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Roles of neuronal lysosomes in the etiology of parkinson’s disease

Neural Regeneration Research 2024年第9期19卷 1981-1983页

作者： mattia Volta Institute for Biomedicine Eurac ResearchBolzanoItaly

Therapeutic progress in neurodegenerative conditions such as parkinson’s disease has been hampered by a lack of detailed knowledge of its molecular *** advancements in genetics and genomics have provided fundamental insights into specific protein players and the cellular processes involved in the onset of *** this respect,the autophagy-lysosome system has emerged in recent years as a strong point of convergence for genetics,genomics,and pathologic indications,spanning both familial and idiopathic parkinson’s ***,if not all,genes linked to familial disease are involved,in a regulatory capacity,in lysosome function(e.g.,LRRK2,alpha-synuclein,VpS35,parkin,and pINK1).Moreover,the majority of genomic loci associated with increased risk of idiopathic parkinson’s cluster in lysosome biology and regulation(GBA as the prime example).Lastly,neuropathologic evidence showed alterations in lysosome markers in autoptic material that,coupled to the alpha-synuclein proteinopathy that defines the disease,strongly indicate an alteration in *** this Brief Review article,I present a personal perspective on the molecular and cellular involvement of lysosome biology in parkinson’s pathogenesis,aiming at a larger vision on the events underlying the onset of the *** attempts at targeting autophagy for therapeutic purposes in parkinson’s have been mostly aimed at“indiscriminately”enhancing its activity to promote the degradation and elimination of aggregate protein accumulations,such as alpha-synuclein Lewy ***,this approach is based on the assumption that protein pathology is the root cause of disease,while pre-pathology and pre-degeneration dysfunctions have been largely observed in clinical and pre-clinical *** addition,it has been reported that unspecific boosting of autophagy can be ***,it is important to understand the mechanisms of specific autophagy forms and,even more,the adjustment of specific lysosome f

关键词： alpha-synuclein autophagy LRRK2 lysosome neuroprotection neurotransmission parkinson’s disease Rit2 synapse

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Dislocation of primary total hip arthroplasty:Analysis of risk factors and preventive options

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World Journal of Orthopedics 2024年第6期15卷 501-511页

作者： Dario Regis mattia Cason Bruno Magnan Department of Orthopedic and Trauma Surgery Integrated University HospitalVerona 37126VenetoItaly

Total hip arthroplasty(THA)is one of the most successful elective operations in orthopedic surgery for improving pain and functional disability in patients with end-stage joint ***,dislocation continues to be a troublesome complication after THA,as it is a leading cause of revision and is associated with substantial social,health,and economic *** is a relatively rare,usually early occurrence that depends on both the patients’characteristics and the surgical *** most recent and important finding is the special attention to be given preoperatively to spinopelvic mobility,which is closely related to the incidence of ***,clinical and radiographic assessment of the lumbar spine is mandatory to identify an altered pelvic tilt that could suggest a different positioning of the *** spinal fusion is currently considered a risk factor for dislocation and revision regardless of whether it is performed prior to or after *** options for its treatment and prevention include the use of prostheses with large diameter of femoral head size,dual mobility constructs,constrained liners,and modular neck stems.

关键词： Dislocation Total hip arthroplasty Revision surgery Review Risk factors Complication

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Compact and effective photon-resolved image scanning microscope

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Advanced photonics 2024年第1期6卷 84-95页

作者： Giorgio Tortarolo Alessandro Zunino Simonluca piazza mattia Donato Sabrina Zappone Agnieszka pierzyńska-Mach Marco Castello Giuseppe Vicidomini Istituto Italiano di Tecnologia Molecular Microscopy and SpectroscopyGenoaItaly Genoa Instruments GenoaItaly University of Genoa Dipartimento di InformaticaBioingegneriaRobotica e Ingegneria dei SistemiGenoaItaly Istituto Italiano di Tecnologia Nanoscopy and NIC@IITGenoaItaly École polytechnique Fédérale de Lausanne Laboratory of Experimental BiophysicsLausanneSwitzerland

Fluorescence confocal laser-scanning microscopy(LSM)is one of the most popular tools for life science *** popularity is expected to grow thanks to single-photon array detectors tailored for *** detectors offer unique single-photon spatiotemporal information,opening new perspectives for gentle and quantitative superresolution ***,a flawless recording of this information poses significant challenges for the microscope data acquisition(DAQ)*** present a DAQ module based on the digital frequency domain principle,able to record essential spatial and temporal features of *** use this module to extend the capabilities of established imaging techniques based on single-photon avalanche diode(SpAD)array detectors,such as fluorescence lifetime image scanning ***,we use the module to introduce a robust multispecies approach encoding the fluorophore excitation spectra in the time ***,we combine time-resolved stimulated emission depletion microscopy with image scanning microscopy,boosting spatial *** results demonstrate how a conventional fluorescence laser scanning microscope can transform into a simple,information-rich,superresolved imaging system with the simple addition of a SpAD array detector with a tailored data acquisition *** expected a blooming of advanced single-photon imaging techniques,which effectively harness all the sample information encoded in each photon.

关键词： fluorescence lifetime image scanning microscopy digital frequency domain single photon

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Non-anatomical liver resection for hepatocellular carcinoma:the SegSubTe classification to overcome the problem of heterogeneity

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Hepatobiliary & pancreatic Diseases International 2024年第3期23卷 265-271页

作者： mattia Garancini Alessandro Fogliati Mauro Alessandro Scotti Cristina Ciulli Francesca Carissimi Antonio Rovere Luca Gianotti Fabrizio Romano Unit of Hepatobiliopancreatic Surgery Department of SurgeryASST-MonzaSan Gerardo HospitalUniversity of Milano-Bicoccavia Pergolesi 33MonzaMB 20052Italy Interventional Radiology Department of RadiologyASST-MonzaSan Gerardo HospitalMilano-Bicocca Universityvia Pergolesi 33MonzaMB 20052Italy

Background:The superiority of anatomical resection(AR)***-anatomical resection(NAR)in the surgical management of hepatocellular carcinoma(HCC)is *** are well-defined procedures,whereas the lack of NAR standardization results in heterogeneous *** study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the ***:A single-center retrospective analysis of pre-and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was *** quality of surgery was assessed classifying the type of vascular supply and the level of surgical section(segmental,subsegmental or terminal next to the tumor)of vascular pedicles feeding the HCCs;then,the population was divided in“SegSubTe-IN”or“SegSubTe-OUT”groups,and the tumor recurrence and survival were ***:Ninety-seven patients who underwent NAR were included;76%were SegSubTe-IN and 24%were *** disease recurrence,local recurrence and cut-edge recurrence in the SegSubTe-IN ***-OUT groups were 50%vs.83%(p=0.006),20%vs.52%(p=0.003)and 16%vs.39%(p=0.020),***-OUT odds ratio for local recurrence was 4.1 at univariate regression ***-,three-,and five-year disease-free survival rates in the SegSubTe-IN ***-OUT groups were 81%,58%and 35%vs.46%,21%and 11%,respectively(pproving long-term oncological outcomes and reducing the heterogeneity of quality of NAR for HCC.

关键词： Hepatocellular carcinoma Intraoperative ultrasound Liver surgery Computed tomography Surgical procedure

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Effects of early postnatal gastric and colonic microbiota transplantation on piglet gut health

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Journal of Animal Science and Biotechnology 2024年第2期15卷 645-658页

作者： Christina Larsen Simone Margaard Offersen Anders Brunse mattia pirolo Soumya Kanti Kar Luca Guadabassi Thomas Thymann Department of Veterinary and Animal Science University of CopenhagenDyrlagevej 681870 Frederiksberg CDenmark Animal Nutrition Wageningen Livestock ResearchWageningen University&Research1 De Elst6708 WageningenThe Netherlands

Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig *** and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the *** secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning *** objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and *** Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single ***,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all pprevalence on d 27(ppha diversity and a difference in beta diversity compared to CON(pparaclinical endpoints were similar across *** In conclusion,only CcFT reduced ETEC-related post-weaning ***,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration

关键词： Colonic content filtrate transplantation Colonic microbiota transplantation Gastric microbiota transplantation Gut microbiota Mucosa Neonatal post-weaning diarrhea

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Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

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World Journal of Stem Cells 2024年第5期16卷 604-614页

作者： Edoardo Agosti Marco Zeppieri mattia Ghidoni Tamara Ius Alessandro Tel Marco Maria Fontanella pier paolo panciani Division of Neurosurgery Department of Medical and Surgical SpecialtiesRadiological Sciences and Public HealthUniversity of BresciaBrescia 25123Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Neurosurgery Unit Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy Clinic of Maxillofacial Surgery Department of Head-Neck and NeuroScienceUniversity Hospital of UdineUdine 33100Italy

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and *** stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and *** studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular *** mechanisms can involve different cellular pathways,most of which have been recently reported in the *** progress,targeted therapeutic approaches lack consensus due to GSCs’high *** To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying *** A systematic search was conducted across major medical databases(pubMed,Embase,and Cochrane Library)up to September 30,*** search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text *** them,201 were deemed eligible after excluding 168 for various *** temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma *** analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance *** molecules with mTOR(18.2%),CHK1/2(15.2%),and ATp binding cassette

关键词： Glioma stem cells Chemoresistance Radioresistance Molecular pathways Targeted therapies Systematic review

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Laser-optimized pt-Y alloy nanoparticles embedded in pt-Y oxide matrix for high stability and ORR electrocatalytic activity

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Journal of Energy Chemistry 2024年第5期92卷 508-520页

作者： Riccardo Brandiele Andrea Guadagnini mattia p.rnigotto Federico pini Vito Coviello Denis Badocco paolo pastore Gian Andrea Rizzi Andrea Vittadini Daniel Forrer Vincenzo Amendola Christian Durante Department of Chemical Sciences University of PaduaVia Marzolo 135131 PadovaItaly Istituto di Chimica della Materia Condensata e di Tecnologie per l’Energia ICMATE-CNR via Marzolo 1 I-35131 PadovaItaly

The development of active yet stable catalysts for oxygen reduction reaction(ORR)is still a major issue for the extensive permeation of fuel cells into everyday *** nanostructured pt catalysts are to date the best available systems in terms of activity,the same is not true for stability,particularly under operating *** this work,pt_(Х)Y alloy nanoparticles are proposed as active and durable electrocatalysts for ***_(Х)Y nanoalloys are synthesized and further optimized by laser ablation in liquid followed by laser fragmentation in *** novel integrated laser-assisted methodology succeeded in producing pt_(Х)Y nanoparticles with the ideal size(pt catalysts,yet resulting remarkably more active with E_(1/2)=0.943 V ***,specific activity=1095μA cm^(-2) and mass activity>1000 A g^(-1).At the same time,the nanoalloys are embedded in a fine pt oxide matrix,which allows a greater stability of the catalyst than the commercial pt reference,as directly verified on a gas diffusion electrode.

关键词： Electrocatalysis GDE ORR pt_(2)Y pt_(3)Y LAL LFL Oxide support pto Nanoalloys

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The challenge of molecular selection in liver-limited metastatic colorectal cancer for surgical resection: a systematic review and meta-analysis in the context of current and future approaches

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Oncology Research 2024年第9期32卷 1407-1422页

作者： ROSSANA RONCATO JERRY pOLESEL FEDERICA TOSI ELENA pERUZZI ERIKA BRUGUGNOLI CLAUDIA LAURIA pANTANO MARIA FURFARO FILIppO DI GIROLAMO ALESSANDRO NANI ARIANNA pANI NOEMI MILAN ELENA DE mattia ANDREA SARTORE-BIANCHI ERIKA CECCHIN Experimental and Clinical pharmacology Unit Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano33081Italy Department of Medicine(DMED) University of UdineUdine33100Italy Unit of Cancer Epidemiology Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano33081Italy Department of Oncology and Hemato-Oncology Universitàdegli Studi di MilanoMilan20122Italy Department of Hematology Oncologyand Molecular MedicineGrande Ospedale Metropolitano NiguardaMilan20122Italy Oncology pharmacy Unit IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino AmadoriMeldola47014Italy pharmacy Unit Fondazione IRCCS Istituto Tumori di MilanoMilan20122Italy Department of pharmacy Ca’Foncello Treviso Regional HospitalPiazzale Ospedale 1Treviso31100Italy Department of Medical Surgical and Health Sciences University of TriesteTrieste34127Italy Hospital pharmacy Cattinara HospitalAzienda Sanitaria Universitaria Giuliano IsontinaTrieste34148Italy Department of Oncology and Onco-Hematology Postgraduate School of Clinical Pharmacology and ToxicologyUniversity of MilanMilan20122Italy

Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this *** meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC(i.e.,RAS,BRAF,SMAD4,pIK3CA)as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM ***:A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM,stratified according to RAS,BRAF,pIK3CA,and SMAD4 mutational *** ratios(HRs)from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were *** search was conducted in numerous databases,including MEDLINE(pubMed),Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL)(EBSCO host),and WHO Global Index Medicus,through March 18th,***-analyses,editorials,letters to the editor,case reports,studies on other primary cancers,studies with primary metastatic sites other than the liver,studies lacking specific oncological outcome variables or genetic data,non-English language studies,and studies omitting residual disease data from liver metastasectomy were *** remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically ***:RAS mutation status was negatively associated with overall survival(OS)(HR,1.68;95%CI,1.54–1.84)and recurrence free survival(RFS)(HR,1.46;95%CI,1.33–1.61).A negative association was also found for BRAF regarding OS(HR,2.64;95%CI,2.15–3.24)and RFS(HR,1.89;95%CI,1.32–2.73)and SMAD4 regarding OS(HR,1.93;95%CI,1.56–2.38)and RFS(HR,1.95;95%CI,1.31–2.91).For pIK3CA only three studies were eligible and no significant associati

关键词： Metastasectomy Liver metastases RAS BRAF SMAD4 pIK3CA Colorectal

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Virtual earth cloud: a multi-cloud framework for enabling geosciences digital ecosystems

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International Journal of Digital Earth 2023年第1期16卷 43-65页

作者： mattia Santoro paolo Mazzetti Stefano Nativi National Research Council of Italy Institute of Atmospheric Pollution Research-Unit of FlorenceRomaItaly Joint Research Centre of the European Commission B6 UnitIspraltaly

Humankind is facing unprecedented global environmental and social challenges in terms of food,water and energy security,resilience to natural hazards,*** address these challenges,international organizations have defined a list of policy actions to be achieved in a relatively short and medium-term *** development and use of knowledge platforms is key in helping the decision-making process to take significant decisions(providing the best available knowledge)and avoid potentially negative impacts on society and the *** knowledge platforms must build on the recent and next coming digital technologies that have transformed society–including the science and engineering *** Earth Data(BED)science aims to provide the methodologies and instruments to generate knowledge from numerous,complex,and diverse data *** science requires the development of Geoscience Digital Ecosystems(GEDs),which bank on the combined use of fundamental technology units(*** data,learning-driven artificial intelligence,and network-based computing platform)to enable the development of more detailed knowledge to observe and test planet Earth as a *** manuscript contributes to the BED science research domain,by presenting the Virtual Earth Cloud:a multi-cloud framework to support GDE implementation and generate knowledge on environmental and social sustainability.

关键词： Earth observation geosciences digital ecosystem virtual cloud big earth data multi-cloud interoperability science

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Sleep to Survive predators

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Neuroscience Bulletin 2022年第9期38卷 1114-1116页

作者： mattia Aime Antoine R.Adamantidis Department of Neurology Zentrum für Experimentelle NeurologieInselspital University Hospital Bern3010BernSwitzerland Department of Biomedical Research University of Bern3010BernSwitzerland

Sleep is a reversible behavioral state characterized by a higher arousal threshold and transient disconnection from the external ***,sleeping organisms show lowered behavioral responsiveness to sensory stimuli(such as sound,touch,and smell)in the experimental environment[1]that contrastswithheightenedauditory-evokedneuronal responses recorded in the cortex in rodents and non-human primates[2,3].These reports support the hypothesis of sensory gating,as found during sleep spindles,that ultimately preserves sleep from external ***,this strongly contrasts to the high vulnerability to predation associated with sleep states in the natural environment.

关键词： evoked auditory cortex

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