Genomic characterization of peritoneal lavage cytology-positive gastric cancer

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

Controlling atomic phosphorous-mounting surfaces of ultrafine W_(2)C nanoislands monodispersed on the carbon frameworks for enhanced hydrogen evolution

Controllably mounting foreign atoms on the surfaces of earth-abundant electrocatalysts strongly improve their surface electronic properties for optimizing the catalytic performance of surficial sites to an unusual level,and provides a good platform to gain deep insights into catalytic reactions.The present work describes,employing ultrafine W2C nanoislands(average size:2.3 nm)monodispersed on the N,P dual-doped carbon frameworks as a model system,how to regulate the atomic phosphorous-mounting effect on the surfaces of W_(2)C to derive an active and stable P-mounting W_(2)C(WCP)catalyst for both acidic and alkaline hydrogen evolution reaction(HER).Since in situ phosphorus substitution into carbon sites of preformed W_(2)C nanoislands gradually proceeds from surfaces to solids,so that using a proper amount of phosphorus sources can readily control the surface mounting level to avoid the mass P-doping into the bulk.By this way,the activity per active site of WCP catalyst with robust stability can be optimized to 0.07 and 0.56 H_(2 )s^(-1) at-200 mV overpotential in acid and base,respectively,which reach up to the several-fold of pure-phase W_(2)C(0.01 and 0.05 H_(2) s^(-1)).Theoretical investigations suggest that compared with solid P doping,the P mounting on W_(2)C surface can more remarkably enhance its metallicity and decrease the hydrogen release barrier.This finding disclosed a key correlation between surface foreign atom-mounting and catalytic activity,and suggested a logical extension to other earth-abundant catalysts for various catalytic reactions.

空心球壳状MoS_(2)/WS_(2)异质结构的制备及其电催化析氢性能

系统研究一种由空心WS_(2)球壳和花瓣状MoS_(2)组成的异质结构。结果表明,空心球壳结构使活性位点更容易暴露,异质结构的形成有助于激发WS_(2)和MoS_(2)之间的协同效应,从而提高析氢反应性能,具有更好的电子转移能力。更重要的是,密度泛函理论计算进一步阐明了协同机理,表明MoS_(2)/WS_(2)异质结构可有效调节氢吸附自由能,使之在W/Mo原子比为2꞉25时达到最小值。因此,优化后的WMo-2/25催化剂表现出优异的电催化析氢活性,Tafel斜率低,为53 mV/dec,并具有良好的稳定性。

Advances of nanotechnology applied to cancer stem cells

Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their self-renewal,proliferation,and differentiation potential.The elimination of CSCs is thus the key to cure cancer,and targeting CSCs provides a new method for tumor treatment.Due to the advantages of controlled sustained release,targeting and high biocompatibility,a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs.This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs.Furthermore,we identify the problems and future research directions of nanotechnology in CSC therapy.We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.

通风机转子过盈装配松脱转速有限元分析

本文以某型通风机为研究对象,使用Ansys有限元软件分别计算了采用不同过盈配合规格时某风机转子的松脱转速,并根据第四强度理论校核了应力。通过对比分析,得到了适合该风机转子的过盈配合规格。不仅为通风机转子松脱转速分析提供了新方法,还为过盈配合规格的选择提供了理论依据。

大型通风机定子结构减重优化设计研究

大型通风机的结构设计应满足强度、刚度、稳定性和动力响应等诸多限制条件。为节省材料、降低成本,提高市场竞争力,风机的质量不能过大。本文提出了带加强筋板的大型风机定子减重优化设计方法。采用结构优化的设计方法,以机壳厚度、筋板高度和筋板厚度为设计变量,考虑应力、位移、稳定性等约束,通过敏感性分析,给出了机壳减重设计的主要途径,以及安全可行的机壳减重设计方案。

固载过氧化氢酶微球清除家庭漂白后残留过氧化氢的研究

利用仿生矿化法制备了固载过氧化氢酶的碳酸钙微球,研究了该载酶微球的包封情况、在苛刻环境中的稳定性和清除漂白纱布后残留过氧化氢的效果。结果表明,该载酶微球粒径约11μm,孔径为5.53 nm,能有效封装住过氧化氢酶;在过氧化氢酶质量浓度为0.15 mg/m L的条件下,该微球对过氧化氢酶具有最高负载量为24.26 mg/g,此时酶包封率为98%,酶活力保留率为72%。该载酶微球与游离酶相比提升了热稳定性(80℃条件下仍能保留38.99%的相对酶活力)、改变了过氧化氢酶对不同pH环境耐受能力的趋势(最适酶活力pH值由pH 8偏移至pH 11),提升了耐表面活性剂性质(在十二烷基硫酸钠环境中仍保留了85.82%的相对酶活力)。且该载酶微球能在25 min完全清除漂白纱布后残留的过氧化氢。

工业汽轮机汽缸结构强度仿真分析

对某型号抽凝式工业汽轮机的结构强度展开研究,以ANSYS WORKBENCH软件为工具,开展了汽缸温度场、热应力及热变形分析,针对汽缸法兰安全性问题,提出改进方案。由于汽缸处于高温状态,材料会发生蠕变,对汽缸强度和汽密性产生影响,因此,采用多轴蠕变应变对汽缸进行蠕变强度校核,评估汽缸的安全性和可运行性。

Temperature inferential control of a reactive distillation column with double reactive sections

Temperature inferential control (TIC) is studied for a reactive distillation column with double reactive sections (RDC-DRSs) processing a hypothetical two-stage consecutive reversible reaction (A + B■C + D, C + B■E + D with αD > αB > αC > αA > αE). Because of the complicated dynamic behaviors, the controlled stages by sensitivity analysis lead to great steady-state deviations (SSDs) in top and bottom product purities. Since TIC involves considerably reduced settling times in comparison with direct composition control, small SSDs in product qualities correspond generally to small transient deviations (TDs) in product qualities. An objective function that measures SSDs in product qualities is formulated to represent the performance of a TIC system and an iterative procedure is devised to search for the best control configuration. The application of the procedure to the RDC-DRS gives considerably suppressed TDs and SSDs in top and bottom product qualities as compared with the one by sensitivity analysis. The method is simpler in principle and less computationally intensive than the current practice. These striking outcomes show the effectiveness of the proposed principle for the development of TIC systems for complicated reactive distillation columns.

液滴模板法构建疏水杂化囊用于包封SOD酶研究

针对化妆品中生物活性分子保存稳定性问题,通过液滴模板法制备包封超氧化物歧化酶(SOD)的碳酸钙@海藻酸钙(CaCO3@Ca-Alg)杂化囊,再疏水改性壁层来阻止水分子进入,从而提高了包封物的保存稳定性。实验结果表明:该包封SOD的疏水杂化囊具有粒径均一、单分散性良好的优点;随着改性时间的延长,杂化囊疏水性随之提高,当改性时间超过4 h后,杂化囊疏水性保持稳定;杂化囊固定SOD的相对酶活明显高于单纯Ca-Alg囊(最大差值达到了300%);游离SOD在去离子水中保存4 d后完全失活,而包封SOD的疏水杂化囊保存7 d后仍能维持95%以上的相对酶活。

Fabrication of Z-scheme MoO3/Bi2O4 heterojunction photocatalyst with enhanced photocatalytic performance under visible light irradiation

Constructing Z-scheme heterojunction to improve the separation efficiency of photogenerated carriers of photocatalysts has gained extensive attention.In this work,we fabricated a novel Z-scheme MoO3/Bi2O4 heterojunction photocatalyst by a hydrothermal method.XPS analysis results indicated that strong interaction between MoO3 and Bi2O4 is generated,which contributes to charge transfer and separation of the photogenerated carriers.This was confirmed by photoluminescence(PL)and electrochemical impedance spectroscopy(EIS)tests.The photocatalytic performance of the as-synthesized photocatalysts was evaluated by degrading rhodamine B(RhB)in aqueous solution under visible light irradiation,showing that 15%MoO3/Bi2O4(15-MB)composite exhibited the highest photocatalytic activity,which is 2 times higher than that of Bi2O4.Besides,the heterojunction photocatalyst can keep good photocatalytic activity and stability after five recycles.Trapping experiments demonstrated that the dominant active radicals in photocatalytic reactions are superoxide radical( O2-)and holes(h+),indicating that the 15-MB composite is a Z-scheme photocatalyst.Finally,the mechanism of the Z-scheme MoO3/Bi2O4 composite for photo-degrading RhB in aqueous solution is proposed.This work provides a promising strategy for designing Bi-based Z-scheme heterojunction photocatalysts for highly efficient removal of environmental pollutants.

去泛素化酶在结直肠癌中的研究进展

去泛素化酶(deubiquitinating enzymes,DUBs)包括六大亚家族,广泛分布于机体的各种细胞内,对蛋白质产生去泛素化作用,从而调节蛋白质的降解,在细胞的生长增殖、免疫调节、神经功能、肿瘤发生发展及分子信号通路等多方面发挥重要作用.结直肠癌作为发病率、死亡率最高的五大恶性肿瘤之一,严重的威胁了人类健康,越来越多的研究报道发现去泛素化酶家族在结直肠癌的发生发展中起到重要的调控作用,本文就此相关进展作如下综述.

燃料电池汽车能量管理测评研究分析

能量管理对燃料电池汽车的经济性能有着重要的影响。本文从现有燃料电池汽车的驱动模式、控制策略、测试工况以及典型燃料电池汽车的能量流测试4个方面进行了综述分析,提出了燃料电池汽车能量流测试评价的关键指标。

The Soil Moisture and Grain Size Characteristics of Micro-area: A Case Study of Minqin Oasis- Desert Ecotone

To elaborate soil moisture and grain size characteristics of 3 typical micro-areas in Minqin oasis-desert ecotone,samples were collected in runoff generation area and accumulated area using soil profile and multi-point sampling method,for soil moisture and physicochemical property analysis. Research results that( i) water accumulation trace of accumulated area is significant and the vegetation coverage is larger than the runoff generation area. The crust development in clay sand barrier + Haloxylon ammodendron forest accumulated is better than runoff generation area,while the situation is contrary in Nitraria tangutorum sand dune lowland and clay flat land.( ii) Moisture of accumulated area in fixed Nitraria tangutorum sand inter-dune lowland is better than the runoff generation area; the moisture of accumulated area in clay flat land topsoil is significantly better than the runoff generation area,while the topsoil moisture of clay sand barrier + Haloxylon ammodendron forest is better in the runoff generation area than in the accumulated area.( iii) Soil moisture of accumulated area in 3 types of micro-areas is in the range of 20- 40 cm; the fixed Nitraria tangutorum sand inter-dune lowland is better than clay flat land and clay sand barrier + Haloxylon ammodendron forest,while the lowest moisture of corresponding runoff generation area is basically consistent with the depth.( iv) The topsoil clay and powder content in accumulated area of fixed Nitraria tangutorum sand inter-dune lowland is lower than the runoff generation area,while the fine sand content in deep layer of runoff generation area is greater than the accumulated area; soil in two areas of clay flat land mainly consists of coarse and fine sand,and clay particles are better in runoff generation area than in accumulated area. Soil in the clay sand barrier + Haloxylon ammodendron forest is mainly coarse sand and the structure is single. In sum,through adjusting allocation of rainfall,micro-areas influence soil moisture and grain size distribution,and further influence spatial- temporal distribution of vegetation in sand micro-areas.

Green-emitting Polyfluorenes Containing Hexylthiophen-dibenzothiophene-S,S-dioxide Unit with Large Two-photon Absorption Cross Section

Green light-emitting polyfluorenes containing 3,7-bis（4-hexylthiophen-2-yl）dibenzo[b,d]thiophene 5,5-dioxide（DHTSO）unit were synthesized.All the resulted polymers show high thermal stability with the decomposition temperatures（T_d）over 420°C and the glass transition temperatures（T_g）over 75°C.The polymers exhibit the enhanced highest occupied molecular orbital（HOMO）energy levels and the depressed lowest unoccupied molecular orbital（LUMO）energy levels with the increase of DHTSO unit in polymers.The photoluminescence（PL）spectra of the polymers show positive solvatochromism in solution with the variation of solution polarities,indicating remarkable intramolecular charge transfer（ICT）effect in the polymers containing DHTSO moiety.The fluorescence quantum yields（（37）_（PL））are in the range of 34%-67%for PF-DHTSOs in film.All polymers possess two photon absorption（TPA）properties,and the TPA cross sections（？_2）are enhanced with increasing DHTSO unit in polymers.The highest？_2 is 2392 GM for PF-DHTSO15 in chloroform solution upon 740 nm excitation.The device of PF-DHTSO15 shows green emission with the Commission Internationale de L’.Eclairage（CIE）coordinates of（0.26,0.59）,and the maximum luminous efficiency（LE_（max））of 10.8 cd·A^（-1） with the configuration of ITO/PEDOT：PSS/EL/Cs F/Al.These results indicate that introducing DHTSO unit into polyfluorene backbone could be a promising molecular design strategy for TPA and effective green-light emission.

Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

CD 147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression

Major gaps in understanding the molecular mechanisms of colorectal cancer(CRC)progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal disorders.Trefoil factor 3(TFF3)has been reported to be involved in CRC progression and intestinal mucosal repair;however,how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly understood.Here,we found that the upregulated TFF3 in CRC predicted a worse overall survival rate.TFF3 deficiency impaired mucosal restitution and adenocarcinogenesis.CD147,a membrane protein,was identified as a binding partner for TFF3.Via binding to CD147,TFF3 enhanced CD147-CD44s interaction,resulting in signal transducer and activator of transcription 3(STAT3)activation and prostaglandin G/H synthase 2(PTGS2)expression,which were indispensable for TFF3-induced migration,proliferation,and invasion.PTGS2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype(PTGER4)and contributed to TFF3-stimulated CRC progression.Solution NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 expression.The ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 inhibitor.Blockade of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in mice.Our findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression,which widens and deepens the understanding of the molecular function of trefoil factors.

Insulin gene enhancer protein 1 mediates glycolysis and tumorigenesis of gastric cancer through regulating glucose transporter 4

Background:Insulin gene enhancer protein 1,(ISL1),a LIM-homeodomain transcription factor,is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes.However,the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer(GC)is unclear.In this study,we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis.Methods:We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction(PCR).Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 knockdown.RNA-sequencing was performed to identify differentially expressed genes,followed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA)to reveal key signaling pathways likely regulated by ISL1 in GC.Alteration of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)and by detecting glucose consumption and lactate production.The expression of glucose transporter 4(GLUT4)and ISL1 was assessed by Western blotting,immunohistochemistry,and immunofluorescent microscopy.The luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on GLUT4.Results:High levels of ISL1 and GLUT4 expression was associated with short survival of GC patients.ISL1 knockdown inhibited cell proliferation both in vitro and in vivo.KEGG analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown,which was validated by reduced glucose uptake and lactate production,decreased ECAR,and increased OCR.Mechanistic investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its promoter.Conclusion:ISL1 facilitates glycolysis and tumorigenesis in GC via the transcriptional regulation of GLUT4.

SDCBP-AS1 destabilizesβ-catenin by regulating ubiquitination and SUMOylation of hnRNP K to suppress gastric tumorigenicity and metastasis

Background:Gastric cancer(GC)is among the most malignant tumors,yet the pathogenesis is not fully understood,especially the lack of detailed information about the mechanisms underlying long non-coding RNA(lncRNA)-mediated post-translational modifications.Here,the molecular mechanisms and clinical significance of the novel lncRNA syndecan-binding protein 2-antisense RNA 1(SDCBP2-AS1)in the tumorigenesis and progression of GC were investigated.Methods:The expression levels of SDCBP2-AS1 in 132 pairs of GC and adjacent normal tissues were compared,and the biological functions were assessed in vitro and in vivo.RNA pull-down and immunoprecipitation assays were conducted to clarify the interactions of SDCBP2-AS1 and heterogeneous nuclear ribonucleoprotein(hnRNP)K.RNA-sequencing,immunoprecipitation,immunofluorescence,and luciferase analyses were performed to investigate the functions of SDCBP2-AS1.Results:SDCBP2-AS1 was significantly downregulated in GC tissues and pre-dictive of poor patient prognosis.Silencing of SDCBP2-AS1 promoted the proliferation and migration of GC cells both in vitro and in vivo.Mechanically,SDCBP2-AS1 physically bound to hnRNP K to repress SUMOylation of hnRNP K and facilitated ubiquitination of hnRNP K andβ-catenin,thereby promoting the degradation ofβ-catenin in the cytoplasm.Silencing of SDCBP2-AS1 caused SUMOylation of hnRNP K and stabilizedβ-catenin activity,which altered tran-scription of downstream genes,resulting in tumorigenesis and metastasis of GC.Moreover,the knockdown of hnRNP K partially abrogated the effects of SDCBP2-AS1.Conclusions:SDCBP2-AS1 interacts with hnRNP K to suppress tumorigenesis and metastasis of GC and regulates post-transcriptional modifications of hnRNP K to destabilizeβ-catenin.These findings suggest SDCBP2-AS1 as a potential target for the treatment of GC.

Blue light-emitting polyfluorenes containing dibenzothiophene-S,S-dioxide unit in alkyl side chain

Blue light-emitting polyfluorenes containing dibenzothiophene-S,S-dioxide(SO) unit in alkyl side chain(PF-FSOs and PF-CzSOs) were synthesized. All the polymers show high thermal stability with the decomposition temperatures over400 °C. The highest occupied molecular orbital(HOMO) and the lowest unoccupied molecular orbital(LUMO) energy levels of the copolymer slightly decrease with the increase of SO content in side chain. PL spectra of the polymers show slightly red shift and broadening with the increase of solvent polarities, indicating unremarkable intramolecular charge transfer(ICT) effect in the polymers containing SO unit in alkyl side chain. EL spectra of the polymers are almost unchanged in the current densities from 100 to 400 mA cm.2, indicating the superb EL stability of the resulted polymers. The EL spectra of the copolymers exhibit obvious blue-shift and narrowing with the CIE of(0.18, 0.11) for PF-FSO10 and(0.17, 0.11) for PF-CzSO10, respectively,compared with PF-SO10 containing SO unit in main chain with the CIE of(0.16, 0.17) and PFO with the CIE of(0.18, 0.18).The superior device performances were obtained with the luminous efficiency(LEmax) of 1.17 and 0.68 cd A.1 for PF-FSO15 and PF-CzSO20, respectively, compared with the LEmax of 0.37 cd A.1 for PFO. The results indicate that linking SO unit to alkyl side chain of the polyfluorene is a promising strategy for efficient blue light-emitting polymers.