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Expanding the horizons of targeted protein degradation:A non-small molecule perspective

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2402-2427页

作者： Xiaowei Huang Fengbo Wu Jing Ye lian Wang Xiaoyun Wang Xiang Li gu He Department of Pharmacy and Department of Dermatology&Venerology West China HospitalSichuan UniversityChengdu 610041China Department of Urology West China HospitalSichuan UniversityChengdu 610041China Laboratory of Dermatology Clinical Institute of Inflammation and ImmunologyFrontiers Science Center for Disease-Related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond ***-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing *** we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.

关键词： Targeted protein degradation Proteolysis targeting chimera Endocytosis Autophagy Proximity-inducing modality Post-translational modification

Comparison of Plastic Surgery Training Programs Between Hong Kong and Shanghai

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Chinese Journal of Plastic and Reconstructive Surgery 2020年第3期2卷 169-173,176页

作者： Manhon CHUNG Xiang lian Bin gu Zhichao WANG Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

The field of plastic surgery has developed rapidly in the last couple of decades in Hong Kong and Shanghai,*** cities have their own educational system for training plastic *** training programs differ in many ways,including the surgical exposure of undergraduate studies,the structure,curriculum,and operative requirements of residency *** general,Hong Kong has a single pathway of residency training with more early clinical exposure in an undergraduate *** the contrary,Shanghai has multiple pathways of residency training that are heavily emphasized in academic *** Hong Kong and Shanghai should complement each other to modify their plastic surgery training programs that will eventually benefit the field of plastic surgery education。

关键词： Plastic surgery Residency training Hong Kong Shanghai China

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Evolutionary game dynamics of combining the Moran and imitation processes

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Chinese Physics B 2019年第2期28卷 94-105页

作者： Xian-Jia Wang Cui-Ling gu Shao-Jie Lv Ji quan Economics and Management School Wuhan University Institute of Systems Engineering Wuhan University School of Management Wuhan University of Technology

One of the assumptions of previous research in evolutionary game dynamics is that individuals use only one rule to update their strategy. In reality, an individual's strategy update rules may change with the environment, and it is possible for an individual to use two or more rules to update their strategy. We consider the case where an individual updates strategies based on the Moran and imitation processes, and establish mixed stochastic evolutionary game dynamics by combining both processes. Our aim is to study how individuals change strategies based on two update rules and how this affects evolutionary game dynamics. We obtain an analytic expression and properties of the fixation probability and fixation times(the unconditional fixation time or conditional average fixation time) associated with our proposed process. We find unexpected results. The fixation probability within the proposed model is independent of the probabilities that the individual adopts the imitation rule update strategy. This implies that the fixation probability within the proposed model is equal to that from the Moran and imitation processes. The one-third rule holds in the proposed mixed model. However, under weak selection, the fixation times are different from those of the Moran and imitation processes because it is connected with the probability that individuals adopt an imitation update rule. Numerical examples are presented to illustrate the relationships between fixation times and the probability that an individual adopts the imitation update rule, as well as between fixation times and selection intensity. From the simulated analysis, we find that the fixation time for a mixed process is greater than that of the Moran process, but is less than that of the imitation process. Moreover, the fixation times for a cooperator in the proposed process increase as the probability of adopting an imitation update increases; however, the relationship becomes more complex than a linear relationshi

关键词： evolutionary game dynamics Moran process imitation process fixation probability fixation time

Roll Shape Setting Technology of Hot Galvanizing and Planishing Mill

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Journal of Iron and Steel Research International 2007年第1期14卷 33-36页

作者： BAI Zhen-hua YANG Li-po LI Xing-dong gu Ting-quan Key Laboratory of Metastable Materials Science and Technology Yanshan University Qinhuangdao 066004 Hebei China College of Mechanical Engineering Yanshan University Qinhuangdao 066004 Hebei China Technique Center Baoshan Iron and Steel Co Ltd Shanghai 210900 China

A roll shape setting model was built for the hot galvanizing and planishing mill. The uniform transversal distributions of the front tension in the exit and the unit pressure were considered as the objective function. At the same time, the quality of the products, the stability of zinc layer, and the homogeneity of spangles were of considerable significance in the planishing process. The model was applied to the roll shape setting of the 1800 cold rolling 3# CGL hot galvanizing and planishing mill of Baosteel Co Ltd. After being planished, the flatness of a strip that was less than 6 I was more than 97%, and the flatness of others were less than 10 I; the pass percentage of the zinc lay- ers reached 100%.

关键词： hot galvanizing planishing mill roll shape optimization

Prediction and Experimental Validation of Forming Limit Curve of a Quenched and Partitioned Steel

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Journal of Iron and Steel Research International 2016年第6期23卷 580-585页

作者： Xue-li GAO Jun-ying MIN Ling ZHANG quan-chao LI Chang-wei lian Jian-ping LIN School of Mechanical Engineering Tongji University Shanghai 201804 China Chair of Production Systems Ruhr-University Bochum Bochum 44801 Germany State Key Laboratory of Development and Application Technology of Automotive Steels (Baosteel) Shanghai 201900 China

Forming limit curve（FLC）is an effective tool to evaluate the formability of sheet *** accurate FLC prediction for a sheet metal is beneficial to its engineering application.A quenched and partitioned steel,known as QP980,is one of the 3rd generation advanced high strength steels and is composed of martensite,ferrite and a considerable amount of retained austenite（RA）.Martensite transformation from RA induced by deformation,namely,transformation induced plasticity（TRIP）,promotes the capability of work hardening and consequently *** tests were carried out to obtain the experimental forming limit strains with the aid of digital image correlation *** electron microscopy（SEM）was employed to examine the fracture morphologies of Nakazima specimens of the QP980 *** observed dimple pattern indicated that tensile stress was the predominant factor which led to failure of QP980 ***,maximum tensile stress criterion（MTSC）was adopted as the forming limit *** predict the FLC of QP980 steel,Von-Mises yield criterion and power hardening law were adopted according to the tested mechanical properties of QP980 *** were compared with those derived from other three representative instability theories,*** criterion,Storen-Rice vertex theory and Bressan-Williams model,which shows that the MTSC based FLC is in better agreement with the experimental results.

关键词： criterion tensile martensite hardening plasticity TRIP austenite steels ferrite quenched

Aspiration therapy for acute embolic occlusion of the superior mesenteric artery

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World Journal of Gastroenterology 2019年第7期25卷 848-858页

作者： Yi-Ren Liu Zhu Tong Cheng-Bei Hou Shi-Jun Cui lian-Rui guo Yi-Xia Qi Li-Xing Qi Jian-Ming guo Yong-quan gu Department of Vascular Surgery Xuanwu Hospital Capital Medical University Center of Evidence-Based Medicine Xuanwu Hospital Capital Medical University

BACKGROUND Embolic superior mesenteric artery(SMA) occlusion is associated with high mortality rates. Delayed treatment often leads to serious consequences, including intestinal necrosis, resection, and even patient death. Endovascular repair is being introduced, which can improve clinical symptoms and prognosis and decrease the incidence of exploratory laparotomy. Many reports have described successful endovascular revascularization of embolic SMA occlusion. However,most of those reports are case reports, and there are few reports on Chinese patients. In this paper, we describe the technical and clinical outcomes of aspiration therapy using a guiding catheter and long sheath technique which facilitates the endovascular repair *** To evaluate the complications, feasibility, effectiveness, and safety of endovascular treatment for the acute embolic occlusion of the *** This retrospective study reviewed eight patients(six males and two females)from August 2013 to October 2018 at Xuanwu Hospital, Capital Medical University. The patients presented with acute embolic occlusion of the SMA on admission and were initially diagnosed by computed tomography angiography(CTA). The patients who underwent endovascular treatment with a guiding catheter had no obvious evidence of bowel infarct. No intestinal necrosis was identified by gastrointestinal surgeons through peritoneal puncture or CTA. The complications, feasibility, effectiveness, safety, and mortality were *** Six(75%) patients were male, and the mean patient age was 70.00 ± 8.43 years(range, 60-84 years). The acute embolic occlusion of the SMA was initially diagnosed by CTA. All patients had undertaken anticoagulation primarily, and percutaneous aspiration using a guiding catheter was then undertaken because the emboli had large amounts of thrombus residue. No death occurred among the patients. Complete patency of the suffering artery trunk was achieved in six patients, and defect filling w

关键词： Superior mesenteric artery Acute embolic occlusion Aspiration embolectomy Transcatheter thrombolysis Endovascular repair

Phylogenetic Analysis of mtDNA from the Ancient Human of Yuan Dynasty in Inner Mongolia in China

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Chemical Research in Chinese Universities 2006年第2期22卷 177-180页

作者： FU Yu-qin XU Xue-lian ZHANG Xiao-lei ZHANG quan-chao ZHOU Hui ZHU Hong Ancient DNA Laboratory Research Center for Chinese Frontier Archaeology Jilin UniversityChangchun 130012 P. R. China College of Life Science Jilin University 130021 P. R. China

A study of the genetic structure of an ancient human excavated from the Yikeshu site of Yuanshangdu ancient city in Inner Mongolia and the relationships between the ancient population and the extant populations was carried out. Sequences of the control region and coding region of mtDNA from the ancient human were analyzed by using direct sequencing and restriction-fragment length polymorphism （RFLP） methods, Phylogenetic analysis and multidimensional scaling analysis were also performed on the mtDNA data of the ancient population and 12 extant populations. These results show that the ancient individuals of Yikeshu site can be assigned to D, G, B and Z haplogroups that are prevalent in Duars and Mongolians from Inner Mongolia. The ancient population is also closer to Duar and Mongolian populations in genetic distance than other compared populations. This study reveals that the ancient population from Yikeshu site in the Yuan Dynasty shares a common ancestor with Mongolic-speaking Daur and Mongolian tribes.

关键词： MtDNA Polymorphism Phylogenetic analysis

Discrepancy in fine root turnover estimates between diameter-based and branch-order-based approaches:a case study in two temperate tree species

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Journal of Forestry Research 2012年第4期23卷 575-581页

作者： SUN Jing-jue gu Jia-cun WANG Zheng-quan School of Forestry Northeast Forestry UniversityHarbin 150040China

Fine root turnover plays a key role in carbon （C） budgets and nutrients cycles in forest ecosystems. However, the difference between branch-order-based and diameter-based approaches in estimating fine root turnover is still unclear. We studied root biomass turnover based on multiplying root standing biomass by turnover rate （inverse of median root longevity） in two Chinese temperate tree species, Fraxinus mand- shurica Rupr. and Larix gmelinii Rupr. The minirhizotron （MR） tech- nique was used to estimate longevities for first and second order roots, and total roots （R,o,al） apparent on the MR tube surface. The correspond- ing biomass for each root group was estimated by soil monolith. The difference in biomass turnover between Rtotal and the sum of the first and second order roots was used to represent the discrepancy between di- ameter- and order-based approaches. First order roots had shorter life spans and higher biomass turnover rates than the second order roots in both species. Biomass turnover estimated by the order-based method for F. mandshurica and L. gmelinii were 155.4 *** 158.9 g.m2.a-1, respectively, in comparison with 99.5 g.m^-2-a^-1 and 117.7 g.m^-2.a^-1 estimated by the diameter-based method, indicating that the diameter-based approach underestimated biomass turnover. The most probable reason was that the order-based method enhanced separation of the heterogeneous root population into relatively homogenous root groups with varying turnover rates. We conclude that separating fine root pool into different branch orders can improve the accuracy of estimates for fine root turnover, as well as the understanding of the belowground C allocation and nutrient cycling at ecosystem level.

关键词： Fraxinus mandshurica root life span root longevity Larix gmelinii minirhizotron soil monolith

Optimizing profile line interval for enhanced accuracy in rock joint morphology and shear strength assessments

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International Journal of Mining Science and Technology 2024年第5期34卷 587-608页

作者： Leibo Song quan Jiang Shigui Du Jiamin Song Gang Wang Yanting gu Xingkai Wang Jinzhong Wu School of Civil Engineering Shaoxing UniversityShaoxing 312000China Key Laboratory of Rock Mechanics and Geohazards of Zhejiang Province Shaoxing UniversityShaoxing 312000China State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan 430071China Institute of Rock Mechanics Ningbo UniversityNingbo 315211China

2D profile lines play a critical role in cost-effectively evaluating rock joint properties and shear ***, the interval(ΔI_(L)) between these lines significantly impacts roughness and shear strength assessments. A detailed study of 45 joint samples using four statistical measures across 500 different ΔI_(L)values identified a clear line interval effect with two stages: stable and *** statistical analysis showed a linear relationship between the error bounds of four parameters,shear strength evaluation, and their corresponding maximum ΔI_(L)values, where the gradient k of this linear relationship was influenced by the basic friction angle and normal stress. Accounting for these factors,lower-limit linear models were employed to determine the optimal ΔI_(L)values that met error tolerances(1%–10%) for all metrics and shear strength. The study also explored the consistent size effect on joints regardless of ΔI_(L)changes, revealing three types of size effects based on morphological ***, larger joints required generally higher ΔI_(L)to maintain the predefined error limits, suggesting an increased interval for large joint analyses. Consequently, this research provides a basis for determining the optimal ΔI_(L), improving accuracy in 2D profile line assessments of joint characteristics.

关键词： Rock joint Roughness Shear strength Size effect Profile line interval effect