 26 (47.3%), p = 0.003] was significantly lower than in the OSA group. Conclusion: OFA in patients who received video-assisted lung surgery led to lower severity of acute postoperative motion-induced pain and fewer PCEA-related adverse events on the first POD than in the patients in the OSA group. Clinical trial registration: clinicaltrials.gov, identifier (NCT05063396).

Artifact Detection and Restoration in Histology Images With Stain-Style and Structural Preservation.

The artifacts in histology images may encumber the accurate interpretation of medical information and cause misdiagnosis. Accordingly, prepending manual quality control of artifacts considerably decreases the degree of automation. To close this gap, we propose a methodical pre-processing framework to detect and restore artifacts, which minimizes their impact on downstream AI diagnostic tasks. First, the artifact recognition network AR-Classifier first differentiates common artifacts from normal tissues, e.g., tissue folds, marking dye, tattoo pigment, spot, and out-of-focus, and also catalogs artifact patches by their restorability. Then, the succeeding artifact restoration network AR-CycleGAN performs de-artifact processing where stain styles and tissue structures can be maximally retained. We construct a benchmark for performance evaluation, curated from both clinically collected WSIs and public datasets of colorectal and breast cancer. The functional structures are compared with state-of-the-art methods, and also comprehensively evaluated by multiple metrics across multiple tasks, including artifact classification, artifact restoration, downstream diagnostic tasks of tumor classification and nuclei segmentation. The proposed system allows full automation of deep learning based histology image analysis without human intervention. Moreover, the structure-independent characteristic enables its processing with various artifact subtypes. The source code and data in this research are available at https://github.com/yunboer/AR-classifier-and-AR-CycleGAN.

CO2 emissions are first aggravated and then alleviated with economic growth in China: a new multidimensional EKC analysis.

CO2 emissions have become a topical issue worldwide, but few studies have considered the spatial effect of income on carbon emissions and explored the relationship between CO2 emissions and income by establishing direct, indirect, and total environmental Kuznets curves (EKCs). Using an annual panel dataset collected over the 1997-2017 period in China, this study first analyzed the spatiotemporal evolutionary process of CO2 emissions and subsequently developed direct, indirect, and total EKC-based spatial Durbin model (SDM) and partial derivative approach. These results indicate that, first, CO2 emissions have characteristic positive spatial autocorrelation, with gravity centers that have shifted westward. Second, the direct EKC forms a line, while the total EKC resembles a lying-S shape as well as the total EKC, which indicates that compared to local economic growth, neighboring growth plays a very different role in impacting local CO2 emissions. Furthermore, neighboring economic growth seems to have stronger impacts on local emissions, and the turning point of the total EKC comes much earlier than that of the conventional EKC due to the spillover effects of economic growth. Finally, the growth of the population, as well as the rise of energy intensity, can stimulate CO2 emissions in both local and neighboring regions. Industrialization seems to have a nonsignificant impact on emission changes due to the offsetting effects of the positive direct and negative indirect impacts of the share of secondary industry. Improvements in local urbanization may lead to an increase in emissions, while neighboring improvements may have stronger restricting effects; thus, urbanization improvement is beneficial to emissions reduction. This study provides more scientific information from both local and neighboring perspectives, which may differ from conventional results but still be beneficial for emissions reduction policy-makers to introduce corresponding measures.

Rapid sequence induction with a "modified timing principle" of rocuronium provides excellent intubating conditions: A randomised trial.

The present study was designed to compare the intubating conditions of rocuronium giving by "a modified timing principle" in rapid induction and intubation (RSII) with that of the gold standard, succinylcholine. One hundred and twenty-four patients were randomly divided into rocuronium group (group R, n = 62) or succinylcholine group (group S, n = 62). In group R, after rocuronium 0.6 mg kg-1 was given, anaesthesia was induced with propofol 2 mg kg-1 and remifentanil 2 µg kg-1, and tracheal intubation was performed 60 sec after rocuronium administration. In group S, succinylcholine 1.5 mg kg-1 was given after patient lost consciousness induced by the same regimen of group R, and tracheal intubation was performed 60 sec after succinylcholine administration. Our primary endpoint was the intubating conditions. The numbers of patients with excellent and good intubating conditions in group R were 90.0% and 6.7%, respectively, which were comparable with those in group S (91.7% and 5.0% respectively). The apnoea time in group S (79.7 ± 5.1 sec) was longer than that of group R (56.6 ± 4.6 sec) (p = 0.0063). The average BIS values at the time of intubation in group R (64.1 ± 4.1) was higher than that of group S (43.2 ± 5.5) (p = 0.018). In the context of a RSII with lidocaine-remifentanil-propofol, the application of this "modified timing principle" with rocuronium 0.6 mg kg-1 could provide comparable intubating conditions with those achieved by succinylcholine 1.5 mg kg-1. Additionally, this modified timing principle with rocuronium was associated with shorter apnoea time.

FOXO4 peptide targets myofibroblast ameliorates bleomycin-induced pulmonary fibrosis in mice through ECM-receptor interaction pathway.

Pulmonary fibrosis (PF) is a progressive interstitial lung disease with limited treatment options. The incidence and prevalence of PF is increasing with age, cell senescence has been proposed as a pathogenic driver, the clearance of senescent cells could improve lung function in PF. FOXO4-D-Retro-Inverso (FOXO4-DRI), a synthesis peptide, has been reported to selectively kill senescent cells in aged mice. However, it remains unknown if FOXO4-DRI could clear senescent cells in PF and reverse this disease. In this study, we explored the effect of FOXO4-DRI on bleomycin (BLM)-induced PF mouse model. We found that similar as the approved medication Pirfenidone, FOXO4-DRI decreased senescent cells, downregulated the expression of senescence-associated secretory phenotype (SASP) and attenuated BLM-induced morphological changes and collagen deposition. Furthermore, FOXO4-DRI could increase the percentage of type 2 alveolar epithelial cells (AEC2) and fibroblasts, and decrease the myofibroblasts in bleomycin (BLM)-induced PF mouse model. Compared with mouse and human lung fibroblast cell lines, FOXO4-DRI is inclined to kill TGF-ß-induced myofibroblast in vitro. The inhibited effect of FOXO4-DRI on myofibroblast lead to a downregulation of extracellular matrix (ECM) receptor interaction pathway in BLM-induced PF. Above all, FOXO4-DRI ameliorates BLM-induced PF in mouse and may be served as a viable therapeutic option for PF.

A base-mediated aerobic oxidative synthesis of cyclopent-2-enol derivatives from doubly activated cyclopropanes and substituted acetonitriles.

We report here that polysubstituted cyclopent-2-enols can be constructed by the one-pot reaction of doubly activated cyclopropanes and α-EWG substituted acetonitriles under mild basic conditions via a domino-ring-opening-cyclization/deacylation/oxidation sequence. Moreover, the synthetic applications of these cyclopent-2-enols have been demonstrated in the late-stage derivatization into functionalized cyclopentapyrimidin-4-ones and 2-hydroxy cyclopentanones with good yields.

The effects of erector spinae plane block on perioperative opioid consumption and rehabilitation in video assisted thoracic surgery.

BACKGROUND: This study aimed to determine whether ultrasound-guided continuous erector spinae plane block (ESPB) had an effect on opioid consumption and postoperative rehabilitation in patients undergoing video-assisted thoracic surgery (VATS). METHODS: In this prospective study, 120 patients aged 20-70 years who underwent elective VATS were randomly allocated to one of three groups: group C (general anesthesia with patient-controlled intravenous analgesia [PCIA]), group T (general anesthesia with patient-controlled epidural analgesia [PCEA]), or group E (general anesthesia with continuous ESPB and PCIA). Perioperative opioid consumption, visual analog scale (VAS) scores, preoperative and postoperative Quality of Recovery-15 scores, and postoperative opioid-related adverse events were all assessed. RESULTS: Intraoperative sufentanil consumption in groups T and E was significantly lower than that in group C (both P < 0.001), and the postoperative sufentanil consumption in group E was also significantly lower than that in group C (P = 0.001). Compared with group C, the VAS scores at rest or during coughing immediately out of the post-anesthesia care unit at 6 h, 12 h, and 24 h postoperatively were significantly lower in group T (P < 0.05). However, the VAS scores at rest at 6 h and 12 h postoperatively in group E were lower than those of group C (P < 0.05), but were significantly higher than those of group T at all study times (P < 0.05). CONCLUSION: Ultrasound-guided continuous ESPB significantly reduced perioperative opioid consumption during VATS and improved postoperative rehabilitation. However, these effects were inferior to those of thoracic epidural anesthesia. TRIAL REGISTRATION: The present study was prospectively registered at http://www.chictr.org/cn /(registration number: ChiCTR1900023050 ); registration date: May 82,019.

Mouse parabiosis model promotes recovery of lymphocytes in irradiated mice.

PURPOSE: Total body irradiation (TBI) -induced hematopoietic system injury is mainly due to the failure of self-renewal and to the differentiation ability of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) after radiation exposure. The mouse parabiosis model is mainly used in the field of aging research to explore whether circulating factors in peripheral blood can improve the functions of aged tissues and organs. In this study, we generated a mouse model to verify whether non-irradiated peripheral circulation can improve the circulatory environment in irradiated mice and ameliorate TBI-induced hematopoietic system injury. MATERIALS AND METHODS: Six- to eight-week-old male C57BL/6 mice were adjoined by a surgical operation. Four weeks later, one mouse in the pair was exposed to 8 Gy or 6 Gy X-ray, and B and T cells in the peripheral blood, bone marrow, spleen, mesenteric lymph nodes and thymus were then detected by flow cytometry. Hematopoietic stem/progenitor cells in bone marrow cells and their levels of ROS and apoptosis were also detected in this study. RESULTS: The results showed decreased percentages of B and T lymphocytes in the peripheral blood, bone marrow (BM), spleen and mesenteric lymph nodes (MLNs) in the isotype irradiated mice. The proportions of CD4-positive, CD8-positive, and CD4 and CD8 double-negative cells were also increased, while the proportion of CD4 and CD8 double-positive cells in the irradiated thymus was decreased. Thus, all of the above lymphocyte injuries in the parabiosis model were improved to nearly the levels of the control. We further detected radiation-induced HSC and HPC injury; however, the reduced HSC and HPC numbers, ROS levels and apoptosis percentages were not ameliorated in the parabiotic irradiated mice. CONCLUSIONS: Above all, our results showed that non-irradiated peripheral circulation can promote the recovery of TBI-induced lymphocyte injury, further indicating that the recovery of immune cells may play a very important role in the repair of TBI-induced damage.

Positive Impact of Intraoperative Epidural Ropivacaine Infusion on Oncologic Outcomes in Pancreatic Cancer Patients Undergoing Pancreatectomy: A Retrospective Cohort Study.

Background: Previous literatures have demonstrated that regional anesthesia such as epidural anesthesia may affect long-term survival of cancer patients. In the present study, we conducted a retrospective cohort study to investigate the survival impact of intraoperatively epidural ropivacaine infusion on pancreatic ductal adenocarcinoma (PDAC) patients. Methods: PDAC patients who underwent pancreatic surgery in Zhongshan Hospital Fudan University from January, 2015 to June, 2018 were included. The surgical procedure was performed under combined endotracheal general anesthesia and thoracic epidural anesthesia, and patient-controlled epidural analgesia (PCEA) with 0.12% ropivacaine was given after surgery for further pain control. Patients were divided into two groups according to their intraoperative epidural ropivacaine concentration: high (0.375%-0.5%) and low (0.15%-0.25%). Survival outcome was compared between groups. Results: A total of 215 patients were enrolled and their baseline characteristics were balanced between groups, except that patients with high concentration ropivacaine received higher total dose opioid and had longer operative time. Resected PDAC patients who were administrated with high concentration ropivacaine through epidural catheter intraoperatively had improved overall survival (median overall survival, mOS, high VS low, 37.6 VS 23.7 months, p=0.04). High epidural ropivacaine concentration was an independent prognostic factor (hazard ratio [HR]=0.65, 95% confidence interval [CI], 0.44-0.94; p=0.03). Subgroups analyses shown that T3M0 PDAC patients with preoperative CA 19-9 higher than 200 U/ml, negative resection margin, and those without tumor deposit and adjuvant radiotherapy could benefit from high concentration of ropivacaine. Conclusion: Intraoperatively epidural infusion with high concentration of ropivacaine was associated with improved OS in PDAC patients undergoing pancreatectomy.

BIG1 mediates sepsis-induced lung injury by modulating lipid raft-dependent macrophage inflammatory responses.

Sepsis is a systemic inflammatory response syndrome with high mortality. It has been reported that brefeldin A-inhibited guanine nucleotide-exchange factor 1 (BIG1) is involved in the pathogenesis of sepsis. However, the mechanism is not fully elucidated. In the present study, we explored the role of BIG1 in mediating lipid raft-dependent macrophage inflammatory response and its impact on lung injury in murine sepsis. In vitro studies revealed that BIG1 deficiency reduces the upregulation and secretion of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-1ß and inhibits the activation of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88-dependent nuclear factor kappa-B signaling pathway induced by the lipopolysaccharide (LPS) treatment. Further experiments revealed that the inhibitory effects of BIG1 deficiency on LPS-induced inflammation are due to the upregulation of adenosine triphosphate-binding cassette transporter A1. This promotes the free-cholesterol efflux from lipid rafts and results in the reduction of lipid raft TLR4 content. The decrease in TLR4 content in lipid raft thereby inhibits the LPS-induced inflammatory response. Furthermore, using the cecal ligation and puncture-induced polymicrobial sepsis mouse model, we found that conditional knockout (cKO) of the myeloid cell BIG1 significantly reduced the serum concentrations of TNF-α, IL-6, and IL-1ß, and downregulated their mRNA expressions in the lungs. Pathological analysis confirmed that the BIG1 cKO alleviated the sepsis-induced lung injury. These results revealed the crucial new role of BIG1 in mediating lipid raft-dependent macrophage inflammatory response. Hence, BIG1 may be a potential promising therapeutic target for the treatment of septic lung injury.

NICE-3-knockdown induces cell cycle arrest and autophagy in lung adenocarcinoma cells via the AKT/mTORC1 signaling pathway.

The NICE-3 protein serves an oncogenic role in hepatocellular carcinoma, but its role in lung adenocarcinoma (LUAD) remains unknown. The aim of the present study was to investigate the potential role and underlying mechanisms of NICE-3 in LUAD. In the present study, NICE-3 expression in LUAD tissues and its association with patient prognosis were analyzed using datasets from The Cancer Genome Atlas and Gene Express Omnibus. After NICE-3-knockdown with small interfering RNA in LUAD cells, cell proliferation was measured by cell counting, cell cycle was examined by flow cytometry, cell invasion and migration were detected by Transwell assays and autophagic markers LC3 and p62, as well as phosphorylation of S6K and AKT, were determined by western blotting. The results of public database analysis demonstrated that compared with normal lung tissues, NICE-3 expression was increased in LUAD tissues, where high expression levels were associated with a poor prognosis. The results of in vitro experimentation in LUAD cells indicated that NICE-3-knockdown inhibited proliferation, cell cycle, migration and invasion, but enhanced autophagy. Notably, NICE-3-knockdown inhibited AKT/mTORC1 signaling. The present results suggested that NICE-3 may serve an oncogenic role in LUAD via the AKT/mTORC1 signaling pathway and may therefore be a potential therapeutic target for LUAD.

The Role of Pink1-Mediated Mitochondrial Pathway in Propofol-Induced Developmental Neurotoxicity.

The mechanisms underlying propofol-induced toxicity in developing neurons are still unclear. The aim of present study was to explore the role of Pink1 mediated mitochondria pathway in propofol-induced developmental neurotoxicity. The primary Neural Stem Cells (NSCs) were isolated from the hippocampus of E15.5 mice embryos and then treated with propofol. The effects of propofol on proliferation, differentiation, apoptosis, mitochondria ultrastructure and MMP of NSCs were investigated. In addition, the abundance of Pink1 and a group of mitochondria related proteins in the cytoplasm and/or mitochondria were investigated, which mainly included CDK1, Drp1, Parkin1, DJ-1, Mfn1, Mfn2 and OPA1. Moreover, the relationship between Pink1 and these molecules was explored using gene silencing, or pretreatment with protein inhibitors. Finally, the NSCs were pretreated with mitochondrial specific antioxidant (MitoQ) or Drp1 inhibitor (Mdivi-1), and then the toxic effects of propofol on NSCs were investigated. Our results indicated that propofol treatment inhibited NSCs proliferation and division, and promoted NSCs apoptosis. Propofol induced significant NSCs mitochondria deformation, vacuolization and swelling, and decreased MMP. Additional studies showed that propofol affected a group of mitochondria related proteins via Pink1 inhibition, and CDK1, Drp1, Parkin1 and DJ-1 are the important downstream proteins of Pink1. Finally, the effects of propofol on proliferation, differentiation, apoptosis, mitochondrial ultrastructure and MMP of NSCs were significantly attenuated by MitoQ or Mdivi-1 pretreatment. The present study demonstrated that propofol regulates the proliferation, differentiation and apoptosis of NSCs via Pink1mediated mitochondria pathway.

Novel synthesis of fused spiro piperidone-cyclopropanes from cyclopropyl amides and electron-deficient alkenes.

We report here that a series of bridged O,O-ketal fused spiro piperidone-cyclopropane derivatives 3 can be constructed with excellent yields and good diastereoselectivity by the one-pot reaction of 1-acylcyclopropanecarboxamides 1 with electron-deficient alkene 2a (EWG = CHO) via the domino process involving [4 + 2] annulation/intermolecular electrophilic addition/intramolecular cyclization. Furthermore, reactions of 1 with 2b/2c (EWG = CN, COOMe), leading to spiro piperidone-cyclopropane derivatives 4 or 5 by base catalyst selection, were also presented.

Methyltransferase-like 1 regulates lung adenocarcinoma A549 cell proliferation and autophagy via the AKT/mTORC1 signaling pathway.

Methyltransferase-like 1 (METTL1) is a transfer RNA and microRNA modifying enzyme. However, its role in lung adenocarcinoma (LUAD) remains unknown. The present study aimed to investigate the effect of METTL1 in LUAD and determine the association between METTL1 expression and prognosis of patients with LUAD. The expression profile of METTL1 in LUAD tissues was downloaded from public cancer databases and analyzed using the Gene Expression Profiling Interactive Analysis database and UALCAN online software. In addition, the association between METTL1 expression and prognosis of patients with LUAD was assessed using the Kaplan-Meier Plotter software. The effect of METTL1 in the A549 cell line was determined in vitro via overexpression and knockdown experiments. The results demonstrated that METTL1 was upregulated in LUAD tissues, and its increased expression was associated with unfavorable prognosis. Furthermore, METTL1 promoted proliferation and colony formation of A549 cells, and inhibited autophagy via the AKT/mechanistic target of rapamycin complex 1 signaling pathway. Taken together, the results of the present study suggest that METTL1 acts as an oncogene in LUAD, thus may be a potential prognostic predictor and therapeutic target for LUAD.

MYG1 promotes proliferation and inhibits autophagy in lung adenocarcinoma cells via the AMPK/mTOR complex 1 signaling pathway.

Melanocyte proliferating gene 1 (MYG1) is an exonuclease that participates in RNA processing and is required for normal mitochondrial function. However, its role in tumorigenesis remains unknown. The present study aimed to investigate the role of MYG1 and its underlying mechanisms in human lung adenocarcinoma (LUAD). The expression levels of MYG1 in tumor tissues of patients with LUAD were obtained from public cancer databases and analyzed using the UALCAN online software. The association between MYG1 expression levels and the prognosis of patients with LUAD was analyzed using the Kaplan-Meier plotter. In addition, the role of MYG1 in the LUAD A549 and H1993 cell lines was determined by knocking down MYG1 expression with a specific small interfering RNA or by overexpressing it with a MYG1-containing plasmid. The results demonstrated that MYG1 expression levels were upregulated in LUAD tissues compared with those in normal lung tissues from healthy subjects, and high MYG1 expression levels were associated with an unfavorable prognosis. MYG1 promoted the proliferation, migration and invasion of A549 and H1993 cells. In addition, MYG1 inhibited autophagy via the AMP-activated protein kinase/mTOR complex 1 signaling pathway. Collectively, the present results suggested that MYG1 may serve an oncogenic role in LUAD and may be a potential therapeutic target for LUAD.

Intraoperative thermal insulation in off-pump coronary artery bypass grafting surgery: a prospective, double blind, randomized controlled, single-center study.

BACKGROUND: About 50% patients who underwent off-pump coronary artery bypass grafting (OPCAB) experienced perioperative hypothermia. Pre-warming and intraoperative infusion of amino acid injection are the most popular perioperative insulation measures in recent years, but neither of them can completely prevent intraoperative hypothermia. The objective is to investigate the effect of preoperative warming and/or intraoperative infusion of amino acid injection on body temperature in patients undergoing OPCAB. METHODS: A prospective, double blind, randomized controlled, single-center study. Seventy-two patients were randomly divided into 4 groups: control group, pre-warming group, amino-acid group and multi-mode group. Pre-warming and multi-mode group were pre-heated with warming blankets and forced-air warming system before induction. After that, amino-acid and multi-mode group were infused with 18-amino acid solution. The perioperative temperature and complications were monitored. RESULTS: The temperature of control and amino-acid group decreased significantly, but amino-acid group recovered to preoperative level faster. The temperature of pre-warming group was stable, and that in multi-mode group increased at 60 min after the start of surgery. There was a significant difference in temperature at each time, and no difference in the incidence of complications between the groups. CONCLUSIONS: Preoperative warming and/or intraoperative infusion of amino acid injection can effectively reduce hypothermia in OPCAB surgery. Pre-warming before anesthesia is more effective, and the combination of the two methods has the best effect.

DEPDC1 up-regulates RAS expression to inhibit autophagy in lung adenocarcinoma cells.

DEP domain containing 1(DEPDC1) is involved in the tumorigenesis of a variety of cancers. But its role in tumorigenesis of lung adenocarcinoma (LUAD) is not fully understood. Here, we investigated the role and the underlying mechanisms of DEPDC1 in the development of LUAD. The expression and prognostic values of DEPDC1 in LUAD were analysed by using the data from public databases. Gene enrichment in TCGA LUAD was analysed using GSEA software with the pre-defined gene sets. Cell proliferation, migration and invasion of A549 cells were examined with colony formation, Transwell and wound healing assays. The function of DEPDC1 in autophagy and RAS-ERK1/2 signalling was determined with Western blot assay upon DEPDC1 knockdown and/or overexpression in A549, HCC827 and H1993 cells. The results demonstrated that DEPDC1 expression was up-regulated in LUAD tissues, and its high expression was correlated with unfavourable prognosis. The data also showed that DEPDC1 knockdown impaired proliferation, migration and invasion of A549 cells. Most notably, the results showed that DEPDC1 up-regulated RAS expression and thus enhanced ERK1/2 activity, through which DEPDC1 could inhibit autophagy. In conclusion, our study revealed that DEPDC1 is up-regulated in LUAD tissues and plays an oncogenic role in LUAD, and that DEPDC1 inhibits autophagy through the RAS-ERK1/2 signalling in A549, HCC827 and H1993 cells.

Heterogeneity of influential factors across the entire air quality spectrum in Chinese cities: A spatial quantile regression analysis.

Most of the previous researches estimate influencing factors impact on air quality average without considering the heterogeneity of influential factors on different levels of air quality. In order to detect the different effects of influencing factors on air quality index (AQI) between lower-AQI and higher-AQI cities, this study applies a spatial quantile regression model (SQRM) to investigate heterogeneity of influential factors on AQI, while accounting for spatial autocorrelation of AQI. The results show that heterogeneity effects of windspeed, terrain slope, urbanization sprawl and spatial autocorrelation on AQI are large across the entire AQI spectrum, while heterogeneity effects of precipitation, temperature, relative humidity, terrain fluctuation and urbanization intensity on AQI are not obvious. The spatial positive autocorrelation of AQI in higher-AQI cities is greater than that in lower-AQI cities. Compared with higher-AQI cities, the negative impact of terrain slope on AQI is lager in lower-AQI cities. One unit increase in wind speed contributes AQI to decrease 9.31 to 5.64 then to 5.39 for lower, medium and higher-AQI cities. One unit increase in urbanization sprawl would lead AQI increase 25.6 to 15.6 then to 10.5 for lower, medium and higher-AQI cities. The heterogeneity analysis of meteorological, topographic and socioeconomic factors effects on air quality are of guiding significance for realizing the differentiation of policy measures for air pollution prevention and control.

Total body irradiation induced mouse small intestine senescence as a late effect.

Radiation can induce senescence in many organs and tissues; however, it is still unclear how radiation stimulates senescence in mouse small intestine. In this study, we use the bone marrow transplantation mouse model to explore the late effects of total body irradiation on small intestine. Our results showed that almost all of the body hairs of the irradiated mice were white (which is an indication of aging) 10 months after the exposure to radiation. Furthermore, compared with the age-matched control mice, there were more SA-ß-galactosidase (SA-ß-gal)-positive cells and an upregulation of p16 and p21 in 8 Gy-irradiated mice intestinal crypts, indicating that radiation induced senescence in the small intestine. Intestinal bacterial flora profile analysis showed that the diversity of the intestinal bacterial flora decreased in irradiated mice; in addition it showed that the principal components of the irradiated and control mice differed: there was increased abundance of Bacteroidia and a decreased abundance of Clostridia in irradiated mice. To explore the underlying mechanism, an RNA-sequence was executed; the results suggested that pancreatic secretion, and the digestion and absorption of proteins, carbohydrates, fats and vitamins were damaged in irradiated mice, which may be responsible for the body weight loss observed in irradiated mice. In summary, our study suggested that total body irradiation may induce senescence in the small intestine and damage the health status of the irradiated mice.