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Harnessing naturally occurring mutations for T-cell therapy:a potential new avenue to enhance treatment efficacy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1799-1801页

作者： Michael Hiltensperger jürgen Ruland Kilian Schober Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und HygieneFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany Institute of Clinical Chemistry and Pathobiochemistry School of MedicineTechnical University of MunichMunichGermany TranslaTUM Center for Translational Cancer ResearchTechnical University of MunichMunichGermany German Cancer Consortium(DKTK) HeidelbergGermany German Center for Infection Research(DZIF) partner site MunichMunichGermany FAU Profile Center Immunomedicine Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Garcia et al.use a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rejection and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.

关键词： al. cancer potential

Reply to the note by Li Piani et al.

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Defence Technology（防务技术） 2024年第1期31卷 603-606页

作者： T.Li Piani j.Weerheijm L.j.Sluys TU Delft Stevinweg 12628 CNDelftthe Netherlands TNO PO Box 452280 AARijswijkthe Netherlands NLDA Faculty of Military Sciences1781 CADen Helderthe Netherlands

In 2017,a ballistic phenomenological model was proposed by the authors of Ref.[1] to numerically simulate the experimental depths of small caliber projectiles impacting walls made of adobe.The opportunity for a new model in the field revealed from the observation that two older models recently used by the authors of Ref.[2] shared a linear relationship between the penetration depth P and the impacting velocity v_(O).

关键词： Penetration Adobe Modeling

Wettability,reactivity,and interface structure in Mg/Ni system

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journal of Magnesium and Alloys 2024年第2期12卷 659-672页

作者： S.Terlicka N.Sobczak Ł.Maj P.Darłak j.j.Sobczak Institute of Metallurgy and Materials Science Polish Academy of Sciences25 Reymonta Str.KrakowPoland Faculty of Foundry Engineering AGH University23 Reymonta Str.KrakowPoland

The sessile drop method was applied to the experimental investigation of the wetting and spreading behaviors of liquid Mg drops on pure Ni substrates.For comparison,the experiments were performed in two variants:(1)using the Capillary Purification(CP)procedure,which allows the non-contact heating and squeezing of a pure oxide-free Mg drop;(2)by classical Contact Heating(CH)procedure.The high-temperature tests were performed under isothermal conditions(CP:760℃for 30 s;CH:715℃for 300 s)using Ar+5 wt%H_(2) atmosphere.During the sessile drop tests,images of the Mg/Ni couples were recorded by CCD cameras(57 fps),which were then applied to calculate the contact angles of metal/substrate couples.Scanning and transmission electron microscopy analyses,both coupled with energy-dispersive X-ray spectroscopy,were used for detailed structural characterization of the solidified couples.It was found that an oxide-free Mg drop obtained by the CP procedure showed a wetting phenomenon on the Ni substrate(an average contact angleθ<90°in<1 s),followed by fast spreading and good wetting over the Ni substrate(θ_((CP))~20°in 5 s)to form a final contact angle ofθ_(f(CP))~18°.In contrast,a different wetting behavior was observed for the CH procedure,where the unavoidable primary oxide film on the Mg surface blocked the spreading of liquid Mg showing apparently non-wetting behavior after 300 s contact at the test temperature.However,in both cases,the deep craters formed in the Ni substrates under the Mg drops and significant change in the structure of initially pure Mg drops to Mg-Ni alloys suggest a strong dissolution of Ni in liquid Mg and apparent values of the final contact angles measured for the Mg/Ni system.

关键词： Magnesium-based alloys Sessile drop tests Capillary purification procedure Wettability Reactivity Contact angle

Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue jia Gemma Solé-Guardia Amanda j.Kiliaan Department of Medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

Current concepts in the management of non-cirrhotic non-malignant portal vein thrombosis

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World journal of Hepatology 2024年第5期16卷 751-765页

作者： Adam j Willington Dhiraj Tripathi Department of Hepatology University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWUnited Kingdom Department of Hepatology University Hospitals BirminghamBirmingham B152THUnited Kingdom

Non-cirrhotic non-malignant portal vein thrombosis(NCPVT)is an uncommon condition characterised by thrombosis of the portal vein,with or without extension into other mesenteric veins,in the absence of cirrhosis or intra-abdominal malignancy.Complications can include intestinal infarction,variceal bleeding and portal biliopathy.In this article,we address current concepts in the management of NCPVT including identification of risk factors,classification and treatment,and review the latest evidence on medical and interventional management options.

关键词： Non-cirrhotic portal vein thrombosis Portal vein Mesenteric veins Venous thrombosis Portal hypertension

Innovative pathways allow safe discharge of mild acute pancreatitis from the emergency room

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World journal of Gastroenterology 2024年第11期30卷 1475-1479页

作者： Darshan j Kothari Sunil G Sheth Division of Gastroenterology Duke University Medical CenterDurhamNC 27710United States Division of Gastroenterology&Hepatology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215United States

Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion annually.The severity of AP is determined by the presence of pancreatic complications and end-organ damage.While moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and burden.In this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the pathway.We discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the pathway.We conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical outcomes.We also identify a subset of patients most likely to succeed in this pathway.

关键词： Emergency department Mild pancreatitis Pathways Hospitalization Predictors

Glycolysis and glucose metabolism as a target for bioenergetic and neuronal protection in glaucoma

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Neural Regeneration Research 2024年第8期19卷 1637-1638页

作者： Pete A.Williams Robert j.Casson Department of Clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden Ophthalmic Research Laboratories Discipline of Ophthalmology and Visual SciencesUniversity of AdelaideAdelaideAustralia

Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic diseases.Glaucoma refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.

关键词： metabolism glaucoma globally

The impact of maternal immune activation on the morphology and electrophysiological properties of postnatally-born neurons in the offspring

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Neural Regeneration Research 2024年第2期19卷 399-400页

作者： Emilio j.Galván Angelica Zepeda Departamento de Farmacobiología CINVESTAV Unidad Sur CdMxMéxico、Centro de Investigaciones sobre el EnvejecimientoCIE-CinvestavCdMxMéxico Departamento de Medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoUNAMCdMxMéxico

Pregnancy comes with a combination of physical changes and physiological immunosuppression that increases the susceptibility of women to pathogens and in turn,rises the prevalence of infectious diseases.

关键词： prevalence activation impact

In situ characterization of particle formation in spray flame synthesis using wide-angle light scattering

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Particuology 2024年第3期86卷 304-312页

作者： Simon Aβmann Franz j.T.Huber Stefan Will Lehrstuhl für Technische Thermodynamik(LTT) Friedrich-Alexander-Universitat Erlangen-Nürnberg(FAU)Erlangen91058Germany Erlangen Graduate Schoolin Advanced Optical Technologies(SAOT) Friedrich-Alexander-Universitat Erlangen-Nurnberg(FAU)Erlangen91052Germany Competence Unit Engineering of Advanced Materials(EAM) Friedrich-Alexander-Universitat Erlangen-Nürnberg(FAU)Erlangen91052Germany

Wide-angle light scattering(WALS)was used for in situ measurements of droplet and nanoparticle size distributions during the synthesis of titania and iron oxide particles from liquid precursor solutions in the standardized SpraySyn burner for spray flame synthesis.Titania was synthesized from titanium tetraisopropoxide(TTIP)and iron oxide from iron(II)nitrate nonahydrate(INN)using ethanol(EtOH)as solvent.Scattering images were taken at heights up to 120 mm above the burner surface and classified into droplet and particle scattering.Droplet size distributions were derived from a sequential analysis of scattering data containing the oscillating Mie pattern,the lognormal size distribution parameters for spherical and fractal particle fractions from a multivariate approach on averaged particle scattering data.The results show that the precursor addition leads to altered evaporation behavior and even droplet disruption probably induced by puffing or micro-explosions compared to pure EtOH.In the case of TTIP(a hygroscopic alkoxide),the synthesis of a large fraction of spheres was observed,while the nitrate INN leads to the formation of mostly fractal aggregates.

关键词： Spray flame synthesis Metal oxide particles Elastic light scattering Droplet size distribution Nanoparticle morphology Particle size distribution