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A pH-responsive nanoparticle delivery system containing dihydralazine and doxorubicin-based prodrug for enhancing antitumor efficacy

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Aggregate 2024年第1期5卷 436-450页

作者： Lianxue Zhang Jianxiang Huang damiano Buratto Panli Han Zaixing Yang Ruhong Zhou Institute of Quantitative Biology Shanghai Institute for Advanced StudyCollege of Life SciencesZhejiang UniversityHangzhouChina State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences(RAD-X)Soochow UniversitySuzhouChina Cancer Center Zhejiang UniversityHangzhouChina Department of Chemistry Columbia UniversityNew YorkNew YorkUSA

The efficacy of nanoparticle(NP)-based drug delivery technology is hampered by aberrant tumor stromal microenvironments(TSMs)that hinder NP ***,the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical ***,we propose a potential solution using a dihydralazine(HDZ)-loaded nanoparticle drug delivery system containing a pH-responsive,cyclic RGD peptide-modified prodrug based on doxorubicin(cRGD-Dex-DOX).With a combined experimental and theoretical approach,we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor *** can notably downregulate the expression levels of hypoxia-inducible factor 1α(HIF1α),α-smooth muscle actin,and fibronectin through the dilation of tumor blood *** changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors,suggesting that such a system may offer an effective“multifunctional therapy”through both improving the chemotherapeutic effect and enhancing the immune response to *** vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens,with the lowest side effects as well.

关键词： antitumor dihydralazine drug delivery system tumor stromal microenvironment vasculature

Long-term normothermic machine perfusion of fatty livers:towards transplanting untransplantable livers?

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 681-685页

作者： damiano Patrono Nicola De Stefano Elena Vissio Alessandro Gambella Renato Romagnoli General Surgery 2U–Liver Transplant Unit Azienda Ospedaliero Universitaria Cittàdella Salute e della Scienza di TorinoTurinItaly Pathology Unit Azienda Ospedaliero Universitaria Cittàdella Salute e della Scienza di TorinoTurinItaly Department of Medical Sciences University of TurinTurinItaly

Since the very early days of clinical liver transplantation(LT),transplant surgeons and professionals have been confronted with the increased risk of failure associated with the use of fatty liver grafts(1).Notwithstanding the wide variability in steatosis assessment across different centers and pathologists(2),utilization of livers with moderate(≥30%)or severe(≥60%)macrovesicular steatosis has been consistently associated with an increased risk of primary non-function,early allograft dysfunction,acute kidney injury,as well as inferior graft and patient survival(3).The mechanisms behind the increased susceptibility of steatotic livers to ischemia-reperfusion injury(IRI)are multiple,including disturbances to microcirculation due to sinusoidal narrowing,increased oxidative stress upon reperfusion and enhanced lipid peroxidation,leading to an increased release of inflammatory mediators like IL6,IL1βand so-called damage associated molecular patterns(DAMP),like cell-free DNA and mitochondrial ***,this is reflected by hepatocyte death by necrosis rather than apoptosis,pseudopeliotic steatosis(i.e.,the expulsion of lipid droplets into the extracellular space)and lately,by tissue remodelling and fibrosis(4,5).

关键词： Liver transplantation(LT) steatosis macrovesicular steatosis large droplet fat normothermic machine perfusion

Use of infrared thermography to detect reactions to stressful events:does animal personality matter?

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Integrative Zoology 2024年第2期19卷 224-239页

作者： Maria Vittoria MAZZAMUTO Marina MORANDINI William LAMPMAN Lucas Armand WAUTERS damiano PREATONI John Lad KOPROWSKI Adriano MARTINOLI School of Natural Resources and Environment College of Agriculture and Life ScienceUniversity of ArizonaArizonaUSA Unitàdi Analisi e Gestione delle Risorse Ambientali Dipartimento di Scienze Teoriche e ApplicateGuido Tosi Research GroupUniversitàdegli Studi dell’InsubriaVareseItaly Haub School of Environment and Natural Resources University of WyomingWyomingUSA

The study of the relationship between animal stress and personality for free-ranging animals is limited and provides contrasting *** perception of stressors by an individual may vary due to its personality,and certain personality traits may help individuals to better cope with *** non-invasive infrared thermography(IRT),we investigated the link between physiological and behavioral components expressed during an acute stress event by free-ranging Fremont’s squirrels(Tamiasciurus fremonti).We expected that,during the acute stress event of being approached by the researcher,individuals that showed a fast pace-of-life syndrome(bolder,more active,and less social/more aggressive)based on an arena test would exhibit stronger sympathetic-adrenal-medullary system reactivity showing a more intense stress-induced hyperthermia(high core body temperature and low peripheral temperature)than individuals with a slow pace of life(shy,less active,and more social).We successfully employed IRT technology to images of Fremont’s squirrels with identification of the individuals’body parts(eye,nose,ear,hind foot).However,we found no support for our ***’body surface temperatures told us more about a squirrel’s external environment and less about the thermal state of the body in that environment following a stressful *** studies need to assess how to make IRT effective and efficient in the field and improve its performance in studying the relationships between physiology and personality in wildlife.

关键词： non-invasive method open field test physiology stress-induced hyperthermia Tamiasciurus fremonti

The Dallas Donation after Circulatory Death Transplantation Summit:expanding donation after circulatory death procedures through process improvement,broader utilization,and innovation

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 824-836,I0009页

作者： Michele Finotti Anji Wall Anthony D’Alessandro Gary Schwartz Chris Sonnenday David Goldberg Ashish Shah Peter Friend Jeff P.Orlowski Greg McKenna Steve Newton Brad Adams William C.Chapman Amit Mathur Marwan Abouljoud Tim Pruett Amelia Hessheimer James F.Trotter Sumeet K.Asrani Giuliano testa Simmons Transplant Institute Baylor University Medical CenterDallasTXUSA Hepatobiliary and General Surgery Unit Regional Hospital TrevisoDISCOGUniversity of PaduaPaduaItaly Division of Transplantation Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonWIUSA Department of Thoracic Surgery and Lung Transplantation Baylor University Medical CenterCenter for Advanced Heart and Lung DiseaseDallasTXUSA Department of Surgery University of MichiganAnn ArborMIUSA Division of Digestive Health and Liver Diseases Department of MedicineUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Cardio-Thoracic Surgery Vanderbilt University Medical CenterNashvilleTNUSA Nuffield Department of Surgical Sciences University of OxfordOxfordUK LifeShare Transplant Donor Services of Oklahoma Oklahoma CityOKUSA Administration Baylor University Medical CenterDallasTXUSA Southwest Transplant Alliance DallasTXUSA Department of Surgery/Transplantation Washington UniversitySt.LouisMOUSA Division of Transplant Surgery Department of SurgeryMayo Clinic ArizonaAlix School of MedicinePhoenixAZUSA Divisions of Transplant and Hepatobiliary Surgery Henry Ford HospitalDetroitMIUSA Department of Surgery University of MinnesotaMinneapolisMNUSA General and Digestive Surgery Hospital Universitario La PazIdiPAZMadridSpain

Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its *** is still room for expansion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in *** convened a multidisciplinary transplantation summit to examine various aspects of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transplantation,including abdominal and cardiothoracic surgeons,organ procurement organization directors,hepatologists,and *** conference focused on identifying barriers to DCD organ utilization and strategies to overcome these *** divide the barriers to DCD utilization into three mains categories:(Ⅰ)policy and process variation;(II)logistical and transportation challenges;and(Ⅲ)higher risk perceptions related to DCD *** each barrier,we proposed a variety of solutions,providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of *** is a specific focus on ex situ machine perfusion,normothermic regional perfusion,and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.

关键词： Donation after circulatory death donation(DCD donation) marginal graft donor pool machine perfusion(MP)

Hermitian Generalization of the Rarita-Schwinger Operators

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Acta Mathematica Sinica,English Series 2010年第2期26卷 311-330页

作者： Alberto damiano David EELBODE Mathematics Institute of Charles University Department of Mathematics and Computer Science University of Antwerp

We introduce two new linear differential operators which are invariant with respect to the unitary group SU（n）. They constitute analogues of the twistor and the Rarita-Schwinger operator in the orthogonal case. The natural setting for doing this is Hermitian Clifford Analysis. Such operators are constructed by twisting the two versions of the Hermitian Dirac operator 6z_ and 6z_ and then projecting on irreducible modules for the unitary group. We then study some properties of their spaces of nullsolutions and we find a formulation of the Hermitian Rarita-Schwinger operators in terms of Hermitian monogenic polynomials.

关键词： Hermitian Clifford analysis Rarita-Schwinger operator

Multiscale Mechanics and Optimization of Gastropod Shells

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Journal of Bionic Engineering 2011年第4期8卷 357-368页

作者： Mostafa Yourdkhani damiano Pasini Francois Barthelat Department of Mechanical Engineering McGill University 817 Sherbrooke Street West Montreal QC H3A 2K6 Canada

A vast majority of mollusks grow a hard shell for protection. The structure of these shells comprises several levels of hierarchy that increase their strength and their resistance to natural threats. This article focuses on nacreous shells, which are composed of two distinct layers. The outer layer is made of calcite, which is a hard but brittle material, and the inner layer is made of nacre, a tough and ductile material. The inner and outer layers are therefore made of materials with distinct structures and properties. In this article, we demonstrate that this system is optimum to defeat attacks from predators. A two-scale mod- eling and optimization approach was used. At the macroscale, a two-layer finite element model of a seashell was developed to capture shell geometry. At the microscale, a representative volume element of the microstructure of nacre was used to model the elastic modulus of nacre as well as a multiaxial failure criterion, both expressed as function of microstructural parameters. Experiments were also performed on actual shells of red abalone to validate the results obtained from simulations and gain insight into the way the shell fails under sharp perforation. Both optimization and experimental results revealed that the shell displays optimum performance when two modes of failure coincide within the structure. Finally, guidelines for designing two-layer shells were proposed to improve the performance of engineered protective systems undergoing similar structural and loading conditions.

关键词： seashell multiscale modeling representative volume element failure criterion nacre multiscale optimization

Hot topics in pancreatic cancer management

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World Journal of Gastrointestinal Surgery 2023年第2期15卷 121-126页

作者： damiano Caputo Department of General Surgery Fondazione Policlinico Universitario Campus Bio-MedicoRome 00128Italy General Surgery Research Unit University Campus Bio-Medico di RomaRome 00128Italy

Pancreatic ductal adenocarcinoma(PDAC)is a sneaky and lethal disease burdened by poor *** is often detected too late to be successfully cured,and it has been estimated that it will be a leading cause of cancer-related deaths in the near *** the last decade,multimodal treatments involving surgery,chemotherapy and radiotherapy have contributed to improving the prognosis of this disease;however,long-term results are still not *** morbidity and mortality rates remain high,and systemic treatments are burdened by toxicity in both neoadjuvant and adjuvant *** in technologies,targeted therapies,immunotherapy and PDAC microenvironment modulation strategies may represent useful potential weapons in the ***,in the fight against this dreadful disease,there is an urgent need for new,cheap and user-friendly tools for early *** this field,promising results have been found in nanotechnologies and“omics”analyses that search for new biomarkers to be used in primary and secondary ***,there are many issues that need to be solved before considering these tools in daily clinical *** editorial reported the state of the art of pancreatic cancer management.

关键词： Pancreatic cancer Pancreatic ductal adenocarcinoma Nanotechnology Neoadjuvant therapy Adjuvant therapy Omics

CO2 adsorption in a confined fluidized bed of zeolite pellets: Influence of operating velocity

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Particuology 2019年第5期17卷 67-74页

作者： Rossella Girimonte Brunello Formisani Flaviano testa Diparcimento di Ingegneria Informatica Modellistica Elettronica e Sistemistica Universita della Calabria 187030 Arcavacata di Rende Cosenza Italy

CO2 adsorption is performed across a fluidized bed comprising a commercial pelletized 13X zeolite con-fined to the interstitial void network of a coarse glass sphere packed bed. Compared with traditional fixed bed adsorption, the packed fluidized system allows operation across a wide-range of gas velocities without a substantial increase in pressure drop. Additionally, with respect to conventional fluidization regimes, the technique adopted herein prevents the formation of bubbles in favour of enhancing the bed expansion ability. Furthermore, for a given mass of sorbent, the C02 uptake capacity is observed to increase as a result of improved thermal conditions and in eliminating any by-pass effect at the gas-particle interface, which is associated to the suppression of bubbling.

关键词： CO2 capture Adsorption Zeolite 13X Confined fluidized beds Packed fluidized bed

Adult to adult living related liver transplantation: Where do we currently stand?

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World Journal of Gastroenterology 2012年第46期18卷 6729-6736页

作者： Erica M Carlisle Giuliano testa Department of Surgery Baylor University Medical Center

Adult to adult living donor liver transplantation (AALDLT) was first preformed in the United States in 1997. The procedure was rapidly integrated into clinical practice, but in 2002, possibly due to the first widely publicized donor death, the number of living liver donors plummeted. The number of donors has since reached a steady plateau far below its initial peak. In this review we evaluate the current climate of AALDLT. Specifically, we focus on several issues key to the success of AALDLT: determining the optimal indications for AALDLT, balancing graft size and donor safety, assuring adequate outflow, minimizing biliary complications, and maintaining ethical practices. We conclude by offering suggestions for the future of AALDLT in United States transplantation centers.

关键词： Adult to adult living donor liver transplantation Outflow Graft size Liver failure Ethics Biliary complications