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Mesenchymal stem cell-based TRAIL delivery inhibits the metastatic state of clinical therapy-resistant progressive neuroblastoma

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World Journal of Pediatrics 2024年第3期20卷 287-293页

作者： Dinesh Babu Somasundaram Andrew Maher Sheeja Aravindan Zhongxin Yu brian MBesch Natarajan Aravindan Department of Radiation Oncology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Stephenson Cancer Center Oklahoma CityOKUSA Department of Pathology University of Oklahoma Health Sciences CenterOklahoma CityOKUSA Radiation Biology Laboratory University of Oklahoma Health Sciences CenterBSEB 302F941 Stanton L.Young BoulevardOklahoma CityOK 73104USA

Progressive neuroblastomas(pNBs)that defy current intensive multimodal clinical therapy(IMCT)are a significant contributor to overall childhood cancer deaths[l].Neuroblastomas(NBs)that survive first-line IMCT actively evolve to acquire genetic and molecular rearrangements and display unparalleled plasticity and evolution,which causes frequent relapses in a rapidly accelerating timeline[2-4].

关键词： neuroblastoma clinical evolve

Aerosol jet printing of surface acoustic wave microfluidic devices

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Microsystems & Nanoengineering 2024年第1期10卷 231-242页

作者： Joseph Rich brian Cole Teng Li Brandon Lu Hanyu Fu Brittany N.Smith Jianping Xia Shujie Yang Ruoyu Zhong James L.Doherty Kanji Kaneko Hiroaki Suzuki Zhenhua Tian Aaron D.Franklin Tony Jun Huang Department of Biomedical Engineering Duke UniversityDurhamNC 27708USA Department of Electrical and Computer Engineering Duke UniversityDurhamNC 27708USA Department of Mechanical Engineering Virginia Polytechnic Institute and State UniversityBlacksburgVA 24061USA Thomas Lord Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Deptartment of Precision Mechanics Faculty of Science and EngineeringChuo UniversityTokyo 112-8551Japan Department of Chemistry Duke UniversityDurhamNC 27708USA

The addition of surface acoustic wave(SAW)technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes,including high-precision manipulation,versatility,integrability,biocompatibility,contactless nature,and rapid actuation.However,the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based processing.To simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions,we utilized the additive manufacturing technique of aerosol jet printing.We successfully fabricated customized SAW microfluidic devices of varying materials,including silver nanowires,graphene,and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS).To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts,the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler vibrometry.Finally,to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications,we successfully conducted acoustic streaming and particle concentration experiments.Overall,we demonstrated a novel solution-based,direct-write,single-step,cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology,chemistry,engineering,and medicine.

关键词： printing wave fluid

Injectable bioorthogonal hydrogel (BIOGEL) accelerates tissue regeneration in degenerated intervertebral discs

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Bioactive Materials 2023年第5期23卷 551-562页

作者： Jeffrey Luo Anjani Darai Thanapat Pongkulapa brian Conley Letao Yang Inbo Han Ki-Bum Lee Department of Chemistry and Chemical Biology RutgersThe State University of New JerseyPiscatawayNJ08854USA Department of Neurosurgery CHA University School of MedicineCHA Bundang Medical Center59 Yaptap-roBundang-guSeongnam-siGyeonggi-do13496Republic of Korea

Intervertebral disc(IVD)degeneration is a leading cause of back pain and precursor to more severe conditions,including disc herniation and spinal stenosis.While traditional growth factor therapies(e.g.,TGFβ)are effective at transiently reversing degenerated disc by stimulation of matrix synthesis,it is increasingly accepted that bioscaffolds are required for sustained,complete IVD regeneration.Current scaffolds(e.g.,metal/polymer composites,non-mammalian biopolymers)can be improved in one or more IVD regeneration demands:biodegradability,noninvasive injection,recapitulated healthy IVD biomechanics,predictable crosslinking,and matrix repair induction.To meet these demands,tetrazine-norbornene bioorthogonal ligation was combined with gelatin to create an injectable bioorthogonal hydrogel(BIOGEL).The liquid hydrogel precursors remain free-flowing across a wide range of temperatures and crosslink into a robust hydrogel after 5-10 min,allowing a human operator to easily inject the therapeutic constructs into degenerated IVD.Moreover,BIOGEL encapsulation of TGFβpotentiated histological repair(e.g.,tissue architecture and matrix synthesis)and functional recovery(e.g.,high water retention by promoting the matrix synthesis and reduced pain)in an in vivo rat IVD degeneration/nucleotomy model.This BIOGEL procedure readily integrates into existing nucleotomy procedures,indicating that clinical adoption should proceed with minimal difficulty.Since bioorthogonal crosslinking is essentially non-reactive towards biomolecules,our developed material platform can be extended to other payloads and degenerative injuries.

关键词： Bioorthogonal chemistry Growth factor Injectable hydrogel Intervertebral disc degeneration Tissue engineering

Comments by opponents on the British Medical Association’s guidance on non-therapeutic male circumcision of children seem one-sided and may undermine public health

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World Journal of Clinical Pediatrics 2023年第5期12卷 244-262页

作者： Stephen Moreton Guy Cox Mark Sheldon Stefan A Bailis Jeffrey D Klausner brian J Morris CircFacts Warrington WA51HYCheshireUnited Kingdom Australian Centre for Microscopy&Microanalysis and School of Aeronautical Mechanical and Mechatronic EngineeringUniversity of SydneySydney 2006New South WalesAustralia Medical Humanities and Bioethics Program Feinberg School of MedicineNorthwestern UniversityChicagoIL 60661United States Cornerstone Therapy&Recovery Center St.PaulMN 55101United States Department of Medicine Population and Public Health SciencesKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90089United States School of Medical Sciences University of SydneySydney 2006New South WalesAustralia

The British Medical Association(BMA)guidance on non-therapeutic circumcision(NTMC)of male children is limited to ethical,legal and religious issues.Here we evaluate criticisms of the BMA’s guidance by Lempert et al.While their arguments promoting autonomy and consent might be superficially appealing,their claim of high procedural risks and negligible benefits seem one-sided and contrast with high quality evidence of low risk and lifelong benefits.Extensive literature reviews by the American Academy of Pediatrics and the United States Centers for Disease Control and Prevention in developing evidence-based policies,as well as risk-benefit analyses,have found that the medical benefits of infant NTMC greatly exceed the risks,and there is no reduction in sexual function and pleasure.The BMA’s failure to consider the medical benefits of early childhood NTMC may partly explain why this prophylactic intervention is discouraged in the United Kingdom.The consequence is higher prevalence of preventable infections,adverse medical conditions,suffering and net costs to the UK’s National Health Service for treatment of these.Many of the issues and contradictions in the BMA guidance identified by Lempert et al stem from the BMA’s guidance not being sufficiently evidence-based.Indeed,that document called for a review by others of the medical issues surrounding NTMC.While societal factors apply,ultimately,NTMC can only be justified rationally on scientific,evidence-based grounds.Parents are entitled to an accurate presentation of the medical evidence so that they can make an informed decision.Their decision either for or against NTMC should then be respected.

关键词： Circumcision,Male Child Infections Risk Policy Public health

Parity Violation in Weak Nuclear Interactions

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Journal of High Energy Physics, Gravitation and Cosmology 2022年第2期8卷 330-344页

作者： brian Albert Robson Department of Fundamental and Theoretical Physics Research School of Physics The Australian National University Canberra Australia

The treatment of parity violations in the weak nuclear interactions is discussed within the frameworks of both the Standard Model (SM) and the Generation Model (gm) of particle physics. It will be demonstrated that several important differences between these two models lead to the SM merely describing the parity violations, while the gm provides an understanding of the cause of the parity violations in weak nuclear interactions. The significant differences arising from several dubious assumptions made during the development of the SM, lead to very different conclusions concerning the nature of the parity violations in the two models. While the SM is able to describe the observed parity violations in terms of a “V-A” theory of the weak nuclear interactions, the gm is also able to demonstrate the cause of the observed parity violations: in the gm, the observed parity violations arise as a consequence of the negative intrinsic parity of both the W massive bosons, which mediate these so-called charge-changing (CC) weak nuclear interactions.

关键词： Standard Model Generation Model Parity Violation

Opto-thermoelectric pulling of light-absorbing particles

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Light(Science & Applications) 2020年第1期9卷 1686-1696页

作者： Linhan Lin Pavana Siddhartha Kollipara Abhay Kotnala Taizhi Jiang Yaoran Liu Xiaolei Peng brian A.Korgel Yuebing Zheng Walker Department of Mechanical Engineering The University of Texas at AustinAustinTX 78712USA Materials Science&Engineering Program and Texas Materials Institute The University of Texas at AustinAustinTX 78712USA State Key Laboratory of Precision Measurement Technology and Instruments Department of Precision InstrumentTsinghua UniversityBeijing 100084People’s Republic of China McKetta Department of Chemical Engineering The University of Texas at AustinAustinTX 78712USA Department of Electrical and Computer Engineering The University of Texas at AustinAustinTX 78712USA

Optomechanics arises from the photon momentum and its exchange with low-dimensional objects.It is well known that optical radiation exerts pressure on objects,pushing them along the light path.However,optical pulling of an object against the light path is still a counter-intuitive phenomenon.Herein,we present a general concept of optical pulling-opto-thermoelectric pulling(OTEP)—where the optical heating of a light-absorbing particle using a simple plane wave can pull the particle itself against the light path.This irradiation orientation-directed pulling force imparts self-restoring behaviour to the particles,and three-dimensional(3D)trapping of single particles is achieved at an extremely low optical intensity of 10^(−2)mWμm^(−2).Moreover,the OTEP force can overcome the short trapping range of conventional optical tweezers and optically drive the particle flow up to a macroscopic distance.The concept of selfinduced opto-thermomechanical coupling is paving the way towards freeform optofluidic technology and lab-on-achip devices.

关键词： absorbing light trapping

Perspective on the q-bio Summer School anc Conference： 2007- 2014 and beyond

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Frontiers of Electrical and Electronic Engineering in China 2014年第1期9卷 54-58页

作者： Orna Resnekov brian Munsky William S. Hlavacek Molecular Sciences Institute Berkeley CA 94704 USA Department of Chemical and Biological Engineering Colorado State University Fort Collins CO 80523 USA New Mexico consortium Los Alamos NM87544 US-A Theoretical Division and Center for Nonlinear Studies Los Alamos National Laboratory Los Alamos NM 87545 USA

INTRODUCTIONThe q-bio Conference and the associated q-bio Summer School were started in 2007 by a prescient group of researchers based at Los Alamos National Laboratory （LANL） and the University of New Mexico （J. Edwards, J. Faeder, W. Hlavacek, Y. Jiang, I. Nemenman and M. Wall） who envisioned a systems biology community focused on modeling,

关键词： Summer School Quantitative Biology Program Committee Member Synthetic Circuit Advisory Committee Member

Bile acid homeostasis in female mice deficient in Cyp7a1 and Cyp27a1

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3847-3856页

作者： Daniel Rizzolo Bo Kong Rulaiha E.Taylora Anita Brinker Michael Goedken brian Buckley Grace L.Guo Department of Pharmacology and Toxicology School of PharmacyRutgers UniversityPiscatawayNJ 08854USA Environmental and Occupational Health Institute Rutgers UniversityPiscatawayNJ 08854USA Office of Research and Economic Development Research Pathology ServicesRutgers UniversityPiscatawayNJ 08854USA Rutgers Center of Lipid Research Rutgers UniversityNew BrunswickNJ 08901USA Department of Veterans Affairs New Jersey Health Care System East OrangeNJ 07018USA

Bile acids(BAs) are amphipathic molecules important for metabolism of cholesterol,absorption of lipids and lipid soluble vitamins,bile flow,and regulation of gut microbiome.There are over 30 different BA species known to exist in humans and mice,which are endogenous modulators of at least 6 different membrane or nuclear receptors.This diversity of ligands and receptors play important roles in health and disease;however,the full functions of each individual BA in vivo remain unclear.We generated a mouse model lacking the initiating enzymes,CYP7 A1 and CYP27 A1,in the two main pathways of BA synthesis.Because females are more susceptible to BA related diseases,such as intrahepatic cholestasis of pregnancy,we expanded this model into female mice.The null mice of Cyp7 a1 and Cyp27 a1 were crossbred to create double knockout(DKO) mice.BA concentrations in female DKO mice had reductions in serum(63%),liver(83%),gallbladder(94%),and small intestine(85%),as compared to WT mice.Despite low BA levels,DKO mice had a similar expression pattern to that of WT mice for genes involved in BA regulation,synthesis,conjugation,and transport.Additionally,through treatment with a synthetic FXR agonist,GW4064,female DKO mice responded to FXR activation similarly to WT mice.

关键词： Bile acids Farnesoid X receptor Female Fibroblast growth factor 15 CYP7A1 CYP27A1

Acoustofluidic separation enables early diagnosis of traumatic brain injury based on circulating exosomes

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Microsystems & Nanoengineering 2021年第2期7卷 59-69页

作者： Zeyu Wang Haichen Wang Ryan Becker Joseph Rufo Shujie Yang brian E.Mace Mengxi Wu Jun Zou Daniel T.Laskowitz Tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC27708USA Department of Neurology Duke UniversityDurhamNC27708USA Department of Biomedical Engineering Duke UniversityDurhamNC27708USA Department of Geriatrics Duke UniversityDurhamNC27708USA Department of Electrical&Computer Engineering Texas A&M UniversityCollege StationTX77840USA

Traumatic brain injury(TBI)is a global cause of morbidity and mortality.Initial management and risk stratification of patients with TBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available,noninvasive diagnostic biomarker.In particular,a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild TBI(mTBI).Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue injury.By applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after TBI.Acoustofluidic isolation eliminated interference from other blood components,making it possible to detect exosomal biomarkers for TBI via flow cytometry.Flow cytometry analysis indicated that exosomal biomarkers for TBI increase in the first 24 h following head trauma,indicating the potential of using circulating exosomes for the rapid diagnosis of TBI.Elevated levels of TBI biomarkers were only detected in the samples separated via acoustofluidics;no changes were observed in the analysis of the raw plasma sample.This finding demonstrated the necessity of sample purification prior to exosomal biomarker analysis.Since acoustofluidic exosome separation can easily be integrated with downstream analysis methods,it shows great potential for improving early diagnosis and treatment decisions associated with TBI.

关键词： diagnosis separation injury