Prevailing concerns on mountainous biodiversity are concentrated on the impacts of climate change at higher elevations. However, the lower elevations are facing additional human disturbance and are expected to suffer ...Prevailing concerns on mountainous biodiversity are concentrated on the impacts of climate change at higher elevations. However, the lower elevations are facing additional human disturbance and are expected to suffer from higher extinction risk but have attracted less conservation attention. Here, we employed population genomics to compare extinction risk two common songbirds—the Vinous-throated Parrotbill (Sinosuthora webbiana) and the Rufous-capped Babbler (Cyanoderma ruficeps)—at lower and higher elevations on the Taiwan island. As the result, we observed decreased genetic diversity and increased genetic load and thus elevated extinction risk in the low-elevation populations of both birds in the eastern slope of the Central Mountains on the Taiwan island. In contrast, genetic-load patterns of both birds in the western slope might be confused by substantial gene flow across lower and higher elevations. These results, on the one hand, call for conservation efforts to lower elevations in mountains and, on the other hand, highlight the importance of population connection in maintaining population viability under impending global change.展开更多
To the Editor:ADP-ribosylation factor 1 (ARF1) plays a critical role in regulating vesicle formation and transport1. The dysregulation of ARF1 expression and/or activity is involved in many human cancers, such as brea...To the Editor:ADP-ribosylation factor 1 (ARF1) plays a critical role in regulating vesicle formation and transport1. The dysregulation of ARF1 expression and/or activity is involved in many human cancers, such as breast cancer2,3. Therefore, ARF1 is one of the promising therapeutic targets for cancer treatment.展开更多
The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant challenges.The activation of STING is a multi-step process that includes binding with c G...The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant challenges.The activation of STING is a multi-step process that includes binding with c GAMP,self-oligomerization,and translocation from the endoplasmic reticulum to the Golgi apparatus,ultimately inducing the expression of IRF3 and NF-κB-mediated interferons and inflammatory cytokines.It has been demonstrated that disruption of any of these steps can effectively inhibit STING activation.Traditional structure-based drug screening methodologies generally focus on specific binding sites.In this study,a Transformer CPI model based on protein primary sequences and independent of binding sites is employed to identify compounds capable of binding to the STING protein.The natural product Licochalcone D(Lico D)is identified as a potent and selective STING inhibitor.Lico D does not bind to the classical ligandbinding pocket;instead,it covalently modifies the Cys148 residue of STING.This modification inhibits STING oligomerization,consequently suppressing the recruitment of TBK1 and the nuclear translocation of IRF3 and NF-κB.Lico D treatment ameliorates the inflammatory phenotype in Trex1-/-mice and inhibits the progression of DSS-induced colitis and AOM/DSS-induced colitis-associated colon cancer(CAC).In summary,this study reveals the potential of Lico D in treating STING-driven inflammatory diseases.It also demonstrates the utility of the Transformer CPI model in discovering allosteric compounds beyond the conventional binding pockets.展开更多
基金supported by the National Natural Science Foundation of China (32170440 and 31772437)the West Light Foundation of the Chinese Academy of Sciencesthe Yunnan Applied Basic Research Project (202401AS070078)
文摘Prevailing concerns on mountainous biodiversity are concentrated on the impacts of climate change at higher elevations. However, the lower elevations are facing additional human disturbance and are expected to suffer from higher extinction risk but have attracted less conservation attention. Here, we employed population genomics to compare extinction risk two common songbirds—the Vinous-throated Parrotbill (Sinosuthora webbiana) and the Rufous-capped Babbler (Cyanoderma ruficeps)—at lower and higher elevations on the Taiwan island. As the result, we observed decreased genetic diversity and increased genetic load and thus elevated extinction risk in the low-elevation populations of both birds in the eastern slope of the Central Mountains on the Taiwan island. In contrast, genetic-load patterns of both birds in the western slope might be confused by substantial gene flow across lower and higher elevations. These results, on the one hand, call for conservation efforts to lower elevations in mountains and, on the other hand, highlight the importance of population connection in maintaining population viability under impending global change.
基金supported by the National Natural Science Foundation of China (81903639 to Sulin Zhang,China)Lingang Laboratory (LG202102-01-02 to Mingyue Zheng,China,LG-QS-202204-01 to Sulin Zhang,China)+1 种基金Shanghai Municipal Science and Technology Major Project (Hualiang Jiang,China)Shanghai Sailing Program (19YF1457800 to Sulin Zhang,China)。
文摘To the Editor:ADP-ribosylation factor 1 (ARF1) plays a critical role in regulating vesicle formation and transport1. The dysregulation of ARF1 expression and/or activity is involved in many human cancers, such as breast cancer2,3. Therefore, ARF1 is one of the promising therapeutic targets for cancer treatment.
基金financial support from National Natural Science Foundation of China (T2225002,82273855,82304379,81903639)National Key Research and Development Program of China (2022YFC3400504)+5 种基金the Youth Innovation Promotion Association CAS (2023296)the SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program (E2G805H)the open fund of state key laboratory of Pharmaceutical Biotechnology,Nanjing University,China (KF-202301)the Natural Science Foundation of Shanghai (22ZR1474300)Lingang Laboratory (LG202102-01-02,LG-QS-202204-01)Young Elite Scientists Sponsorship Program by CAST (2023QNRC001)。
文摘The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant challenges.The activation of STING is a multi-step process that includes binding with c GAMP,self-oligomerization,and translocation from the endoplasmic reticulum to the Golgi apparatus,ultimately inducing the expression of IRF3 and NF-κB-mediated interferons and inflammatory cytokines.It has been demonstrated that disruption of any of these steps can effectively inhibit STING activation.Traditional structure-based drug screening methodologies generally focus on specific binding sites.In this study,a Transformer CPI model based on protein primary sequences and independent of binding sites is employed to identify compounds capable of binding to the STING protein.The natural product Licochalcone D(Lico D)is identified as a potent and selective STING inhibitor.Lico D does not bind to the classical ligandbinding pocket;instead,it covalently modifies the Cys148 residue of STING.This modification inhibits STING oligomerization,consequently suppressing the recruitment of TBK1 and the nuclear translocation of IRF3 and NF-κB.Lico D treatment ameliorates the inflammatory phenotype in Trex1-/-mice and inhibits the progression of DSS-induced colitis and AOM/DSS-induced colitis-associated colon cancer(CAC).In summary,this study reveals the potential of Lico D in treating STING-driven inflammatory diseases.It also demonstrates the utility of the Transformer CPI model in discovering allosteric compounds beyond the conventional binding pockets.
