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Efficient and multiplex gene upregulation in plants through CRISPR-Cas-mediated knockin of enhancers

Molecular Plant 2024年第9期17卷 1472-1483页

作者： Qi Yao Rundong Shen yang Shao Yifu Tian Peijin Han Xuening Zhang jian-Kang Zhu Yuming Lu Shanghai Collaborative Innovation Center of Agri-Seeds Joint Center for Single-Cell BiologySchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China Shanghai Center for Plant Stress Biology Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 201602China University of the Chinese Academy of Sciences BeijingChina College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China institute of Advanced Biotechnology and School of Medicine Southern University of Science and TechnologyShenzhen 518055China

Geneupregulation through genome editing is important for plant research and *** insertion of short transcriptional enhancers(STEs)into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with ***,we introduce an“in locus activation”technique in rice that leverages well-characterized STEs for refined,heritable,and multiplexed gene *** address the scarcity of potent enhancers,we developed a large-scale mining approach and discovered a suite of STEs that are capable of enhancing gene expression in rice *** in locus integration of these STEs into eight rice genes resulted in substantial tran-scriptional upregulation in the edited plants,with up to 869.1-fold increases in their transcript ***-ploying a variety of STEs,we achieved delicate control of gene expression,enabling the fine-tuning of key phenotypic traits such as plant *** approach also enabled efficient multiplexed gene upregu-lation,with up to four genes activated simultaneously,significantly enhancing the nicotinamide mononucleotide metabolic ***,heritability studies from the To to T3 generations confirmed the stable and heritable nature of STE-driven gene ***,our work demon-strates that coupled with STE mining,leveraging genome editing for in locus activation and gene upregu-lation holds great promise to be widely adopted in fundamental plant research and crop breeding.

关键词： genome editing short transcriptional enhancers gene upregulation crop breeding

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Comparison of thermal shock resistance capabilities of the rotary swaged pure tungsten,potassium-doped tungsten,and W-La2O3 alloys

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Tungsten 2024年第4期6卷 759-766页

作者： Tao yang Hao Wang Fan Feng Xiang Liu Xue-Yu Gong You-Yun Lian jian-Bao Wang School of Nuclear Science and Technology University of South China Southwestern Institute of Physics

Tungsten-based materials are one of the most important candidates for the plasma facing materials（PFMs） of future fusion reactors,and it is necessary to study the properties of tungsten-based materials under the service conditions of fusion devices to ensure the long-term steady-state operation of future fusion *** this paper,different tungsten-based materials made by the same rotary swaging process are selected to simulate the transient thermal loads on the PFMs of a fusion reactor using an electron beam,and thermal load experiments are carried out by changing the power density of a loading pulse and the pulse *** is found that different tungsten-based materials made by the same process have large differences in thermal shock resistance,and the doped tungsten materials（W-K and W-La2O3） are significantly better than the pure tungsten materials with the increase in thermal shock power density and the number of cycles,especially the W-K materials,which have excellent performance.

关键词： Electron beam Rotary swaging Thermal shock Tungsten materials

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Enhanced extracellular production of alpha-lactalbumin from Bacillus subtilis through signal peptide and promoter screening

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Food Science and Human Wellness 2024年第4期13卷 2310-2316页

作者： Yuqi Zhu Pengdong Sun Chunjian Li Yu Zhang Yu Wang Jingyuan Li Yanfeng Liu jian Chen yang Deng College of Food Science and Engineering Qingdao Agricultural UniversityQingdao 266109China Key Laboratory of Special Food Processing(Co-construction by Ministry and Province) Ministry of Agriculture Rural AffairsQingdao Agricultural UniversityQingdao 266109China Qingdao Special Food Research Institute Qingdao 266109China Science Center for Future Foods Engineering Research Center of Ministry of Education on Food Synthetic BiotechnologyJiangsu Province Engineering Research Center of Food Synthetic BiotechnologyJiangnan UniversityWuxi 214122China Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China

Alpha-lactalbumin(α-LA)is a major whey protein found in breast milk and plays a crucial role in the growth and development of *** this study,Bacillus subtilis RIK1285 harboring AprE signal peptide(SP)was selected as the original strain for the production ofα-*** was found thatα-LA was identified in the pellet after ultrasonic disruption and centrifugation instead of in the fermentation *** original strain most likely only producedα-LA intracellular,but not *** improve the expression and secretion ofα-LA in RIK1285,a library of 173 homologous SPs from the *** 168 genome was fused with target LALBA gene in the pBE-S vector and expressed extracellularly in *** YjcN was determined to be the best signal *** in supernatant were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and purified by nickel column to calculate the highest yield signal *** addition,different promoters(P_(aprE),P_(43),and P_(glv))were compared and *** results indicated that the strain RIK1285-pBE-P_(glv)-YjcN-LALBA had the highestα-LA yield,reaching 122.04μg/*** study demonstrates successful expression and secretion of humanα-LA in *** and establishes a foundation for simulating breast milk for infant formulas and developing bioengineered milk.

关键词： Bacillus subtilis Alpha-lactalbumin Bioengineering milk Signal peptide Promoter screening

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Research on Anthropomorphic Obstacle Avoidance Trajectory Planning for Adaptive Driving Scenarios Based on Inverse Reinforcement Learning Theory

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Engineering 2024年第2期33卷 133-145页

作者： jian Wu yang Yan Yulong Liu Yahui Liu School of Mechanical and Automotive Engineering Liaocheng UniversityLiaocheng 252000China 2 School of Vehicle and Mobility Tsinghua UniversityBeijing 100084China

The forward design of trajectory planning strategies requires preset trajectory optimization functions,resulting in poor adaptability of the strategy and an inability to accurately generate obstacle avoidance trajectories that conform to real driver behavior *** addition,owing to the strong time-varying dynamic characteristics of obstacle avoidance scenarios,it is necessary to design numerous trajectory optimization functions and adjust the corresponding ***,an anthropomorphic obstacle-avoidance trajectory planning strategy for adaptive driving scenarios is ***,numerous expert-demonstrated trajectories are extracted from the HighD natural driving ***,a trajectory expectation feature-matching algorithm is proposed that uses maximum entropy inverse reinforcement learning theory to learn the extracted expert-demonstrated trajectories and achieve automatic acquisition of the optimization function of the expert-demonstrated ***,a mapping model is constructed by combining the key driving scenario information that affects vehicle obstacle avoidance with the weight of the optimization function,and an anthropomorphic obstacle avoidance trajectory planning strategy for adaptive driving scenarios is ***,the proposed strategy is verified based on real driving *** results show that the strategy can adjust the weight distribution of the trajectory optimization function in real time according to the“emergency degree”of obstacle avoidance and the state of the ***,this strategy can generate anthropomorphic trajectories that are similar to expert-demonstrated trajectories,effectively improving the adaptability and acceptability of trajectories in driving scenarios.

关键词： Obstacle avoidance trajectory planning Inverse reinforcement theory Anthropomorphic Adaptive driving scenarios

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Differential distribution of fibrovascular proliferative membranes in 25-gauge vitrectomy for proliferative diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1462-1468页

作者： Nan Lu Shi-Lin yang Shuo Guo Dong-Ni yang Li Liu Chun-Hui Fan Ying Guo jian Liu Wei Zhao Department of Ophthalmology the First Hospital of QinhuangdaoQinhuangdao 066000Hebei ProvinceChina School of Control Engineering Northeastern University at QinhuangdaoQinhuangdao 066004Hebei ProvinceChina

AIM:To analyze the distribution of fibrovascular proliferative membranes(FVPMs)in proliferative diabetic retinopathy(PDR)patients that treated with pars plana vitrectomy(PPV),and to evaluate the outcomes ***:This was a retrospective and cross-sectional *** 25-gauge(25-G)PPV cases operated for PDR from May 2018 to April *** to the FVPMs images outlined after operations,subjects were assigned into three groups:arcade type group,juxtapapillary type group,and central type *** patients were followed up for over one *** characteristics,operation-related variables,postoperative parameters and complications were ***:Among 103 eyes recruited,the FVPMs distribution of nasotemporal and inferiosuperioral was significantly different(both P<0.01),with 95(92.23%)FVPMs located in the nasal quadrants,and 74(71.84%)in the *** eyes with a central FVPM required the longest operation time,with silicon oil used in most patients,generally combined with tractional retinal detachment(RD)and rhegmatogenous RD,the worst postoperative bestcorrected visual acuity(BCVA)and the highest rates of recurrent RD(all P<0.05).FVPM type,age of onset diabetes mellitus,preoperative BCVA,and combined with tractional RD and rhegmatogenous RD were significantly associated with BCVA improvement(all P<0.05).Compared with the central type group,the arcade type group had higher rates of BCVA ***:FVPMs are more commonly found in the nasal and inferior mid-peripheral retina in addition to the area of arcade *** 25-G PPV for treating PDR eyes with central FVPM have relatively worse prognosis.

关键词： proliferative diabetic retinopathy fibrovascular proliferative membrane 25-gauge pars plana vitrectomy

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3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma

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Food Science and Human Wellness 2024年第3期13卷 1453-1464页

作者： Mengjie Liu Xuqiang Liu Kaiyue He Yongping jian Yujia Li Jinrong Guo Jingyu yang Zhixiang Xu Wenyi Kang School of Life Sciences Henan UniversityKaifeng 475004China National R&D Center for Edible Fungus Processing Technology Henan UniversityKaifeng 475004China Joint International Research Laboratory of Food&Medicine Resource Function Kaifeng 475004China Shenzhen Research Institute of Henan University Shenzhen 518000China

3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)is a pentacyclic triterpene mainly distributed in food and medicinal plants,which exhibits various pharmacological ***,whether these functions are attributed to eBAG or additional components in these plants remain ***,we report that eBAG exerted an inhibitory activity against hepatocellular carcinoma and esophageal cancer *** induced non-apoptotic cell death in hepatocellular carcinoma *** eBAG-induced cell death was inhibited by knock-down of autophagy related gene(ATG)5 and ATG7,by administration of 3-methyladenine,a selective autophagy inhibitor that suppresses phosphoinositide 3-kinase(PI3K),and by chloroquine,a classic autophagy flux *** demonstrated that eBAG induced an autophagy-mediated cell *** of eBAG mimicked cellular bioenergetics depletion leading to the reduction of intracellular ATP,activation of AMP-activated protein kinase(AMPK),and inhibition of ***-treatment with compound C,an AMPK inhibitor,abrogated cell death induced by *** further validated the anti-tumor effect of eBAG in the murine xenograft model of hepatocellular carcinoma and found that eBAG treatment promoted the induction of autophagy and reduction of tumor growth in *** a functional food ingredient,eBAG is a potential therapeutic agent for the treatment of hepatocellular carcinoma and esophageal cancer.

关键词： eBAG Autophagy ATP AMPK Hepatocellular carcinoma

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A 128×128 SPAD LiDAR sensor with column-parallel 25 ps resolution TA-ADCs

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Journal of Semiconductors 2024年第8期45卷 34-40页

作者： Na Tian Zhe Wang Kai Ma Xu yang Nan Qi jian Liu Nanjian Wu Runjiang Dou Liyuan Liu State Key Laboratory of Superlattices and Microstructures Institute of SemiconductorsChinese Academy of SciencesBeijing 100049China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China

This paper presents a design of single photon avalanche diode(SPAD)light detection and ranging(LiDAR)sensor with 128×128 pixels and 128 column-parallel time-to-analog-merged-analog-to-digital converts(TA-ADCs).Unlike the conventional TAC-based SPAD LiDAR sensor,in which the TAC and ADC are separately implemented,we propose to merge the TAC and ADC by sharing their capacitors,thus avoiding the analog readout noise of TAC’s output buffer,improving the conversion rate,and reducing chip *** reverse start-stop logic is employed to reduce the power of the *** in a 180 nm CMOS process,our prototype sensor exhibits a timing resolution of 25 ps,a DNL of+0.30/−0.77 LSB,an INL of+1.41/−2.20 LSB,and a total power consumption of 190 mW.A flash LiDAR system based on this sensor demonstrates the function of 2D/3D imaging with 128×128 resolution,25 kHz inter-frame rate,and sub-centimeter ranging precision.

关键词： 3D imaging CMOS imagers direct time-of-flight(dTOF) time-to-analog converter(TAC)

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Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking LOXL2-mediated vascularization

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Bone Research 2024年第2期12卷 372-389页

作者： Longqing Wang Wenhao jiang Siyuan Zhao Dong Xie Qing Chen Qi Zhao Hao Wu jian Luo Lili yang Spine Center Department of OrthopaedicsShanghai Changzheng HospitalSecond Affiliated Hospital of Naval Medical UniversityShanghai 200003PR China yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center) Tongji University School of MedicineShanghaiPR China Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghaiPR China Department of Orthopaedics No.905 Hospital of PLA NavyShanghaiPR China

Ossification of the Posterior Longitudinal Ligament(OPLL)is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone,resulting in limited spinal mobility and nerve *** both bulk and single-cell RNA sequencing,we elucidate the molecular characteristics,cellular components,and their evolution during the OPLL process at a single-cell resolution,and validate these findings in clinical *** study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in ***,our study identifies LOXL2 as a key regulator in this *** gain-and loss-of-function studies,we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament *** acts via the HIF1A pathway,promoting the secretion of downstream VEGFA and *** function is not related to the enzymatic activity of ***,we identify sorafenib,a broad-spectrum tyrosine kinase inhibitor,as an effective suppressor of LOXL2-mediated vascular *** disrupting the coupling between vascularization and osteogenesis,sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone *** findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.

关键词： LOXL2 ligament finding

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High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 787-797页

作者： Peng-yang Zhou De-Xiang Zhu Yi-Jiao Chen Qing-yang Feng Yi-Hao Mao Ao-Bo Zhuang jian-Min Xu Department of General Surgery Zhongshan Hospital Fudan UniversityShanghai 200032China

BACKGROUND Patatin like phospholipase domain containing 8(PNPLA8)has been shown to play a significant role in various cancer *** studies have focused on its roles as an antioxidant and in lipid ***,the role of PNPLA8 in colorectal cancer(CRC)progression is *** To explore the prognostic effects of PNPLA8 expression in *** A retrospective cohort containing 751 consecutive CRC patients was ***8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive *** patients were divided into high and low PNPLA8 expression groups based on the cut-off va-lues,which were calculated by X-tile *** prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression *** over-all survival(OS)rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank *** PNPLA8 expression was significantly associated with distant metastases in our cohort(P=0.048).CRC patients with high PNPLA8 expression indicated poor OS(median OS=35.3,P=0.005).CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter *** patients with left-sided colon and rectal cancer,the survival curves of two PN-PLA8-expression groups showed statistically significant *** analysis also confirmed that high PNPLA8 expression was an independent prog-nostic factor for overall survival(hazard ratio HR=1.328,95%CI:1.016-1.734,P=0.038).

关键词： Biomarker Colorectal cancer Expression level Overall survival Patatin like phospholipase domain containing 8 Prognosis

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Effect of screening colonoscopy frequency on colorectal cancer mortality in patients with a family history of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 354-363页

作者： Li Zheng Bin Li Ling Lei Li-Jia Wang Zhi-Ping Zeng jian-Dong yang Department of Gastroenterology The First Hospital of NanchangNanchang 330008Jiangxi ProvinceChina Department of General Surgery The First Hospital of NanchangNanchang 330008Jiangxi ProvinceChina

BACKGROUND Colorectal cancer is a common malignant tumor in China,and its incidence in the elderly is increasing *** bowel disease is a group of chronic non-specific intestinal inflammatory diseases,including ulcerative colitis and Crohn’s *** included the clinicopathological and follow-up data of patients with colorectal cancer who underwent laparoscopic colectomy or open colectomy at our Gastrointestinal Department between January 2019 and December *** indicators,oncological indicators,and survival rates were compared between the *** results of 104 patients who met the above criteria were extracted from the database(laparoscopic colectomy group=63,open colectomy group=41),and there were no statistically significant differences in the baseline data or follow-up time between the two *** Intraoperative blood loss,time to first ambulation,and time to first fluid intake were significantly lower in the laparoscopic colectomy group than in the open colectomy *** differences in overall mortality,tumor-related mortality,and recurrence rates between the two groups were not statistically significant,and survival analysis showed that the differences in the cumulative overall survival,tumor-related survival,and cumulative recurrence-free rates between the two groups were not statistically *** In elderly patients with colorectal cancer,laparoscopic colectomy has better short-term outcomes than open colectomy,and laparoscopic colectomy has superior long-term survival outcomes compared with open colectomy.

关键词： Colorectal cancer Laparoscopic surgery Open surgery Prognosis Laparoscopic colectomy Open colectomy

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