Multi-model ensemble prediction is an effective approach for improving the prediction skill short-term climate prediction and evaluating related uncertainties. Based on a combination of localized operation outputs of ...Multi-model ensemble prediction is an effective approach for improving the prediction skill short-term climate prediction and evaluating related uncertainties. Based on a combination of localized operation outputs of Chinese climate models and imported forecast data of some international operational models, the National Climate Center of the China Meteorological Administration has established the China multi-model ensemble prediction system version 1.0 (CMMEv1.0) for monthly-seasonal prediction of primary climate variability modes and climate elements. We verified the real-time forecasts of CMMEv1.0 for the 2018 flood season (June-August) starting from March 2018 and evaluated the 1991-2016 hindcasts of CMMEv1.0. The results show that CMMEv1.0 has a significantly high prediction skill for global sea surface temperature (SST) anomalies, especially for the El Nino-Southern Oscillation (ENSO) in the tropical central-eastern Pacific. Additionally, its prediction skill for the North Atlantic SST triple (NAST) mode is high, but is relatively low for the Indian Ocean Dipole (IOD) mode. Moreover, CMMEv1.0 has high skills in predicting the western Pacific subtropical high (WPSH) and East Asian summer monsoon (EASM) in the June-July-August (JJA) season. The JJA air temperature in the CMMEv1.0 is predicted with a fairly high skill in most regions of China, while the JJA precipitation exhibits some skills only in northwestern and eastern China. For real-time forecasts in March-August 2018, CMMEv1.0 has accurately predicted the ENSO phase transition from cold to neutral in the tropical central-eastern Pacific and captures evolutions of the NAST and IOD indices in general. The system has also captured the main features of the summer WPSH and EASM indices in 2018, except that the predicted EASM is slightly weaker than the observed. Furthermore, CMMEv1.0 has also successfully predicted warmer air temperatures in northern China and captured the primary rainbelt over northern China, except that it predicted much more precipitation in the middle and lower reaches of the Yangtze River than observation.展开更多
Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling t...Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction.Here,we discovered the critical role of RING finger 138(RNF138)in CRC tumorigenesis through regulating the NF-кB signaling,which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response.RNF138^(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy,which coincided with sustained aberrant NF-кB signaling in the colonic cells.Furthermore,RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein(NIBP)to the cytoplasm,which requires the ubiquitin interaction motif(UIM)domain.More importantly,we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings,raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling.Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients,we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth.Overall,our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression,and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.展开更多
基金Supported by the National Key Research and Development Program of China(2017YFC1502306,2017YFC1502302,and 2018YFC-1506004)China Meteorological Administration Special Project for Developing Key Techniques for Operational Meteorological Forecast(YBGJXM201805)
文摘Multi-model ensemble prediction is an effective approach for improving the prediction skill short-term climate prediction and evaluating related uncertainties. Based on a combination of localized operation outputs of Chinese climate models and imported forecast data of some international operational models, the National Climate Center of the China Meteorological Administration has established the China multi-model ensemble prediction system version 1.0 (CMMEv1.0) for monthly-seasonal prediction of primary climate variability modes and climate elements. We verified the real-time forecasts of CMMEv1.0 for the 2018 flood season (June-August) starting from March 2018 and evaluated the 1991-2016 hindcasts of CMMEv1.0. The results show that CMMEv1.0 has a significantly high prediction skill for global sea surface temperature (SST) anomalies, especially for the El Nino-Southern Oscillation (ENSO) in the tropical central-eastern Pacific. Additionally, its prediction skill for the North Atlantic SST triple (NAST) mode is high, but is relatively low for the Indian Ocean Dipole (IOD) mode. Moreover, CMMEv1.0 has high skills in predicting the western Pacific subtropical high (WPSH) and East Asian summer monsoon (EASM) in the June-July-August (JJA) season. The JJA air temperature in the CMMEv1.0 is predicted with a fairly high skill in most regions of China, while the JJA precipitation exhibits some skills only in northwestern and eastern China. For real-time forecasts in March-August 2018, CMMEv1.0 has accurately predicted the ENSO phase transition from cold to neutral in the tropical central-eastern Pacific and captures evolutions of the NAST and IOD indices in general. The system has also captured the main features of the summer WPSH and EASM indices in 2018, except that the predicted EASM is slightly weaker than the observed. Furthermore, CMMEv1.0 has also successfully predicted warmer air temperatures in northern China and captured the primary rainbelt over northern China, except that it predicted much more precipitation in the middle and lower reaches of the Yangtze River than observation.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1-066,2017-I2M-4-002 to H.Z.,2021-I2M-1-019 to W.S.,2021-1-I2M-014 to C.Z.L.)the National Natural Science Foundation of China(81972311,82141127 and 81672461 to H.Z.,81672472,and 31970794 to W.S.,81570780 to C.Z.L.,32000586 to K.L.)+4 种基金the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310026 to H.Z.)Sanming Project of Medicine in Shenzhen(SZSM202011010 to H.Z.)the National Key Research and Development Program of China(2018YFC1003500 to W.S.)the State Key Laboratory Special fund from the Ministry of Science(2060204 to W.S.)the State Key Project on Infection Diseases of China(2017ZX10201021-007-003 to H.Z.).
文摘Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction.Here,we discovered the critical role of RING finger 138(RNF138)in CRC tumorigenesis through regulating the NF-кB signaling,which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response.RNF138^(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy,which coincided with sustained aberrant NF-кB signaling in the colonic cells.Furthermore,RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein(NIBP)to the cytoplasm,which requires the ubiquitin interaction motif(UIM)domain.More importantly,we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings,raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling.Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients,we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth.Overall,our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression,and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.