Circulating tumor cells: Biological features and survival mechanisms

Circulating tumor cells(CTCs)are neoplastic cells that are detached from primary tumors and enter circulation.Enumeration and characterization of CTCs are of significance in cancer diagnosis,prognosis,and treatment monitoring.CTC survival in the bloodstream is a limiting step for the development of metastases in distant organs.Recent technological advances,especially in single-cell molecular analyses have uncovered heterogeneous CTC survival mechanisms.Undergoing epithelial-to-mesenchymal transition(EMT),increasing stem cell-like properties,and forming cell clusters enable CTCs to adapt to the harsh microenvironment of the circulation.Expressing and releasing several immunosuppressive molecules help CTCs escape from anti-cancer immune mechanisms.This review article summarizes the biological characteristics of CTCs and focuses on the recent understanding of the mechanisms by which CTCs survive in circulation.Additionally,the clinical and therapeutic implications of CTCs are discussed.

基于双核咪唑盐阴离子交换膜的制备与表征

采用两步法合成了双核溴化1-乙烯基-3-(6-(1-丁基咪唑))己基咪唑盐[VBIm HIm][Br]2,并通过1H-NMR对[VBIm HIm][Br]2的化学结构进行了表征;然后将[VBIm HIm][Br]2与苯乙烯、丙烯腈混合均匀后,通过紫外光引发聚合,得到碱性阴离子交换膜。通过傅里叶变换红外光谱对阴离子交换膜的结构进行了表征,并系统对膜的吸水率、溶胀度、热稳定性、力学性能及电导率等进行了研究。研究结果表明,该类阴离子交换膜降解温度达到300℃,[VBIm HIm][Br]2含量为10%的阴离子交换膜25℃时的吸水率为96%,溶胀度只有44%,拉伸强度为38. 32 MPa,最大断裂伸长率可达26. 37%;在80℃时,其离子的电导率可达22 m S/cm,该类阴离子交换膜有望应用于碱性阴离子交换膜燃料电池领域。

Does CMIP6 Inspire More Confidence in Simulating Climate Extremes over China?

Based on climate extreme indices calculated from a high-resolution daily observational dataset in China during 1961–2005,the performance of 12 climate models from phase 6 of the Coupled Model Intercomparison Project(CMIP6),and 30 models from phase 5 of CMIP(CMIP5),are assessed in terms of spatial distribution and interannual variability.The CMIP6 multi-model ensemble mean(CMIP6-MME)can simulate well the spatial pattern of annual mean temperature,maximum daily maximum temperature,and minimum daily minimum temperature.However,CMIP6-MME has difficulties in reproducing cold nights and warm days,and has large cold biases over the Tibetan Plateau.Its performance in simulating extreme precipitation indices is generally lower than in simulating temperature indices.Compared to CMIP5,CMIP6 models show improvements in the simulation of climate indices over China.This is particularly true for precipitation indices for both the climatological pattern and the interannual variation,except for the consecutive dry days.The arealmean bias for total precipitation has been reduced from 127%(CMIP5-MME)to 79%(CMIP6-MME).The most striking feature is that the dry biases in southern China,very persistent and general in CMIP5-MME,are largely reduced in CMIP6-MME.Stronger ascent together with more abundant moisture can explain this reduction in dry biases.Wet biases for total precipitation,heavy precipitation,and precipitation intensity in the eastern Tibetan Plateau are still present in CMIP6-MME,but smaller,compared to CMIP5-MME.

Rational Construction of Hierarchically Porous Fe–Co/N-Doped Carbon/rGO Composites for Broadband Microwave Absorption

Developing lightweight and broadband microwave absorbers for dealing with serious electromagnetic radiation pollution is a great challenge.Here,a novel Fe-Co/N-doped carbon/reduced graphene oxide(Fe-Co/NC/rGO)composite with hierarchically porous structure was designed and synthetized by in situ growth of Fe-doped Cobased metal organic frameworks(Co-MOF)on the sheets of porous cocoon-like rGO followed by calcination.The Fe-Co/NC composites are homogeneously distributed on the sheets of porous rGO.The Fe-Co/NC/rGO composite with multiple components(Fe/Co/NC/rGO)causes magnetic loss,dielectric loss,resistance loss,interfacial polarization,and good impedance matching.The hierarchically porous structure of the Fe-Co/NC/rGO enhances the multiple reflections and scattering of microwaves.Compared with the Co/NC and Fe-Co/NC,the hierarchically porous Fe-Co/NC/rGO composite exhibits much better microwave absorption performances due to the rational composition and porous structural design.Its minimum reflection loss(RLmin)reaches?43.26 dB at 11.28 GHz with a thickness of 2.5 mm,and the effective absorption frequency(RL≤?10 dB)is up to 9.12 GHz(8.88-18 GHz)with the same thickness of 2.5 mm.Moreover,the widest effective bandwidth of 9.29 GHz occurs at a thickness of 2.63 mm.This work provides a lightweight and broadband microwave absorbing material while offering a new idea to design excellent microwave absorbers with multicomponent and hierarchically porous structures.

Renal tubule-targeted dexrazoxane suppresses ferroptosis in acute kidney injury by inhibiting ACMSD

Acute kidney injury(AKI)is a heterogeneous clinical complication with no existing definite or particular therapies.Therefore,molecular mechanisms and approaches for treating acute kidney injury are in urgent need.Herein,we demonstrated that dexrazoxane(DXZ),a U.S.Food and Drug Administration(FDA)-approved cardioprotective drug,can both functionally and histologically attenuate cisplatin or ischemia-reperfusion injury-induced AKI in vitro and in vivo via inhibiting ferroptosis specifically.This effect is characterized by decreasing lipid peroxidation,shown by the biomarker of oxidative stress 4-hydroxynonenal(HNE)and prostaglandinendoperoxide synthase 2(Ptgs2),while reversing the downregulation of glutathione peroxidase 4(GPX4)and ferritin 1(FTH-1).Mechanistically,the results revealed that DXZ targeted at the renal tubule significantly inhibits ferroptosis by suppressingα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase(ACMSD).Furthermore,the conjugation of dexrazoxane and polysialic acid(DXZ-PSA)is specifically designed and utilized to enhance the therapeutic effect of DXZ by long-term effect in the kidney,especially retention and targeting in the renal tubules.This study provides a novel therapeutic approach and mechanistic insight for AKI by inhibiting ferroptosis through a new type drug DXZPSA with the enhanced renal distribution.

Intercomparison of multi-model ensemble-processing strategies within a consistent framework for climate projection in China

Climate change adaptation and relevant policy-making need reliable projections of future climate.Methods based on multi-model ensemble are generally considered as the most efficient way to achieve the goal.However,their efficiency varies and inter-comparison is a challenging task,as they use a variety of target variables,geographic regions,time periods,or model pools.Here,we construct and use a consistent framework to evaluate the performance of five ensemble-processing methods,i.e.,multimodel ensemble mean(MME),rank-based weighting(RANK),reliability ensemble averaging(REA),climate model weighting by independence and performance(ClimWIP),and Bayesian model averaging(BMA).We investigate the annual mean temperature(Tav)and total precipitation(Prcptot)changes(relative to 1995–2014)over China and its seven subregions at 1.5 and 2℃warming levels(relative to pre-industrial).All ensemble-processing methods perform better than MME,and achieve generally consistent results in terms of median values.But they show different results in terms of inter-model spread,served as a measure of uncertainty,and signal-to-noise ratio(SNR).ClimWIP is the most optimal method with its good performance in simulating current climate and in providing credible future projections.The uncertainty,measured by the range of 10th–90th percentiles,is reduced by about 30%for Tav,and 15%for Prcptot in China,with a certain variation among subregions.Based on ClimWIP,and averaged over whole China under 1.5/2℃global warming levels,Tav increases by about 1.1/1.8℃(relative to 1995–2014),while Prcptot increases by about 5.4%/11.2%,respectively.Reliability of projections is found dependent on investigated regions and indices.The projection for Tav is credible across all regions,as its SNR is generally larger than 2,while the SNR is lower than 1 for Prcptot over most regions under 1.5℃warming.The largest warming is found in northeastern China,with increase of 1.3(0.6–1.7)/2.0(1.4–2.6)℃(ensemble’s median and range of the 10th–90th percentiles)under 1.5/2℃warming,followed by northern and northwestern China.The smallest but the most robust warming is in southwestern China,with values exceeding 0.9(0.6–1.1)/1.5(1.1–1.7)℃.The most robust projection and largest increase is achieved in northwestern China for Prcptot,with increase of 9.1%(–1.6–24.7%)/17.9%(0.5–36.4%)under 1.5/2℃warming.Followed by northern China,where the increase is 6.0%(–2.6–17.8%)/11.8%(2.4–25.1%),respectively.The precipitation projection is of large uncertainty in southwestern China,even with uncertain sign of variation.For the additional half-degree warming,Tav increases more than 0.5℃throughout China.Almost all regions witness an increase of Prcptot,with the largest increase in northwestern China.

从CMIP5到CMIP6的中国极端气候预估的新认识

根据最新的参与第六次耦合模式相互比较计划(CMIP6)的模式模拟结果,预估了在全球变暖1.5、2和3℃下中国极端气候的变化,并与其对应的CMIP5的模式模拟结果进行了比较.研究表明,相较于CMIP5模式,CMIP6模式对历史参考期(1985~2005年)中国区域的温度和降水指数的模拟更接近于观测,尤其是极端降水.CMIP6预估未来气候的变化幅度大于CMIP5,在全球增温1.5、2和3℃下,中国区域平均温度分别增加了1.49、2.21和3.53℃,而CMIP5中增温则为1.20、1.93和3.39℃;CMIP6预估总降水量增加5.3%、8.6%和16.3%,CMIP5中则分别为4.4%、7.0%和12.8%.在极端指数方面,虽然CMIP5和CMIP6中极端指数未来变化的空间结构相似,但在一些区域的变化幅度上存在明显差异,如在CMIP6中,中国东北和西北地区的日最高温度、南方地区的日最低温度增加幅度显著高于该区域CMIP5的结果,长江流域以南以及40°N附近的总降水量和强降水增加也较CMIP5更加明显.进一步分析表明,这些差异可能主要源自CMIP6模式物理过程等的改进,而与排放情景不同的关系不大.

Development of the National Air Quality Health Index-China,2013−2018

What is already known about this topic?While the establishment of an air quality health index(AQHI)in some countries yielded positive outcomes in communicating health risks of air pollution,China lagged behind in developing its own AQHI.Several research studies of AQHI were conducted in China,but this scientific research has not yet been applied to standards.What is added by this report?This report introduced the method of calculation of Chinese AQHI to be launched in pilot cities.The index in this report was established on the basis of fully drawing on international experience and considering Chinese characteristics.What are the implications for public health practice?The purpose of this report is to guide unified application of the AQHI throughout China and translate scientific evidence into public services to promote public health.Based on the AQHI construction method in this report,an AQHI real-time computing platform and data transfer interface will be developed.The release of AQHI aims to communicate health risk of air pollution and provide scientific health protective guidance to the general public,accordingly to protect people’s health.

Short-term Exposure to Fine Particles and Risk of Cause-Specific Mortality--China,2013-2018

What is already known about this topic?Short-term exposure to PM2.5 has been associated with population excess death.This issue is of critical concern in China given its high level of exposure to PM2.5 compared to that of the rest of the world.What is added by this report?Existing studies were conducted from 2013-2015 and have failed to capture the full effects of China’s actions towards cleaner air in recent years,such as the first Action Plan for Air Pollution Prevention and Control issued in 2013.This study uses the longest time series data to date from 2013-2018,provides the latest evidence on PM2.5 and cause-specific death nationwide,and identifies regional patterns of PM2.5-related effects as well as PM2.5-related susceptible populations.What are the implications for public health practice?This study suggests that the development of standards and the implementation of actions to clean the air and protect public health should be tailored to PM2.5-related sensitive diseases,susceptible populations,and regional patterns.

In situ synthesis of graphene oxide/gold nanorods theranostic hybrids for efficient tumor computed tomography imaging and photothermal therapy

Graphene oxide/gold nanorod （GO/GNR） nanohybrids were synthesized with a GO- and gold-seed-mediated in situ growth method at room temperature by mixing polystyrene sulfonate （PSS） functionalized GO, secondary growth solution, and gold seeds. Compared with ex situ preparation methods of GO/GNRs or graphene （G）/GNRs, the in situ synthesis of GO/GNRs addressed the issue of the aggregation of the GNRs before their attachment onto the GO. The method is straightforward and environment-friendly; The GO/GNRs showed a remarkable photothermal effect in vitro. The temperature of the GO/GNR nanohybrids increased from 25 to 49.9 ℃ at a concentration of 50 μg/mL after irradiation with an 808-nm laser （0.4 W/cm2） for 6 min. Additionally; the GO/GNRs exhibited good optical and morphological stability and photothermal properties after six cycles of laser irradiation. Upon injection of the GO/GNRs into xenograft tumors, excellent computed tomography （CT） imaging properties and photothermal effect were obtained. The preclinical CT agent iohexol was combined with the GO/GNRs and further enhanced CT imaging. Therefore, the GO/GNR nanohybrids have great potential for predse CT-image-guided tumor photothermal treatment.

Transcriptome-wide association studies: a view from Mendelian randomization

Background:Genome-wide association studies(GWASs)have identified thousands of genetic variants that are associated with many complex traits.However,their biological mechanisms remain largely unknown.Transcriptome-wide association studies(TWAS)have been recently proposed as an invaluable tool for investigating the potential gene regulatory mechanisms underlying variant-trait associations.Specifically,TWAS integrate GWAS with expression mapping studies based on a common set of variants and aim to identify genes whose GReX is associated with the phenotype.Various methods have been developed for performing TWAS and/or similar integrative analysis.Each such method has a different modeling assumption and many were initially developed to answer different biological questions.Consequently,it is not straightforward to understand their modeling property from a theoretical perspective.Results:We present a technical review on thirteen TWAS methods.Importantly,we show that these methods can all be viewed as two-sample Mendelian randomization(MR)analysis,which has been widely applied in GWASs for examining the causal effects of exposure on outcome.Viewing different TWAS methods from an MR perspective provides us a unique angle for understanding their benefits and pitfalls.We systematically introduce the MR analysis framework,explain how features of the GWAS and expression data influence the adaptation of MR for TWAS,and re-interpret the modeling assumptions made in different TWAS methods from an MR angle.We finally describe future directions for TWAS methodology development.Conclusions:We hope that this review would serve as a useful reference for both methodologists who develop TWAS methods and practitioners who perform TWAS analysis.