Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

Novel spontaneous myelodysplastic syndrome mouse model

Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to leukemia.Although recently progress has been made in identifying underlying genetic mutations,many questions still remain.Animal models of MDS have been produced by introduction of specific mutations.However,there is no spontaneous mouse model of MDS,and an animal model to simulate natu-ral MDS pathogenesis is urgently needed.Methods:In characterizing the genetically diverse mouse strains of the Collaborative Cross(CC)we observed that one,designated JUN,had abnormal hematological traits.This strain was thus further analyzed for phenotypic and pathological iden-tification,comparing the changes in each cell population in peripheral blood and in bone marrow.Results:In a specific-pathogen free environment,mice of the JUN strain are rela-tively thin,with healthy appearance.However,in a conventional environment,they become lethargic,develop wrinkled yellow hair,have loose and light stools,and are prone to infections.We found that the mice were cytopenic,which was due to abnor-mal differentiation of multipotent bone marrow progenitor cells.These are common characteristics of MDS.Conclusions:A mouse strain,JUN,was found displaying spontaneous myelodysplas-tic syndrome.This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models.JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

Modifying regeneration strategies classification to enhance the understanding of dominant species growth in fire-prone forest in Southwest China

Background:In fire-prone ecosystems,plant species having different post-fire regeneration strategies(PFRS)coexist at the local scale while showing different growth dynamics.To evaluate the effect of PFRS on species regeneration,we investigated the plant communities burned in different years in the central Yunnan Province,Southwest China.Several indicators describing plant growth and population importance were measured to compare the regeneration of four dominant tree species,including one facultative seeders(FS)and three obligate resprouters(OR).Partial correlation and mixed linear effect modeling were applied to disentangle the contribution of intrinsic and environmental factors to the interspecific variation in post-fire regeneration.Results:We identified two subtypes of plant growth strategy in the early post-fire stage for OR species;i.e.,number growth(ORþN)priority and height growth(ORþH)priority for sprouting stems.Generally,the FS and OR species varied in height growth rate with different temporal dynamics.The ORþN species occupied post-fire space horizontally with more resprouts and larger coverage than ORþH and FS species at the earlier stage.In contrast,the ORþH species generally had far less resprouts per clump,more variations in stem height and basal diameter.Factor analysis showed that the variation of post-fire plant regeneration was not effectively explained by environmental factors(R2<20%);however,the linear mixed models with the modified PFRS as a random effect substantially increased the explanation.Conclusions:The differentiated regeneration dynamics and growth priorities in the four dominant tree species indicated a critical dichotomy of habitat occupation strategy for the resprouter species during the early stage of post-fire forest restoration.Our study uncovered a trade-off between height versus number growth priority in the post-fire tree growth strategy and provides a novel perspective in understanding the living space occupying(niche partitioning)process and species coexistence in post-fire forest community assembly.

Particulate Amines in the Background Atmosphere of the Yangtze River Delta,China:Concentration,Size Distribution,and Sources

Amines are important for new particle formation and subsequent growth in the atmosphere.Consequently,the processes involved are receiving more attention in recent years.Here,we conduct a field observation in order to investigate the atmospheric particulate amines at a background site in the Yangtze River Delta(YRD)during the summer of 2018.Four amines in PM_(2.5),i.e.,methylamine(MA),dimethylamine(DMA),diethylamine(DEA),and trimethylamine(TMA),were collected,twice daily and analyzed.During the campaign,our measurements found the concentrations of MA,DMA,DEA,and TMA of 15.0±15.0,6.3±6.9,20.4±30.1,and 4.0±5.9 ng m^-(3),respectively,and the four amines correlated well with each other.The concentration of amines appear to be independent of whether they were collected during the day or night.Both MA and DMA exhibited a bimodal size distribution that had peaks at 0.67 and 1.1μm,suggesting amines preferably distribute on submicron particles.Boundary layer height(BLH),relative humidity,and pH of aerosols were found have a negative relationship with amines,while aerosol liquid water content(ALWC)was found to have a positive relationship with amines.The PMF(positive matrix factorization)source apportionment results showed that the main source of amines in Chongming Island was of anthropogenic origin such as industrial and biomass emission,followed by marine sources including sea salt and marine biogenic sources.Given that the YRD region is still suffering from complex atmospheric pollution and that the knowledge on aerosol amines is still limited,more field studies are in urgent need for a better understanding of the pollution characteristics of amines.

滇中半湿润常绿阔叶林木本植物的功能特征和功能多样性及其影响因子

半湿润常绿阔叶林是中国常绿阔叶林西部中亚热带类型的代表,为了解其群落的功能多样性,本研究对云南滇中地区金光寺、鸡足山、雕翎山、筇竹寺和珠江源5个半湿润常绿阔叶林分布点进行群落调查和木本植物性状测定,分析不同样地和群落类型的植物功能特征和群落功能多样性,探究滇中半湿润常绿阔叶林木本植物之间的差异及其环境影响因素。结果表明:(1)不同样地和不同群落类型下功能性状的群落加权平均值大致相当;灌木层的比叶面积平均值高于乔木层;乔木层、灌木层的木材平均密度无显著差异(约0.5 g/cm~3);(2)基于最大株高、比叶面积和木材密度计算的半湿润常绿阔叶林乔木层功能多样性在不同样地间差异显著(P<0.05),其中鸡足山和雕翎山的乔木层功能丰富度、均匀度和冗余度较高,群落更稳定。不同群落类型所占的功能空间大小不同,但群落内物种功能分异度、均匀度和冗余度相似。此外,灌木层的物种丰富度高于乔木层,功能丰富度却相对较低;(3)功能丰富度和功能冗余度都与物种丰富度显著正相关(P<0.05),与其他多样性指数关系不显著。环境因子中气候和土壤因素共同解释群落乔木层、灌木层功能性状和功能多样性的60%以上变异性,人类活动也会对植物群落功能多样性造成一定影响。本研究揭示了半湿润常绿阔叶林不同群落类型和层次的植物功能性状差异及其区域变化,为该植被类型的生物多样性和生态系统功能保护与恢复提供科学依据。

Chemical characteristics of haze particles in Xi＇an during Chinese Spring Festival： Impact of fireworks burning

Fireworks burning releases massive fine particles and gaseous pollutants, significantly deteriorating air quality during Chinese Lunar New Year （LNY） period. To investigate the impact of the fireworks burning on the atmospheric aerosol chemistry, 1-hr time resolution of PM2.5 samples in Xi＇an during the winter of 2016 including the LNY were collected and detected for inorganic ions, acidity and liquid water content （LWC） of the fine aerosols. PM2.5 during the LNY was 167 ± 87 μg/m^3, two times higher than the China National Ambient Air Quality Standard （75 μg/m^3）. K^＋ （28 wt.% of the total ion mass） was the most abundant ion in the LNY period, followed by SO^2-4 （25 wt.%） and C1^- （18 wt.%）. In contrast, NO^-3 （34 wt.%） was the most abundant species in the haze periods （hourly PM2.5 〉 75 μg/m^3）, followed by SO^2-4 （29.2 wt.%） and NH^＋4 （16.3 wt.%）, while SC94 （35 wt.%） was the most abundant species in the clean periods （hourly PM2.5 〈 75 μg/m^3）, followed by NO^-3 （23.1 wt.%） and NH^＋4 （11 wt.%）. Being different from the acidic nature in the non-LNY periods, aerosol in the LNY period presented an alkaline nature with a pH value of 7.8 ± 1.3. LWC during the LNY period showed a robust linear correlation with K2SO4 and KC1, suggesting that aerosol hygroscopicity was dominated by inorganic salts derived from fireworks burning. Analysis of correlations between the ratios of NO^-3/SO^2-4 and NH^＋4/SO^2-4 indicated that heterogeneous reaction of HNO3 with NH3 was an important formation pathway of particulate nitrate and ammonium during the LNY period.

The antidepressive effect of the complex consisting of Radix Pseudostellariae,Radix Pueraria and Herba Epimedii:the involvement of NRSF/NRSE-TPH2 signaling

Depression is a psychological disease with no particularly effective therapy currently available.In the present study,we aimed to examine the antidepressive activity of a pharmaceutical Chinese medicine called TaiZi(TZ)capsule,consisting of total polysaccharides of Radix Pseudostellariae and total flavonoids of both Radix Pueraria and Herba Epimedii.A tail suspension test and forced swimming test were performed to assess the effect of TZ in vivo.A plasmid of TPH2(tryptophan hydroxylase-2)was constructed to determine the exact target of TZ in vitro.In addition,mRNA expression was detected using a real-time PCR assay,and the protein expression was investigated using a Western blotting analysis.The results showed that TZ had an anti-depression effect in mouse and rat models with increased serotonin in the brain,and in the upregulation of mRNA and protein expression of TPH2 in the brain simultaneously by inhibition of NRSF(neuron restrictive silencer factor)expression because NRSF could bind to NRSE(neuron restrictive silencer element)to repress TPH2 transcription during the depression conditions.Icariin could bind to NRSE directly and block NRSF protein toward to NRSE for TPH2 inhibition.Therefore,we concluded that TZ had potential antidepressive effects because it could ameliorat the depression-like behavior in the animals,and the underlying mechanism of the effect was involved in NRSF/NRSE-TPH2 signaling.Icariin was identified as the active component of TZ.This study provided a new perspective for the development of antidepression drugs(Chinese medicines)based on NRSF/NRSE-TPH2 signaling.