Predicting PM_(2.5) Concentration in the Yangtze River Delta Region Using Climate System Monitoring Indices and Machine Learning

Changing meteorological conditions during autumn and winter have considerable impact on air quality in the Yangtze River Delta(YRD)region.External climatic factors,such as sea surface temperature and sea ice,together with the atmospheric circulation,directly affect meteorological conditions in the YRD region,thereby modulating the variation in atmospheric PM_(2.5) concentration.This study used the evolutionary modeling machine learning technique to investigate the lag relationship between 144 climate system monitoring indices and autumn/winter PM_(2.5) concentration over 0-12 months in the YRD region.After calculating the contribution ratios and lagged correlation coefficients of all indices over the previous 12 months,the top 36 indices were selected for model training.Then,the nine indices that contributed most to the PM_(2.5) concentration in the YRD region,including the decadal oscillation index of the Atlantic Ocean and the consistent warm ocean temperature index of the entire tropical Indian Ocean,were selected for physical mechanism analysis.An evolutionary model was developed to forecast the average PM_(2.5) concentration in major cities of the YRD in autumn and winter,with a correlation coefficient of 0.91.In model testing,the correlation coefficient between the predicted and observed PM_(2.5) concentrations was in the range of 0.73-0.83 and the root-mean-square error was in the range of 9.5-11.6μg m-3,indicating high predictive accuracy.The model performed exceptionally well in capturing abnormal changes in PM_(2.5) concentration in the YRD region up to 50 days in advance.

USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency

The homeobox transcription factor Nanog has a vital role in maintaining pluripotency and self-renewal of embryonic stem cells(ESCs).Stabilization of Nanog proteins is essential for ESCs.The ubiquitin–proteasome pathway mediated by E3 ubiquitin ligases and deubiquitylases is one of the key ways to regulate protein levels and functions.Although ubiquitylation of Nanog catalyzed by the ligase FBXW8 has been demonstrated,the deubiquitylase that maintains the protein levels of Nanog in ESCs yet to be defined.In this study,we identify the ubiquitin-specific peptidase 21(USP21)as a deubiquitylase for Nanog,but not for Oct4 or Sox2.USP21 interacts with Nanog protein in ESCs in vivo and in vitro.The C-terminal USP domain of USP21 and the C-domain of Nanog are responsible for this interaction.USP21 deubiquitylates the K48-type linkage of the ubiquitin chain of Nanog,stabilizing Nanog.USP21-mediated Nanog stabilization is enhanced in mouse ESCs and this stabilization is required to maintain the pluripotential state of the ESCs.Depletion of USP21 in mouse ESCs leads to Nanog degradation and ESC differentiation.Overall,our results demonstrate that USP21 maintains the stemness of mouse ESCs through deubiquitylating and stabilizing Nanog.

Up-regulation of miR-1245 by c-myc targets BRCA2 and impairs DNA repair

BRCA2,a clinical prognostic factor,is significantly up-regulated in mRNA level,while its protein expression is often decreased in sporadic breast cancer.However,how BRCA2 protein expressions are suppressed in these tumors remains unknown.In this study,we demonstrated that miR-1245 directly suppressed BRCA23′-UTR and translation,impaired homologous recombination(HR)-mediated repair,reduced DNA damage-induced Rad51 nuclear foci,and rendered cells hypersensitive to g-irradiation(IR),ul-timately inducing high chromosomal abnormalities in normal breast cells and breast cancer cells.Conversely,inhibiting miR-1245 in breast cancer cells enhanced BRCA2 levels and induced resistance to IR.Furthermore,we demonstrated that c-myc up-regulated miR-1245 expression via direct binding to the miR-1245 promoter,which led to down-regulation of BRCA2 and reduction in HR efficiency.Significantly,miR-1245 levels in primary breast tumors correlated with c-myc overexpression and BRCA2 suppression.These findings uncover a BRCA2 regulatory and signaling pathway in sporadic breast cancer and support a functionally and clinically relevant epigenetic mechanism in cancer pathogenesis.