High plasma fibrinogen concentration and platelet count unfavorably impact survival in non–small cell lung cancer patients with brain metastases

High expression of fibrinogen and platelets are often observed in non–small cell lung cancer(NSCLC) patients with local regional or distant metastasis. However, the role of these factors remains unclear. The aims of this study were to evaluate the prognostic significance of plasma fibrinogen concentration and platelet count, as well as to determine the overall survival of NSCLC patients with brain metastases. A total of 275 NSCLC patients with brain metastasis were enrolled into this study. Univariate analysis showed that high plasma fibrinogen concentration was associated with age ≥ 65 years(P = 0.011), smoking status(P = 0.009), intracranial symptoms(P = 0.022), clinical T category(P = 0.010), clinical N category(P = 0.003), increased partial thromboplastin time(P < 0.001), and platelet count(P < 0.001). Patients with low plasma fibrinogen concentration demonstrated longer overall survival compared with those with high plasma fibrinogen concentration(median, 17.3 months versus 11.1 months; P ≤ 0.001). A similar result was observed for platelet counts(median, 16.3 months versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma fibrinogen concentration and platelet count were independent prognostic factors for NSCLC with brain metastases(R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001, respectively). Our results suggest that high plasma fibrinogen concentration and platelet count indicate poor prognosis for NSCLC patients with brain metastases. Thus, these two biomarkers might be independent prognostic predictors for this subgroup of NSCLC patients.

Efect of body mass index on survival of patients with stage I non-small cell lung cancer

Background:Body mass index(BMI)has a U?shaped association with lung cancer risk.However,the effect of BMI on prognosis is controversial.This retrospective study aimed to investigate the effect of BMI on the survival of patients with stage I non?small cell lung cancer(NSCLC)after surgical resection.Methods:In total,624 consecutive stage I NSCLC patients who underwent radical resection were classified into four groups according to their BMI:underweight(BMI<18.5 kg/m^2),normal weight(BMI obese(BMI>28.0 kg/m^2).The effect of BMI on progress=18.5–22.4 kg/m2),overweight(BMI=22.5–28.0 kg/m^2),andion?free survival(PFS)and over?all survival(OS)was estimated using the Kaplan–Meier method and Cox proportional hazards model.Postoperative complications in each group were analyzed using the Chi square test or Fisher’s exact test.Results:A univariate analysis showed that PFS and OS were longer in the overweight group than in other groups(both P<0.05).A multivariate analysis showed that OS was longer in the overweight group than in other groups(compared with the other three groups in combination:hazard ratio[HR]e underweight group:HR=1.87,95%confidence interval[CI]1.30–2.68,P=0.003;compared with th3,P=2.24,95%CI 1.18–4.25,P=0.013;compared with the normal weight group:HR 1.48–5.59,P=1.58,95%CI 1.07–2.3=0.022;compared with the obese group:HR=2.87,95%CIwe=0.002),but PFS was similar among the groups(HRd an association between being overweight and pro=1.28,95%CI 0.97–1.68,P longed OS in patients at sta=0.080).A subgroup analysis shoge T1a(P 0.001).Overweight=0.024),T1b(P=0.051),and T2a(P=0.02),as well as in patients with a non?smoking history(P=patients had lower rates of postoperative complications,such as respiratory failure(compared with the underweight and obese groups:P=0.014),myocardial infarction(compared with the obese group:P=0.033),and perioperative death(com?pared with the other three groups:P=0.016).Conclusions:Preoperative BMI is an independent prognostic factor for stage I NSCLC patients after resection,with overweight patients having a favorable prognosis.

Improving the UV-light stability of silicon heterojunction solar cells through plasmon-enhanced luminescence downshifting of YVO_(4):Eu^(3+),Bi^(3+)nanophosphors decorated with Ag nanoparticles

The ultraviolet(UV)light stability of silicon heterojunction(SHJ)solar cells should be addressed before large-scale production and applications.Introducing downshifting(DS)nanophosphors on top of solar cells that can convert UV light to visible light may reduce UV-induced degradation(UVID)without sacrificing the power conversion efficiency(PCE).Herein,a novel composite DS nanomaterial composed of YVO_(4):Eu^(3+),Bi^(3+)nanoparticles(NPs)and AgNPs was synthesized and introduced onto the incident light side of industrial SHJ solar cells to achieve UV shielding.The YVO_(4):Eu^(3+),Bi^(3+)NPs and Ag NPs were synthesized via a sol-gel method and a wet chemical reduction method,respectively.Then,a composite structure of the YVO_(4):Eu^(3+),Bi^(3+)NPs decorated with Ag NPs was synthesized by an ultrasonic method.The emission intensities of the YVO_(4):Eu^(3+),Bi^(3+)nanophosphors were significantly enhanced upon decoration with an appropriate amount of~20 nm Ag NPs due to the localized surface plasmon resonance(LSPR)effect.Upon the introduction of LSPR-enhanced downshifting,the SHJ solar cells exhibited an~0.54%relative decrease in PCE degradation under UV irradiation with a cumulative dose of 45 k W h compared to their counterparts,suggesting excellent potential for application in UV-light stability enhancement of solar cells or modules.

ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties

S1-M1-80 cells,derived from human colon carcinoma S1 cells,are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR).In this study,S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo.Our results showed that the proliferation,cell cycle,and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts(named xS1-M1-80 cells).Consistently,xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan,but remained sensitive to the non-ABCG2 substrate cisplatin.Furthermore,the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan.These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks.Thus,this model could serve as a good system for further investigation of ABCG2-mediated MDR.

体质指数对Ⅰ期非小细胞肺癌患者预后的影响

背景与目的体质指数(body mass index, BMI)与肺癌的发生存在U?型相关性,但其对肺癌预后的影响仍存有争议。本研究回顾分析BMI对I期非小细胞肺癌(non?small cell lung cancer, NSCLC)患者手术预后的影响。方法将624例行根治性切除术的I期NSCLC患者按BMI分为四组:低体质量(BMI <18.5 kg/m2)、正常(BMI=18.5–22.4 kg/m2)、超重(BMI=22.5–28.0 kg/m2)和肥胖(BMI> 28 kg/m2)。采用Kaplan?Meier法和Cox比例风险模型分析BM I对无进展生存期(progression?freesur v ival,PFS)和总生存期(overall sur vival,OS)的影响。采用χ2检验或精确概率Fisher检验分析BMI与术后并发症的相关性。结果单因素分析结果显示,超重组的PFS和OS均比其他组长(P <0.05)。多因素分析结果显示,超重组的OS比其他组长(与其他三组联合相比:HR=1.87, 95%CI:1.30–2.68, P=0.003;与低体质量组相比:HR=2.24, 95%CI:1.18–4.25, P=0.013;与正常组相比:HR=1.58, 95%CI:1.07–2.33, P=0.022;与肥胖组相比:HR=2.87, 95%CI:1.48–5.59,P=0.002),但各组间的PFS相似(HR=1.28, 95%CI:0.97–1.68, P=0.080)。亚组分析表明,超重与T1a(P=0.024)、T1b (P=0.051)、T2a(P=0.02)期和非吸烟(P=0.001)患者的OS延长相关。超重患者术后并发症:呼吸衰竭(与低体质量和肥胖组相比:P=0.014)、心肌梗死(与肥胖组相比:P=0.033)、围手术期死亡(与其他三组相比:P=0.016)的发生率较低。结论术前BMI是I期非小细胞肺癌患者手术预后的独立影响因素,超重患者预后较好。

Arabidopsis transcription factor TCP4 represses chlorophyll biosynthesis to prevent petal greening

Green petals pose a challenge for pollinators to distinguish flowers from leaves,but they are valuable as a specialty flower trait.However,little is understood about the molecular mechanisms that underlie the development of green petals.Here,we report that CINCINNATA(CIN)-like TEOSINTE BRANCHED 1/CYCLOIDEA/PCF(TCP)proteins play key roles in the control of petal color.The septuple tcp2/3/4/5/10/13/17 mutant produced flowers with green petals due to chlorophyll accumulation.Expression of TCP4 complemented the petal phenotype of tcp2/3/4/5/10/13/17.We found that chloroplasts were converted into leucoplasts in the distal parts of wild-type petals but not in the proximal parts during flower development,whereas plastid conversion was compromised in the distal parts of tcp2/3/4/5/10/13/17 petals.TCP4 and most CIN-like TCPs were predominantly expressed in distal petal regions,consistent with the green–white pattern in wild-type petals and the petal greening observed in the distal parts of tcp2/3/4/5/10/13/17 petals.RNA-sequencing data revealed that most chlorophyll biosynthesis genes were downregulated in the white distal parts of wild-type petals,but these genes had elevated expression in the distal green parts of tcp2/3/4/5/10/13/17 petals and the green proximal parts of wild-type petals.We revealed that TCP4 repressed chlorophyll biosynthesis by directly binding to the promoters of PROTOCHLOROPHYLLIDE REDUCTASE(PORB),DIVINYL REDUCTASE(DVR),and SUPPRESSOR OF OVEREXPRESSION OF CO 1(SOC1),which are known to promote petal greening.We found that the conversion of chloroplasts to leucoplasts and the green coloration in the proximal parts of petals appeared to be conserved among plant species.Our findings uncover a major molecular mechanism that underpins the formation of petal color patterns and provide a foundation for the breeding of plants with green flowers.

Crystal structures of N-terminal WRKY transcription factors and DNA complexes

Dear Editor,Plant-specific WRKY transcription factors(TFs)are among the largest families of TFs in higher plants;they are also found in the unicellular eukaryote Giardia lamblia and the slime mold Dictyostelium discoideum(Ulker and Somssich,2004),but not in animals.WRKY TFs participate in diverse developmental and physiological processes in plants,such as disease resistance,abiotic stress responses,senescence,seed and trichome development,as well as additional developmental and hormone-controlled processes(Agarwal et al.,2011).

Transcriptome analyses of insect cells to facilitate baculovirus-insect expression

The High Five cell line （BTI-TN-5B1-4） isolated from the cabbage looper, Trichoplusia ni is an insect cell line widely used for baculovirus-mediated recombinant protein expression. Despite its widespread application in industry and academic laboratories, the genomic background of this cell line remains unclear. Here we sequenced the transcriptome of High Five cells and assembled 25,234 transcripts. Codon usage analysis showed that High Five cells have a robust codon usage capacity and therefore suit for expressing proteins of both eukaryotic- and prokaryotic-origin. Genes involved in glycosylation were profiled in our study, providing guidance for engineering glycosylated proteins in the insect cells. We also predicted signal peptides for transcripts with high expression abundance in both High Five and Sf21 cell lines, and these results have important implications for optimizing the expression level of some secretory and membrane proteins.

On the origin of SARS-CoV-2——The blind watchmaker argument

In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.

Monte Carlo simulation of fast neutron-induced fission of 237Np

The potential-driving model is used to describe the driving potential distribution and to calculate the preneutron emission mass distributions for different incident energies in the 237 Np(n, f)reaction. The potential-driving model is implemented in Geant4 and used to calculate the fission-fragment yield distributions, kinetic energy distributions, fission neutron spectrum and the total nubar for the 237 Np(n, f)reaction. Compared with the built-in G4 ParaFissionModel, the calculated results from the potential-driving model are in better agreement with the experimental data and evaluated data. Given the good agreement with the experimental data, the potential-driving model in Geant4 can describe well the neutron-induced fission of actinide nuclei, which is very important for the study of neutron transmutation physics and the design of a transmutation system.

Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein

Background:A novel coronavirus(the SARS-CoV-2)has been identified in January 2020 as the causal pathogen for COVID-19,a pandemic started near the end of 2019.The Angiotensin converting enzyme 2 protein(ACE2)utilized by the SARS-CoV as a receptor was found to facilitate the infection of SARS-CoV-2,initiated by the binding of the spike protein to human ACE2.Methods:Using homology modeling and molecular dynamics(MD)simulation methods,we report here the detailed structure and dynamics of the ACE2 in complex with the receptor binding domain(RBD)of the SARS-CoV-2 spike protein.Results:The predicted model is highly consistent with the experimentally determined structures,validating the homology modeling results.Besides the binding interface reported in the crystal structures,novel binding poses are revealed from all-atom MD simulations.The simulation data are used to identify critical residues at the complex interface and provide more details about the interactions between the SARS-CoV-2 RBD and human ACE2.Conclusion:Simulations reveal that RBD binds to both open and closed state of ACE2.Two human ACE2 mutants and rat ACE2 are modeled to study the mutation effects on RBD binding to ACE2.The simulations show that the N-terminal helix and the K353 are very important for the tight binding of the complex,the mutants are found to alter the binding modes of the CoV2-RBD to ACE2.

Evaluation of pre-neutron-emission mass distributions of neutron-induced typical actinide fission using scission point model

The scission point model is improved by considering the excitation-dependent liquid drop model to calculate mass distributions for neutron-induced actinide nuclei fission.Excitation energy effects influence the deformations of light and heavy fragments.The improved scission point model shows a significant advance with regard to accuracy for calculating pre-neutron-emission mass distributions of neutron-induced typical actinide fission with incident-neutron-energies up to 99.5 MeV.The theoretical frame assures that the improved scission point model is suitable for evaluating the fission fragment mass distributions,which will provide guidance for studying fission physics and designing nuclear fission engineering and nuclear transmutation systems.