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Development of novel 5-FU modified siRNA against BCL-2 with enhanced efficacy and vehicle-free cellular uptake

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Genes & Diseases 2024年第1期11卷 23-25页

作者： Andrew Fesler ga-Ram Hwang Jingfang Ju Department of Pathology Renaissance School of MedicineStony Brook UniversityStony BrookNY 11794USA The Northport Veteran's Administration Medical Center NorthportNY 11768USA Curamir Therapeutics Inc. WoburnMA 01801USA

One of the major obstacles for nucleic acid-based medicine is cellular uptake due to the concern of efficiencyand potential toxicity of the *** this work,we developed a novel approach to eliminate the need for a vehicle to allow for the cellular uptake of siRNA-based therapy with a unique modification strategy that also further enhances therapeutic *** discovery may be of great importance for the development of siRNA-based therapeutics as cellular uptake remains a critical *** this study,we have tested the potential of this modification strategy for siRNA using a siRNA that targets B-cell lymphoma-2(BCL-2).

关键词： eliminate uptake modified

The first record of a Konservat-Lagerstätten in which early post-settlement stages of fossil archaeobalanids(Cirripedia:Balanomorpha)are preserved

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Integrative Zoology 2024年第2期19卷 200-223页

作者： Tomáš KOCÍ Rok gaŠPARIC John BUCKERIDGE Martina KOCOVÁ VESELSKÁ Aleš ŠOSTER Ivancická581 PragueCzech Republic Palaeontological Department Natural History MuseumNational MuseumPragueCzech Republic Oertijdmuseum Bosscheweg 80Boxtel5293 WBThe Netherlands Institute for Palaeobiology and Evolution Novi TrgKamnikSlovenia Earth and Oceanic Systems Group RMIT UniversityMelbourneAustralia Museums Victoria CarltonVictoriaAustralia Department of Paleobiology and Paleoecology Institute of Geology of the Czech Academy of SciencesPragueCzech Republic Institute of Geology and Palaeontology Charles UniversityPragueCzech Republic Faculty of Natural Sciences and Engineering University of LjubljanaLjubljanaSlovenia

A diverse sessile barnacle fauna from a Miocene shallow-water deposit at Dolnja Stara vas in Slovenia is *** includes the first descriptions of early post settlement juveniles of Actinobalanus sloveniensis attached to mangrove *** represent three distinct growth phases,the earliest being interpreted as being less than 24 h post settlement,the others being 1 to 2 days post *** assessment of their taphonomy is *** adult balanomorphs are attached to a variety of organic substrates,including mangrove leaves and branches,fragments of the conifers?Taxodioxylon,Carapoxylon,pine cones,molluscs,and cetacean *** barnacles include ***,Amphibalanus venustus,and Perforatus perforatus—many with opercula retained within the *** retains some of the original shell *** is the second record of barnacle–plant associations from the Central Paratethys from Kamnik and *** paleoecology and paleogeography of the site are discussed.

关键词： acorn barnacles barnacle metamorphosis epibiont paleoecology taxonomy

SPEED:an integrated,smartphone-operated,handheld digital PCR Device for point-of-care testing

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Microsystems & Nanoengineering 2024年第3期10卷 149-158页

作者： Haoqing Zhang Xiaocheng Liu Xinlu Wang Zhiqiang Yan Ying Xu Martina gaňová TomášŘezníček Marie Korabečná Pavel Neuzil Ministry of Education Key Laboratory of Micro and Nano Systems for Aerospace School of Mechanical EngineeringNorthwestern Polytechnical University127 West Youyi RoadXi’anShaanxi 710072PR China The Key Laboratory of Biomedical Information Engineering of the Ministry of Education School of Life Science and TechnologyXi’an Jiaotong UniversityXi’anShaanxi 710049PR China Bioinspired Engineering and Biomechanics Center(BEBC) Xi’an Jiaotong UniversityXi’an 710049PR China School of Marine Science and Technology Northwestern Polytechnical UniversityXi’anShaanxi 710072PR China Central European Institute of Technology Brno University of TechnologyPurkyňova 12361300 BrnoCzech Republic ITD Tech S.R.O Osvoboditelu100573581 BohumínCzech Republic Institute of Biology and Medical Genetics First Faculty of MedicineCharles University and General University Hospital of PragueAlbertov 412800 PragueCzech Republic

This study elaborates on the design,fabrication,and data analysis details of SPEED,a recently proposed smartphonebased digital polymerase chain reaction(dPCR)*** dPCR chips incorporate partition diameters ranging from 50μm to 5μm,and these partitions are organized into six distinct blocks to facilitate image *** to the superior thermal conductivity of Si and its potential for mass production,the dPCR chips were fabricated on a Si substrate.A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle *** optical design employs four 470 nm light-emitting diodes as light sources,with filters and mirrors effectively managing the light emitted during *** algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format,partition identification,skew correction,and the generation of an image correction *** validated the device using a range of deoxyribonucleic acid targets,demonstrating its potential applicability across multiple ***,we provide guidance and verification of the design and testing of the recently proposed SPEED device.

关键词： correction smart testing

Percutaneous ultrasound-guided coaxial core needle biopsy for the diagnosis of multiple splenic lesions: A case report

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World Journal of gastrointestinal Surgery 2024年第2期16卷 616-621页

作者： Sha-Hong Pu Wu-Yong-ga Bao Zhen-Peng Jiang Rui Yang Qiang Lu Department of Medical Ultrasound West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND The overlap of imaging manifestations among distinct splenic lesions gives rise to a diagnostic ***,a definitive diagnosis primarily relies on his-tological *** ultrasound(US)-guided coaxial core needle biopsy(CNB)not only procures sufficient tissue to help clarify the diagnosis,but reduces the incidence of puncture-related *** SUMMARY A 41-year-old female,with a history of pulmonary tuberculosis,was admitted to our hospital with multiple indeterminate splenic ***-scale ultrasono-graphy demonstrated splenomegaly with numerous well-defined hypoechoic *** contrast-enhanced computed tomography(CT)showed an en-larged spleen with multiple irregular-shaped,peripherally enhancing,hypodense *** emission CT revealed numerous abnormal hyperglycemia *** imaging findings strongly indicated the possibility of infectious disease as the primary concern,with neoplastic lesions requiring *** obtain the precise pathological diagnosis,the US-guided coaxial CNB of the spleen was ca-rried *** patient did not express any discomfort during the *** Percutaneous US-guided coaxial CNB is an excellent and safe option for obtaining precise splenic tissue samples,as it significantly enhances sample yield for exact pathological analysis with minimum trauma to the spleen parenchyma and sur-rounding tissue.

关键词： Spleen Splenic disease Ultrasound Biopsy Ultrasound-guided coaxial core needle biopsy Case report

Pancreatic pseudocyst:The past,the present,and the future

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World Journal of gastrointestinal Surgery 2024年第7期16卷 1986-2002页

作者： Jonathan ga Koo Matthias Yi Quan Liau Igor A Kryvoruchko Tamer AAM Habeeb Christopher Chia Vishal G Shelat Department of General Surgery Khoo Teck Puat HospitalSingapore 768828Singapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 308232Singapore Department of Surgery No.2 Kharkiv National Medical UniversityKharkiv 61022Ukraine Department of General Surgery Faculty of Medicine Zagazig UniversitySharkia 44511Egypt Department of gastroenterology Woodlands General HospitalSingapore 737628Singapore Department of General Surgery Tan Tock Seng HospitalSingapore 308433Singapore

A pancreatic pseudocyst is defined as an encapsulated fluid collection with a welldefined inflammatory wall with minimal or no *** diagnosis cannot be made prior to 4 wk after the onset of *** clinical presentation is often nonspecific,with abdominal pain being the most common *** a diagnosis is suspected,contrast-enhanced computed tomography and/or magnetic resonance imaging are performed to confirm the diagnosis and assess the characteristics of the *** ultrasound with cyst fluid analysis can be performed in cases of diagnostic *** of the pancreas can lead to complications such as hemorrhage,infection,and *** management of pancreatic pseudocysts depends on the presence of symptoms and the development of complications,such as biliary or gastric outlet *** options include endoscopic or surgical *** aim of this review was to summarize the current literature on pancreatic pseudocysts and discuss the evolution of the definitions,diagnosis,and management of this condition.

关键词： Pancreatic pseudocyst Pancreatic fluid collection Cystic pancreatic lesions Pancreatitis Endoscopic ultrasound

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

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Food Science and Human Wellness 2024年第4期13卷 2266-2276页

作者： Yu ga Yuanyuan Wei Qingyu Zhao Yimeng Fan Yannan Zhang Zhifang Zhang Sijia Hao Lixia Wang Zhifen Wang Jinlong Han Shuang Wu Zhihui Hao Innovation Centre of Chinese Veterinary Medicine College of Veterinary MedicineChina Agricultural UniversityBeijing 100086China National Center of Technology Innovation for Medicinal Function of Food National Food and Strategic Reserves AdministrationBeijing 100193China Inner Mongolia Medical University Hohhot 010059China China Agricultural University Yantai Institute Yantai 264670China Shandong Academy of Agricultural Sciences Jinan 250100China

Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal *** Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal *** aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR *** chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other *** results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC *** also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin *** treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression *** addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of *** results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.

关键词： Puerariae Radix Ulcerative colitis Molecular mechanisms Pyroptosis NOD-like receptor protein 3 inflammasome

gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2732-2747页

作者： Bo Xiao Yuqi Liang ga Liu Lingshuang Wang Zhan Zhang Libin Qiu Haiting Xu Sean Carr Xiaoxiao Shi Rui LReis Subhas CKundu Zhenghua Zhu Department of gastroenterology the First Affiliated Hospital of Nanchang UniversityNanchang 330006China College of Sericulture Textileand Biomass SciencesSouthwest UniversityChongqing 400715China Department of Neurology School of MedicineEmory UniversityAtlantaGA 30322USA Atlanta Veterans Affairs Medical Center DecaturGA 30033USA Department of Surgery School of MedicineEmory UniversityAtlantaGA 30322USA Bs Research Group I3Bs—Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkBarcoGuimaraes 4805-017Portugal

The progression of ulcerative colitis(UC)is associated with immunologic derangement,intestinal hemorrhage,and microbiota *** traditional medications mainly focus on mitigating inflammation,it remains challenging to address multiple ***,a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO_(2) nanospheres with Cu_(2)O *** resulting CaO_(2)–Cu_(2)O possessed a desirable diameter(291.3 nm)and a uniform size *** could be efficiently internalized by colonic epithelial cells and macrophages,scavenge intracellular reactive oxygen/nitrogen species,and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 *** nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen *** administration of CaO_(2)–Cu_(2)O could stanch the bleeding,repair the disrupted colonic epithelial layer,and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation,anti-oxidation,wound healing,and ***,it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria(e.g.,Odoribacter and Bifidobacterium)and decreasing the abundances of harmful bacteria(e.g.,Prevotellaceae and Helicobacter).Our gas-driven CaO_(2)–Cu_(2)O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

关键词： Nanomotor Anti-inflammation Blood coagulation Immune regulation Hematopexis Microbiota rebalance Ulcerative colitis Rectal administration

M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3169-3183页

作者： Ha Eun Shin Jun-Hyeok Han Seungyong Shin ga-Hyun Bae Boram Son Tae-Hyung Kim Hee Ho Park Chun Gwon Park Wooram Park Department of Integrative Biotechnology Sungkyunkwan University(SKKU)SuwonGyeonggi 16419Republic of Korea Deparment of Inteligent Precision Healthcare Convergence SKKUSuwonGyeonggi 16419Republic of Korea Department of MetaBioHealth SKKU Institute for ConvergenceSKKUSuwonGyeonggi 16419Republic of Korea Department of Bioengineering Hanyang UniversitySeoul 04763Republic of Korea Department of Integrative Engineering Chung-Ang UniversitySeoul 06974Republic of Korea Department of Biomedical Engineering SKKUSuwonGyeonggi 16419Republic of Korea Korea Institute of Science and Technology(KIST) Seoul 02792Republic of Korea

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene *** nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 *** study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid *** dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor *** retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth *** findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.

关键词： Genetic-immunotherapy M1 macrophage-derived cellular nanovesicles Lipid nanoparticles(LNPs) Gene therapy siRNA Cancer immunotherapy Solid tumor Tumor microenvironment(TME)

土工织物加固土质坝堤加高工程的离心模型试验研究

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岩土工程学报 2024年第S01期46卷 112-116页

作者：李笑琳张嘎清华大学水利水电工程系北京100084

土工织物是一种广泛用于边坡加固的合成材料,但土工织物在土质坝堤加高工程中尚未得到合理应用。针对水位变动条件下土工织物加固的加高土质坝堤进行了离心模型试验,观测了加高坝堤的变形破坏响应过程。试验结果表明,土工织物加固的加... 详细信息

土工织物是一种广泛用于边坡加固的合成材料,但土工织物在土质坝堤加高工程中尚未得到合理应用。针对水位变动条件下土工织物加固的加高土质坝堤进行了离心模型试验,观测了加高坝堤的变形破坏响应过程。试验结果表明,土工织物加固的加高土质坝堤的破坏呈现出新旧坝堤各异的特点,新旧坝堤呈现出不同的破坏特性,离土工织物较远的旧坝堤先发生破坏,土工织物加固的新坝堤的破坏发生较晚,且呈现从上到下渐进发展的特性;加高坝堤的最终破坏是由变形局部化和局部破坏相互耦合渐进发展导致的;土工织物分为加固段和约束段,在约束段坝堤给土工织物提供约束力,在加固段土工织物限制了坝堤的变形,土工织物的加固机理是将坝堤深部的约束力传递到坝堤表面,从而增强了坝堤浅层的抗滑能力;水位变动引起坝堤的变形增加,土工织物的加固作用也随之增强。

关键词：坝堤加高土工织物离心模型试验水位变动