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Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles

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药学学报:英文版 2023年第9期13卷 3945-3955页

作者： Mei Lu Haonan Xing Wanxuan Shao Pengfei Wu Yuchuan Fan Huining He stefan barth Aiping Zheng Xing-Jie Liang Yuanyu Huang Advanced Research Institute of Multidisciplinary Science School of Life ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Chinese Academy of Sciences(CAS)Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China South African Research Chair in Cancer Biotechnology Institute of Infectious Disease and Molecular Medicine(IDM)Department of Integrative Biomedical SciencesFaculty of Health SciencesUniversity of Cape TownCape Town 7925South Africa

Immunotherapy has revolutionized the landscape of cancer ***,single immunotherapy only works well in a small subset of *** immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic ***,the synergistic,additive or antagonistic antitumor effects of combined immunotherapies have been rarely ***,we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4(PAK4)silencing with immunogenic phototherapy in engineered extracellular vesicles(EVs)that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with si RNA against PAK4 and a photoactivatable *** engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy,thus contributing to effective antitumor effects in vitro and in ***,the antitumor synergism of the combined treatment was quantitatively determined by the Compu Syn *** combination index(CI)and isobologram results confirmed that there was an antitumor synergism for the combined ***,the dose reduction index(DRI)showed favorable dose reduction,revealing lower toxicity and higher biocompatibility of the engineered ***,the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs,which is promising for boosting the therapeutic outcome of cancer immunotherapy.

关键词： Antitumor synergism Combined cancer immunotherapy p21-activated kinase 4 RNA interference Immunogenic phototherapy Extracellular vesicles Immune infiltration CompuSyn

Experimental investigation on slip conditions during thread rolling with flat dies

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Friction 2024年第1期12卷 136-143页

作者： stefan VOLZ Peter GROCHE Institute for Production Engineering and Forming Machines Technical University DarmstadtOtto-Berndt Straße 2Darmstadt 64287Germany

The process design of flat die rolling operations can be a tedious and costly process due to the challenges posed by small process *** this work,an effort is made to closely investigate and understand the process limits caused by excessive slippage of the *** measurements are carried out to capture the characteristics of excessive slippage and the influence of the stroke rate and the tribological system on this process *** differences in slippage were observed,depending on the tribological *** systems with polymer based lubricants showed excessive slippage at low stroke rates,systems using oil or no lubricant endured higher stroke rates before process limits were *** optical measurements revealed three major forms of slippage:successful rolling without slippage,failure due to excessive slippage at process start,and failure due to excessive slippage at around one workpiece rotation.

关键词： rolling incremental forming thread rolling slippage profile rolling

The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

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Neural Regeneration Research 2024年第8期19卷 1647-1648页

作者： Sven Marcel stefan Muhammad Rafehi Drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany Department of Pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of Clinical Pharmacology University Medical Center GöttingenGöttingenGermany Department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

Implementation and validation of a bonded particle model to predict rheological properties of viscoelastic materials

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Particuology 2024年第6期89卷 198-210页

作者： Michael Mascara Arno Mayrhofer stefan Radl Christoph Kloss Institute of Process and Particle Engineering Graz University of TechnologyInffeldgasse 13Graz8010Austria DCS Computing GmbH Industriezeile 35Linz4020Austria

This work focuses on implementing a particle-based method able to characterize viscoelastic materials whose rheological properties,such as storage modulus G′and loss modulus G″,are *** is based on the bonded particle model,with the elastic constitutive relation here substituted with a viscoelastic one to capture time-scale *** Burgers model,vastly used in literature to model viscoelastic systems,is discretized and *** test case used for calibration comprises of a cubic lattice,sheared with a periodic motion,to mimic the effect of a shear *** appropriate filtering of the stress response,the rheological properties are obtained,highlighting the effect of the lattice geometry,as well as the particle size,on the accuracy of the ***,the Burgers parameters are calibrated by analytically fitting the experimental dataset,showing the limitation of the Burgers *** micro-contact parameters are obtained from the macro parameters through appropriate *** completing a frequency sweep,the simulated G′and G″show a relatively large error,around 25%for G’for *** this reason,a more robust model,namely the generalized Maxwell model,has been *** calibration procedure is performed in the same fashion as for the Burgers ***,the tangential micro-contact parameters are scaled *** normal *** scaling parameter,calledα,is calibrated by minimizing the root mean square error between simulation and experimental data,giving errors below 10%in both G′and G″for a large ***,a full ring plate-plate rheometer setup is simulated,and the simulation is compared with the given experimental dataset,again finding a good agreement.

关键词： DEM Rheology Numerical modeling Viscoelasticity

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 *** was synthesized from titanium tetraisopropoxide(TTIP)and iron oxide from iron(II)nitrate nonahydrate(INN)using ethanol(EtOH)as *** images were taken at heights up to 120 mm above the burner surface and classified into droplet and particle *** 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 *** 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 *** 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

Artificial intelligence analysis of videos to augment clinical assessment:an overview

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Neural Regeneration Research 2024年第4期19卷 717-718页

作者： David C.Wong stefan Williams University of Leeds Leeds Teaching Hospitals Trust LeedsUK

Observation is a fundamental part of the practice of clinical *** of movement is particularly important for the *** such as Parkinson’s disease,multiple sclerosis,stroke,epilepsy,and many others affect a person’s movement in characteristic *** some conditions,changes in the patient’s voice can be included in this-changes in sound caused by changes in the movements of *** clinician’s detection of a characteristic abnormality,and their judgment of its severity,plays a central role in both diagnosis and the assessment of prognosis or response to ***,that practice depends upon a limited resource of experienced *** addition,these experts are limited by human visual judgment,which cannot reliably or precisely detect and measure small or subtle changes in movement(Williams et al.,2023).

关键词： clinical epilepsy diagnosis

A theoretical framework for improved fire suppression by linking management models with smart early fire detection and suppression technologies

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JOURNAL OF FORESTRY RESEARCH 2024年第1期35卷 1-13页

作者： Meng, Li O'Hehir, Jim Gao, Jing Peters, stefan Hay, Anthony Univ South Australia Adelaide SA Australia Esk Spatial Invermay Tas Australia

Bushfires are devastating to forest managers, owners, residents, and the natural environment. Recent technological advances indicate a potential for faster response times in terms of detecting and suppressing fires. However, to date, all these technologies have been applied in isolation. This paper introduces the latest fire detection and suppression technologies from ground to space. An operations research method was used to assemble these technologies into a theoretical framework for fire detection and suppression. The framework harnesses the advantages of satellite-based, drone, sensor, and human reporting technologies as well as image processing and artificial intelligence machine learning. The study concludes that, if a system is designed to maximise the use of available technologies and carefully adopts them through complementary arrangements, a fire detection and resource suppression system can achieve the ultimate aim: to reduce the risk of fire hazards and the damage they may cause.

关键词： Forest fire Resource suppression Smart fire detection and suppression system Forest fire management Holistic system DECISION-SUPPORT-SYSTEM FOREST-FIRES REGRESSION

Theoretical investigation on axial cyclic performance of monopile in sands using interface constitutive models

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第7期16卷 2645-2662页

作者： Pan Zhou Jingpei Li Kaoshan Dai stefan Vogt Seyedmohsen Miraei Department of Geotechnical Engineering Tongji UniversityShanghai200092China Department of Civil Geo and Environmental EngineeringTechnical University of MunichFranz-Langinger-Str.10München81245Germany Department of Civil Engineering Sichuan UniversityChengdu610065China

Cyclic loads generated by environmental factors,such as winds,waves,and trains,will likely lead to performance degradation in pile foundations,resulting in issues like permanent displacement accumulation and bearing capacity *** paper presents a semi-analytical solution for predicting the axial cyclic behavior of piles in *** solution relies on two enhanced nonlinear load-transfer models considering stress-strain hysteresis and cyclic degradation in the pile-soil *** parameters are calibrated through cyclic shear tests of the sand-steel interface and laboratory geotechnical testing of sands.A novel aspect involves the meticulous formulation of the shaft loadtransfer function using an interface constitutive model,which inherently inherits the interface model’s advantages,such as capturing hysteresis,hardening,degradation,and particle *** semi-analytical solution is computed numerically using the matrix displacement method,and the calculated values are validated through model tests performed on non-displacement and displacement piles in *** results demonstrate that the predicted values show excellent agreement with the measured values for both the static and cyclic responses of piles in *** displacement pile response,including factors such as bearing capacity,mobilized shaft resistance,and convergence rate of permanent settlement,exhibit improvements compared to non-displacement piles attributed to the soil squeezing *** methodology presents an innovative analytical framework,allowing for integrating cyclic interface models into the theoretical investigation of pile responses.

关键词： Piles Cyclic degradation Load-transfer models Interface constitutive model Semi-analytical solution Model tests

Quality assessment of surgery for colorectal cancer:Where do we stand?

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 982-987页

作者： stefan Morarasu Cristian Livadaru Gabriel-Mihail Dimofte The Second Department of Surgical Oncology Regional Institute of OncologyIasi 707483Romania

Quality assurance in surgery has been one of the most important topics of debate among colorectal surgeons in the past *** has produced new surgical standards that led in part to the impressive oncological outcomes we see in many units *** mesorectal excision,complete mesocolic excision(CME),and the Japanese D3 lymphadenectomy are now benchmark techniques embraced by many surgeons and widely recommended by surgical ***,there are still ongoing discrepancies in outcomes largely based on surgeon *** is one of the main reasons why many countries have shifted colorectal cancer surgery only to high volume *** markers of surgical quality is thus a perquisite to ensure that standards and oncological outcomes are met at an institutional *** the evolution of CME surgery,various quality markers have been described,mostly based on measurements on the surgical specimen and lymph node yield,while others have proposed radiological markers(*** stumps)measured on postoperative scans as part of the routine cancer *** is no ideal marker;however,taken together and assembled into a new score or set of criteria may become a future point of reference for reporting outcomes of colorectal cancer surgery in research studies and defining subspecialization requirements both at an individual and hospital level.

关键词： Colorectal cancer Colon surgery Arterial stump Complete mesocolic excision Surgical quality