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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

A randomized,controlled,open label non-inferiority trial of intravenous ferric carboxymaltose versus iron sucrose in patients with iron deficiency anemia in China

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Frontiers of Medicine 2024年第1期18卷 98-108页

作者： Jie Jin Zhihua ran Emanuele Noseda Bernard roubert Matthieu Marty Anna Mezzacasa udo Michael Göring The First Affiliated Hospital Zhejiang University College of MedicineHangzhou310058China renji Hospital Shanghai Jiao Tong University School of MedicineShanghai200025China Vifor Pharma Glattbrugg8152Switzerland

Iron deficiency(ID)and ID anemia(IDA)pose significant public health concerns in *** iron sucrose(IS)treatment is well-established in the country,ferric carboxymaltose(FCM)offers the advantage of higher doses and fewer *** open label,randomized,controlled,non-inferiority trial was conducted at multiple sites in China to compare the outcomes of FCM(maximum of 2 doses,500 or 1000 mg iron)and IS(up to 11 infusions,200 mg iron)treatments in subjects with *** primary endpoint was the achievement of hemoglobin(Hb)response(an increase of⩾2 g/dL from baseline)within 8 weeks,whereas secondary endpoints included changes in Hb,transferrin saturation,and serum ferritin *** the 371 randomized subjects,a similar percentage of subjects treated with FCM and IS achieved Hb-response(FCM 99.4%,IS 98.3%),thereby confirming the non-inferiority of FCM compared with IS(difference 1.12(−2.15,4.71;95%confidence interval(CI))).Furthermore,a significantly higher proportion of FCM-treated subjects achieved early Hb-response at Week 2(FCM 85.2%,IS 73.2%;difference 12.1(3.31,20.65;95%CI)).Additionally,the increase in TSAT and serum ferritin levels from baseline was significantly greater at all time points for FCM-treated *** safety profiles of FCM and IS were comparable,with the exception of transient hypophosphatemia and pyrexia,which are consistent with FCM’s known safety *** conclusion,FCM proves to be an efficacious treatment for IDA,providing faster Hb-response and correction of ID with fewer administrations than IS.

关键词： iron deficiency anemia intravenous iron ferric carboxymaltose iron sucrose Hb response early response

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

Tri-axial accelerometry allows to determine parental food provisioning behaviour in a marine bird

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Avian research 2024年第3期15卷 345-351页

作者： Monserrat Del caño Flavio Quintana Giacomo Dell’Omo Agustina Gómez-Laich Instituto de Biología de Organismos Marinos(IBIOMAr) CONICETBoulevard Brown 2915U9120ACDPuerto MadrynChubutArgentina Ornis Italica Piazza Crati 1500199RomeItaly Departamento de Ecología Genética y Evolución(EGE)and Instituto de EcologíaGenética y Evolución de Buenos Aires(IEGEBA)CONICETFacultad de CienciasExactas y NaturalesUniversidad de Buenos AiresPabellón II Ciudad UniversitariaC1428EGACiudad Autónoma de Buenos AiresArgentina

The study of parental food provisioning is essential for understanding the breeding ecology of *** conducted the first study using accelerometry to detect food provisioning in birds,using Support Vector Machine(SVM)models to identify when adults feed chicks of three different age *** were attached to the head of adult female Imperial Shags(Leucocarbo atriceps),and various attributes derived from the acceleration signals were used to train SVM models for each chick age *** performance improved with chick age class,with SVM models achieving high overall accuracy(>88%)and highest sensitivity in older chick categories(>91%).However,precision values,especially for younger chicks,remained relatively low(between 26%and 45%).The application of a time filter based on the minimum duration of the observed food provisioning behaviours for each chick age category,improved model performance by reducing false provisioning behaviours,particularly in the model for older chicks,which showed the highest precision(72.4%).This study highlights the effectiveness of accelerometry and machine learning in studying parental food provisioning in birds,providing a rapid and accurate data collection method to complement traditional *** described methodology can be applied to any bird species that exhibits distinctive movements while feeding its offspring and has suitable characteristics for attaching an accelerometer to the body part that best captures this ***,it is hoped that the results of this study will contribute to future research on key questions in parental investment theory and reproductive strategies in birds.

关键词： Accelerometry Food provisioning Imperial shag Leucocarbo atriceps Seabird Support vector machine

game changer:How Janus kinase inhibitors are reshaping the landscape of ulcerative colitis mana

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World Journal of gastroenterology 2024年第35期30卷 3942-3953页

作者： Antonio M caballero-Mateos Guillermo Arturo cañadas-de la Fuente Department of gastroenterology and Hepatology San Cecilio University HospitalGranada 18014Spain Department of Nursing Faculty of Health SciencesUniversity of GranadaGranada 18004Spain

recent advancements in the treatment landscape of ulcerative colitis(UC)have ushered in a new era of possibilities,particularly with the introduction of Janus kinase(JAK)-signal transducer and activator of transcription *** novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory *** approved JAK inhibitors(JAKis),such as tofacitinib,filgotinib,and upadacitinib,clinicians now have powerful tools to modulate immune responses and gene expression,potentially revolutionizing the treatment algorithm for *** trials have demonstrated the efficacy of JAKis in inducing and maintaining remission,presenting viable options for patients who have failed conventional ***-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy,particularly in patients with aggressive disease phenotypes or refractory to biologic *** rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC,offering timely relief for patients with active disease and facilitating personalized treatment *** safety concerns,including cardiovascular risks and infections,ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.

关键词： Ulcerative colitis Janus kinase inhibitors Filgotinib Tofacitinib Upadacitinib

基于干细胞的胶质细胞源性神经营养因子和睫状神经营养因子对CLN7型神经元蜡样脂褐质沉积症小鼠模型视网膜退行性病变的治疗研究

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中华眼底病杂志 2024年第7期40卷 526-537页

作者：魏莹莹 udo Bartsch 汉堡-埃彭多夫大学医学中心眼科德国汉堡100731 长沙湘江爱尔眼科医院长沙410011

目的观察CLN7型神经元蜡样脂褐质沉积症小鼠模型视网膜变性的形态学和功能学改变,以及基于神经干细胞(NSC)的胶质细胞源性神经营养因子(GDNF)和(或)睫状神经营养因子(CNTF)对小鼠光感受器细胞的治疗效果。方法鼠龄14 d的CLN7型小鼠100... 详细信息

目的观察CLN7型神经元蜡样脂褐质沉积症小鼠模型视网膜变性的形态学和功能学改变,以及基于神经干细胞(NSC)的胶质细胞源性神经营养因子(GDNF)和(或)睫状神经营养因子(CNTF)对小鼠光感受器细胞的治疗效果。方法鼠龄14 d的CLN7型小鼠100只随机分为实验组、对照组,分别为80、20只。鼠龄14 d的C57BL/6J小鼠20只设定为野生型组(WT组)。对照组、WT组小鼠不作任何处理,于2、4、6月龄时,采用免疫组织化学染色观察视网膜视锥细胞、视杆-双极细胞、视锥-双极细胞分布和数量变化;采用视网膜电图(ErG)检查记录暗视a、b波及明视b波振幅。实验组小鼠随机选取单侧眼为实验眼,玻璃体腔分别注射2μl CNTF-NSC、GDNF-NSC、CNTF-NSC和GDNF-NSC 1:1细胞混合物(GDNF/CNTFNSC),并据此再分为CNTF-NSC组、GDNF-NSC组、GDNF/CNTF-NSC组;对侧眼玻璃体腔注射不含神经营养因子(NTF)的NSC 2μl作为自身对照组。实验组不同治疗亚组于小鼠2、4月龄时,采用免疫组织化学染色观察光感受器细胞的数量;采用ErG检查记录暗视a、b波及明视b波振幅;小鼠4月龄时,观察移植的NSC分化情况和NTF表达。两组间比较采用双因素方差分析。结果与WT组比较,小鼠2、4、6月龄时,对照组小鼠周边区视网膜视锥细胞密度(F=285.10),中央区、周边区视网膜视杆-双极细胞密度(F=823.20、346.20)、视锥-双极细胞密度(F=356.30、210.60)以及暗视a、b波振幅(F=1911.00、387.10)均显著降低,差异有统计学意义(P0.05)。结论随年龄增长,CLN7型小鼠表现出渐进性加重的退行性变化,这种变化在光感受器细胞和双极细胞的形态结构及功能上是一致的。基于NSC玻璃体内递送的CNTF和GDNF/CNTF均对光感受器细胞有保护作用,但联合使用GDNF/CNTF并未展现出比各自单独使用时更显著的协同保护效果。GDNF对CLN7型小鼠视网膜的形态和功能均没有治疗效果。

关键词：神经元蜡样质脂褐质沉积症7型胶质细胞源性神经营养因子睫状神经营养因子慢病毒神经干细胞眼内干细胞移植神经保护

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

Structural Foundation and Geometry of the Material Singularity (and Its Quantum Entanglement)

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第3期10卷 1095-1137页

作者： rafael cañete Mesa Independent researcher Seville Spain

In this paper we develop and study, as the second part of one more general development, the energy transmutation equation for the material singularity, previously obtained through the symmetrisation of a wave packet, that is, we develop the correlation between the terms of this equation, which accounts for the formation of matter from a previous vibrational state, and the different possible energy species. These energetic species are ascribed, in a simplified form, to the equation E¯ω=E¯k+E¯f, which allows us, through its associated phase factor, to gain an insight into the wave character of the kinetic energy and thus to attain the basis of the matter-wave, and all sorts of related phenomenologies, including that concerning quantum entanglement. The formation of the matter was previously identified as an energetic process, analogous to the kinetic one, in which finally the inertial mass is consolidated as a mass in a different phase, now, in addition, the mass of the material singularity is identified as a volumetric density of waves of toroidal geometry created in the process of singularisation or energy transfer between species, which makes it possible to establish the real relation or correspondence between the corpuscular and photonic energy equation (E=mc2=hν), i.e. to explain through m the intimate sense of the first equivalence, which explains what νis in the second one.

关键词： Standard Model Wave-Packet Material Singularity Wave-Particle Dualism Wave Symmetrisation Matter-Wave Energetic Transmutation Quantum Entanglement