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A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy

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Chinese Chemical Letters 2024年第10期35卷 353-359页

作者： Han Han bi-Te Chen Jia-Rong ding Jin-ming Si Tian-Jiao Zhou Yi Wang Lei Xing Hu-Lin Jiang State Key Laboratory of Natural medicines Department of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China College of Pharmacy .Yanbian UniversityYanji 133002China Department of Nephrology Changhai HospitalNaval Medical UniversityShanghai 200433China

Activated pancreatic stellate cells(PSCs)are the main source of collagen layer deposition and the key target in pancreatic ***,no effective treatment specific to pancreatic fibrosis clinically,owing to the drug accumulation blocked by the collagen barrier and thus it is difficult to inhibit activated PSCs ***,a PSCs-targeting nano-system based on“nanodrill”strategy(LA-PC)was designed to enhance the accumulation of all-trans retinoic acid(ATRA)in PSCs,relying on the platelet-derived growth factor receptor beta(PDGFRβ)-targeting peptide(p Pb:C*SRNLIDC*)and collagenase(Col).After being injected into fibrotic mice via tail vein,the Col modified on LA-PC can remove the excess collagen layer,and the drug delivery efficiency through pPb targeting peptide was more than 5 times higher than that of free ATRA,as well as the degree of fibrosis significantly ***,this nano-system effectively inhibited platelet-derived growth factor subunit b(PDGF-bb)/PDGFRβaxis on PSCs via a down-regulated extracellular signal-regulated protein kinase(eRK)pathway,and accordingly reduced the level of ***,the smart platform provided a promising strategy for the treatment of pancreatic fibrosis to achieve the precise regulation of PSCs.

关键词： Pancreatic fibrosis Pancreatic stellate cells Liposome PDGFRβ pPb peptide

effect of antioxidants on the efficiency of jet milling and the powder characteristics of Sm2Co17 permanent magnets

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Chinese Physics b 2024年第9期33卷 615-620页

作者： Da-Shuai Xu Lei Liu Jian-Hui Yuan bo Zhou Chuang-Hui Dong Feng-Qing Wang Yong ding Ying-Li Sun A-Ru Yan School of materials Science and engineering Shanghai University of Engineering ScienceShanghai 201620China CISRI&NImTe Joint Innovation Center for Rare earth Permanent magnets CAS Key Laboratory of Magnetic Materials and DevicesZhejiang Province Key Laboratory of Magnetic Materials and Application TechnologyNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China University of Chinese Academy of Sciences Beijing 100049China

This study investigated the effect of antioxidants on the grinding efficiency,magnetic powder characteristics,microstructure,and magnetic properties of 2:17 type SmCo permanent magnet *** results show that adding antioxidants helps improve the dispersion among magnetic powders,leading to a 33.3%decrease in jet milling time and a 15.8%increase in magnet powder production ***,adding antioxidants enhances the oxidation resistance of the magnetic *** being stored in a constant temperature air environment at 25C for 48 h,the O content in the powder decreased by 33%compared to samples without *** in the magnet body,the O content decreased from 0.21 wt.%to 0.14 wt.%,which helps increase the effective Sm content and domain wall pinning uniformity in the *** magnetic properties were obtained in the magnet with added antioxidants:b_(r)=11.6 kGs,SF=79.6%,H_(cj)=16.8 kOe,and(bH)_(max)=32.5 mGOe.

关键词： antioxidant SmCo permanent magnet oxidation resistance grinding efficiency

The lysine methyltransferase SmYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis

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Acta Pharmaceutica Sinica b 2024年第2期14卷 712-728页

作者： Xiaoxuan Zhong Xiang Wei Yan Xu Xuehai Zhu bo Huo Xian Guo Gaoke Feng Zihao Zhang Xin Feng Zemin Fang Yuxuan Luo Xin Yi ding-Sheng Jiang Division of Cardiovascular Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Key Laboratory of Organ Transplantation Ministry of EducationNHC Key Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhan 430030China School of Life Science and Technology Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjing 210096China Department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart ***,we show that lysine methyltransferase SmYD2 expression in the nucleus is significantly elevated in serum-and PDGF-bb-induced vascular smooth muscle cells(VSmCs),and in tissues of carotid artery injury-induced neointimal ***2 overexpression in VSmCs(Smyd2-vTg)facilitates,but treatment with its specific inhibitor LLY-507 or SmYD2 knockdown significantly inhibits VSmC phenotypic switching and carotid artery injury-induced neointima formation in *** sequencing revealed that SmYD2 knockdown represses the expression of serum response factor(SRF)target genes and that SRF overexpression largely reverses the inhibitory effect of SmYD2 knockdown on VSmC ***3 directly interacts with and deacetylates SRF,which enhances SRF transcriptional activity in ***,SmYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its ***966,a specific inhibitor of HDAC3,not only counteracts the pro-proliferation effect of SmYD2 overexpression on VSmCs,but also inhibits carotid artery injury-induced neointima formation in ***3 partially abolishes the inhibitory effect of SmYD2 knockdown on VSmC proliferation in a deacetylase activity-dependent *** results reveal that the SmYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSmC phenotypic switching and neointimal hyperplasia.

关键词： Neointimaformation Histonemethylation Histoneacetylation SRFacetylation SmYD2 HDAC3 LLY-507 RGFP966

Fine mapping of two recessive genes TaFLA1 and TaSPL8 controlling flag leaf angle in bread wheat

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The Crop Journal 2024年第4期12卷 1159-1167页

作者： Qiushi Wang Jiaxing bai Hongchun Xiong Yongdun Xie Chaojie Wang Jiayu Gu Linshu Zhao Huiyuan Li Jinfeng Zhang Shirong Zhao Yuping ding Zhengwu Fang Huijun Guo Luxiang Liu College of Agriculture Yangtze University/MARA Key Laboratory of Sustainable Crop Production in the Middle Reaches of the Yangtze River(Co-Construction by Ministry and Province)Jingzhou 434000HubeiChina State Key Laboratory of Crop Gene Resources and breeding/National engineering Laboratory of Crop molecular breeding/CAeA Research and Development Centre on Nuclear Technology Applications for Irradiation mutation breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China

Flag leaf angle is one of the key target traits in high yield wheat breeding.A smaller flag leaf angle reduces shading and enables plants to grow at a higher density,which increases *** we identified a mutant,je0407,with an 84.34%-89.35%smaller flag leaf angle compared with the wild *** mutant also had an abnormal lamina joint and no ligule or *** analysis indicated that the ligule was controlled by two recessive genes,which were mapped to chromosomes 2AS and *** mutant allele on chromosome 2AS was named Tafla1b,and it was fine mapped to a 1 mb physical *** mutant allele on chr.2DL was identified as Taspl8b,a novel allele of TaSPL8 with a missense mutation in the second exon,which was used to develop a cleaved amplified polymorphic sequence marker.F3 and F4 lines derived from crosses between Jing411 and je0407 were genotyped to investigate interactions between the Tafla1b and Taspl8b *** with the Tafla1b/Taspl8a genotype had 58.41%-82.76%smaller flag leaf angles,6.4%-24.9%shorter spikes,and a greater spikelet density(0.382 more spikelets per cm)compared with the wild *** with the Tafla1a/Taspl8b genotype had 52.62%-82.24%smaller flag leaf angles and no differences in plant height or spikelet density compared with the wild ***1b/Taspl8b plants produced erect leaves with an abnormal lamina *** two alleles had dosage effects on ligule formation and flag leaf angle,but no significant effect on thousand-grain *** mutant alleles provide novel resources for improvement of wheat plant architecture.

关键词： Wheat Ligule Flag leaf angle Fine mapping Tafla1 Taspl8

Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eeF2-mediated HmGb2 mRNA translation

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Cancer Communications 2024年第9期44卷 1018-1041页

作者： Hailing Liu Lei Xu Shiwei Yue Hongfei Su Xing Chen Qiumeng Liu Hui Li Huifang Liang Xiaoping Chen Jiefeng He Zeyang ding bixiang Zhang Hepatic Surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei Key Laboratory of Hepato‑Pancreatic‑biliary Diseases Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Hepatopancreatobiliary Surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiangP.R.China Department of Hepatobiliary Pancreatic Tumor Center Chongqing University Cancer HospitalSchool of MedicineChongqing UniversityChongqingP.R.China Key Laboratory of Organ Transplantation Ministry of EducationWuhanHubeiP.R.China Department of Hepatobiliary Surgery Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province(Preparatory)Shanxi Bethune HospitalShanxi Academy of Medical SciencesShanxi Medical UniversityTaiyuanShanxiP.R.China

background:N4-acetylcytidine(ac4C)represents a novel messenger RNA(mRNA)modification,and its associated acetyltransferaseN-acetyltransferase 10(NAT10)plays a crucial role in the initiation and progression of tumors by regulating mRNA ***,its role in hepatocellular carcinoma(HCC)development and prognosis is largely *** study aimed to elucidate the role of NAT10-mediated ac4C in HCC progression and provide a promising therapeutic ***:The ac4C levels were evaluated by dot blot and ultra-performance liquid chromatography-tandem mass spectrometry with harvested HCC *** expression of NAT10 was investigated using quantitative real-time polymerase chain reaction,western blotting,and immunohistochemical staining across 91 cohorts of HCC *** explore the underlying mechanisms of NAT10-ac4C in HCC,we employed a comprehensive approach integrating acetylated RNA immunoprecipitation and sequencing,RNA sequencing and ribosome profiling analyses,along with RNA immunoprecipitation,RNA pulldown,mass spectrometry,and site-specific mutation *** drug affinity responsive targets stability,cellular thermal shift assay,and surface plasmon resonance assays were performed to assess the specific binding of NAT10 and ***,the efficacy of targeting NAT10-ac4C for HCC treatment was elucidated through in vitro experiments using HCC cells and in vivo HCCmouse ***:Our investigation revealed a significant increase in both the ac4C RNA level and NAT10 expression in ***,elevated NAT10 expression was associated with poor outcomes in HCC ***,silencing NAT10 suppressed HCC proliferation and metastasis in vitro and in ***,NAT10 stimulates the ac4C modification within the coding sequence(CDS)of high mobility group protein b2(HmGb2),which subsequently enhances HmGb2 translation by facilitating eukaryotic elongation factor 2(eeF2)binding to the ac4C sites on HmGb2 mRNA’s C

关键词： N4-acetylcytidine N-acetyltransferase 10 hepatocellular carcinoma mRNA translation targeted therapy

Demonstration of normally-off p-channel GaN transistor with high threshold voltage and low subthreshold swing based on single p-GaN

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Science China(Information Sciences) 2024年第9期67卷 348-349页

作者： Yangfeng LI Zian DONG Shuai CHeN Qin WANG Tong LI Shulin CHeN Kun ZHeNG Jie ZHANG Guojian ding Yang WANG Haiqiang JIA Rong YANG Lei LIAO Changsha Semiconductor Technology and Application Innovation Research Institute College of Semiconductors (College of Integrated Circuits) Hunan University Hunan San'an Semiconductor Co. Ltd. Songshan Lake materials Laboratory

GaN outperforms silicon in applications with high power and high frequency owing to the high critical electric field and high electron mobility. However, the hole-based GaN transistors which are pivotal to the GaN-based CmOS circuits and high-side switching are still under investigation. Two-dimensional hole gas(2DHG) has been used to demonstrate the p-channel GaN field-effect-transistors(FeTs) [1–5].

关键词： mOSFeTS

High-probability ground motion simulation in maduo County for the maduo m7.4 earthquake in 2021: A possible supershear earthquake

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Journal of earth Science 2024年

作者： Zongchao Li Zhiwei Ji Jize Sun Hiroe miyake Yanna Zhao Hongjun Si mengtan Gao Yi ding Institute of Geophysics， China earthquake Administration Institute of earthquake Forecasting， China earthquake Administration Shenzhen Academy of Disaster Prevention and Reduction earthquake Research Institute， The University of Tokyo Geophysical exploration Center， China earthquake Administration beijing University of Technology

On may 22， 2021， an ms7.4 earthquake occurred in maduo County， Qinghai Province， on the western plateau of China. The level of seismic monitoring in this area was inadequate， and incomplete seismic waveforms were obtained from a few broadband seismometers located within 300 km of the epicentre. All waveforms showed "truncation" phenomena. The waveforms of earthquakes can guide ground motion inputs in near-fault areas. This paper uses the empirical Green's function method to consider the uncertainties in source parameters and source rupture processes by synthesizing high-probability， accurate waveforms in maduo County （mAD station） near the epicentre. The acceleration waveform at the DAW strong-motion station， located 176 km from the epicentre， is first synthesized with the observed waveform of the mainshock. This critical step not only provides a more accurate source and rupture model of the maduo earthquake but also establishes an essential reference standard. Secondly， the inferred models are rigorously applied to synthesize the acceleration waveform of the mAD station， ensuring that the results maintain a high accuracy and probability. The findings suggest that （1） the simulated acceleration waveform for the mAD station can better characterize the actual ground motion characteristics of the ms7.4 earthquake in maduo County， with high accuracy and probability in peak ground acceleration （Abbreviated as PGA） ranges of 140–240 cm/s2and 350–390 cm/s2， respectively， and （2） the ms7.4 earthquake did not undergo a complete supershear rupture process. The first asperity located on the east side of the epicentre is most likely to undergo supershear rupture. However， the maduo earthquake may have been a complete subshear rupture. （3） The fault dislocation model of the three-asperity model better matches the actual source rupture process of the maduo earthquake. This method can provide relatively accurate acceleration waveforms for regions with limited earthquake monitoring

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benchmark experiment on slab^(238)U with D-T neutrons for validation of evaluated nuclear data

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Nuclear Science and Techniques 2024年第2期35卷 145-159页

作者： Yan-Yan ding Yang-bo Nie Yue Zhang Zhi-Jie Hu Qi Zhao Huan-Yu Zhang Kuo-Zhi Xu Shi-Yu Zhang Xin-Yi Pan Chang-Lin Lan Jie Ren Xi-Chao Ruan Key Laboratory of Nuclear Data China Institute of Atomic EnergyBeijing 102413China School of Nuclear Science and Technology Lanzhou UniversityLanzhou 730000China Institute of Fluid Physics China Academy of Engineering PhysicsMianyang 62100China

A benchmark experiment on^(238)U slab samples was conducted using a deuterium-tritium neutron source at the China Institute of Atomic *** leakage neutron spectra within energy levels of 0.8-16 meV at 60°and 120°were measured using the time-of-flight *** samples were prepared as rectangular slabs with a 30 cm square base and thicknesses of 3,6,and 9 *** leakage neutron spectra were also calculated using the mCNP-4C program based on the latest evaluated files of^(238)U evaluated neutron data from CeNDL-3.2,eNDF/b-Ⅷ.0,JeNDL-5.0,and *** on the comparison,the deficiencies and improvements in^(238)U evaluated nuclear data were *** results showed the following.(1)The calculated results for CeNDL-3.2 significantly overestimated the measurements in the energy interval of elastic scattering at 60°and 120°.(2)The calculated results of CeNDL-3.2 overestimated the measurements in the energy interval of inelastic scattering at 120°.(3)The calculated results for CeNDL-3.2 significantly overestimated the measurements in the 3-8.5 meV energy interval at 60°and 120°.(4)The calculated results with JeNDL-5.0 were generally consistent with the measurement results.

关键词： Leakage neutron spectra Uranium D-T neutron source evaluated nuclear data

Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AmPK axis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 758-771页

作者： Xin Han Yan Ning Xinyue Dou Yiwen Wang Qiyuan Shan Kao Shi Zeping Wang Chuan ding min Hao Kuilong Wang mengyun Peng Haodan Kuang Qiao Yang Xianan Sang Gang Cao School of Pharmacy Zhejiang Chinese Medical UniversityHangzhou311400China

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying *** vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-b(TGF-b).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw *** ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-mS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AmP)-activated protein kinase(AmPK)*** note,cornus officinalis activated AmPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and *** interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AmPK activity and its mediated-apoptosis through *** conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AmPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

关键词： Liver fibrosis SIRT3 Cornus officinalis AmPK Caspase6