In order to solve the problems of difficult test, high cost and long cycle in the development of large-scale airborne negative pressure isolation system, the simulation analysis of negative pressure response characteristics is carried out around various aviation conditions such as aircraft ascending, leveling and descending, especially rapid decompression, based on the computational fluid dynamics (CFD) method. The results showed that the isolation cabin could achieve -50 Pa pressure difference environment and form a certain pressure gradient. The exhaust air volume reached the maximum value in the early stage of the aircraft's ascent, and gradually decreased with the increase of altitude until it was level flying. In the process of aircraft descent, the exhaust fan could theoretically maintain a pressure difference far below -50 Pa without working; Under the special condition of rapid pressure loss, it was difficult to deal with the rapid change of low pressure only by the exhaust fan, so it was necessary to design safety valve and other anti-leakage measures in the isolation cabin structure. Therefore, the initial stage of aircraft ascent is the key stage for the adjustment and control of the negative pressure isolation system. By controlling the exhaust air volume and adjusting parameters, it can adapt to the change of low pressure under normal flight conditions, form a relatively stable negative pressure environment, and meet the needs of biological control, isolation and transport.
Aircraft ; Computer Simulation ; Aviation/instrumentation* ; Humans ; Hydrodynamics ; Air Pressure ; Equipment Design ; Pressure

Objective:To investigate the effect of nuclear receptor subfamily 2 group F member 2(NR2F2)on the biological behaviors of human ovarian cancer SKOV3 cells,and to clarify its molecular mechauism and provide the new idea for treatment of ovarian cancer.Methods:Gene Expression Profiling Interactive Analysis(GEPIA)Database analyse the expression level of NR2F2 gene in ovarian tissue,and analyse its correlation with clinical prognosis of ovarian cancer patients.The human ovarian cancer SKOV3 cells were divided into control group and NR2F2 over-expression(NR2F2 OE)group,which were transfected with mCherry control virus and NR2F2 OE over-expression virus,respectively,when the cell deusity reached 70％,and the stable transfection SKOV3 cell lines were screened with puromycin(puro)48h lafter.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the transfection efficiencies of the cells;RT-qPCR method was used to detect the expression levels of NR2F2 and sex-determining region Y-box 2(SOX2)mRNA in the cells in two groups;Western blotting method was used to detect the expression levels of NR2F2,ATP-binding cassette superfamily G member 2(ABCG2),and programmed cell death 1-ligand 1(PD-L1)protcins in the cells in two groups.CCK-8 assay was used to detect the proliferation activities of the cells in two groups;Wound assay was used to detect the migration rates of the cells in two groups;Transwell chamber assay was used to detect the number of transmembrane cells;Spheroidization assay was used to detect the numbers of spheroids in the cells;peripheral blood mononuclear cells(PBMCs)-mediated tumor cell killing assay was used to detect the relative densities of surviving tumor cells;CCK-8 assay was used to detect the half maximal inhibitory concentration(IC50)of paclitaxel(PTX)and carboplatin(CBP).Results:Compared with normal ovarian tissue,the expression level of NR2F2 gene in ovarian tumor tissue was decreased(P＜0.05),and decreased with the improvement of clinical pathological grading of ovarian tumor.The patients with higher expression level of NR2F2 gene had better clincal prognosis.The SKOV3 cells with NR2F2 over-expresson were successfully constructed,and the expression levels of NR2F2 mRNA and protein in the cells in NR2F2 OE group were increased compared with control group(P＜0.001).The CCK-8 assay results showed that compared with control group,the proliferation activities of the cells in NR2F2 OE group were decreased at different time points(1,2,3,and 4 d)(P＜0.05 or P＜0.01).The cell wound assay results showed that compared with control group,the migration rate of the cells in NR2F2 OE group was decreased(P＜0.001).The Transwell assay results showed that compared with control group,the number of transmembrane cells in NR2F2 OE group was decreased(P＜0.01).Compared with control group,the number of the spheroids in NR2F2 OE group was decreased(P＜0.05),and the expression levels of SOX2 mRNA(P＜0.01)and protein(P＜0.001)were increased.Compared with control group,the relative density of surviving tumor cells in NR2F2 OE group was decreased,but the difference was not significant(P＜0.05),and the expression level of PD-L1 protein was decreased(P＜0.05).Compared with control group,the proliferation activities of cells in NR2F2 OE group were decreased(P＜0.05),and the drug sensitivities of the cells to PTX and CBP were enhanced(P＜0.05);the IC50 of PTX was significantly reduced,while the IC50of CBP could not be calculated due to excessively high drug concentration;the expression level of ABCG2 protein was decreased(P＜0.05).Conclusion:The over-expression of NR2F2 may inhibit the proliferation,migration,and invasion of the human ovarian cancer SKOV3 cells,decrease the expression levels of SOX2,PD-L1 and ABCG2 proteins,suppress the stemness and immune evasion ability of the SKOV3 cells,and enhance the sensitivities of the SKOV3 cells to PTX and CBP.

The Hedgehog(HH)signaling pathway is involved in various developmental processes of vertebrates and invertebrates,including embryogenesis,stem cell renewal,tissue regeneration,the occurrence and development of tumor and chemotherapy resistance.Overactivation and abnormal expression of key components in the HH signaling pathway are associated with the development of various malignant tumors.Phosphorylation plays an important role in regulating the activity and function of proteins in normal cells,and the disorder of phosphorylation-dephosphorylation cascade is closely related to tumorigenesis.The abnormal activation of this signaling pathway is also related to protein phosphorylation,while its complex underlying mechanism needs to be further explored.This article reviewed the research progress of the HH signaling pathway and protein phosphorylation modification in malignant tumors,focusing on the regulatory effect of phosphorylation modification on the activity of HH signaling pathway and its effect on the occurrence and development of malignant tumors,in order to provide a theoretical basis for the in-depth development and clinical application of targeted drugs for phosphatase/dephosphatase.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

Objective:To discuss the effect of urolithin C(UC)on the proliferation,apoptosis,and autophagy of the acute myeloid leukemia(AML)HL-60 cells,and to clarify its mechanism.Methods:The HL-60 cells were divided into different concentrations(20,40,60,80,and 100 μmol·L-1)of urolithin A(UA)groups,urolithin B(UB)groups,and UC groups.CCK-8 assay was used to detect the proliferation activity of the cells in various groups;the morphology of the cells in different concentrations of UC groups was observed under optical microscope.The HL-60 cells were divided into different concentrations(0,20,40,and 80 μmol·L-1)of UC groups and 3-methyladenine(3-MA)combined with different concentrations(0,20,40,and 80 μmol·L-1)of UC groups.CCK-8 assay was used to detect the proliferation activities of the cells in various groups.The HL-60 cells were divided into control group(0 μmol·L-1)and different concentrations(20,40,and 80 μmol·L-1)of UC groups.The live/dead cell staining method was used to detect the dead rates of the cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups;the autophagy of the cells was detected by autophagy staining kit(monodansylcadaverine,MDC)method;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Beclin 1,autophagy related gene 9(ATG9),and autophagy related gene 7(ATG7)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of cysteinyl aspartate specific proteinase-3(Caspase-3),cleaved cysteinyl aspartate specific proteinase-3(Cleaved Caspase-3),microtubule-associated protein 1 light 3(LC-3),extracellular regulated protein kinases(ERK),phosphorylated ERK(p-ERK),AMP-activated protein kinase(AMPK),and phosphorylated AMPK(p-AMPK)in the cells in various groups.Results:The CCK-8 assay results showed that after cultured for 24,48,and 72 h,compared with 0 μmol·L-1 UA,UB,and UC groups,the proliferation activities of the cells in different concentrations of UA,UB,and UC groups were decreased(P＜0.01)with a concentration-and time-dependent manner;at 48 h,compared with UA and UB,the half-maximal inhibitory concentration(IC50)of UC was the lowest.The cell morphology observation results showed that compared with control group,the intercellular connection and the number of the cells were decreased with the increasing of UC concentration,and the cell fragment was increased.The CCK-8 assay results showed that compared with 40 and 80 μmol·L-1 UC groups,the proliferation activities of the cells in 3-MA combined with 40 and 80 μmol·L-1 UC groups were increased(P＜0.05 or P＜0.01).The live/dead cell staining results showed that compared with control group,the dead rates of the cells in 40 and 80 μmol·L-1 UC groups were increased(P＜0.01).The flow cytometry results showed that compared with control group,the apoptotic rate of the cells in 80 μmol·L-1 UC group was increased(P＜0.01).The MDC method results showed that with the increasing of UC concentration,the green fluorescence in the cells in different concentrations of UC groups was gradually intensified.The RT-qPCR results showed that compared with control group,the expression levels of Beclin 1,ATG9,and ATG7 mRNA in the cells in 80 μmol·L-1 UC group were increased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of Cleaved Caspase-3 protein in the cells in 20,40,and 80 μmol·L-1 UC groups were increased(P＜0.01),the ratio of membrane LC3/cytoplasmic LC3(LC3-Ⅱ/LC3-Ⅰ)in the cells in 80 μmol·L-1 UC group was increased(P＜0.05),and the ratios of p-AMPK/AMPK and p-ERK/ERK in the cells in 40 and 80 μmol·L-1 UC groups were increased(P＜0.01).Conclusion:UC can inhibit the proliferation of the AML HL-60 cells,induce the apoptosis and autophagy,and increase the phosphorylation levels of ERK and AMPK proteins in the cells.

In order to detect the environmental data of isolated cabin under various environmental conditions,a negative pressure cabin environment detector for aviation was developed,which was composed of a shell,a differential pressure transmitter,a pressure sensor,a carbon dioxide concentration sensor,an oxygen concentration sensor,a temperature and humidity sensor,a data processing module,a liquid crystal display(LCD)screen and USB data interface.It could environmental data such as carbon dioxide concentration,oxygen concentration,temperature,humidity,pressure difference between cabin and outside the cabin and air pressure outside the cabin in real time,the data processing module collected and processed the data,the data and data change curves was displayed in real time by the LCD screen,and the detection data was extracted through the USB data interface.When used in aviation environment,the detector could work continuously without fault for no less than 300 hours,and the average fault repair time was about 30 minutes,with good performance and high detection accuracy,which can provide convenience for the environmental data detection of negative pressure cabins,and is worthy of popularization.

Objective To study the effects and mechanism of norcantharidin(NCTD)on proliferation and apoptosis of NB4 and K562 human leukemic cells by regulating phosphoprotein phosphatase 5 catalytic(PPP5C).Methods PC3.1 and PPP5C-PC3.1 plasmids were electroporated into NB4 and K562 cells.Stable NB4 and K562 cell lines were selected with geneticin(G418).Protein and mRNA expression levels of PPP5C were measured by Western blot and RT-qPCR,respectively.Proliferation,migration,and apoptosis of NB4 and K562 cells were determined by a CCK-8 assay,transwell assay,and Live & Dead? animal cell viability/toxicity detection kit,respectively.NB4 and K562 cells were divided into 0 μg/mL NCTD group and various NCTD dose groups,and cultured in RPMI 1640 medium containing 0,8,16,or 32 μg/ml NCTD.The Live & Dead? animal cell viability/toxicity detection kit measured the numbers of dead and live cells,and cell morphology was observed under a microscope.Western blot was used to measure protein expression levels of caspase 3,Cleaved caspase 3,JNK,p-JNK,p38,p-p38,and α-Tubulin.Results Proliferation,migration,and apoptosis of NB4 and K562 cells were enhanced by overexpression of PPP5C.Compared with 0 μg/mL NCTD group,NCTD promoted apoptosis in a dose-dependent manner.PPP5C overexpression antagonized the killing effect of NCTD on leukemic cells.Mechanistic investigations showed that PPP5C reduced the protein level of p-JNK by dephosphorylating and regulating the expression of apoptosis-related protein Cleaved caspase 3.Conclusions NCTD promotes apoptosis of NB4 and K562 cells and inhibits their proliferation by inhibiting PPP5C.

Gene editing tools with nucleases as the main component have now implemented programmable targeted mutagenesis or insertion or deletion of mammalian genomes.From zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR/Cas system to safer and more accurate Cas9 fusion protein gene editing tools and other nuclease gene editing tools, this paper systematically describes the development and evolution of gene editing, with detailed introduction to the development and optimization of next-generation gene editing tools, and a prospect of the clinical application of and challenges for gene editing tools.

Objective:To study the specific mechanism of LINC01018 involved in the pathogenesis of colon cancer.Methods:The expression of LINC01018 in colon cancer tissues and cells and normal colon tissues and cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR). HT-29 cell line which overexpresses LINC01018 stably was established. RNA binding protein immunoprecipitation (RIP) assay was used to detect the interaction between LINC01018 and E2F1 protein. Dual luciferase assay was used to detect the regulatory effect of E2F1 on CDK6 promoter. The expression of E2F1 or CDK6 was up-regulated in HT-29 cell line which overexpresses LINC01018, then the proliferation, invasion and migration of HT-29 cells and the expression of CDK6 and matrix metalloproteinase-2 (MMP-2) in HT-29 cells were detected by cell counting method (CCK-8) assay, Transwell assay and Western blot.Results:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. The result of RIP assay showed that LINC01018 interacted with E2F1 protein. The result of dual luciferase assay showed that E2F1 protein could enhance the efficiency of CDK6 promoter, and E2F1 had a positive regulatory effect on CDK6. Overexpression of LINC01018 could attenuate the positive regulatory effect of E2F1 on CDK6. Up-regulation of E2F1 or CDK6 expression could attenuate the effects of LINC01018 overexpression on the proliferation, invasion, migration and expression of CDK6 and MMP-2 in HT-29 cells.Conclusions:The expression of LINC01018 was abnormally low in colon cancer tissues and cells. LINC01018 may regulate the proliferation, invasion and migration of HT-29 cells through E2F1/CDK6/MMP-2 axis, and participate in the pathogenesis of colon cancer.

Objective:To evaluate biological dose and retrospective biodosimetry of a case of large area back skin injury caused by suspected interventional procedure.Methods:Peripheral blood from the patient was collected at about 7 months after interventional procedure, and the chromosomal aberrations in peripheral blood cells were analyzed to evaluate the retrospective biodosimetry using the correction factor of dose estimation, Dolphin′s model and Qdr method, respectively. Results:Based on the amounts of semi-automated dic and manually detected dic plus ring, the whole-body average absorbed dose of the victim was estimated to be 0.68-0.95 Gy by four different dose response curves. Over dispersion of dic or dic plus ring was also detected, and the efficiency of dose assessment was obviously increased using dic semi-automatic detection. Based on three different retrospective biodosimetry models, the estimated average absorbed dose was further corrected to be between 1.80-2.86 Gy, which was consistent with clinical diagnosis of degree Ⅳ radiation skin injury.Conclusions:A case of suspected radiation skin injury was confirmed by chromosomal aberration analysis and it’s biodosimetry was reconstructed, suggesting that the unstable chromosomal aberration analysis may be applicable to assess the retrospective biodosimetry of non-uniform local radiation exposure.