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| 1 | Development of the novel ACLY inhibitor 326E as a promising treatment for hypercholesterolemia显示文摘Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia,which results in atherosclerosis and cardiovascular disease(CVD).ATP-citrate lyase(ACLY)is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle(TCA cycle)to acetyl-CoA in the cytoplasm.Therefore,ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis.In this study,we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor,and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC_(50)=5.31±1.2μmol/L in vitro.326E treatment reduced de novo lipogenesis,and increased cholesterol efflux in vitro and in vivo.326E was rapidly absorbed after oral administration,exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid(BA)used for hypercholesterolemia.Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia.Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE^(-/-)mice to a greater extent than that of BA treatment.Taken together,our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia. | Zhifu Xie Mei Zhang Qian Song Long Cheng Xinwen Zhang Gaolei Song Xinyu Sun Min Gu Chendong Zhou Yangming Zhang Kexin Zhu Jianpeng Yin Xiaoyan Chen Jingya Li Fajun Nan | 2023 | Acta Pharmaceutica Sinica B2023，13，2： | 1 |
| 2 | The Breeding and Cultivation Techniques of Zhangzagu No.22显示文摘Zhangzagu No.22 was a new high-quality millet cultivar adapted to the climate characteristics of the summer sowing areas,which was selected by the Zhangjiakou Academy of Agricultural Sciences with sterile line A2 as the female parent and‘32×ISE375×Xia1 father’as the male parent.Zhangzagu No.22 has a growth period of 88 d in summer,and exhibits green seedlings,spindle-shaped panicles,a plant height of 135-145 cm,a panicle length of 23-28 cm,a grain weight per panicle of 18-22 g,a 1000-grain weight of 2.90 g,yellow rice,and resistance to herbicide Nabujing.In 2018,it passed the registration of non-major crop varieties by the Ministry of Agriculture,with the registration number:GPD Millet(2018)130193.This study introduced the breeding process,variety characteristics and related cultivation techniques of Zhangzagu No.22. | Qian WANG Wenjie BAI Lina ZHANG Xiaolei FENG Jianyong YANG Gaolei SHI Shuai MENG Guoliang SONG Zhihai ZHAO Guangyu FAN | 2021 | Agricultural Biotechnology2021，10，2： | 0 |
| 3 | Clay Mineralogy and its Paleoclimatic Significance of the OligoceneMiocene Sediments in the Gerze Basin, Tibet显示文摘This study collected the early Oligocene to middle Miocene sediments from the Gerze Basin of Tibet, and used X-Ray diffraction(XRD) and Scanning Electron Microscope(SEM) to discuss their clay mineralolgy, clay indices, better understand the clay mineralogy and its paleoclimatic significance. The results show that clay minerals of the Gerze Basin sediments are mainly composed of illite and chlorite, with minor amounts of smectite and kaolinite, and their relative content varies along the section. Variations of relative contents and clay indices suggest that the Gerze Basin has experienced three-stage evolution of paleoclimate: Ⅰ) high illite and chlorite contents, with fluctuant smectite and low(I+Ch)/(K+S) ratio, indicative of a dominant seasonal arid climate from the early Oligocene to late Oligocene; Ⅱ) higher illite and chlorite contents and larger(I+Ch)/(K+S) ratio but absence of kaolinite, indicating a colder and drier climate from the late Oligocene to early Miocene; Ⅲ) high illite and chlorite contents with fluctuant(I+Ch)/(K+S) ratios and occasional occurrence of kaolinite, suggesting that the climate became warmer and more humid compared with that of stage Ⅱin the mid-Miocene. These conclusions were also reinforced by the clay morphology, which suggests that physical weathering dominated in stage Ⅱ, while relatively strong chemical weathering was dominant in stages Ⅰ and Ⅲ. Clay minerals of the sediments mainly consist of illite and chlorite, indicating that the source rock played a significant role in clay origin. It is inferred that global cooling and the enhancement of denudation and obstruction of northward moisture due to the uplift of the Qinghai-Tibet Plateau were responsible for the provenance of illite and chlorite under weak chemical weathering. Though the Qinghai-Tibet Plateau reached a certain elevation by the mid-Miocene, yet the mid-Miocene widespread warming might have largely impacted the Gerze climate. | SONG Eping ZHANG Kexin CHEN Jiangjun WANG Chaowen JIANG Gaolei YIN Ke HONG Hanlie CHURCHMAN Jock Gordon | 2014 | Acta Geologica Sinica(English Edition)2014，88，5： | 0 |
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