Xiangyu Zhang

North China Electric Power University

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Sheng Jiang

China Pharmaceutical University

Kuojun Zhang

China Pharmaceutical University

Tianyu Wang

China Pharmaceutical University

Babak Razani

Washington University in St. Louis

Kaizhen Wang

China Pharmaceutical University

Shiqing Ma

University of Massachusetts Amherst

Guanhong Tao

Purdue University West Lafayette

Siyuan Cheng

Tencent (China)

Xiangzhe Xu

Purdue University West Lafayette

Guangyu Shen

Purdue University West Lafayette

Cooperative Institutions

Chinese Academy of Sciences

139

Central South University

Sun Yat-sen University

University of Chinese Academy of Sciences

Huazhong University of Science and Technology

Shanghai Jiao Tong University

Chinese Academy of Medical Sciences & Peking Union Medical College

Sichuan University

China Pharmaceutical University

Peking University

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Discovery of Benzo[d]oxazoles as Novel Dual Small-Molecule Inhibitors Targeting PD-1/PD-L1 and VISTA Pathway

Journal of Medicinal Chemistry (2024)

Kaizhen Wang Shi Cai Yao Cheng Zhihao Qi Xiang Ni

The blockers of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway have achieved great clinical success. However, the limited efficacy and low tumor response rate of anti-PD-1/PD-L1 monotherapy limit the clinical application of PD-1/PD-L1 inhibitors. V-domain immunoglobulin suppressor of T-cell activation (VISTA), a novel checkpoint regulator, exhibits potential synergy with PD-1/PD-L1 in enhancing antitumor immunity. Herein, we report the discovery of benzo[

10.1021/acs.jmedchem.4c01899

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Identification of flavonolignans from Silybum marianum seeds as allosteric protein tyrosine phosphatase 1B inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry (2018)

Ningbo Qin Tatsunori Sasaki Wei Li Jian Wang Xiangyu Zhang

Protein tyrosine phosphatase 1B (PTP1B) is an attractive molecular target for anti-diabetes, anti-obesity, and anti-cancer drug development. From the seeds of Silybum marianum, nine flavonolignans, namely, silybins A, B (1, 2), isosilybins A, B (3, 4), silychristins A, B (5, 6), isosilychristin A (7), dehydrosilychristin A (8), and silydianin (11) were identified as a novel class of natural PTP1B inhibitors (IC50 1.3 7–23.87 µM). Analysis of structure–activity relationship suggested that the absolute configurations at C-7" and C-8" greatly affected the PTP1B inhibitory activity. Compounds 1–5 were demonstrated to be non-competitive inhibitors of PTP1B based on kinetic analyses. Molecular docking simulations resulted that 1–5 docked into the allosteric site, including α3, α6, and α7 helix of PTP1B. At a concentration inhibiting PTP1B completely, compounds 1–5 moderately inhibited VHR and SHP-2, and weakly inhibited TCPTP and SHP-1. These results suggested the potentiality of these PTP1B inhibitors as lead compounds for further drug developments.

Silybum marianum

Docking (animal)

10.1080/14756366.2018.1497020

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Citations (16)

Abstract 384: Low Carbohydrate High Protein (LCHP) Diets are Atherogenic by Supplying Excess Amino Acids to Alter the Macrophage mTORC1-Autophagy Signaling Axis

Arteriosclerosis Thrombosis and Vascular Biology (2017)

Xiangyu Zhang Ismail Sergin Trent D. Evans Astrid R Vélez Babak Razani

Low carbohydrate high protein (LCHP) diets are commonly used in weight loss programs. However, the overall health benefits of such regimens are controversial with recent studies even suggesting an increased cardiovascular risk in certain populations. A few reports in animal models corroborate these concerns demonstrating increased LCHP-induced atherosclerosis. Interestingly, the downstream sequelae of such diets on tissues and cellular signaling are largely inferred with relevant mechanisms undefined. We first confirmed in the ApoE-null mouse model that LCHP diets are indeed atherogenic with the development of complex lesions. Using mass spectrometry, we find high protein feeding not only increases serum amino acid levels but increases amino acid load to tissues including the spleen and aorta with resultant activation of the mTORC1 signaling pathway particularly in macrophages. The involvement of mTORC1 is clearly causal as the atherogenic effect of LCHP-feeding is abrogated in macrophage-specific Raptor-null mice. Further mechanistic evaluation of the effects of amino acids on macrophages reveals dichotomous roles on a predominant mTORC1 target, autophagy. Certain amino acids such as Leucine potently activate mTORC1 via recruitment to lysosome and in turn suppress autophagy via ULK1 phosphorylation, whereas others such as glutamine act indirectly by downregulating the transcription of autophagy chaperones including p62/SQSTM1. This combined suppressive effect on autophagy leads to macrophage inflammasome activation and IL-1β release, accumulation of deleterious protein aggregates, and increased cell death. The in vivo relevance of this LCHP-amino acid-mTORC1-autophagy axis is supported by 1) the absence of increased atherosclerosis in macrophage autophagy-deficient (ATG5-/-) mice fed a LCHP diet, and 2) the absence of reduced atherosclerosis in mice dually deficient in macrophage mTORC1 and autophagy (Raptor/ATG5-/-). Our data provide the first mechanistic details of the deleterious effects of high protein diets on macrophages and the development of atherosclerosis. Incorporation of these concepts in clinical studies will be important to define the vascular effects of dietary protein.

10.1161/atvb.37.suppl_1.384

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Path sensitive static analysis of web applications for remote code execution vulnerability detection

2013 35th International Conference on Software Engineering (ICSE) (2013)

Yunhui Zheng Xiangyu Zhang

Remote code execution (RCE) attacks are one of the most prominent security threats for web applications. It is a special kind of cross-site-scripting (XSS) attack that allows client inputs to be stored and executed as server side scripts. RCE attacks often require coordination of multiple requests and manipulation of string and non-string inputs from the client side to nullify the access control protocol and induce unusual execution paths on the server side. We propose a path- and context-sensitive interprocedural analysis to detect RCE vulnerabilities. The analysis features a novel way of analyzing both the string and non-string behavior of a web application in a path sensitive fashion. It thoroughly handles the practical challenges entailed by modeling RCE attacks. We develop a prototype system and evaluate it on ten real-world PHP applications. We have identified 21 true RCE vulnerabilities, with 8 unreported before.

Cross-Site Scripting

Code (set theory)

Vulnerability

Server-side

Client-side

10.1109/icse.2013.6606611

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Citations (51)

Abstract 638: Delivery of Rapamycin-enriched Nanoparticles to Atherosclerotic Plaques Provides Targeted Regulation of the Macrophage Mtorc1-autophagy Signaling Axis

Arteriosclerosis Thrombosis and Vascular Biology (2018)

Xiangyu Zhang

Atherosclerotic vascular disease remains the leading cause of death in the United States with the majority of mortality due to coronary artery disease and myocardial infarction. Confirming several prior animal studies, we find the classic mTOR inhibitor, rapamycin, has potent atheroprotective effects in ApoE-null mice. However, an unfavorable system side-effect profile and a poor mechanistic understanding has significantly limited further evaluation of this promising therapy. Our previous work has indicated that macrophage mTORC1 signaling plays a critical role in plaque progression by inhibiting autophagy. We desired to develop a nanoparticle system to enable targeted delivery of rapamycin to plaque macrophages. Utilizing a chemokine receptor type 2 (CCR2)-binding peptide conjugated to tetraazacyclododecane tetraacetic acid (DOTA) and labeled with the fluorochrome Texas Red, we first prepared a nanoparticle system targeting macrophages and suitable for tracing in vivo. We show the specificity of these nanoparticles to macrophages in cell culture and plaque macrophages in vivo. We next loaded these nanoparticles with Rapamycin and show efficient inactivation of macrophage mTORC1 signaling and corresponding rescue of autophagy inhibition. Although the effects of this nanoparticle system in animal models of atherosclerosis is ongoing, our data support the utility of such targeted therapies in ameliorating the deleterious effects of macrophages in atherosclerosis.

Sirolimus

10.1161/atvb.38.suppl_1.638

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XNN: Paradigm Shift in Mitigating Identity Leakage within Cloud-Enabled Deep Learning

arXiv (Cornell University) (2024)

Kaixin Liu Huixin Xiong Bingyu Duan Zexuan Cheng Xinyu Zhou

In the domain of cloud-based deep learning, the imperative for external computational resources coexists with acute privacy concerns, particularly identity leakage. To address this challenge, we introduce XNN and XNN-d, pioneering methodologies that infuse neural network features with randomized perturbations, striking a harmonious balance between utility and privacy. XNN, designed for the training phase, ingeniously blends random permutation with matrix multiplication techniques to obfuscate feature maps, effectively shielding private data from potential breaches without compromising training integrity. Concurrently, XNN-d, devised for the inference phase, employs adversarial training to integrate generative adversarial noise. This technique effectively counters black-box access attacks aimed at identity extraction, while a distilled face recognition network adeptly processes the perturbed features, ensuring accurate identification. Our evaluation demonstrates XNN's effectiveness, significantly outperforming existing methods in reducing identity leakage while maintaining a high model accuracy.

Paradigm shift

Leakage (economics)

10.48550/arxiv.2408.04974

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Effects of Natural and Artificial Seawater on Digestive Gland and Gill Microorganisms of the Manila Clam (Ruditapes philippinarum) during Temporary Rearing without Feeding

Aquaculture Research (2023)

Feixia Zhu Xiangyu Zhang Jiao Liu Xiaohan Ma Jing Yang

The bacteria of shellfish bioaccumulate mainly in the gill and digestive gland tissues, which can affect shellfish health status and disease susceptibility under stressful conditions or environmental effects. Ruditapes philippinarum is a filter-feeding shellfish with both ecological and economic significance, and it is classified as a Mollusca (phylum), Bivalvia (class), Veneridae (family), and Ruditapes (genus). In this study, 16S high-throughput sequencing was used to explore the microbiomics of digestive glands and gills of R. philippinarum under temporary rearing without feeding (including the purification process) in different water environments (natural vs. artificial seawater) from 0–7 days. The results revealed that the digestive glands and gills of R. philippinarum had their own unique bacterial community structures. Tissue microorganisms under the overlap of different water environments and starvation factors showed different dynamic effects within 0–7 days. The sand spitting and purification steps (posttransport rehydration stage of 24 hours) effectively reduced microorganism abundance. There were different biomarkers in the prerearing and postrearing periods, and R. philippinarum may be more susceptible to the enrichment of opportunistic pathogenic bacteria during the postrearing period in artificial seawater.

Ruditapes

10.1155/2023/1042316

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Citations (3)

Table of Contents

2022 IEEE 5th Advanced Information Management, Communicates, Electronic and Automation Control Conference (IMCEC) (2022)

Shihua Liu Sheng Wen Min Wang Yucheng Zheng Min Wang

Table (database)

10.1109/imcec55388.2022.10020060

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Context-aware code generation with synchronous bidirectional decoder

Journal of Systems and Software (2024)

Xiangyu Zhang Yu Zhou Guang Yang Tingting Han Taolue Chen

Code (set theory)

Tree (set theory)

Forcing (mathematics)

10.1016/j.jss.2024.112066

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Citations (1)

An umbrella review of Lianhuaqingwen combined with Western medicine for the treatment of coronavirus disease 2019

Acupuncture and Herbal Medicine (2022)

Kelu Yang Jiaoyan Zhang Liang Zhao Luying Cheng Yuanyuan Li

Lianhua Qingwen combined with Western medicine (LHQW+WM) has been proposed as a viable treatment for coronavirus disease 2019 (COVID-19). Interestingly, umbrella reviews of systematic reviews (SRs), which provide the most comprehensive evidence, are the best evidence in evidence-based medicine. Therefore, an umbrella review of SRs that summarizes and evaluates the efficacy of LHQW+WM for COVID-19 is urgently required.

10.1097/hm9.0000000000000041

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Citations (13)