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| 1 | Generation of B Cell-Deficient Pigs by Highly Efficient CRISPR/Cas9-Mediated Gene Targeting显示文摘Generating B cell-deficient mutant is the first step to produce human antibody repertoires in large animal models. In this study, we applied the clustered regularly interspaced short palindromic repeat(CRISPR)/CRISPR-associated(Cas) system to target the JHregion of the pig Ig M heavy chain gene which is crucial for B cell development and differentiation. Transfection of Ig M-targeting Cas9 plasmid in primary porcine fetal fibroblasts(PFFs) enabled inducing gene knock out(KO) in up to 53.3% of colonies analyzed, a quarter of which harbored biallelic modification, which was much higher than that of the traditional homologous recombination(HR). With the aid of somatic cell nuclear transfer(SCNT) technology, three piglets with the biallelic Ig M heavy chain gene mutation were produced. The piglets showed no antibody-producing B cells which indicated that the biallelic mutation of the Ig M heavy chain gene effectively knocked out the function of the Ig M and resulted in a B cell-deficient phenotype. Our study suggests that the CRISPR/Cas9 system combined with SCNT technology is an efficient genome-editing approach in pigs. | Fengjiao Chen Ying Wang Yilin Yuan Wei Zhang Zijian Ren Yong Jin Xiaorui Liu Qiang Xiong Qin Chen Manling Zhang Xiaokang Li Lihua Zhao Ze Li Zhaoqiang Wu Yanfei Zhang Feifei Hu Juan Huang Rongfeng Li Yifan Dai | 2015 | Journal of Genetics and Genomics2015，42，8： | 15 |
| 2 | Bright-field holography:cross-modality deep learning enables snapshot 3D imaging with bright-field contrast using a single hologram显示文摘Digital holographic microscopy enables the 3D reconstruction of volumetric samples from a single-snapshot hologram.However,unlike a conventional bright-field microscopy image,the quality of holographic reconstructions is compromised by interference fringes as a result of twin images and out-of-plane objects.Here,we demonstrate that cross-modality deep learning using a generative adversarial network(GAN)can endow holographic images of a sample volume with bright-field microscopy contrast,combining the volumetric imaging capability of holography with the speckle-and artifact-free image contrast of incoherent bright-field microscopy.We illustrate the performance of this“bright-field holography”method through the snapshot imaging of bioaerosols distributed in 3D,matching the artifact-free image contrast and axial sectioning performance of a high-NA bright-field microscope.This data-driven deep-learning-based imaging method bridges the contrast gap between coherent and incoherent imaging,and enables the snapshot 3D imaging of objects with bright-field contrast from a single hologram,benefiting from the wave-propagation framework of holography. | Yichen Wu Yilin Luo Gunvant Chaudhari Yair Rivenson Ayfer Calis Kevin de Haan Aydogan Ozcan | 2019 | Light(Science & Applications)2019，8，1： | 12 |
| 3 | Focal adhesion protein Kindlin-2 regulates bone homeostasis in mice显示文摘Our recent studies demonstrate that the focal adhesion protein Kindlin-2 is critical for chondrogenesis and early skeletal development. Here, we show that deleting Kindlin-2 from osteoblasts using the 2.3-kb mouse Col1 a1-Cre transgene minimally impacts bone mass in mice, but deleting Kindlin-2 using the 10-kb mouse Dmp1-Cre transgene, which targets osteocytes and mature osteoblasts, results in striking osteopenia in mice. Kindlin-2 loss reduces the osteoblastic population but increases the osteoclastic and adipocytic populations in the bone microenvironment. Kindlin-2 loss upregulates sclerostin in osteocytes,downregulates β-catenin in osteoblasts, and inhibits osteoblast formation and differentiation in vitro and in vivo. Upregulation ofβ-catenin in the mutant cells reverses the osteopenia induced by Kindlin-2 deficiency. Kindlin-2 loss additionally increases the expression of RANKL in osteocytes and increases osteoclast formation and bone resorption. Kindlin-2 deletion in osteocytes promotes osteoclast formation in osteocyte/bone marrow monocyte cocultures, which is significantly blocked by an anti-RANKLneutralizing antibody. Finally, Kindlin-2 loss increases osteocyte apoptosis and impairs osteocyte spreading and dendrite formation.Thus, we demonstrate an important role of Kindlin-2 in the regulation of bone homeostasis and provide a potential target for the treatment of metabolic bone diseases. | Huiling Cao Qinnan Yan Dong Wang Yumei Lai Bo Zhou Qi Zhang Wenfei Jin Simin Lin Yiming Lei Liting Ma Yuxi Guo Yishu Wang Yilin Wang Xiaochun Bai Chuanju Liu Jian QFeng Chuanyue Wu Di Chen Xu Cao Guozhi Xiao | 2020 | Bone Research2020，8，1： | 8 |
| 4 | HPLC–MS and HPLC–MS/MS analysis of seven active constituents of Xiao-Xu-Ming decoction and application to a pharmacokinetic study after oral administration to rat显示文摘Xiao-xu-ming decoction(XXMD)is a traditional Chinese medicine that has been widely used to treat theoplegia and its sequelae.This paper reports the development of three separate assays based on reversed phase high-performance liquid chromatography–mass spectrometry(HPLC–MS)and HPLC–MS/MS for the determination of seven active constituents of XXMD viz oroxylin A-7-O-glucuronide,wogonoside,liquiritigenin,cimifugin,5-O-methylvisammiol,glycyrrhizic acid and glycyrrhetinic acid in rat plasma.All calibration curves were linear(r >0.99)with lower limits of quantitation(LLOQs)<12.4 ng/mL.Intra-and inter-day precisions(as relative standard deviation)were all <10.7% with recoveries in the range of 88.7–113%.In addition,the seven analytes were shown to be stable in rat plasma samples under relevant storage conditions.The validated methods were successfully applied to a pharmacokinetic study in rat after oral administration of XXMD. | Yilin Wang Chunguang Ding Caisheng Wu Kehe Du Jinlan Zhangn Hailin Qin Jinfeng Hou Guanhua Du | 2012 | Acta Pharmaceutica Sinica B2012，2，2： | 6 |
| 5 | Comparative genomic and transcriptomic analyses uncover the molecular basis of high nitrogen-use efficiency in the wheat cultivar Kenong 9204显示文摘Studying the regulatory mechanisms that drive nitrogen-use efficiency(NUE)in crops is important for sustainable agriculture and environmental protection.In this study,we generated a high-quality genome assembly for the high-NUE wheat cultivar Kenong 9204 and systematically analyzed genes related to nitrogen uptake and metabolism.By comparative analyses,we found that the high-affinity nitrate transporter gene family had expanded in Triticeae.Further studies showed that subsequent functional differentiation endowed the expanded family members with saline inducibility,providing a genetic basis for improving the adaptability of wheat to nitrogen deficiency in various habitats.To explore the genetic and molecular mechanisms of high NUE,we compared genomic and transcriptomic data from the high-NUE cultivar Kenong 9204(KN9204)and the low-NUE cultivar Jing 411 and quantified their nitrogen accumulation under high-and low-nitrogen conditions.Compared with Jing 411,KN9204 absorbed significantly more nitrogen at the reproductive stage after shooting and accumulated it in the shoots and seeds.Transcriptome data analysis revealed that nitrogen deficiency clearly suppressed the expression of genes related to cell division in the young spike of Jing 411,whereas this suppression of gene expression was much lower in KN9204.In addition,KN9204 maintained relatively high expression of NPF genes for a longer time than Jing 411 during seed maturity.Physiological and transcriptome data revealed that KN9204 was more tolerant of nitrogen deficiency than Jing 411,especially at the reproductive stage.The high NUE of KN9204 is an integrated effect controlled at different levels.Taken together,our data provide new insights into the molecular mechanisms of NUE and important gene resources for improving wheat cultivars with a higher NUE trait. | Xiaoli Shi Fa Cui Xinyin Han Yilin He Long Zhao Na Zhang Hao Zhang Haidong Zhu Zhexin Liu Bin Ma Shusong Zheng Wei Zhang Jiajia Liu Xiaoli Fan Yaoqi Si Shuiquan Tian Jianqing Niu Huilan Wu Xuemei Liu Zhuo Chen Deyuan Meng Xiaoyan Wang Liqiang Song Lijing Sun Jie Han Hui Zhao Jun Ji Zhiguo Wang Xiaoyu He Ruilin Li Xuebin Chi Chengzhi Liang Beifang Niu Jun Xiao Junming Li Hong-Qing Ling | 2022 | Molecular Plant2022，15，9： | 6 |
| 6 | Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer:a subpopulation analysis of the JACOB trial显示文摘Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.Methods:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January 2016.The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable toxicity.Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin.The primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,respectively.The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group.The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable.The most common grade 3-5adverse events were neutropenia,anemia,and leukopenia.However,due to the nature of being a post hoc subgroup analysis,the results presented here are descriptive only and need to be interpreted with caution.Conclusions:OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first-line treatment in Chinese HER2-positive gastric cancer/GEJC patients,and this regimen demonstrated an acceptable safety profile. | Tianshu Liu Yanru Qin Jin Li Ruihua Xu Jianming Xu Shujun Yang Shukui Qin Yuxian Bai Changping Wu Yixiang Mao Haiyan Wu Yilin Ge Lin Shen | 2019 | Cancer Communications2019，39，1： | 6 |
| 7 | “Exploring petroleum inside source kitchen”: Shale oil and gas in Sichuan Basin显示文摘The Sichuan Basin is rich in shale oil and gas resources,with favorable geological conditions that the other shale reservoirs in China cannot match.Thus,the basin is an ideal option for fully'exploring petroleum inside source kitchen'with respect to onshore shale oil and gas in China.This paper analyzes the characteristics of shale oil and gas resources in the United States and China,and points out that maturity plays an important role in controlling shale oil and gas composition.US shale oil and gas exhibit high proportions of light hydrocarbon and wet gas,whereas Chinese marine and transitional shale gas is mainly dry gas and continental shale oil is generally heavy.A comprehensive geological study of shale oil and gas in the Sichuan Basin reveals findings with respect to the following three aspects.First,there are multiple sets of organic-rich shale reservoirs of three types in the basin,such as the Cambrian Qiongzhusi Formation and Ordovician Wufeng Formation-Silurian Longmaxi Formation marine shale,Permian Longtan Formation transitional shale,Triassic Xujiahe Formation lake-swamp shale,and Jurassic lacustrine shale.Marine shale gas enrichment is mainly controlled by four elements:Deep-water shelf facies,moderate thermal evolution,calcium-rich and silicon-rich rock association,and closed roof/floor.Second,the'sweet section'is generally characterized by high total organic carbon,high gas content,large porosity,high brittle minerals content,high formation pressure,and the presence of lamellation/bedding and natural microfractures.Moreover,the'sweet area'is generally characterized by very thick organic-rich shale,moderate thermal evolution,good preservation conditions,and shallow burial depth,which are exemplified by the shale oil and gas in the Wufeng-Longmaxi Formation,Longtan Formation,and Daanzhai Member of the Ziliujing Formation.Third,the marine,transitional,and continental shale oil and gas resources in the Sichuan Basin account for 50%,25%,and 30%of the respective types of shale oil and gas geological resources in China,with great potential to become the cradle of the shale oil and gas industrial revolution in China.Following the'Conventional Daqing-Oil'(i.e.,the Daqing oilfield in the Songliao Basin)and the'Western Daqing-Oil&Gas'(i.e.,the Changqing oilfield in the Ordos Basin),the Southwest oil and gas field in the Sichuan Basin is expected to be built into a'Sichuan-Chongqing Daqing-Gas'in China. | Caineng ZOU Zhi YANG Shasha SUN Qun ZHAO Wenhua BAI Honglin LIU Songqi PAN Songtao WU Yilin YUAN | 2020 | Science China Earth Sciences2020，63，7： | 6 |
| 8 | The landscape of aging显示文摘Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels. | Yusheng Cai Wei Song Jiaming Li Ying Jing Chuqian Liang Liyuan Zhang Xia Zhang Wenhui Zhang Beibei Liu Yongpan An Jingyi Li Baixue Tang Siyu Pei Xueying Wu Yuxuan Liu Cheng-Le Zhuang Yilin Ying Xuefeng Dou Yu Chen Fu-Hui Xiao Dingfeng Li Ruici Yang Ya Zhao Yang Wang Lihui Wang Yujing Li Shuai Ma Si Wang Xiaoyuan Song Jie Ren Liang Zhang Jun Wang Weiqi Zhang Zhengwei Xie Jing Qu Jianwei Wang Yichuan Xiao Ye Tian Gelin Wang Ping Hu Jing Ye Yu Sun Zhiyong Mao Qing-Peng Kong Qiang Liu Weiguo Zou Xiao-Li Tian Zhi-Xiong Xiao Yong Liu Jun-Ping Liu Moshi Song Jing-Dong J.Han Guang-Hui Liu | 2022 | Science China(Life Sciences)2022，65，12： | 4 |
| 9 | Development of a rapid and sensitivity magnetic chemiluminescence immunoassay for DNA methyltransferase 1 in human serum显示文摘DNA methyltransferase 1(DNMT1)is a useful biomarker for lung cancer in early clinical diagnosis.A rapid magnetic chemiluminescence immunoassay(MCLIA)for DNMT1 in human serum has been developed.Horseradish peroxidase(HRP)-second-Ab was used to labeled polyclonal antibodies of anti-DNMT1.DNMT1 in sample integrates with specific immunomagnetic beads and can constitute a supersandwiched immunoreaction.In magnetic field,nonspecific materials can be separated.After luminescent substrate luminol-H2O2-BIP was added,the relative light unit(RLU)of HRP was detected and was discovered to be directly proportional to the content of DNMT1 in sample.The correlative variables involved in the MCLIA value were optimized and the methodological evaluation was carried out.After optimization,in the range of0.5–128 ng/mL,the linear regression equation was y=0.5014 x+1.769(x was logCDNMT1,y was relative luminescence units(RLU)/RLU0),and the limit of detection was 0.01 ng/mL.The RSD of intra-and interassays were 15.8%–16.9%and 14.3%–18.1%,respectively.The recovery was from 70.0%to 106.2%.Furthermore,paralleled with purchasable enzyme-linked immunosorbent assay(ELISA)kits,MCLEIA had lower detection limit,wider linear range and shorter detection time.Therefore,the MCLEIA established in this study could be used for the sensitive detection of DNMT1 in serum sample. | Sitian He Leiliang He Beibei Liu Songcheng Yu Li'e Liu Yongmei Tian Jia Wang Lihua Ding Yilin Wang Lingbo Qu Fei Yu Yongjun Wu | 2019 | Chinese Chemical Letters2019，30，5： | 4 |
| 10 | Distribution of bacterial communities across plateau freshwater lake and upslope soils显示文摘Microorganisms are involved in a variety of biogeochemical processes in natural environments.The differences between bacterial communities in freshwaters and upslope soils remain unclear. The present study investigated the bacterial distribution in a plateau freshwater lake,Erhai Lake(southwestern China), and its upslope soils. Illumina MiS eq sequencing illustrated high bacterial diversity in lake sediments and soils. Sediment and soil bacterial communities were mainly composed of Proteobacteria, Acidobacteria, Actinobacteria,Bacteroidetes, Chloroflexi and Planctomycetes. However, a distinctive difference in bacterial community structure was found between soil and sediment ecosystems. Water content, nitrogen and p H affected the distribution of the bacterial community across Erhai Lake and its upslope soils. Moreover, the soil bacterial community might also be shaped by plant types. This work could provide some new insights into plateau aquatic and terrestrial microbial ecology. | Yihui Chen Yu Dai Yilin Wang Zhen Wu Shuguang Xie Yong Liu | 2016 | Journal of Environmental Sciences2016，28，5： | 4 |
| 11 | Dynamic multi-objective differential evolution algorithm based on the information of evolution progress显示文摘The multi-objective differential evolution(MODE)algorithm is an effective method to solve multi-objective optimization problems.However,in the absence of any information of evolution progress,the optimization strategy of the MODE algorithm still appears as an open problem.In this paper,a dynamic multi-objective differential evolution algorithm,based on the information of evolution progress(DMODE-IEP),is developed to improve the optimization performance.The main contributions of DMODE-IEP are as follows.First,the information of evolution progress,using the fitness values,is proposed to describe the evolution progress of MODE.Second,the dynamic adjustment mechanisms of evolution parameter values,mutation strategies and selection parameter value based on the information of evolution progress,are designed to balance the global exploration ability and the local exploitation ability.Third,the convergence of DMODE-IEP is proved using the probability theory.Finally,the testing results on the standard multi-objective optimization problem and the wastewater treatment process verify that the optimization effect of DMODE-IEP algorithm is superior to the other compared state-of-the-art multi-objective optimization algorithms,including the quality of the solutions,and the optimization speed of the algorithm. | HOU Ying WU YiLin LIU Zheng HAN HongGui WANG Pu | 2021 | Science China(Technological Sciences)2021，64，8： | 3 |
| 12 | NUMB maintains bone mass by promoting degradation of PTEN and GLI1 via ubiquitination in osteoblasts显示文摘The adaptor protein NUMB is involved in asymmetric division and cell fate determination and recognized as an antagonist of Notch.Previous studies have proved that Notch activation in osteoblasts contributes to a high bone mass. In this study, however, an osteopenic phenotype was found in 9-week-old mice using osteoblastic specific Col1a1–2.3-Cre to ablate both Numb and its homologue Numbl. The trabecular bone mass decreased dramatically while the cortical bone mass was unaffected. Here, the Notch signal was not activated,while the tensin homologue deleted on human chromosome 10(PTEN), which dephosphorylates phosphatidylinositide 3-kinases, was elevated, attenuating protein kinase B(Akt). The ubiquitination assay revealed that NUMB may physiologically promote PTEN ubiquitination in the presence of neural precursor cell-expressed developmentally downregulated protein 4–1. In addition, the deficiency of Numb/Numbl also activated the Hedgehog pathway through GLI1. This process was found to improve the ratio of the receptor activator of nuclear factor-k B ligand to osteoprotegerin, which enhanced the differentiation of osteoclasts and bone resorption. In conclusion, this study provides an insight into new functons of NUMB and NUMBL on bone homeostasis. | Ling Ye Feng Lou Fanyuan Yu Demao Zhang Chenglin Wang Fanzi Wu Xin Li Yilin Ping Xiao Yang Jing Yang Dian Chen Bo Gao Dingming Huang Peng Liu | 2018 | Bone Research2018，6，4： | 3 |
| 13 | Denitrification and the controlling factors in Yunnan Plateau Lakes(China): Exploring the role of enhanced internal nitrogen cycling by algal blooms显示文摘Denitrification plays an important role in nitrogen(N) removal in freshwater ecosystems.This internal process regulates the fluctuations of N concentration, especially for lakes with high nutrients concentrations and long residence time. Lakes in Yunnan plateau(southwestern China) provide typical cases, while studies in this region have been rare.Therefore, we studied denitrification of two lakes(Lake Dianchi in hypereutrophic state and Lake Erhai in mesotrophic) in this region. We used acetylene inhibition technique to quantify potential denitrification rate(PDR) of these lakes in April and August, 2015 and 2016. PDR of the sediments ranged 0–1.21 μmol/(N·m^2·hr), and that of overlying water ranged 0–0.24 μmol/(N·L·hr). Then, we used Least Angle Regression to determine the controlling factors for denitrification. Nutrients controlled PDR from two aspects: providing essential nitrogen sources; and affecting the richness and metabolism of denitrifying bacteria. In April, both aspects limited PDR; while only nitrogen sources limited PDR in August, due to depleted nitrate and enhanced denitrifying bacteria activity. Ammonia was most significant to denitrification, indicating that nitrate from nitrification transported to the bottom of wellmixed lake provide major N source by denitrification. The high PDR and low nitrate concentrate in August were evidence of an enhanced internal N cycling by algal blooms. | Sifeng Wu Zhen Wu Zhongyao Liang Yong Liu Yilin Wang | 2019 | Journal of Environmental Sciences2019，31，2： | 3 |
| 14 | Distribution and Transport of Residual Lead and Copper Along Soil Pro?les in a Mining Region of North China显示文摘Residual heavy metals are commonly considered to be immobile in soils,leading to an underestimation of their environmental risk.This study investigated the distribution and transport of residual heavy metals along soil pro?les,using the Xiaoqinling gold mining region in North China as a case study.Soil samples were collected at three depths from three locations near the tailing heap.The speciation of copper(Cu) and lead(Pb)(exchangeable,carbonate-bound,Fe-Mn oxide-bound,organic matter-bound,and residual fractions) was determined using a sequential extraction procedure.The residual fraction's morphology was observed using scanning electron microscopy(SEM).Results showed that metal fraction distributions along the soil pro?les were in?uenced by each fraction's mobility.Residual fraction with high chemical stability can not be transformed from or into other fractions.This led to the conclusion that the high concentration of residual metals in soils mainly resulted from residual fraction transport.The SEM analysis showed that ?ne particles(submicrons) were mainly attached to large particles and were likely released and transported by water?ow.The more sorptive fractions(non-residual fractions) were mainly retained in the top soil,and the more mobile fractions(residual fraction) were mainly leached to the deep soil.Cu and Pb concentrations in the residual fraction decreased slightly and those in the non-residual fractions decreased signi?cantly with soil depth.These suggest a relatively higher residual metal mobility along the soil pro?les.Therefore,residual metals can be transported in soils and their environmental risk can not be ignored in assessing soil contamination. | LU Cong WU Yaoguo HU Sihai ZHANG Xiaoyan FU Yilin | 2016 | Pedosphere2016，26，6： | 2 |
| 15 | Structures of a P4-ATPase lipid flippase in lipid bilayers显示文摘Dear Editor,Phospholipid molecules are unevenly distributed in membrane bilayers of eukaryotic cells.Phosphatidylethanolamine(PE)and phosphatidylserine(PS)are concentrated in the cytoplasmic leaflet,whereas phosphatidylcholine(PC)is enriched in the exoplasmic leaflet(lumenal or extracellular leaflet)(van Meer et al.2008).Type 4 P-type ATPases(P4-ATPases)are the phospholipid flippases which move specific lipids from the exoplasmic leaflet to the cytoplasmic leaflet.P4-ATPases belong to the P-type ATPase family.P4-ATPases are conserved in eukaryotes. | Yilin He Jinkun Xu Xiaofei Wu Long Li | 2020 | Protein & Cell2020，11，6： | 2 |
| 16 | Precise in vivo genome editing via single homology arm donor mediated intron-targeting gene integration for genetic disease correction显示文摘In vivo genome editing represents a powerful strategy for both understanding basic biology and treating inherited diseases.However,it remains a challenge to develop universal and efficient in vivo genome-editing tools for tissues that comprise diverse cell types in either a dividing or non-dividing state.Here,we describe a versatile in vivo gene knock-in methodology that enables the targeting of a broad range of mutations and cell types through the insertion of a minigene at an intron of the target gene locus using an intracellularly linearized single homology arm donor.As a proof-of-concept,we focused on a mouse model of prematureaging caused by a dominant point mutation,which is difficult to repair using existing in vivo genome-editing tools.Systemic treatment using our new method ameliorated aging-associated phenotypes and extended animal lifespan,thus highlighting the potential of this methodology for a broad range of in vivo genome-editing applications. | Keiichiro Suzuki Mako Yamamoto Reyna Hernandez-Benitez Zhe Li Christopher Wei Rupa Devi Soligalla Emi Aizawa Fumiyuki Hatanaka Masakazu Kurita Pradeep Reddy Alejandro Ocampo Tomoaki Hishida Masahiro Sakurai Amy NNemeth Estrella Nunez Delicado Josep MCampistol Pierre Magistretti Pedro Guillen Concepcion Rodriguez Esteban Jianhui Gong Yilin Yuan Ying Gu Guang-Hui Liu Carlos Lopez-Otin Jun Wu Kun Zhang Juan Carlos Izpisua Belmonte | 2019 | Cell Research2019，29，10： | 2 |
| 17 | Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI显示文摘Background The association between perivascular space(PVS)and white matter hyperintensity(WMH)has been unclear.Normal-appearing white matter(NAWM)around WMH is also found correlated with the development of focal WMH.This study aims to investigate the topological connections among PVS,deep WMH(dWMH)and NAWM around WMH using 7 Tesla(7T)MRI.Methods Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic.We compared the PVS burden between patients with and without WMHs using a 5-point scale.Then,the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site(without WMH)in the contralateral hemisphere.In this study,we define NAWM as an area within the radius of 1 cm around each dWMH.Furthermore,we assessed the spatial relationship between dWMH and PVS.Results Higher PVS scores in the centrum semiovale were found in patients with>5 dWMHs(median 3)than subjects without dWMH(median 2,p=0.014).We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites(p<0.001,p<0.001).In addition,79.59%of the dWMHs were spatially connected with PVS.Conclusion dWMH,NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease.Future study of WMH and NAWM should not overlook MRI-visible PVS. | Yajing Huo Yilin Wang Cen Guo Qianyun Liu Lili Shan Mingyuan Liu Haibo Wu Guanwu Li Huihui Lv Lingdan Lu Yintin Zhou Jianfeng Feng Yan Han | 2023 | Stroke & Vascular Neurology2023，8，2： | 2 |
| 18 | Biomarkers of aging显示文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant. | Aging Biomarker Consortium Hainan Bao Jiani Cao Mengting Chen Min Chen Wei Chen Xiao Chen Yanhao Chen Yu Chen Yutian Chen Zhiyang Chen Jagadish K Chhetri Yingjie Ding Junlin Feng Jun Guo Mengmeng Guo Chuting He Yujuan Jia Haiping Jiang Ying Jing Dingfeng Li Jiaming Li Jingyi Li Qinhao Liang Rui Liang Feng Liu Xiaoqian Liu Zuojun Liu Oscar Junhong Luo Jianwei Lv Jingyi Ma Kehang Mao Jiawei Nie Xinhua Qiao Xinpei Sun Xiaoqiang Tang Jianfang Wang Qiaoran Wang Siyuan Wang Xuan Wang Yaning Wang Yuhan Wang Rimo Wu Kai Xia Fu-Hui Xiao Lingyan Xu Yingying Xu Haoteng Yan Liang Yang Ruici Yang Yuanxin Yang Yilin Ying Le Zhang Weiwei Zhang Wenwan Zhang Xing Zhang Zhuo Zhang Min Zhou Rui Zhou Qingchen Zhu Zhengmao Zhu Feng Cao Zhongwei Cao Piu Chan Chang Chen Guobing Chen Hou-Zao Chen Jun Chen Weimin Ci Bi-Sen Ding Qiurong Ding Feng Gao Jing-Dong JHan Kai Huang Zhenyu Ju Qing-Peng Kong Ji Li Jian Li Xin Li Baohua Liu Feng Liu Lin Liu Qiang Liu Qiang Liu Xingguo Liu Yong Liu Xianghang Luo Shuai Ma Xinran Ma Zhiyong Mao Jing Nie Yaojin Peng Jing Qu Jie Ren Ruibao Ren Moshi Song Zhou Songyang Yi Eve Sun Yu Sun Mei Tian Shusen Wang Si Wang Xia Wang Xiaoning Wang Yan-Jiang Wang Yunfang Wang Catherine CL Wong Andy Peng Xiang Yichuan Xiao Zhengwei Xie Daichao Xu Jing Ye Rui Yue Cuntai Zhang Hongbo Zhang Liang Zhang Weiqi Zhang Yong Zhang Yun-Wu Zhang Zhuohua Zhang Tongbiao Zhao Yuzheng Zhao Dahai Zhu Weiguo Zou Gang Pei Guang-Hui Liu | 2023 | Science China(Life Sciences)2023，66，5： | 2 |
| 19 | STUDY ON CORRELATION BETWEEN THE MAST CELL AND THE ACUPOINT显示文摘In the new born rats or babies no low electric resistance(ER)at the acupoint wasfound,and the skin mast cells were round in shape distritiuted in uniform pattern everywhere.Therewas a tendancy toward decrease of ER at the acupoint in the rat or baby aged nearby one month,andthe rat mast cells were increased in number at the acupoint when compared with that beside the acupoint.In the human amputated lower extremity the mast cells became slender and more in number atthe dermal reticular layer of the acupoint.In the adult rats the ER decreased markedly and a numerous of mast cells(more predominent than that in the adult human)appeared oval in shape,distributedin un-uniform pattern with polarity;many rows(or chains)of mast cells,each of which consisted ofa few of mast cells contacting end to end along the cell length were packed into a longitudinal zone,rather corresponding to location of the″meridian″than located along the blood vessel.The resultssuggest that the mast cell may involve in | Zhong Anmin, Wu Jinglan, Hu Yilin, FengYan and Deng XinguoDept. of Histology &. Embryology, Henan Medical University, Zhengzhou 450052, China | 1994 | World Journal of Acupuncture-Moxibustion1994，4，4： | 1 |
| 20 | Green‑Solvent Processed Blade‑Coating Organic Solar Cells with an Efficiency Approaching 19%Enabled by Alkyl‑Tailored Acceptors显示文摘Power-conversion-efficiencies(PCEs)of organic solar cells(OSCs)in laboratory,normally processed by spin-coating technology with toxic halogenated solvents,have reached over 19%.However,there is usually a marked PCE drop when the bladecoating and/or green-solvents toward large-scale printing are used instead,which hampers the practical development of OSCs.Here,a new series of N-alkyl-tailored small molecule acceptors named YR-SeNF with a same molecular main backbone are developed by combining selenium-fused central-core and naphthalene-fused endgroup.Thanks to the N-alkyl engineering,NIR-absorbing YR-SeNF series show different crystallinity,packing patterns,and miscibility with polymeric donor.The studies exhibit that the molecular packing,crystallinity,and vertical distribution of active layer morphologies are well optimized by introducing newly designed guest acceptor associated with tailored N-alkyl chains,providing the improved charge transfer dynamics and stability for the PM6:L8-BO:YRSeNF-based OSCs.As a result,a record-high PCE approaching 19%is achieved in the blade-coating OSCs fabricated from a greensolvent o-xylene with high-boiling point.Notably,ternary OSCs offer robust operating stability under maximum-power-point tracking and well-keep>80%of the initial PCEs for even over 400 h.Our alkyl-tailored guest acceptor strategy provides a unique approach to develop green-solvent and blade-coating processed high-efficiency and operating stable OSCs,which paves a way for industrial development. | Hairui Bai Ruijie Ma Wenyan Su Top Archie Dela Pea Tengfei Li Lingxiao Tang Jie Yang Bin Hu Yilin Wang Zhaozhao Bi Yueling Su Qi Wei Qiang Wu Yuwei Duan Yuxiang Li Jiaying Wu Zicheng Ding Xunfan Liao Yinjuan Huang Chao Gao Guanghao Lu Mingjie Li Weiguo Zhu Gang Li Qunping Fan Wei Ma | 2023 | Nano-Micro Letters2023，15，12： | 1 |
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