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Multifunctional Gd-CuS loaded UCST polymeric micelles for MR/PA imaging-guided chemo-photothermal tumor treatment

Nano Research 2022年第3期15卷 2288-2299页

作者： Yan Du Di Liu Mingchen Sun Gaofeng Shu Jing Qi Yuchan You Yiting xu Kai Fan Xiaoling xu Feiyang Jin Jun Wang Qiying Shen luwen Zhu Xiaoying Ying Jiansong Ji Liming Wu Daren Liu Yongzhong Du Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research Lishui Hospital of Zhejiang UniversityZhejiang University School of MedicineLishui 323000China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of General Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Hepatocellular carcinoma(HCC)is a life-threatening disease for which there is no effective treatment *** theranostics simultaneously having excellent imaging and therapeutic functions are highly desired in cancer ***,we develop the sialic acid(SA)modified polymeric micelles at an upper critical solution temperature(UCST)of 43℃(sialic acid-poly(ethylene glycol)-poly(acrylamide-co-acrylonitrile),SA-PEG-p(AAm-co-AN)),which further encapsulated with doxorubicin(DOX)and Gd-CuS nanoparticles(Gd-CuS NPs)for chemo-photothermal treatment of HCC guided by magnetic resonance(MR)/photoacoustic(PA)dual-mode *** resultant SA-PEG-p(AAm-co-AN)/DOX/Gd-CuS(SPDG)had an excellent photothermal conversion efficiency,enabling SPDG with an instantaneous release behavior of DOX under near-infrared(NIR)*** study also revealed that SPDG could actively target to HCC,which was due to that SA had a high affinity with E-selectin overexpressed at the tumor ***,benefiting from the HCC-targeted ability and NIR light-controlled on-demand delivery of DOX,SPDG showed a superior potential in MR/PA dual-mode imaging-guided chemo-photothermal ***,our study reveals that the designed SPDG may be used as an ideal multifunctional nanoplatform for cancer theranostics.

关键词： hepatocellular carcinoma upper critical solution temperature(UCST) Gd-CuS nanoparticles chemo-photothermal therapy magnetic resonance(MR)/photoacoustic(PA)dual-mode imaging

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The Effect of Sodium Glucose Cotransporter-2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis

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PHARMACOEPIDEMIOLOGY AND DRUG SAFETY 2024年第8期33卷 e5876-e5876页

作者： Wang, Tiansheng Ji, Dongze Stuermer, Til Ismail, Sherin Dong, Shujie Shen, Peng Lin, Hongbo Shi, luwen Guan, Xiaodong xu, Yang Univ North Carolina Chapel Hill Gillings Sch Global Publ Hlth Dept Epidemiol Chapel Hill NC USA Peking Univ Sch Pharmaceut Sci Dept Pharm Adm Hlth Sci Ctr Beijing Peoples R China Peking Univ Sch Pharmaceut Sci Clin Pharm Hlth Sci Ctr Beijing Peoples R China Peking Univ Third Hosp Dept Pharm Beijing Peoples R China Yinzhou Dist Ctr Dis Control & Prevent Dept Chron Dis & Hlth Promot Ningbo Peoples R China Peking Univ Int Res Ctr Med Adm Beijing Peoples R China Karolinska Inst Dept Med Epidemiol & Biostat Stockholm Sweden

PurposeThe role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c *** 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation *** a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008;for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity *** to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

关键词： acute kidney injury causal mediation DPP-4 inhibitor hemoglobin A1c SGLT2 inhibitor

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Low Remanent Polarization for High Energy Density by Poly(vinylidene fluoride-co-chlorotrifluoroethylene)/Silicon Dioxide Nanocomposites

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JOURNAL OF ELECTRONIC MATERIALS 2019年第12期48卷 8172-8180页

作者： Lou, Hanyu Wen, Fei Xiao, Jie Zhou, Bing Ye, Jianfei Yuan, Hongbin xu, Zhuo Wang, luwen Wang, Gaofeng Li, Lili Wu, Wei Hangzhou Dianzi Univ Coll Elect & Informat Minist Educ Key Lab RF Circuits & Syst Hangzhou 310018 Zhejiang Peoples R China Kunming Univ Sci & Technol Fac Met & Energy Engn Key Lab Adv Battery Mat Yunnan Prov Natl & Local Joint Engn Lab Lithium Ion Batteries Kunming 650093 Yunnan Peoples R China Hangzhou Normal Univ Qianjiang Coll Hangzhou 310012 Zhejiang Peoples R China Xi An Jiao Tong Univ Elect Mat Res Lab Key Lab Minist Educ Xian 710049 Shaanxi Peoples R China Xi An Jiao Tong Univ Int Ctr Dielect Res Xian 710049 Shaanxi Peoples R China Univ Wollongong Inst Superconducting & Elect Mat Australian Inst Innovat Mat Wollongong NSW 2500 Australia

Nowadays, dielectric materials with high energy storage density play a vital role in the energy storage capacitors. To increase the storage density, 0-3 composite films based on poly(vinylidene fluoride-co-chlorotrifluoroethylene) [P(VDF-CTFE)] and silicon dioxide (SiO2) nanoparticles were prepared by a solution casting method. The composite with 10% SiO2 has a discharged energy density of 2.73 J/cm(3) at 200 MV/m. Furthermore, the local electric field distribution in the P(VDF-CTFE)/SiO2 nanocomposites was analyzed by experiments combined with model simulation. And the relationship of displacement (D) and remanent polarization (P-r) with the current at the applied electric field was investigated. It indicates that during the charging phase, a large positive (+) current value is conducive to obtaining high electrical displacement while in the discharge phase, a small negative current value will be beneficial to achieve a smaller remanent polarization value. Therefore, the addition of low dielectric permittivity fillers (SiO2) contributes to the displacement of the composite at higher electric fields and maintains the P-r in a small range, thus achieving a higher discharged energy density.

关键词： P(VDF-CTFE) displacement high energy density current SiO2

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W7-05 The latent membrane protein 1 of Epstein-Barr virus (EBV) primes EBV latency Cells for Type Ⅰ interferon production

W7-05 The latent membrane protein 1 of Epstein-Barr virus (E...

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第一届世界华人免疫学大会(International Conference on Immunology 2007)

作者： Dongsheng xu Kristen Brumm luwen Zhang Nebraska Center for Virology School of Biological SciencesUniversity of NebraskaLincolnNebraska 68588

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Query-oriented two-stage attention-based model for code search

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JOURNAL OF SYSTEMS AND SOFTWARE 2024年 210卷

作者： Yang, Huanhuan xu, Ling Liu, Chao Huangfu, luwen Chongqing Univ Key Lab Dependable Serv Comp Cyber Phys Soc Minist Educ Chongqing Peoples R China Chongqing Univ Sch Big Data & Software Engn Chongqing Peoples R China San Diego State Univ Fowler Coll Business San Diego CA 92182 USA San Diego State Univ Ctr Human Dynam Mobile Age San Diego CA 92182 USA

Applying code search models to search through a large-scale codebase can significantly contribute to developers finding and reusing existing code. Researchers have applied deep learning (DL) techniques to code search models, which first compute deeper semantics representation for query and candidate code snippets, and then rank code snippets. However, these models do not well deeply analyze the semantics gap (i.e., the difference and correlation between queries written in natural language and code in programming languages), or suitably apply the correlation to the code search task. Moreover, most DL -based models use complex networks, slowing down code search tasks. To build the correlation of two languages, and apply the correlation well to code search task, we propose a query-oriented code search model named QobCS. QobCS leverage two attention-based stages, which are simple and quick, and the cooperation of the two stages bridges the semantic gap between code and query. Stage1 learns deeper semantics representation for code and query. Stage2 applies their deeper semantic correlation and query's intention to learn better code representation. We evaluated QobCS on two datasets. On dataset1/dataset2 with 485k/542k code snippets, QobCS achieves the MRRs of 0.701/0.595, outperforming DL -based code search models DeepCS, CARLCS-CNN, UNIF, and our prior study TabCS. For efficiency, our model shows desirable performances on both datasets compared to DL -based models.

关键词： Code search Attention mechanism Query-oriented attention mechanism Code structural feature

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Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles

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NATURE COMMUNICATIONS 2021年第1期12卷 1-17页

作者： Qi, Jing Jin, Feiyang You, Yuchan Du, Yan Liu, Di xu, Xiaoling Wang, Jun Zhu, luwen Chen, Minjiang Shu, Gaofeng Wu, Liming Ji, Jiansong Du, Yong-Zhong Zhejiang Univ Coll Pharmaceut Sci Inst Pharmaceut Hangzhou Peoples R China Zhejiang Univ Lishui Hosp Key Lab Imaging Diag & Minimally Invas Intervent Lishui Peoples R China Zhejiang Univ Sch Med Affiliated Hosp 1 Dept Hepatobiliary & Pancreat Surg Hangzhou Peoples R China

Some specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge. Targeting the adenosinergic pathway represents a therapeutic option to overcome tumor-induced immunosuppression. Here the authors design E-selectin-modified thermal-sensitive micelles loaded with doxorubicin and an adenosine A2 receptor antagonist to enhance chemotherapy-induced anti-tumor immune responses.

关键词： Cancer therapy Nanobiotechnology Tumour immunology

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Self-Illuminating Nanoagonist Simultaneously Induces Dual Cell Death Pathways via Death Receptor Clustering for Cancer Therapy

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ACS NANO 2024年第26期18卷 17119-17134页

作者： You, Yuchan Zhu, luwen Song, Yanling Hu, Jiahao Chen, Minjiang Zhang, Jucong xu, Xinyi Huang, Xiajie Wu, Xiaochuan Lu, Jingyi Tong, Xiangmin Ji, Jian-Song Du, Yong-Zhong Zhejiang Univ Coll Pharmaceut Sci Hangzhou 310058 Peoples R China Wenzhou Med Coll Lishui Cent Hosp Key Lab Imaging Diag & Minimally Invas Intervent R Lishui 323000 Peoples R China Wenzhou Med Coll Affiliated Hosp 5 Lishui 323000 Peoples R China Westlake Univ Affiliated Hangzhou Peoples Hosp 1 Dept Hematol Sch Med Hangzhou 310006 Peoples R China Zhejiang Univ Innovat Ctr Transformat Pharm Jinhua Inst Jinhua 321299 Peoples R China

Inducing death receptor 5 (DR5) clustering holds particular promise in tumor-specific therapeutics because it could trigger an apoptotic cascade in cancerous cells. Herein, we present a tumor microenvironment H2O2-responsive self-illuminating nanoagonist, which could induce dual tumor cell death pathways through enhancing DR5 clustering. By conjugating DR5 ligand peptides onto the surfaces of self-illuminating nanoparticles with cross-linking capacity, this strategy not only provides scaffolds for ligands to bind receptors but also cross-links them through photo-cross-linking. This strategy allows for efficient activation of DR5 downstream signaling, initiating the extrinsic apoptosis pathway and immunogenic cell death of tumor cells, and contributes to improved tumor-specific immune responses, resulting in enhanced antitumor efficacy and minimized systemic adverse effects.

关键词： self-illuminating nanoparticle receptor clustering death receptor cancerimmunotherapy photo-cross-linking

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Does Stricter Command-and-Control Environmental Regulation Promote Total Factor Productivity? Evidence from China's Industrial Enterprises

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DISCRETE DYNAMICS IN NATURE AND SOCIETY 2022年第0期2022卷

作者： Chen, Wei Gao, luwen xu, Xing Zeng, Yan Shanghai Univ Finance & Econ Coll Business Shanghai 200433 Peoples R China

China is implementing increasing stringent command-and-control environmental regulations to achieve high-quality development. However, we have limited understanding about whether such policies are effective. This study selects the policy of China's National Environmental Protection "Eleventh Five-Year Plan" as a quasi-natural experiment and uses the difference-in-differences (DID) method to analyze the effect of stricter command-controlled environmental regulations on total factor productivity from the enterprise level. Our results indicate that stricter command-and-control environmental regulation promotes TFP of enterprises throughout the country. This effect is even greater in long-established, large-scale, or low capital density enterprises. In addition, stricter command-and-control environmental regulation has a greater positive effect on the TFP of companies in industries with high pollution intensity and fierce competition. Furthermore, government transformation and market green preference will magnify the positive effect of stricter command-and-control environmental regulation on corporate TFP. Moreover, stricter command-and-control environmental regulation promotes the growth of enterprise TFP mainly by improving the efficiency of resource allocation within and between enterprises, rather than stimulating innovation. Local governments should refine pollution control policies, optimize the external environment, and enhance the innovation power of enterprises.

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Hybrid hair follicle stem cell extracellular vesicles co-delivering finasteride and gold nanoparticles for androgenetic alopecia treatment

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JOURNAL OF CONTROLLED RELEASE 2024年 373卷 652-666页

作者： Wu, Xiaochuan Huang, Xiajie Zhu, Qi Zhang, Jucong Hu, Jiahao Song, Yanling You, Yuchan Zhu, luwen Lu, Jingyi xu, Xinyi Chen, Minjiang Wang, Wei Song, Xiuzu Ji, Jiansong Du, Yongzhong Zhejiang Univ Inst Pharmaceut Coll Pharmaceut Sci State Key Lab Adv Drug Delivery & Release Syst Hangzhou 310058 Peoples R China Lishui Cent Hosp Key Lab Imaging Diag & Minimally Invas Intervent R Lishui 323000 Peoples R China Hangzhou Third Peoples Hosp Dept Dermatol Hangzhou 310009 Zhejiang Peoples R China Zhejiang Univ Jinhua Inst Jinhua 321299 Peoples R China

Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5 alpha-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 +/- 0.32 nm, -7.50 +/- 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects.

关键词： Extracellular vesicle Liposome Finasteride Gold nanoparticle Topical administration Androgenetic alopecia

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Code semantic enrichment for deep code search

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JOURNAL OF SYSTEMS AND SOFTWARE 2024年 207卷

作者： Deng, Zhongyang xu, Ling Liu, Chao Huangfu, luwen Yan, Meng Chongqing Univ Key Lab Dependable Serv Comp Cyber Phys Soc Minist Educ Chongqing Peoples R China Chongqing Univ Sch Big Data & Software Engn Chongqing Peoples R China San Diego State Univ Fowler Coll Business San Diego CA 92182 USA San Diego State Univ Ctr Human Dynam Mobile Age HDMA San Diego CA USA

Code search aims to retrieve code snippets from a large-scale codebase, where the semantics of the searched code match developers' query intent. Code is a low-level implementation of programming intents, but query is always expressed as clear and high-level semantics, which makes it difficult for DL-based approaches to learn the semantic relationship between them. Through a large-scale empirical analysis on more than 2.2 million pairs of Java code and description, we found that the semantics of code and query can be aligned by enriching code with the descriptions of other code in terms of similar implementation. Based on the finding, we propose a code semantic enrichment approach for deep code search, named SemEnr. Specifically, we first enrich semantics for all code snippets in the training and testing data. We estimated the syntactic similarity of each code snippet from the training data and retrieved the most similar one for each. Thereafter, the semantics of one code snippet is represented by its code tokens and the description of the retrieved most similar code. During the model training, we used the attention mechanism to embed pairs of enriched code and query into the shared high-dimensional vector space. To enhance the quality of our learned representations, we integrated a multi-perspective co-attention mechanism, employing Convolutional Neural Networks (CNNs) to capture local correlations between code and query. Finally, we evaluated the effectiveness of our approach by performing experiments on two extensively used Java datasets. Our experimental results reveal that SemEnr achieves an MRR of 0.698 and 0.631, outperforming the best baseline CAT (a state-of-the-art DL-based model) by 19.93% and 18.83%, respectively. In addition, we conducted a user study involving 50 real-world queries to assess SemEnr's performance, and the findings suggest that SemEnr outperformed baseline models by returning more relevant code snippets.

关键词： Code search Deep learning Semantic enrichment Co-attention mechanism

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