Multi-genome evolutionary study of the ABC1 gene family and identification of the pleiotropic effects of OsABC1-13 in rice development

In four rice genomes,85 ABC1-family genes were identified by comparative genomics,evolution,genetics,and physiology.One,OsABC1-13,was shown by knockdown and knockout experiments to affect plant height,grain size,and photosynthetic capability.

Endurance-test and theoretical prediction of a rare earth nanocathode for the applied field magnetoplasmadynamic thruster

The erosion loss of cathode is essential for the lifetime of magnetoplasmadynamic thruster(MPDT).In this work,an endurance test system for MPDT cathodes was designed and developed,and the erosion characteristics,erosion rate and erosion mechanism of the cathode were studied using the system under vacuum condition.The WCe20 hollow cathode was selected to carry out the long-term erosion of 540 h with the argon propellant supply flow rate of40 ml min^(-1),the input current of 25 A,and the central magnetic field intensity of 96 Gs.In order to predict the theoretical service life of cathode,a steady state erosion numerical model was established.The calculation results show that the total erosion rate of sputtering and evaporation is 11.58 mg h^(-1),which is slightly smaller than the test data of the average cathode corrosion rate of 12.70 mg h^(-1) in the experiment,because the experimental value includes start-up erosion rate.

中性粒细胞胞外诱捕网与肿瘤转移的研究进展

近年来,研究发现中性粒细胞在多种适当刺激下向细胞外释放一种纤维网络状结构,即中性粒细胞胞外诱捕网(neutrophil extracellular traps, NETs)。在机体中具备捕捉和杀死病原体而参与免疫应答的重要生理作用。目前,越来越多研究证据认为NETs除了可以参与炎症、血栓形成等方面,而且与肿瘤的转移密切相关。肿瘤转移过程由多个步骤构成,机制复杂,是造成癌症患者临床上治疗失败和死亡的主要原因之一。因此,NETs参与肿瘤转移相关机制的研究对肿瘤治疗具有重要意义。本文将对NETs与肿瘤转移及相关机制的研究进展做一综述。

恶性肿瘤患者免疫检查点抑制剂导致肝损伤的临床处理2例

免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)作为一种新的抗肿瘤药物,目前在临床的使用日益广泛。然而,ICIs过度激活的免疫系统会攻击人体正常器官,引起相关的免疫不良反应,这种免疫损伤可以累及身体的各个部位,引起相应的症状,被称之为ICIs相关不良反应(immunocheckpoint inhibitors related adverse effects,irAEs)。肝损伤作为irAEs其中一种,临床治疗是以糖皮质激素为主,但是对于≥3级以上肝损伤的治疗以及出现激素耐药后的解救治疗仍会让临床医生感到棘手。本研究分析2例经免疫治疗后出现肝损伤的案例,包括激素敏感型1例,激素耐药型1例,后经免疫球蛋白解救治疗成功。

Ferritin as a diagnostic, differential diagnostic, and prognostic marker for immune-related adverse events

Objective:Distinguishing immune-related adverse events(irAEs)caused by immune checkpoint inhibitors(ICIs)from the AEs caused by chemotherapy,targeted therapy,or infection is highly difficult.This study offers new insights into evaluating the diagnosis,differential diagnostic,and prognostic value of ferritin for irAEs induced by ICIs.Methods:From December 1,2018,to April 1,2019,we examined 318 patients with malignant tumors who received serum ferritin monitoring.The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy,and 87 patients treated with chemotherapy.Of the 231 patients,90 had irAEs(irAE group),70 had non-irAEs(non-irAE group),67 had no AEs(no irAE-non irAE group),and 4 had unclassified AEs.In the 87 patients,60 had AEs(AE group),and 27 had no AEs(no AE group).Statistical analyses were conducted with nonparametric Mann-Whitney tests.Results:At the onset of AEs in the irAE group,ferritin(normal range,35–150μg/L)rose to a median of 927μg/L(range,117–17,825μg/L)from 86μg/L at baseline(range,29–421μg/L)(P<0.001).Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group(median,81μg/L;range,32–478μg/L)(P<0.001)and the AE group(median,103μg/L;range,23–712μg/L)(P<0.001).After treatment in the irAE group,ferritin continuously decreased to a normal range in recovered patients,showed no significant changes in stable patients,and continued to rise in patients who died.Conclusions:Ferritin can be used as a diagnostic,differential diagnostic,and prognostic marker for irAEs in patients treated with ICIs.

ILF2 cooperates with E2F1 to maintain mitochondrial homeostasis and promote small cell lung cancer progression

Objective:Mitochondria play multifunctional roles in carcinogenesis.Deciphering uncertainties of molecular interactions within mitochondria will promote further understanding of cancer.Interleukin enhancer binding factor 2(ILF2)is upregulated in several malignancies,however,much remains unknown regarding ILF2 in small cell lung cancer(SCLC).In the current study,we explored ILF2's role in SCLC and demonstrated its importance in mitochondria quality control.Methods:Colony formation,cell proliferation,cell viability and xenograft studies were performed to examine ILF2's role on SCLC progression.Glucose uptake,lactate production,cellular oxygen consumption rate and extracellular acidification rate were measured to examine the effect of ILF2 on glucose metabolism.RNA-sequencing was utilized to explore genes regulated by ILF2.E2 F1 transcriptional activity was determined by dual luciferase reporter assay.Mitochondria quantification and mitochondrial membrane potential assays were performed to examine mitochondrial quality.Gene expression was determined by RT-qPCR,Western blot and IHC assay.Results:ILF2 promotes SCLC tumor growth in vitro and in vivo.ILF2 elevates oxidative phosphorylation expression and declines glucose intake and lactate production.Genome-wide analysis of ILF2 targets identified a cohort of genes regulated by E2 F1.In consistent with this,we found ILF2 interacts with E2 F1 in SCLC cells.Further studies demonstrated that suppression of E2 F1 expression could reverse ILF2-induced tumor growth and enhanced mitochondria function.Significantly,expression of ILF2 is progressively increased during SCLC progression and high ILF2 expression is correlated with higher histologic grades,which indicates ILF2's oncogenic role in SCLC.Conclusions:Our results demonstrate that ILF2 interacts with E2 F1 to maintain mitochondria quality and confers SCLC cells growth advantage in tumorigenesis.

Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma

Objective:The main reasons for the poor prognoses of pancreatic adenocarcinoma(PA)patients are rapid early-stage progression,advanced stage metastasis,and chemotherapy resistance.Identification of novel diagnostic and prognostic biomarkers of PA is therefore urgently needed.Methods:Three mRNA microarray datasets were obtained from the Gene Expression Omnibus database to select differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for hub genes were performed using DAVID.Correlations between expression levels of hub genes and cancer-infiltrating immune cells were investigated by TIMER.Cox proportional hazard regression analyses were also performed.Serum hub genes were screened using the HPA platform and verified for diagnostic value using ELISAs.Results:We identified 59 hub genes among 752 DEGs.GO analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling pathway.We also discovered that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment.Additionally,DLGAP5 mRNA might be used as an independent risk factor for the prognoses of PA patients.Furthermore,the protein encoded by ISG15,which exists in peripheral blood,was validated as a potential diagnostic biomarker that distinguished PA patients from healthy controls(area under the curve:0.902,95%confidence interval:0.819–0.961).Conclusions:Our study suggested that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment,while DLGAP5 mRNA expression might be an independent risk factor for the survival prognoses of PA patients.Moreover,ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA.

The prognostic landscape of genes and infiltrating immune cells in cytokine induced killer cell treated-lung squamous cell carcinoma and adenocarcinoma

Objective:Patients with non–small cell lung cancer(NSCLC)respond differently to cytokine-induced killer cell(CIK)treatment.Therefore,potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated.The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC.Methods:Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital.We performed whole-exome sequencing(WES)on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC,and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment.Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance.WES and RNA-seq data between lung squamous cell carcinoma(SCC)and adenocarcinoma(Aden)were analyzed and compared.Results:The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS,as analyzed by multivariate Cox proportional hazard regression(P=0.031).The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment.Relatively low expression of HLA class II genes and checkpoint molecules,and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC.Conclusions:Coordinated suppression of the expression of HLA class II genes and checkpoint molecules,as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden.

Cultivated Land Monitoring System Based on Dynamic Wake-Up UAV and Wireless of Distributed Storage

The drawbacks of the traditional multi-hop structure of wireless sensor networks(WSNS)are susceptible to reflection,scattering and diffraction,serious attenuation of signal intensity and phase deviation due to various obstacles in cultivated land environment and mountains.In this paper,the wireless signal intensity is measured and curve fitting is done respectively in both open environment and obstacle-environment with both sending and receiving height of 0 m,1 m,and 2 m.It is found out that packet loss probability is too high when an obstacle exists.In such a case,unmanned aerial vehicle(UAV)is introduced to activate terrestrial nodes and operation mechanism of distributed storage.Experimental results show that both ground-to-air barrier-free communication and communication with obstacles can greatly reduce the energy consumption of each node and packet loss probability,thus greatly improving the reliability of UAV-WSN system.

Comparative Variance and Multiple Imputation Used for Missing Values in Land Price DataSet

Based on the two-dimensional relation table,this paper studies the missing values in the sample data of land price of Shunde District of Foshan City.GeoDa software was used to eliminate the insignificant factors by stepwise regression analysis;NORM software was adopted to construct the multiple imputation models;EM algorithm and the augmentation algorithm were applied to fit multiple linear regression equations to construct five different filling datasets.Statistical analysis is performed on the imputation data set in order to calculate the mean and variance of each data set,and the weight is determined according to the differences.Finally,comprehensive integration is implemented to achieve the imputation expression of missing values.The results showed that in the three missing cases where the PRICE variable was missing and the deletion rate was 5%,the PRICE variable was missing and the deletion rate was 10%,and the PRICE variable and the CBD variable were both missing.The new method compared to the traditional multiple filling methods of true value closer ratio is 75%to 25%,62.5%to 37.5%,100%to 0%.Therefore,the new method is obviously better than the traditional multiple imputation methods,and the missing value data estimated by the new method bears certain reference value.

聚丙烯腈基碳纤维灰分测试灰化时间探索

文章研究了12种国内外碳纤维在900℃下灼烧灰化时间,探索灰化恒重首次称量时间及达到恒重的时间。结果表明:900℃下需要用马弗炉灼烧4h以后可以对碳纤维首次称重,5h达到恒重。

A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers

The composition of serum is extremely complex,which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich lowabundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56%using PC-based proteomic analysis,which was twice the number of proteins identified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

经自然腔道取标本手术(NOSES)在结直肠癌日间手术中的应用探索

经自然腔道取标本手术(NOSES)和加速康复外科(ERAS)的核心理念都是为了能够减少手术创伤和应激,让患者达到快速康复的目的。日间结直肠手术是两者结合的进一步发展,在规范开展高质量手术的前提下,结合ERAS理念的实施,内容包含术前准备,麻醉与镇痛,外科与营养干预及术后康复的全程团队管理。近期,中国医科大学附属第一医院在二者的优化结合方面做了一些探索,通过微创手术、麻醉疼痛管理、全程护理,再加上严格的术前准备、完整的术后随访,使得手术患者的身心应激和创伤最小化。本文以一名直肠癌NOSES手术患者为例,探讨日间手术模式开展结直肠癌根治术的可行性与影响因素。

Propane dehydro-aromatization reaction over PtFe@S-1 coupling with Zn/ZSM-5 tandem catalysts: the role of Zn species

Unraveling the structure-activity relationship and improving the catalytic performance is paramount in propane dehydro-aromatization reactions. Herein, a tandem catalyst with high propane dehydro-aromatization reaction performance was prepared via coupling the PtFe@S-1 with Zn/ZSM-5 zeolites (PtFe@S-1&1.0Zn/ZSM-5), which exhibits high dehydrogenation activity, aromatics selectivity (~60% at ~78% propane conversion), and stability. The addition of zinc inhibits the cleavage of C_(6)^(=) intermediates on ZSM-5 and promotes the aromatization pathway by weakening zeolite acid strength, significantly improving the selectivity to aromatics. This understanding of the structure-activity relationship in propane dehydro-aromatization reaction helps develop future high-performance catalysts.

Autoantibodies targeting to GPER1 promote monocyte cytokines production and inflammation in systemic lupus erythematosus

Dear Editor,Systemic lupus erythematosus(SLE),one of the most common autoimmune diseases in reproductive females,is a multifactorial disease involving genetic,environmental,and hormonal factors.1 It occurs at a 9:1 female-to-male ratio,and the sex predisposition suggests that the estrogen system plays an essential role in the developing of SLE.The effects of estrogen have traditionally been attributed to the classical nuclear estrogen receptors(ERs),ERα,and ERβ,which predominantly regulate transcription.Guanine nucleotide-binding protein-coupled estrogen receptor 1(GPER1)is a transmembrane receptor for estrogen that mediates several rapid cellular effects of estrogen.2 Large amounts of autoantibodies characterize SLE,and anti-estrogen receptor autoantibodies are likely to affect the function of immune cells in SLE but are not yet fully understood.

Auxin signaling module OsSK41-OsIAA10-OsARF regulates grain yield traits in rice

Auxin is an important phytohormone in plants, and auxin signaling pathways in rice play key roles in regulating its growth, development, and productivity. To investigate how rice grain yield traits are regulated by auxin signaling pathways and to facilitate their application in rice improvement, we validated the functional relationships among regulatory genes such as OsIAA10, OsSK41, and OsARF21 that are involved in one of the auxin(OsIAA10) signaling pathways. We assessed the phenotypic effects of these genes on several grain yield traits across two environments using knockout and/or overexpression transgenic lines.Based on the results, we constructed a model that showed how grain yield traits were regulated by OsIAA10 and OsTIR1, OsAFB2, and OsSK41 and OsmiR393 in the OsSK41-OsIAA10-OsARF module and by OsARF21 in the transcriptional regulation of downstream auxin response genes in the OsSK41-OsIAA10-OsARF module. The population genomic analyses revealed rich genetic diversity and the presence of major functional alleles at most of these loci in rice populations. The strong differentiation of many major alleles between Xian/indica and Geng/japonica subspecies and/or among modern varieties and landraces suggested that they contributed to improved productivity during evolution and breeding. We identified several important aspects associated with the genetic and molecular bases of rice grain and yield traits that were regulated by auxin signaling pathways.We also suggested rice auxin response factor(OsARF) activators as candidate target genes for improving specific target traits by overexpression and/or editing subspecies-specific alleles and by searching and pyramiding the ‘best' gene allelic combinations at multiple regulatory genes in auxin signaling pathways in rice breeding programs.

BmTBP upregulates the transcription of BmSuc1 in silkworm (Bombyx mori) by binding to BmTfΙΙA-S

The BmSuc1 gene,which encodes a novel animal-typeβ-fructofuranosidase(EC 3.2.1.26),was first cloned and identified in silkworm(Bombyx mori).As an essential sucrase,the activity of BmSUC1 is unaffected by alkaloidal sugar mimics in mulberry leaves.This enzyme may also directly regulate the degree of sucrose hydrolysis in the silkworm midgut.In addition,BmSUC1 is involved in the synthesis of sericin 1 in the silk gland tissue.However,the mechanism underlying the regulation of BmSuc1 transcription remains unclear.In this study,we analyzed the BmSuc1 promoter activity using a dual-luciferase reporter assay and identified 4 regions that are critical for transcriptional activation.The gene encoding a predicted transcription factor(TATA-box-binding protein;BmTBP)capable of binding to the core promoter regions was cloned.A quantitative real-time polymerase chain reaction analysis indicated the gene was highly expressed in the midgut.Downregulating BmTBP expression via RNA interference decreased the expression of BmSuc1 at the transcript and protein levels.An electrophoretic mobility shift analysis and chromatin immunoprecipitation indicated that BmTBP can bind to the TATA-box cis-regulatory element in the BmSuc1 promoter.Furthermore,a bioinformatics-based analysis and a far-western blot revealed the interaction between BmTBP and another transcription factor(BmTfIIA-S).The luciferase reporter gene assay results confirmed that the BmTBP–BmTfIIA-S complex increases the BmSuc1 promoter activity.Considered together,these findings suggest that BmTBP regulates BmSuc1 expression through its interaction with BmTfIIA-S.

PDCD5 regulates iNKT cell terminal maturation and iNKT1 fate decision

Invariant natural killer T1(iNKT1)cells are characterized by the preferential expression of T-box transcription factor T-bet(encoded by Tbx21)and the production of cytokine IFN-γ,but the relationship between the developmental process and iNKT1 lineage diversification in the thymus remains elusive.We report in the present study a crucial role of programmed cell death 5(PDCD5)in iNKT cell terminal maturation and iNKT1 fate determination.Mice with T cell-specific deletion of PDCD5 had decreased numbers of thymic and peripheral iNKT cells with a predominantly immature phenotype and defects in response toα-galactosylceramide.Loss of PDCD5 also selectively abolished the iNKT1 lineage by reducing T-bet expression in iNKT cells at an early thymic developmental stage(before CD44 upregulation).We further demonstrated that TOX2,one of the high mobility group proteins that was highly expressed in iNKT cells at stage 1 and could be stabilized by PDCD5,promoted the permissive histone H3K4me3 modification in the promoter region of Tbx21.These data indicate a pivotal and unique role of PDCD5/TOX2 in iNKT1 lineage determination.They also suggest that the fate of iNKT1 may be programmed at the developmental stage of iNKT cells in the thymus.

TOWARDS AVOIDING THE HIDDEN TRAPS IN QFD DURING REQUIREMENTS ESTABLISHMENT

The Quality Function Deployment （QFD） is a useful and representative methodology to transform customer needs into different level of requirements in a system hierarchy. Simplifications that are based on assumptions are ubiquitous in the QFD, but these underlying assumptions possibly do not hold true, which renders the simplifications unjustified. Additionally, these assumptions are usually not verified within the context of the application domain. This paper identifies and illustrates eight hidden traps in QFD during the process of establishing the requirements, where the assumptions, and therefore, the simplifications made are not reasonable. These traps are implicit in the understanding of customer needs, establishment of system requirements and the flow down of these requirements to lower levels of the system hierarchy. Suggestions are given to help avoiding these hidden traps, thereby eliminating or alleviating their potentially detrimental effects. The intent of the paper is to make readers aware of these traps when applying QFD for the establishment of requirements, so that they may utilize QFD with a better understanding of its limitations and develop higher quality specifications.

Randomized,multicenter,open-label trial of autologous cytokine-induced killer cell immunotherapy plus chemotherapy for squamous non-small-cell lung cancer:NCT01631357

Dear Editor,Cytokine-induced killer(CIK)cells have been recognized as a new type of anti-tumor effector cells.CIK cells are a mixture of T lymphocytes.Among them,CD3+/CD56+T cells,which are rare in uncultured peripheral blood,are the main effector cells.CIK cells can proliferate rapidly in vitro,with stronger antitumor activity,broader target tumor spectrum,and lower adverse effect than other reported antitumor effector cells.1 Their ease of production in vitro and antitumor potential have made them suitable candidates for cell therapy regimens in solid and hematopoietic tumor treatments.1,2 Our previous retrospective study showed that the median progression-free survival(PFS)and overall survival(OS)in untreated,advanced non-small-cell lung cancer(NSCLC)patients who received CIK cell immunotherapy plus chemotherapy(13 and 24 months,respectively)were significantly longer than in those who received chemotherapy alone(6 and 10 months,respectively).2 But so far,there is no prospective,multicenter clinical study in lung cancer.Based on our previous study,we designed this randomized,multicenter,open-label trial to further evaluate the clinical efficacy of CIK cell immunotherapy plus chemotherapy in patients with advanced squamous NSCLC(ClinicalTrials.gov number,NCT01631357).