Neuroblastoma (NB) is one of the most common extracranial solid tumors in children. MYCN gene amplification is highly associated with poor prognosis in high-risk NB patients. In non-MYCN-amplified high-risk NB patients, the expression of c-MYC (MYCC) and its target genes is highly elevated. USP28 as a deubiquitinase is known to regulate the stability of MYCC. We show here USP28 also regulates the stability of MYCN. Genetic depletion or pharmacologic inhibition of the deubiquitinase strongly destabilizes MYCN and stops the growth of NB cells that overexpress MYCN. In addition, MYCC could be similarly destabilized in non-MYCN NB cells by compromising USP28 function. Our results strongly suggest USP28 as a therapeutic target for NB with or without MYCN amplification/overexpression.

Small non-coding RNAs are widespread in the biological world and have been extensively explored over the past decades. Their fundamental roles in human health and disease are increasingly appreciated. Furthermore, a growing number of studies have investigated the functions of small non-coding RNAs in cancer initiation and progression. In this review, we provide an overview of the biogenesis of small non-coding RNAs with a focus on microRNAs, PIWI-interacting RNAs, and a new class of tRNA-derived small RNAs. We discuss their biological functions in human cancer and highlight their clinical application as molecular biomarkers or therapeutic targets.

Moving models, such as translation, rotation, and other motion modes, are widely applied to improve the microwave heating uniformity. However, due to a variety of motion modes, the deformation of mesh, including discontinuity, crossing, and winding, usually occurs in the process of microwave heating calculation. It is a great challenge to numerical simulation of moving samples because of the lack of a common calculation method. In this article, a novel inheritance algorithm, which inherits both the grid and temperature distribution of the sample, can be used to calculate arbitrary moving models of microwave heating process. It is adopted to inherit the grid and temperature distribution in the finite element method to ensure that each temperature calculation result can perfectly correspond to the temperature value of these mesh nodes. By building a 3-D mathematical model of translation, swing, and rotation, the coupling process of electromagnetic field and thermal phenomena in microwave heating was performed and the proposed method was clearly illustrated. Finally, the calculated results are consistent with the experimental results, confirming the accuracy of the algorithm. Compared with the conventional algorithm, the proposed algorithm has a higher precision and practically and can be used to simulate microwave heating of arbitrary motions.

Background: Nardilysin, (N-arginine dibasic convertase, NRDC) has been reported to play an important role in cancer progression, and is associated with tumor proliferation signals and inflammatory signals, such as tumor necrosis factor-a (TNF-a) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), through the activation of disintegrin and metalloproteinase (ADAM) proteases. NRDC has recently been revealed to be involved in the tumorigenesis of various types of cancer, including intrahepatic cholangiocarcinoma, malignant cerebral infarction, esophageal squamous cell carcinoma, and gastric cancer. However, the expression profiles and biological relevance of NRDC in pancreatic ductal adenocarcinoma have rarely been reported. Methods: We analyzed the NRDC expression profile in pancreatic ductal adenocarcinoma by enzyme-linked immunosorbent assay (ELISA) and identified NRDC as a circulating biomarker in the serum of 112 pancreatic ductal adenocarcinoma patients. The diagnostic value of NRDC was analyzed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test. Results: Our results demonstrated that the clinical prognosis significance of NRDC with the clinical characteristics in pancreatic ductal adenocarcinoma (PDAC). NRDC was notably decreased in PDAC patient serum compared with the control group (p < 0.001). Furthermore, the present study found that the NRDC expression level was correlated with T grade (p < 0.001), metastasis(p < 0.001), differentiation(p < 0.001), and TNM stage (p = 0.011). Further bioinformatics analysis revealed that NRDC correlated with proliferation and migration pathways; in particular, it mediated cell-matrix adhesion-dependent activation in pancreatic ductal adenocarcinoma. Conclusions: Serum NRDC may play a useful diagnostic biomarker to evaluate the aggressive clinical features in PAAD patients.

A novel two-dimensional atmospheric pressure plasma jet device is proposed for large-area processing. A finite element algorithm is adopted to obtain the optimized dimensions of the designed device based on microwave power reflection coefficient |S-11| and electric field intensity. The plasma parameters of electron density n e and electron temperature T e within 0.1 ms after microwave power input were analyzed. When plasma is fully excited, n e is close to 3.5 x 10(18) m(-3), and T e is calculated to be 2 eV. Besides, an experimental system is established, and microwave power of 70 W can process 30 L of argon per minute, which shows a high energy efficiency. Two plasma jets with a width of 10 mm and a length of 5 mm are successfully excited. In addition, reflected power measured by the power meter is only 9.5% of incident power, which is in good agreement with simulation results.

Triple-negative breast cancer (TNBC) is a type of breast tumor that currently lacks options for targeted therapy. Tremendous effort has been made to identify treatment targets for TNBC. Here, we report that the expression level of anaphase promoting complex (APC) coactivator Cdh1 in TNBC is elevated compared to that in the adjacent healthy tissues, and high levels of Cdh1 expression are correlated with poor prognoses, suggesting that Cdh1 contributes to the progression of TNBC. Interfering with the function of Cdh1 can potentiate the cytotoxic effects of PARP inhibitors against BRCA-deficient and BRCA-proficient TNBC cells through inducing DNA damage, checkpoint activation, cell cycle arrest, and apoptosis. Further investigation reveals that Cdh1 promotes BRCA1 foci formation and prevents untangled DNA entering mitosis in response to PARP inhibition (PARPi) in TNBC cells. Collectively, these results suggest that APC/Cdh1 is a potential molecular target for PARPi-based therapies against TNBCs.

Background Kinesin superfamily of proteins (KIFs) has been broadly reported to play an indispensable role in the biological process. Recently, emerging evidence reveals its oncogenic role in various cancers. However, the prognostic, oncological, and immunological values of KIFs have not been comprehensively explored in pancreatic ductal adenocarcinoma (PDAC) patients. We aimed to illustrate the relationship between KIFs and pancreatic ductal adenocarcinoma by using bioinformatical analysis. Methods We use GEPIA, Oncomine datasets, cBioPortal, LOGpc, TIMER, and STRING bioinformatics tools and web servers to investigate the aberrant expression, prognostic values, and oncogenic role of KIFs. The two-gene prognostic model and the correlation between KIFs and KRAS and TP53 mutation were performed using an R-based computational framework. Results Our results demonstrated that KIFC1/2C/4A/11/14/15/18A/18B/20B/23 (we name it prognosis-related KIFs) were upregulated and associated with unfavorable clinical outcome in pancreatic cancer patients. KIF21B overexpression is associated with better clinical outcome. The KIFC1/2C/4A/11/14/15/18A/18B/20B/23 profiles were significantly increased compared to grade 1 and grade 2/3. Besides, KIFC1/2C/4A/11/14/15/18A/18B/20B/23 was significantly associated with the mutation status of KRAS and TP53.Notably, most prognosis-related KIFs have strong correlations with tumor growth and myeloid-derived suppressor cells infiltration (MDSCs). A prognostic signature based on KIF20B and KIF21B showed a reliable predictive performance. Receiver operating characteristic (ROC) curve was employed to assess the predictive power of two-gene signature. Consequently, the gene set enrichment analysis (GSEA) showed that KIF20B and KIF21B’s overexpression was associated with the immunological and oncogenic pathway activation in pancreatic cancer. Finally, real-time quantitative PCR (RT-qPCR) was utilized to investigate the expression pattern of KIF20B and KIF21B in pancreatic cancer cell lines and normal pancreatic cell. Conclusions Knowledge of the expression level of the KIFs may provide novel therapeutic molecular targets and potential prognostic biomarkers to pancreatic cancer patients.

Colorectal cancer (CRC) is one of the most common tumors, ranking second in the global cause of death from cancer. The prognosis of advanced patients is still very poor. In this study, hub modules with the highest association with tumor-infiltrating immune cells were identified by weighted gene co-expression network analysis based on CRC expression data from the Gene Expression Omnibus database. Next, three hub genes (ADAM8, IL-1A, VAV3) related to infiltrating immune cells were identified by co-expression network and prognostic analysis. After analysis and verification of the TIMER database, ADAM8 was selected as a prognostic biomarker. Finally, the result of functional test showed that ADAM8 gene expression down-regulation partially reversed the immune tolerance of CRC cells to TILs. By bioinformatics analysis methods and the experimental techniques, we identified ADAM8 as a prognostic biomarker and clinical therapeutic target related to tumor-infiltrating immune cells in CRC.

Dramatic shortages of filtering facepiece respirator supplies generally occur following the outbreak of a pandemic such as COVID-19. Here, the decontamination and reuse of respirators are considered. Among decontamination methods, microwave irradiation has great potential because of easy access of microwave ovens. However, can a respirator be heated in a microwave oven for a certain time and then be reused? Herein, we demonstrate that dry microwave irradiation cannot heat infectious aerosols or droplets up to their deactivation temperature. The microwave absorption performance of a single aerosol or droplet was analyzed theoretically. The multiphysics simulation results indicate that a single aerosol or droplet can be barely heated under dry microwave irradiation. Experiments were carried out using a traveling wave system to verify the simulation. Following this, we simulated multiple aerosols and droplets on a respirator material, with the results indicating that the aerosols and droplets were at the same temperature as that of the respirator. Experimental measurements using a microwave oven demonstrated that the temperature increase of an N95 respirator under dry heating is less than 10 °C, which is far less than the temperature required to deactivate the COVID-19 virus. Although dry microwave heating cannot be used to heat the aerosols or droplets, microwave-generated steam has proved effective in deactivating infectious biological organisms. Therefore, to successfully decontaminate a used respirator in a microwave oven, a reservoir with a small amount of water beneath the respirator (or a steam bag to accommodate it) is essential to the decontamination process.

Background: In China, burnout, anxiety, depression, and suicidal thoughts among medical staff are common and have been associated with high-intensity work, patient complaints, pressure from public opinion, misunderstanding, and long training and working cycles. However, mental health status of medical personnel has not been well described at a national level. To estimate the mental health status of medical staff, focusing on identifying healthcare providers in the high-risk groups, and executing positive psychological intervention, counseling, treatment initiatives, and moreover, carry out crisis interventions in advance. Methods: This study was using data collected from both the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores, representing the national sample of the medical staff in China, collected from May 2016 to July 2019. The three componentsof mental health, emotional well-being, psychological well-being, and social well-being, were used to evaluate the mental health status of the target population. The survey covered 10 basic information and 40 psychological questions. The main questionnaires were from both the Self-rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), as well as gender, age, marital status, education, professional title, salary, job category, and hospital levels, which were made an electronic questionnaire format by questionnaire star. We sent the message to the healthcare workers’ Wechat group. The responses from 4403 medical physicians (included medical students, refresher doctors, training physicians, and doctors), as well as nursing staff, and medical technicians, were utilized. Findings: The overall pooled prevalence of depression or depressive symptoms among medical personnel in China was 27.8%, and symptoms of anxiety were reported from 22.3% (980 out 4403) physicians. Among these medical staff, the secondary hospital ( P =0.017, P =0.049) and night shift frequency less than 5 days ( P =0.002, P =0.000) and unemotional management-related learning and training ( P =0.000, P =0.000) were significantly associated with SAS and SDS scores. In addition, the study showed that sleep quality (sleep deprivation) were related to gender ( P =0.006) and marital status ( P =0.045), while suicidal ideation were statistically associated with age ( P =0.025), marital status ( P =0.021), occupation ( P =0.028), hospital-level ( P =0.048), professional title ( P =0.037), annual income ( P =0.029), and whether there was emotional management learning ( P =0.001). Interpretation: In this Chinese national study of medical personnel, the findings indicated that the prevalence of depression and anxiety in hospitals at three levels were high. Further research is needed to better understand and identify the high-risk groups of medical staff under high-stress circumstances and to address these issues properly.Trial Registration: Chinese Clinical Trial Registry ChiCTR1800019542Funding Statement: The National Institute on Minority Health and Health Disparities, a component of the National Institutes of Health (5G12MD007592 and 2U54MD00759226).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The West China Hospital approved this study and waiver of informed consent of the Sichuan University institutional review board.

目的 探讨泛素特异性肽酶39(ubiquitin-specific peptidase 39,USP39)对肿瘤细胞DNA损伤应答通路的生物学作用.方法 将不同肿瘤细胞系(293T,HeLa,U2OS,T47D)分别在含有100 mL/L FBS的DMEM或RPMI-1640培养基中,在37℃ 含有50 mL/L CO 2的培养箱中培养;用MTS[3-(4,5-diethylthiazol-2-yl)-5-(3-carboxyme-thoxyphenyl)-2-(4-sulfophenyl)-2 H-etrazolium,inner salt]方法检测敲低USP39对肿瘤细胞放射敏感性的影响;流式细胞术检测同源重组(homologous recombination,HR)和非同源末端连接(non-homologous end joining,NHEJ)修复效率;Western blot检测敲低USP39对DNA损伤应答相关分子的表达情况;用免疫共沉淀、蛋白纯化及质谱技术,检测与USP39相互作用的蛋白并且进行基因本体论(gene ontology,GO)分析;通过微辐射诱导DNA损伤并利用激光共聚焦显微镜检测其募集至DNA损伤位点的情况.结果 敲低USP39导致肿瘤细胞的放射敏感性显著增加(P<0.05);敲低USP39显著抑制肿瘤细胞的HR与NHEJ修复效率(P<0.05);敲低USP39能够促进DNA损伤应答因子蛋白的表达;USP39能够聚集至DNA损伤位点;USP39相互作用蛋白与多个DNA损伤应答相关的信号通路有关.结论 USP39对DNA损伤应答过程具有重要作用.

目的 探讨小分子干扰RNA(siRNA)沉默BAZ1A基因对肺腺癌A549细胞的放疗增敏作用.方法 将A549细胞随机分为3组:空白对照组(Ctrl)、siRNA对照组(siNC)、BAZ1A siRNA转染组(siBAZ1A),Western blot检测转染后BAZ1A蛋白表达水平;平板克隆实验检测不同辐射剂量下细胞的存活分数(SF),并通过单击多靶模型拟合细胞存活曲线,计算放射增敏比(SER);MTS、划痕实验及流式细胞仪分别检测干预后A549细胞的增殖能力、迁移能力以及细胞凋亡率.结果 siBAZ1A可降低BAZ1A蛋白的表达水平,增强放疗对A549细胞克隆形成能力的抑制作用,在2～10 Gy的放射剂量下,siBAZ1A组细胞的SF值均低于其余两组,差异具有统计学意义(P<0.05),siBAZ1A组及siNC组相对于Ctrl组的SER分别为1.06和2.24,siBAZ1A组照射后,细胞增殖能力和细胞迁移能力较对照组减弱,细胞凋亡率增加,差异具有统计学意义(P<0.05).结论 沉默BAZ1A基因对肺腺癌A549细胞具有放射增敏作用.