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Targeting Hypoxia and Autophagy Inhibition via Delivering Sonodynamic Nanoparticles With HIF-2α Inhibitor for Enhancing Immunotherapy in Renal Cell Carcinoma

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ADVANCED HEALTHCARE MATERIALS 2024年第32期13卷 e2402973页

作者： Zhu, Yihao Li, Yajian Li, xuwen Yu, Yuan Zhang, Lingpu Zhang, Hanchen chen, Can chen, Dong Wang, Mingshuai Xing, Nianzeng Yang, Feiya Wasilijiang, Wahafu Ye, Xiongjun Chinese Acad Med Sci & Peking Union Med Coll Dept Urol Natl Canc Ctr Natl Clin Res Ctr CancCanc Hosp Beijing 100021 Peoples R China Chinese Acad Sci Hangzhou Inst Med Zhejiang Canc Hosp Hangzhou 310022 Zhejiang Peoples R China Chinese Acad Sci Inst Chem Lab Polymer Phys & Chem Beijing Natl Lab Mol Sci Beijing 100190 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Zunyi Med Univ Affiliated Hosp 2 Dept Oncol Zunyi 563000 Guizhou Peoples R China Shanxi Med Univ Canc Hosp Dept Urol Shanxi Prov Canc HospShanxi HospCanc HospChine Xian 030013 Shanxi Peoples R China

Immune checkpoint blockers (ICBs) therapy stands as the first-line treatment option for advanced renal cell carcinoma (RCC). However, its effectiveness is hindered by the immunosuppressive tumor microenvironment (TME). Sonodynamic therapy (SDT) generates tumor cell fragments that can prime the host's antitumor immunity. Nevertheless, the hypoxic microenvironment and upregulated autophagy following SDT often lead to cancer cell resistance. In response to these challenges, a hypoxia-responsive polymer (Poly(4,4 '-azobisbenzenemethanol-PMDA)-mPEG(5k), P-APm) encapsulating both a HIF-2 alpha inhibitor (belzutifan) and the ultrasonic sensitize (Chlorin e6, Ce6) is designed, to create the nanoparticle APm/Ce6/HIF. APm/Ce6/HIF combined with ultrasound (US) significantly suppresses tumor growth and activates antitumor immunity in vivo. Moreover, this treatment effectively transforms the immunosuppressive microenvironment from "immune-cold" to "immune-hot", thereby enhancing the response to ICBs therapy. The findings indicate that APm/Ce6/HIF offers a synergistic approach combining targeted therapy with immunotherapy, providing new possibilities for treating RCC.

关键词： HIF-2 alpha immunotherapy renal cell carcinoma sonodynamic therapy

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Path Sensitive Fuzzing for Native Applications

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IEEE TRANSACTIONS ON DEPENDABLE AND SECURE COMPUTING 2022年第3期19卷 1544-1561页

作者： Gan, Shuitao Zhang, Chao Qin, Xiaojun Tu, xuwen Li, Kang Pei, Zhongyu chen, Zuoning State Key Lab Math Engn & Adv Comp Wuxi Jiangsu Peoples R China Tsinghua Univ Inst Network Sci & Cyberspace Beijing 100084 Peoples R China Beijing Natl Res Ctr Informat Sci & Technol Beijing 100084 Peoples R China Anonymous Univ Beijing Peoples R China

Coverage-guided fuzzing is a widely used and effective solution to find software vulnerabilities. Tracking code coverage and utilizing it to guide fuzzing are crucial to coverage-guided fuzzers. However, tracking full and accurate path coverage is infeasible in practice due to the high instrumentation overhead. Popular fuzzers (e.g., AFL) often use coarse coverage information, e.g., edge hit counts stored in a compact bitmap, to achieve highly efficient greybox testing. Such inaccuracy and incompleteness in coverage introduce serious limitations to fuzzers. First, it causes path collisions, which prevent fuzzers from discovering potential paths that lead to new crashes. More importantly, it prevents fuzzers from making wise decisions on fuzzing strategies. In this article, we propose a coverage sensitive fuzzing solution CollAFL. It mitigates path collisions by providing more accurate coverage information, while still preserving low instrumentation overhead. It also utilizes the coverage information to apply three new fuzzing strategies, promoting the speed of discovering new paths and vulnerabilities. We implemented two variants of this solution, namely CollAFL (based on AFL) and CollAFL-bin (based on AFL-dyninst), to test applications with and without source code respectively, and evaluated them on 24 popular applications. The results showed that path collisions are common, i.e., up to 75 percent of edges could collide with others in some applications. But our solutions CollAFL and CollAFL-bin could reduce the edge collision ratio to nearly zero. Moreover, armed with the three fuzzing strategies, they outperform their counterparts (i.e., AFL and AFL-dyninst) in terms of both code coverage and vulnerability discovery. On average, CollAFL covered 20 percent more program paths, and found 320 percent more unique crashes and 260 percent more bugs than AFL in 200 hours. Moreover, CollAFL-bin covered 15 percent more paths, and found 200 percent more unique crashes and 15

关键词： Fuzzing Computer bugs Instruments Security Grammar Cyberspace Coverage-guided fuzzing path collision bitmap seed selection policy source code binary code

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Hypothesis paper: electroacupuncture targeting the gut-brain axis to modulate neurocognitive determinants of eating behavior-toward a proof of concept in the obese minipig model

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EATING AND WEIGHT DISORDERS-STUDIES ON ANOREXIA BULIMIA AND OBESITY 2021年第1期26卷 61-74页

作者： Zhang, xuwen chen, Hanwei Val-Laillet, David Panyu Cent Hosp Guangzhou Peoples R China Guanzhou Univ Chinese Med Guangzhou Peoples R China Univ Rennes INRAE INSERM Nutr Metabol & CancNuMeCan 16 Le Clos F-35590 Rennes France

Acupuncture has thousands of years of history and perspective for the treatment of many health problems and disorders. Beneficial effects of acupuncture on obesity have been demonstrated at various levels in animals and clinical trials, with almost no adverse effect, even when combined with local electrical stimulation, i.e., electroacupuncture (EA), a way to potentiate the effects of acupuncture. However, there is still scattered evidence about the impact of EA on brain functions related to the control of eating behavior, and notably on the gut-brain axis mechanisms involved in these putative central modulations. During the past 10 years, we have described a convincing diet-induced obese minipig model, and successfully implemented brain imaging and neurocognitive approaches to challenge mechanistic hypotheses and innovative therapeutic strategies. In the present article, we propose to confront the current literature on the acupuncture and EA effects on the gut-brain axis and obesity with the latest developments in nutrition and neuroscience research using the minipig model. Our aims are to (a) elaborate functional hypotheses on the gut-brain mechanisms underlying EA effects on obesity, and especially on the role of the vagus nerve, and (b) present the rational for testing these hypotheses in the minipig model.

关键词： Obesity Vagus nerve Brain activity Brain imaging Pig model

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The derivation of the t3energy-critical nls from quantum many-body dynamics

arXiv

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arXiv 2018年

作者： chen, xuwen Holmer, Justin Department of Mathematics University of Rochester RochesterNY14627 United States Department of Mathematics Brown University 151 Thayer Street ProvidenceRI02912 United States

We derive the 3D energy critical quintic NLS from quantum many-body dynamics with 3-body interaction in the Ts(periodic) setting. Due to the known complexity of the energy critical setting, previous progress was limited in comparison to the 2-body interaction case yielding energy subcritical cubic NLS. Previously, the only result for the 3D energy critical case was [47], which proved the uniqueness part of the argument in the case of small solutions. In the main part of this paper, we develop methods to prove the convergence of the BBGKY hierarchy to the infinite Gross-Pitaevskii (GP) hierarchy, and separately, the uniqueness of large GP solutions. Since the trace estimate used in the previous proofs of convergence is the false endpoint trace estimate in our setting, we instead introduce a new frequency interaction analysis and apply the finite dimensional quantum de Finetti theorem. For the large solution uniqueness argument, we discover the new HUFL (hierarchical uniform frequency localization) property for the GP hierarchy and use it to prove a new type of uniqueness theorem. The HUFL property reduces to a new statement even for NLS. With the help of [28, 48] which proved the global well-posedness for the quintic NLS, this new uniqueness theorem establishes global uniqueness. Copyright © 2018, The Authors. All rights reserved.

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Modifiable factors affects cancer-specific survival: findings from a large population-based prospective cohort study

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JOURNAL OF TRANSLATIONAL MEDICINE 2025年第1期23卷 1-12页

作者： chen, Xiong Zhu, Dongxi Li, chenchen Lin, Yi Lv, Lin Ai, Feiling chen, Zhijian Shen, Runnan Shen, xuwen You, Guochang Jiang, Zhige Zhong, Wenlong Lin, Tianxin Sun Yat Sen Univ Sun Yat Sen Mem Hosp Dept Urol Guangzhou Peoples R China Sun Yat Sen Univ Sun Yat Sen Mem Hosp Guangdong Prov Key Lab Malignant Tumor Epigenet & Guangdong Hong Kong Joint Lab RNA Med Guangzhou Guangdong Peoples R China Guangdong Prov Clin Res Ctr Urol Dis Guangzhou Peoples R China Sun Yat Sen Univ Affiliated Hosp 6 Dept Med Oncol Guangzhou Peoples R China Sun Yat Sen Univ Sch Med Guangzhou Peoples R China Ludwig Maximilian Univ Munich Fac Med Munich Germany

BackgroundModifiable factors affect cancer's survival but literature did not differentiate prior to versus after cancer diagnosis. It is essential to provide references for the intervention prioritized at different *** this prospective cohort study, we analyzed national data from the UK Biobank, including 121,399 participants, to assess the association of modifiable factors with cancer-specific survival (CSS) in two independent cohorts: a pre-cancer cohort (n = 78,027) and a post-cancer cohort (n = 43,372). Additionally, a weighted standardized score was derived to evaluate the joint effects across different domains. Interactions between the six domains and age at diagnosis, sex, and cancer site were evaluated using likelihood ratio tests. Subgroup analyses were then performed for factors showing significant effect modification. Population-attributable fractions (PAF) of different domains on 5-year cancer-specific death were *** study comprehensively presented the differential patterns of modifiable factors' impact on CSS among pre-cancer and post-cancer cohorts, sexes and different cancer sites. In the pre-cancer cohort, CSS were predominantly attributable to smoking/alcohol consumption (PAF 92%) and daily activity (PAF 106%). Men exhibited a higher risk than women for dietary habits (HR:125 versus 118), daily activity (HR:150 versus 129) and living environment (HR:113 versus 103). The impact of modifiable factors, including daily activity, smoking/alcohol consumption, and physical measures, on CSS varied across different cancer sites. In the post-cancer cohort, 186% of 5-year cancer-specific deaths were attributable to unfavourable mental health. In subgroup analysis, the risk of CSS in the domain of smoking/alcohol consumption was higher in men than that in women (HR: 158 versus 134). The impact of modi

关键词： Cancer-specific survival Modifiable factor Population-attributable fractions

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Oral Intervention of Narirutin Ameliorates the Allergic Response of Ovalbumin Allergy

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022年第41期70卷 13313-13326页

作者： Shi, Xiaolei Zhao, Lina Niu, Liyan Yan, Yixuan chen, Qiushi Jin, Yongri Li, xuwen Jilin Univ Coll Food Sci & Engn Changchun 130012 Peoples R China Jilin Univ Coll Chem Changchun 130012 Peoples R China

A new intervention was investigated for the induction of oral tolerance (OT) of OVA using narirutin by in vivo and in vitro experiments combined with network pharmacology and structural analysis of molecular docking. Narirutin (and its metabolism naringenin) has effects on OT by affecting B cell function, DCs, and T cell response by prediction. It was verified that narirutin could affect B cell function of secreting antibodies, thereby reducing the ability of DCs to absorb antigens by affecting GATA3, CCR7, STAT5, and MHCII expression and regulating T cell response by suppressing Th2 and improving Treg cells in vivo. Molecular docking showed that steric hindrance effects may be the reason for weaker binding energy with targets of narirutin. However, this does not mean that it has no bioactivity, for it can inhibit mast cell degranulation. This finding is interesting because it offers the possibility of using natural compounds to promote oral tolerance.

关键词： oral tolerance narirutin food allergy OVA intervention network pharmacology

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Rep-MCA-former: An efficient multi-scale convolution attention encoder for text-independent speaker verification

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COMPUTER SPEECH AND LANGUAGE 2024年 85卷

作者： Liu, Xiaohu chen, Defu Wang, Xianbao Xiang, Sheng Zhou, xuwen Zhejiang Univ Technol Informat Engineer Coll Hangzhou 310023 Zhejiang Peoples R China

In many speaker verification tasks, the quality of speaker embedding is an important factor in affecting speaker verification systems. Advanced speaker embedding extraction networks aim to capture richer speaker features through the multi-branch network architecture. Recently, speaker verification systems based on transformer encoders have received much attention, and many satisfactory results have been achieved because transformer encoders can efficiently extract the global features of the speaker (e.g., MFA-Conformer). However, the large number of model parameters and computational latency are common problems faced by the above approaches, which make them difficult to apply to resource-constrained edge terminals. To address this issue, this paper proposes an effective, lightweight transformer model (MCA-former) with multi-scale convolutional self-attention (MCA), which can perform multi-scale modeling and channel modeling in the temporal direction of the input with low computational cost. In addition, in the inference phase of the model, we further develop a systematic re-parameterization method to convert the multi-branch network structure into the single-path topology, effectively improving the inference speed. We investigate the performance of the MCA-former for speaker verification under the VoxCeleb1 test set. The results show that the MCA-based transformer model is more advantageous in terms of the number of parameters and inference efficiency. By applying the re-parameterization, the inference speed of the model is increased by about 30%, and the memory consumption is significantly improved.

关键词： Speaker verification Transformer encoder Multi-scale convolution Re-parameterization

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Review of Remaining Useful Life for Lithium-Ion Batteries 2

Review of Remaining Useful Life for Lithium-Ion Batteries

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2nd Asia Power and Electrical Technology Conference, APET 2023

作者： Hao, Zhi He, Yadong chen, Jun Luo, Shaowen Zhou, xuwen Duo, Wenbo Dingxi Power Supply Company State Grid Gansu Electric Power Company Dingxi China School of New Energy and Power Engineering Lanzhou Jiaotong University Lanzhou China

ISBN: (纸本)9798350359428

In recent years, with the swift progression of electric vehicles, new energy storage, intelligent robots and other fields, lithium-ion batteries have been widely used to meet the needs of high energy density, high output voltage and wide operating range of the battery. Typically, lithium-ion batteries operate under complex conditions and are accompanied by physical and chemical changes within them. These factors lead to irreversible physical and chemical changes in lithium-ion batteries, and their potential pitfalls can lead to abnormal system operation and even catastrophic events in electrical systems. Therefore, accurate RUL prediction can effectively indicate the health condition of Li-ion battery, and at the same time can ensure the reliability and safety of the system, which is important for the safe operation of the whole Li-ion battery system, and its remaining life assessment has become a research hotspot in the related fields of electrochemistry, intelligent detection and reliability, and has a good development prospect. Therefore, this paper analyzes the common methods and application status of remaining life prediction of lithium-ion batteries, brings together the prediction methods based on model-based methods, data-driven methods and fusion-based methods, and analyzes the advantages and disadvantages of each method to provide reference for relevant technical personnel. © 2023 IEEE.

关键词： Lithium-ion batteries

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Prediction of Subsequent Vertebral Fracture After Acute Osteoporotic Fractures from Clinical and Paraspinal Muscle Features

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CALCIFIED TISSUE INTERNATIONAL 2024年第6期114卷 614-624页

作者： Xiong, Yuchao Zhang, Cici chen, Xiaopei Wu, Li Liang, Shaohua Zhang, Ye Huang, Junbing Guo, Wei Zeng, xuwen Xu, Fan Jinan Univ Guangzhou Red Cross Hosp Dept Radiol Guangzhou Peoples R China

To construct a nomogram based on clinical factors and paraspinal muscle features to predict vertebral fractures occurring after acute osteoporotic vertebral compression fracture (OVCF). We retrospectively enrolled 307 patients with acute OVCF between January 2013 and August 2022, and performed magnetic resonance imaging of the L3/4 and L4/5 intervertebral discs (IVDs) to estimate the cross-sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles. We also collected clinical and radiographic data. We used univariable and multivariable Cox proportional hazards models to identify factors that should be included in the predictive nomogram. Post-OVCF vertebral fracture occurred within 3, 12, and 24 months in 33, 69, and 98 out of the 307 patients (10.8%, 22.5%, and 31.9%, respectively). Multivariate analysis revealed that this event was associated with percutaneous vertebroplasty treatment, higher FI at the L3/4 IVD levels of the psoas muscle, and lower relative CSA of functional muscle at the L4/5 IVD levels of the multifidus muscle. Area under the curve values for subsequent vertebral fracture at 3, 12, and 24 months were 0.711, 0.724, and 0.737, respectively, indicating remarkable accuracy of the nomogram. We developed a model for predicting post-OVCF vertebral fracture from diagnostic information about prescribed treatment, FI at the L3/4 IVD levels of the psoas muscle, and relative CSA of functional muscle at the L4/5 IVD levels of the multifidus muscle. This model could facilitate personalized predictions and preventive strategies.

关键词： Osteoporosis Compression fracture Paraspinal muscles Fat infiltration Nomograms

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Terrain Classification of Polarimetric SAR Images Based on Optimal Polarization Features

Terrain Classification of Polarimetric SAR Images Based on O...

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2022 International Conference on Computer Engineering and Artificial Intelligence, ICCEAI 2022

作者： Wang, Yangyang chen, Weidong Mao, xuwen Lei, Wuhu School of Information Science and Technology University of Science and Technology of China Hefei China National University of Defense Technology Hefei China

ISBN: (数字)9781665468039

ISBN: (纸本)9781665468039

With the continuous progress of remote sensing technology, a large number of airborne and satellite-based polarimetric SAR have been applied in the field of remote sensing to provide decision basis for military intelligence, land use, and urban planning. Terrain classification of PolSAR image has become an important research direction in remote sensing image interpretation. In this paper, polarimetric SAR data of Flevoland area in the Netherlands are selected. First, the coherent speckle noise is suppressed by Refined Lee filtering, and 68-dimensional polarization features are obtained by the polarization target decomposition method. Then, based on the feature judgment factor and feature selection factor, the optimal polarization features are selected quantitatively and analyzed qualitatively with the help of Cloude-Pottier scatter plot. Finally, the selected optimal polarization feature combination is fed into the SVM classifier to realize terrain classification. The results show that the overall accuracy of classification in the Flevoland dataset reaches 95.7% using the method proposed in this paper, which effectively realizes the high-precision terrain classification of PolSAR images. © 2022 IEEE.

关键词： Synthetic aperture radar

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