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Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma: results from a retrospective multicenter trial

《医学前沿（英文）》   页码 878-888 doi: 10.1007/s11684-023-0993-y

摘要： Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.

关键词： uveal melanoma     liver-directed therapy     immune checkpoint blockade     SIRT     anti-PD-1     anti-CTLA-4    

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Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms

《医学前沿（英文）》   页码 805-822 doi: 10.1007/s11684-023-1025-7

摘要： Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.

关键词： CTLA-4     PD-1     PD-L1     immune checkpoint blockade (ICB)     metabolic reprogramming     combined tumor therapeutic strategies    

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Design, synthesis and HIV-RT inhibitory activity of novel thiazolidin-4-one derivatives

Hua CHEN, Zaihong GUO, Qingmei YIN, Xiaoxu DUAN, Yunjing GU, Xiaoliu LI

《化学科学与工程前沿（英文）》 2011年 第5卷 第2期   页码 231-237 doi: 10.1007/s11705-010-1022-7

摘要： A series of 2-aryl-3-(4,5,6-trimethylpyrimidin-2-yl) thiazolidin-4-ones ( – ) and their derivatives bearing a lipophilic substituent, like acetoxy group ( – ), propionyloxy group ( – ), methyl ( and ) at C-5 on thiazolidin-4-one ring were designed, synthesized and evaluated for their HIV-RT inhibitory activity. Using self-catalyzed Pummerer reaction, compounds – and – were obtained in good yield (63.1% 75.2%). Preliminary anti-HIV-RT test of these derivatives indicated that compounds – , (propionyloxy group at C-5) showed moderate HIV-RT inhibitory activity and compounds and with methyl at C-5 showed a weak HIV-RT inhibitory activity. Structure activity relationship analysis suggested that the substituted groups on C-5 would be unfavorable to anti-HIV-RT activity and that the steric effect might play a critical role in the anti-HIV RT activity.

关键词： 5-subsituted thiazolidin-4-ones     Pummerer reaction     anti-HIV-RT activity     SARs    

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Antibacterial and anti-flaming PA6 composite with metathetically prepared nano AgCl@BaSO

Wei Zhang, Boren Xu, Caihong Gong, Chunwang Yi, Shen Zhang

《化学科学与工程前沿（英文）》 2021年 第15卷 第2期   页码 340-350 doi: 10.1007/s11705-020-1942-9

摘要： In this study, a facile and environmentally friendly method with low energy consumption for preparing nanoscale AgCl and BaSO co-precipitates (AgCl@BaSO co-precipitates) was developed based on the metathetical reaction. Then, the dried co-precipitates were melt-compounded with polyamide 6 (PA6) resins at a specified mass ratio in a twin-screw extruder. The results demonstrated that in the absence of any coating agent or carrier, the nanoparticles of AgCl@BaSO co-precipitates were homogeneously dispersed in the PA6 matrix. Further analysis showed that after the addition of AgCl@BaSO co-precipitates, the antibacterial performance, along with the flame-retardance and anti-dripping characteristics of PA6, was enhanced significantly. In addition, the PA6 composites possessed high spinnability in producing pre-oriented yarn.

关键词： nano AgCl@BaSO4 co-precipitates     antibacterial     flame resistance     PA6 composite     PA6 yarn    

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QUANTITATIVE STUDY ON ANTI-PEST ACTIVITY OF NATURAL PRODUCTS BASED ON VISUALIZATION FRAMEWORK OF KNOWLEDGE

《农业科学与工程前沿（英文）》 2023年 第10卷 第2期   页码 306-332 doi: 10.15302/J-FASE-2023488

摘要：

● Using visual analysis to predict the trend of natural product pest resistance.

关键词： anti-pest activity     crop protection     insect pest     natural product     visual analysis    

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Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD

《医学前沿（英文）》 2023年 第17卷 第4期   页码 729-746 doi: 10.1007/s11684-022-0978-2

摘要： The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

关键词： hepatocellular carcinoma     YAP1     Akkermansia muciniphila     anti-PD-1     dihydroartemisinin     bile acid    

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A modular cable-driven humanoid arm with anti-parallelogram mechanisms and Bowden cables

《机械工程前沿（英文）》 2023年 第18卷 第1期 doi: 10.1007/s11465-022-0722-2

摘要： This paper proposes a novel modular cable-driven humanoid arm with anti-parallelogram mechanisms (APMs) and Bowden cables. The lightweight arm realizes the advantage of joint independence and the rational layout of the driving units on the base. First, this paper analyzes the kinematic performance of the APM and uses the rolling motion between two ellipses to approximate a pure-circular-rolling motion. Then, a novel type of one-degree-of-freedom (1-DOF) elbow joint is proposed based on this principle, which is also applied to design the 3-DOF wrist and shoulder joints. Next, Bowden cables are used to connect the joints and their driving units to obtain a modular cable-driven arm with excellent joint independence. After that, both the forward and inverse kinematics of the entire arm are analyzed. Last, a humanoid arm prototype was developed, and the assembly velocity, joint motion performance, joint stiffness, load carrying, typical humanoid arm movements, and repeatability were tested to verify the arm performance.

关键词： modular robotic arm     anti-parallelogram mechanism     Bowden cable     humanoid arm     lightweight joint design    

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Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

《化学科学与工程前沿（英文）》 2023年 第17卷 第12期   页码 1866-1878 doi: 10.1007/s11705-023-2340-x

摘要： Continuous glucose monitoring (CGM) systems play an increasingly vital role in the glycemic control of patients with diabetes mellitus. However, the immune responses triggered by the implantation of poorly biocompatible sensors have a significant impact on the accuracy and lifetime of CGM systems. In this review, research efforts over the past few years to mitigate the immune responses by enhancing the anti-biofouling ability of sensors are summarized. This review divided these works into active immune engaging strategy and passive immune escape strategy based on their respective mechanisms. In each strategy, the various biocompatible layers on the biosensor surface, such as drug-releasing membranes, hydrogels, hydrophilic membranes, anti-biofouling membranes based on zwitterionic polymers, and bio-mimicking membranes, are described in detail. This review, therefore, provides researchers working on implantable biosensors for CGM systems with vital information, which is likely to aid in the research and development of novel CGM systems with profound anti-biofouling properties.

关键词： implantable glucose biosensor     anti-biofouling     continuous glucose monitoring     immune responses    

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Lignin-derived dual-function red light carbon dots for hypochlorite detection and anti-counterfeiting

《化学科学与工程前沿（英文）》 2023年 第17卷 第7期   页码 966-975 doi: 10.1007/s11705-022-2244-1

摘要： The efficient utilization of natural lignin, which is the main by-product of the cellulose industry, is crucial for enhancing its economic value, alleviating the environmental burden, and improving ecological security. By taking advantage of the large sp2 hybrid domain of lignin and introducing amino functional groups, new lignin-derived carbon dots (SPN-CDs) with red fluorescence were successfully synthesized. Compared with green and blue fluorescent materials, red SPN-CDs have desirable anti-interference properties of short-wave background and exhibit superior luminescence stability. The SPN-CDs obtained exhibited sensitive and distinctive visible color with fluorescence-dual responses toward hypochlorite. Considering this feature, a portable, low-cost, and sensitive fluorescence sensing paper with a low limit of detection of 0.249 μmol∙L–1 was fabricated using the SPN-CDs for hypochlorite detection. Furthermore, a new type of visible-light and fluorescence dual-channel information encryption platform was constructed. Low-concentration hypochlorite can be employed as an accessible and efficient information encryption/decryption stimulus, as well as an information “eraser”, facilitating a safe and diversified transmission and convenient decryption of information. This work opens new avenues for high-value-added applications of lignin-based fluorescent materials.

关键词： alkali lignin     red light carbon dots     hypochlorite     encryption and anti-counterfeiting    

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Modulatory effect on dyslipidemia and anti-atherosclerotic function of in newly diagnosed type 2 diabetes

SUN Mingxiao, WANG Yao, CHI Jiamin

《医学前沿（英文）》 2008年 第2卷 第2期   页码 174-177 doi: 10.1007/s11684-008-0032-z

摘要： The modulatory effect of on dyslipidemia and the preventive effect on atherosclerosis in newly diagnosed type 2 diabetic patients were studied. A prospective clinical trial was conducted to test the effectiveness of in selected 201 newly diagnosed type 2 diabetic patients. All patients were randomly divided into two groups: 108 with therapy and 93 without therapy. The mean follow-up period was 22 months. The blood glucose and blood pressure of all patients were under control. Serum levels of total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) were significantly lowered and their decreased percentages were significantly higher in therapy group ( < 0.05). The number of patients with arteria iliaca intima thickening was significantly lower in group of therapy ( = 0.024). With stepwise multivariate logistic regression analysis, the decreased percentage of TG was significantly and independently related with the decreased number of patients with arteria iliaca intima thickening ( = 0.005). The study demonstrates that therapy is effective on modulating dyslipidemia in newly diagnosed type 2 diabetes patients, and may be related with the improvement of early atherosclerosis.
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Preparation of reverse osmosis membrane with high permselectivity and anti-biofouling properties for

《环境科学与工程前沿（英文）》 2022年 第16卷 第7期 doi: 10.1007/s11783-021-1497-0

摘要：

• Nanoparticle incorporation and anti-biofouling grafting were integrated.

关键词： Anti-biofouling grafting     Nanoparticle incorporation     Sterilization rates     Water flux     Water flux recovery    

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Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

《医学前沿（英文）》 doi: 10.1007/s11684-023-1037-3

摘要： The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir–ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir–ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir–ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China’s homegrown anti-COVID-19 drugs.

关键词： COVID-19     antiviral drugs     mindeudesivir    

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Improved dissolution and anti-inflammatory effect of ibuprofen by solid dispersion

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 195-203 doi: 10.1007/s11684-012-0189-3

摘要：

The purpose of this study was to improve the dissolution rate and anti-inflammatory effect of ibuprofen by a solid dispersion (SD) method. Initial screening was developed based on drug solubility in carriers in the liquid state to select a suitable water-soluble carrier system for the preparation of SDs. The dissolution of ibuprofen in urea was higher than in PEG4000 or mannitol. Thus, urea was selected as the carrier for the preparation of SDs. SDs were characterized in terms of dissolution, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. Solid dispersion-based (SDBT) and conventional (CT) tablets were prepared by the wet granulation method. The anti-inflammatory effect of SDBT was evaluated using the mouse ear edema test with xylene. In vitro release results indicated that the ibuprofen dissolution rate was improved by the SD. SD characterization results suggested that ibuprofen partly precipitates in crystalline and amorphous forms after SD preparation and that ibuprofen and urea do not interact. SDBT displayed more significant anti-inflammatory effects than CT. The dissolution rate and anti-inflammatory effect of ibuprofen were significantly enhanced by the ibuprofen-urea SD.

关键词： ibuprofen     solid dispersion     physical mixture     dissolution     anti-inflammatory effect    

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Mobile CRISPR-Cas9 based anti-phage system in E. coli

《化学科学与工程前沿（英文）》 2022年 第16卷 第8期   页码 1281-1289 doi: 10.1007/s11705-022-2141-7

摘要： Escherichia coli is one of the most important microbial cell factories, but infection by bacteriophages in the environment may have a huge impact on its application in industrial production. Here, we developed a mobile CRISPR-Cas9 based anti-phage system for bacteriophages defense in E. coli. Two conjugative plasmids pGM1 (phosphoglucomutase 1) and pGM2 carrying one and two guide RNAs, respectively, were designed to defend against a filamentous phage. The results showed that the pGM1 and pGM2 could decrease the phage infection rate to 1.6% and 0.2% respectively in infected cells. For preventing phage infection in E. coli, the pGM2 decreased the phage infection rate to 0.1%, while pGM1 failed to block phage infection. Sequence verification revealed that point mutations in protospacer or protospacer adjacent motif sequences of the phage genome caused loss of the defense function. These results support the potential application of MCBAS in E. coli cell factories to defend against phage infections.

关键词： phage infections     anti-phage     CRISPR-Cas9     conjugative transfer     synthetic biology    

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近来的局部战争对陆基防空雷达的需求

彭家庭

《中国工程科学》 1999年 第1卷 第2期   页码 19-23

摘要：

从近来的局部战争陆基防空雷达面临的任务出发，简要阐述了近来出现的各种目标的特点以及防空雷达所处的作战环境与电子对抗环境。分析了陆基中低空防空系统在现代防空中的作用和地位。陆基中低空防空系统在现在的防空中是可以发挥它的重要作用的，尤其是在对付巡航导弹、武装直升机、低空飞机（含隐身飞机）、反辐射导弹等目标时，该系统是属于比较优选的武器；归纳了对陆基中低空防空雷达的新的要求，主要是强的抗干扰性能，好的低空特性，满足武器系统需要的探测小目标的能力，快速的搜捕截获目标的能力等；同时也简要分析了这些要求在陆基中低空防空雷达中的技术可实现性。

关键词： 低空     防空雷达     反隐身     返巡航导弹     抗反辐射导弹    

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标题 作者 时间 类型 操作

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma: results from a retrospective multicenter trial

期刊论文

Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms

期刊论文

Design, synthesis and HIV-RT inhibitory activity of novel thiazolidin-4-one derivatives

Hua CHEN, Zaihong GUO, Qingmei YIN, Xiaoxu DUAN, Yunjing GU, Xiaoliu LI

期刊论文

Antibacterial and anti-flaming PA6 composite with metathetically prepared nano AgCl@BaSO

Wei Zhang, Boren Xu, Caihong Gong, Chunwang Yi, Shen Zhang

期刊论文

QUANTITATIVE STUDY ON ANTI-PEST ACTIVITY OF NATURAL PRODUCTS BASED ON VISUALIZATION FRAMEWORK OF KNOWLEDGE

期刊论文

Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD

期刊论文

A modular cable-driven humanoid arm with anti-parallelogram mechanisms and Bowden cables

期刊论文

Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

期刊论文

Lignin-derived dual-function red light carbon dots for hypochlorite detection and anti-counterfeiting

期刊论文

Modulatory effect on dyslipidemia and anti-atherosclerotic function of in newly diagnosed type 2 diabetes

SUN Mingxiao, WANG Yao, CHI Jiamin

期刊论文

Preparation of reverse osmosis membrane with high permselectivity and anti-biofouling properties for

期刊论文

Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

期刊论文

Improved dissolution and anti-inflammatory effect of ibuprofen by solid dispersion

null

期刊论文

Mobile CRISPR-Cas9 based anti-phage system in E. coli

期刊论文

近来的局部战争对陆基防空雷达的需求

彭家庭

期刊论文