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Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering

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Science China Materials 2020年第1期63卷 147-156页

作者： Eric Volta-Duran olivia cano-garrido Naroa Serna Hector Lopez-Laguna Laura Sanchez-Garcia Mireia Pesarrodona Alejandro Sanchez-Chardi Ramon Mangues Antonio Villaverde Esther Vazquez Ugutz Unzueta Institut de Biotecnologia i de Biomedicina Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain Departament de Genetica i de Microbiologia Universitat Autònoma de BarcelonaBellaterra08193 BarcelonaSpain CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN)C/Monforte de Lemos 3-528029 MadridSpain Nanoligent SL Edifici EUREKAUniversitat Autonoma de BarcelonaBellaterra08193 BarcelonaSpain Institut dInvestigacions Biomèdiques Sant Pau and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau08041 BarcelonaSpain Departament de Biologia Evolutiva Ecologia i Ciencies AmbientalsFacultat de BiologiaUniversitat de BarcelonaAv.Diagonal 64308028 BarcelonaSpain Institute for Research in Biomedicine(IRB Barcelona) The Barcelona Institute of Science and Technology08028 BarcelonaSpain

Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4^+ cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 *** these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4^+ human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker.

关键词： nanoparticles protein materials recombinant proteins drug delivery self-assembling cancer cell targeting

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Trends in oxycodone and oxycodone-containing analgesics administration for back pain in emergency departments in the USA(2007–2018)

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World Journal of Emergency Medicine 2024年第3期15卷 169-174页

作者： Jonathan Chabon Jemer garrido Deanna Schreiber-Gregory Jefferson Drapkin Sergey Motov Department of Emergency Medicine Maimonides Medical CenterBrooklyn 11219USA

BACKGROUND:To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments(EDs) in the USA from 2007 to ***:Data were gathered from the National Hospital Ambulatory Medical Care Survey(NHAMCS) from 2007 to *** study population included individuals of all ages presenting to USA *** NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back *** main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time ***:There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007(244,000 visits) to 2018(92,000 visits).The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older(from 43.8% to 57.6%),female patients(from 54.5% to 62.0%),black patients(from 22.5% to 30.4%),and Hispanic/Latino patients(from 9.4% to 19.6%).Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007,with a decrease to 68.5% in *** oxycodone was the second most prescribed medication,accounting for 6.1% in 2007 and 31.5% in ***:The overall number of oxycodone-containing analgesics decreased significantly from 2007 to ***,that number trended upward in 45-year-old and older,female,black,or Hispanic/Latino patients from 2007 to *** total amount of pure oxycodone increased significantly from 2007 to 2008.

关键词： Oxycodone Back pain Emergency department

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重组氯毒素构建细胞靶向的活性纳米颗粒(英文)

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Science China Materials 2019年第6期62卷 892-898页

作者： Raquel Díaz Laura Sánchez-García Naroa Serna Alejandro Sánchez-Chardi olivia cano-garrido Julieta M.Sánchez Ugutz Unzueta Esther Vazquez Antonio Villaverde Institut de Biotecnologia i de Biomedicina Universitat Autònoma de Barcelona Departament de Genètica i de Microbiologia Universitat Autònoma de Barcelona CIBER de Bioingeniería Biomateriales y Nanomedicina(CIBER-BBN) Servei de Microscòpia Universitat Autònoma de Barcelona Biomedical Research Institute Sant Pau(IIB-Sant Pau)and Josep Carreras Research Institute Hospital de la Santa Creu i Sant Pau Universidad Nacional de Córdoba Facultad de Ciencias ExactasFísicas y Naturales.ICTA and Departamento de QuímicaCátedra de Química Biológica.Córdoba.Argentina.CONICETInstituto de Investigaciones Biológicas y Tecnológicas(IIBYT)

功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性.氯毒素(CTX),作为一种重组的蝎毒素,由于其优先结合癌细胞的能力而引起人们的兴趣.本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒,这... 详细信息

功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性.氯毒素(CTX),作为一种重组的蝎毒素,由于其优先结合癌细胞的能力而引起人们的兴趣.本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒,这些纳米颗粒可穿透具有和天然毒素相同受体特异性的培养细胞.这些生物相容且可生物降解的材料,表现出与同时作为载体和治疗剂的重组毒素相应的温和但仍然显著的细胞毒活性,有希望成为用于细胞靶向治疗胶质瘤的药物载体.此外,对CTX侧区域的修改可有效影响纳米颗粒的性能,说明基于CTX的构建体可通过常规基因工程来调节其多重功能性.

关键词：重组DNA技术细胞毒活性纳米颗粒蝎毒素癌细胞可生物降解氯药物载体

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First experience in laparoscopic surgery in low and middle income countries: A systematic review

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 546-553页

作者： Rebekka Troller Jasmine Bawa olivia Baker James Ashcroft Department of Surgery Medway Maritime HospitalGillingham ME75NYKentUnited Kingdom Department of Surgery University Hospital CambridgeCambridge CB20QQUnited Kingdom

BACKGROUND Laparoscopic surgery has reduced morbidity and mortality rates,shorter post-operative recovery periods and lower complication rates than open *** is routine practice in high-income countries and is becoming increasingly common in countries with limited ***,introducing laparoscopic surgery in low-and-middle-income countries(LMIC)can be expensive and requires resour-ces,equipment,and *** To report the challenges and benefits of introducing laparoscopic surgery in LMIC as well as to identify solutions to these challenges for countries with limited finances and *** MEDLINE,EMBASE and Cochrane databases were searched for studies reporting first experience in laparoscopic surgery in *** studies were published between 1996 and 2022 with full text available in *** criteria were studies considering only open surgery,ear,nose,and throat,endoscopy,arthro-scopy,hysteroscopy,cystoscopy,transplant,or bariatric *** Ten studies out of 3409 screened papers,from eight LMIC were eligible for inclusion in the final analysis,totaling 2497 *** reported challenges were related to costs of equipment and training programmes,equipment pro-blems such as faulty equipment,and access to surgical ***-related challenges were reliance on foreign trainers and lack of locally trained surgeons and theatre *** benefits of introducing laparoscopic surgery were economic and clinical,including a reduction in hospital stay,complications,and morbidi-ty/*** introduction of laparoscopic surgery also provided training opportunities for junior *** Despite financial and technical challenges,many studies emphasise the overall benefit of introducing laparoscopic surgery in LMICs such as reduced hospital stay and the related lower cost for *** many of the clinical centres in LMICs have proposed practical solutions to the challenges reported,more support is critical

关键词： Laparoscopic surgery Low and middle income country First experience Training in laparoscopic surgery

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Remediation of amide pesticide-polluted soils by combined solarization and ozonation treatment

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Pedosphere 2024年第3期34卷 641-651页

作者： Isabel garrido Carmen MMARTINEZ Pilar FLORES Pilar HELLIN Fulgencio CONTRERAS Jose FENOLL Department of Sustainability and Quality Group of Fruit and Vegetable Products Instituto Murciano de Investigacion y Desarrollo Agrario y MedioambientalLa Alberca 30150(Spain)

Agriculture has a close relationship with nature,but it can also be the source of negative and permanent environmental *** use of pesticides in modern agriculture is a common practice,but their side effects on the environment cannot be *** this study,we evaluated a combination of solarization and ozonation techniques for the elimination of six amide pesticides(boscalid,chlorantraniliprole,cyflufenamid,fluopyram,napropamide,and propyzamide)in *** experiments were performed with four different soils to assess the efficiency of this methodology at different soil temperatures and ozone dosages under laboratory conditions,and then a greenhouse pot experiment was conducted under controlled conditions during *** days after the onset of the experiments,higher degradation percentages of amide pesticides were observed in ozonized soils than in other treated soils,particularly when ozone was applied at 10 cm soil *** results show that the utilization of ozonation,along with solarization,represents a valid method for degrading residues of the studied pesticides and suggest that this combined technology may be a promising tool for remediating pesticide-polluted soils.

关键词： intermediate ozone pesticide degradation pesticide residue polyethylene film remediation technique

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Survival effects of antibiotic exposure during the larval and adult stages in the West Nile virus vector Culex pipiens

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Insect Science 2024年第2期31卷 542-550页

作者： Marta Garrigos Mario garrido Manuel Morales-Yuste JosuéMartinez-de la Puente Jesus Veiga Faculty of Pharmacy Department of ParasitologyUniversity of GranadaGranadaSpain CIBER de Epidemiologia y Salud Publica(CIBERESP) MadridSpain

The ability of mosquitoes to transmit a pathogen is affected,among other factors,by their survival rate,which is partly modulated by their *** microbiota is acquired during the larval phase and modified during their development and adult feeding behavior,being highly dependent on environmental *** residues including antibiotics are widespread pollutants potentially being present in mosquito breeding waters likely affecting their ***,we used Culex pipiens mosquitoes to assess the impact of antibiotic exposure during the larval and adult stages on the survival rate of adult ***-collected larvae were randomly assigned to two treatments:larvae maintained in water supplemented with antibiotics and control *** adults were subsequently assigned to each of two treatments,fed with sugar solution with antibiotics and fed only with sugar solution(controls).Larval exposure to antibiotics significantly increased the survival rate of adult females that received a control *** addition,the effect of adult exposure to antibiotics on the survival rate of both male and female mosquitoes depended on the number of days that larvae fed ad libitum in the laboratory before *** particular,shorter larval ad libitum feeding periods reduced the survival rate of antibiotic-treated adult mosquitoes compared with those that emerged after a longer larval feeding *** differences were not found in control adult *** results extend the current understanding of the impact of antibiotic exposure of mosquitoes on a key component of vectorial capacity,that is the vector survival rate.

关键词： antibiotics avian malaria microbiota mosquitoes vector competence vector survival

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Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases

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Neural Regeneration Research 2024年第3期19卷 571-577页

作者： Sonia Irais Gonzalez-cano Gonzalo Flores Jorge Guevara Julio Cesar Morales-Medina Samuel Treviño Alfonso Diaz Faculty of Chemical Sciences Benemerita Autonomous University of PueblaPueblaMexico Institute of Physiology Benemerita Autonomous University of PueblaPueblaMexico Department of Biochemistry Faculty of MedicineNational Autonomous University of MexicoMexico CityMexico Animal Reproduction Research Center CINVESTAV-Autonomous University of TlaxcalaTlaxcalaMexico

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity,leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases,including cardiovascular diseases,osteoporosis,cancer,diabetes,and *** is considered the major risk factor for Parkinson’s and Alzheimer’s disease ***,diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative ***,no treatment can effectively reverse these neurodegenerative ***,some antidiabetic drugs have opened the possibility of being used against neurodegenerative *** the previous framework,Vanadium species have demonstrated a notable antidiabetic *** research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic *** results suggest that these polyoxidovanadates induce neuronal and cognitive restoration *** review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain,constituting a therapeutic alternative for aging and neurodegenerative diseases.

关键词： Alzheimer’s disease antidiabetic brain cognition diabetes insulin neurodegeneration neuroinflammation oxidative stress Vanadium species

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Recent advances in the understanding and management of chronic pancreatitis pain

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胰腺病学杂志(英文) 2024年第1期7卷 35-44页

作者： Walker Jessica Babyok olivia L. Saloman Jami L. Phillips Anna Evans Department of Internal Medicine University of Pittsburgh Medical Center Pittsburgh PA United States Division of Gastroenterology Hepatology and Nutrition Department of Medicine School of Medicine University of Pittsburgh Pittsburgh PA United States Center for Pain Research Center for Neuroscience School of Medicine University of Pittsburgh Pittsburgh PA United States

Abdominal pain is the most common symptom of chronic pancreatitis (CP) and is often debilitating for patients and very difficult to treat. To date, there exists no cure for the disease. Treatment strategies focus on symptom management and on mitigation of disease progression by reducing toxin exposure and avoiding recurrent inflammatory events. Traditional treatment protocols start with medical management followed by consideration of procedural or surgical intervention on selected patients with severe and persistent pain. The incorporation of adjuvant therapies to treat comorbidities including psychiatric disorders, exocrine pancreatic insufficiency, mineral bone disease, frailty, and malnutrition, are in its early stages. Recent clinical studies and animal models have been designed to improve investigation into the pathophysiology of CP pain, as well as to improve pain management. Despite the array of tools available, many therapeutic options for the management of CP pain provide incomplete relief. There still remains much to discover about the neural regulation of pancreas-related pain. In this review, we will discuss research from the last 5 years that has provided new insights into novel methods of pain phenotyping and the pathophysiology of CP pain. These discoveries have led to improvements in patient selection for optimization of outcomes for both medical and procedural management, and identification of potential future therapies.

关键词： Central sensitization Chronic pancreatitis Pain phenotyping Peripheral sensitization

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A Tutorial on Federated Learning from Theory to Practice:Foundations,Software Frameworks,Exemplary Use Cases,and Selected Trends

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 824-850页

作者： M.Victoria Luzón Nuria Rodríguez-Barroso Alberto Argente-garrido Daniel Jiménez-López Jose M.Moyano Javier Del Ser Weiping Ding Francisco Herrera Department of Software Engineering Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Computer Science and Artificial Intelligence Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Communications Engineering University of the Basque Country(UPV/EHU)and also with TECNALIABasque Research&Technology Alliance(BRTA)Spain School of Information Science and Technology Nantong UniversityNantong 226019China

When data privacy is imposed as a necessity,Federated learning(FL)emerges as a relevant artificial intelligence field for developing machine learning(ML)models in a distributed and decentralized *** allows ML models to be trained on local devices without any need for centralized data transfer,thereby reducing both the exposure of sensitive data and the possibility of data interception by malicious third *** paradigm has gained momentum in the last few years,spurred by the plethora of real-world applications that have leveraged its ability to improve the efficiency of distributed learning and to accommodate numerous participants with their data *** virtue of FL,models can be learned from all such distributed data sources while preserving data *** aim of this paper is to provide a practical tutorial on FL,including a short methodology and a systematic analysis of existing software ***,our tutorial provides exemplary cases of study from three complementary perspectives:i)Foundations of FL,describing the main components of FL,from key elements to FL categories;ii)Implementation guidelines and exemplary cases of study,by systematically examining the functionalities provided by existing software frameworks for FL deployment,devising a methodology to design a FL scenario,and providing exemplary cases of study with source code for different ML approaches;and iii)Trends,shortly reviewing a non-exhaustive list of research directions that are under active investigation in the current FL *** ultimate purpose of this work is to establish itself as a referential work for researchers,developers,and data scientists willing to explore the capabilities of FL in practical applications.

关键词： Data privacy distributed machine learning federated learning software frameworks

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动态全场光学相干断层扫描结合深度学习在肿瘤患者术中诊断的应用:一项乳腺癌患者的前瞻性队列研究

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Science Bulletin 2024年第11期69卷 1748-1756页

作者：张舒玮杨滨杨后圃赵进张原媛高元绪 olivia Monteiro 张康刘博王殊 Breast Center Peking University People’s HospitalBeijing 100044China China ESG Institute Capital University of Economics and BusinessBeijing 100070China Faculty of Information Technology Beijing University of TechnologyBeijing 100124China Department of Pathology Peking University People’s HospitalBeijing 100044China Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and TechnologyMacao 999078China College of Future Technology Peking UniversityBeijing 100091China School of Mathematical and Computational Sciences Massey UniversityAuckland 0745New Zealand

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin(H&E) histology, such as frozen section, are time-,resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography(D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group(n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma(IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ(DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests(n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%;only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow(approximately 3 min)was significantly shorter than that required for traditional procedures(approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

关键词： Cancer diagnosis Breast neoplasms Dynamic full-field optical coherence tomography Deep learning Image classification

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