2019年度国家自然科学基金临床肿瘤研究方向分析及思考

随着细胞生物学等学科的不断发展和深入,肿瘤学基础研究取得了一定进展,肿瘤学科申请项目数量及质量也逐渐提高。本文总结2019年度国家自然科学基金临床肿瘤学科面上项目、青年科学基金项目以及地区科学基金项目的申请与资助情况,并从不同角度深入分析面上项目的研究方向,针对临床肿瘤中非编码RNA、肿瘤免疫治疗、肿瘤微环境、肿瘤代谢等代表性研究方向,以及淋巴管新生、细胞焦亡及铁死亡、溶酶体及线粒体等研究前沿进行综述。

Capsid destabilization and epitope alterations of human papillomavirus 18 in the presence of thimerosal

Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic exponential decay model.The potential effect of thimerosal on protein function,particularly for thiolcontaining proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.

Perspectives in the investigation of Cockayne syndrome group B neurological disease:the utility of patient-derived brain organoid models

Cockayne syndrome(CS)group B(CSB),which results from mutations in the excision repair cross-complementation group 6(ERCC6)genes,which produce CSB protein,is an autosomal recessive disease characterized by multiple progressive disorders including growth failure,microcephaly,skin photosensitivity,and premature aging.Clinical data show that brain atrophy,demyelination,and calcification are the main neurological manifestations of CS,which progress with time.Neuronal loss and calcification occur in various brain areas,particularly the cerebellum and basal ganglia,resulting in dyskinesia,ataxia,and limb tremors in CSB patients.However,the understanding of neurodevelopmental defects in CS has been constrained by the lack of significant neurodevelopmental and functional abnormalities observed in CSB-deficient mice.In this review,we focus on elucidating the protein structure and distribution of CSB and delve into the impact of CSB mutations on the development and function of the nervous system.In addition,we provide an overview of research models that have been instrumental in exploring CS disorders,with a forward-looking perspective on the substantial contributions that brain organoids are poised to further advance this field.

The Impact of Medical Resources and Oral Antiviral Drugs on SARS-CoV-2 Mortality—Hong Kong SAR,China,2022

Introduction:The Omicron variant of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)demonstrates increased transmissibility compared to earlier strains,contributing to a significant number of fatalities in Hong Kong Special Administrative Region(HKSAR),China.Adequate medical resources and medications are essential in mitigating these deaths.This study evaluates the effects of supplementary resources from the Chinese mainland during the fifth wave of the pandemic in HKSAR.Methods:Vector autoregression(VAR)was employed to analyze data from the Oxford coronavirus disease 2019(COVID-19)Government Response Tracker to assess the effectiveness of control measures during five waves of the pandemic in HKSAR.Additionally,a transmission dynamics model was created to investigate the influence of supplementary medical resources from the Chinese mainland and oral medications on mortality.Results:In the initial four waves,workplace closures,restrictions on public events,international travel bans,and shielding the elderly significantly influenced pandemic management.Contrarily,during the fifth wave,these measures showed no notable effects.When comparing a situation without extra medical resources or COVID-19 oral medication,there was a 17.7%decrease in COVID-19 fatalities with mainland medical resources and an additional 10.2%reduction with oral medications.Together,they contributed to a 26.6%decline in fatalities.Discussion:With the rapid spread of the virus,regional reallocation of medical resources may reduce mortality even when the local healthcare system is overstretched.

Adaptive Fourier Decomposition of the First Three SARS-CoV-2 Infection Waves with Epidemic Intervention—London,UK,2020-2022

Background:This study provides a detailed analysis of the daily fluctuations in coronavirus disease 2019(COVID-19)case numbers in London from January 31,2020 to February 24,2022.The primary objective was to enhance understanding of the interactions among government pandemic responses,viral mutations,and the subsequent changes in COVID-19 case incidences.Methods:We employed the adaptive Fourier decomposition(AFD)method to analyze diurnal changes and further segmented the AFD into novel multi-component groups consisting of one to three elements.These restructured components were rigorously evaluated using Pearson correlation,and their effectiveness was compared with other signal analysis techniques.This study introduced a novel approach to differentiate individual components across various time-frequency scales using basis decomposition methods.Results:Analysis of London’s daily COVID-19 data using AFD revealed a strong correlation between the“stay at home”directive and high-frequency components during the first epidemic wave.This indicates the need for sustained implementation of vaccination policies to maintain their effectiveness.Discussion:The AFD component method provides a comprehensive analysis of the immediate and prolonged impact of governmental policies on the spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).This robust tool has proven invaluable for analyzing COVID-19 pandemic data,offering critical insights that guide the formulation of future preventive and public health strategies.

Observation of low thermal expansion behavior and weak thermal anisotropy in M_(3)A_(2)C phases

M_(3)A_(2)X phases,named 321 phases,are an atypical series of MAX phases featuring in the MA-triangular-prism bilayers,with the A=As/P,exhibiting excellent elastic properties.This work systematically studies the thermal expansion properties of 321 phases.We found their average linear thermal expansion coefficients(TECs),α_(L)=5-6μK^(–1),are the lowest among the reported values of MAX phases.The lowest average TEC was found in Nb_(3)As_(2)C(αa=4.46(4)μK^(–1),αc=5.09(4)μK–1,αL=5.09(4)μK–1).The average TEC and anisotropy factor(αc/αa)of Nb_(3)As_(2)C and Nb_(3)P_(2)C were lower than the ones of the corresponding 211 phases.The best isotropy performance was found in Nb_(3)P_(2)C (αc/αa=1.11).Moreover,our first-principles calculations demonstrate that the weaker chemical bonding between Nb-As/P than Nb-C induces thermal expansion in M_(3)A_(2)X phases.Furthermore,a relatively weaker anharmonic effect in 321 phases than in the 211 phases was revealed by the as-calculated average Grüneisen parameters,which account for the lower TECs in 321 phases.The low TECs and enhanced thermal isotropy make 321 phases outstanding among MAX phases,which could be sound candidates for varying-temperature structural-functional components.