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Aerosolized immunotherapeutic nanoparticle inhalation potentiates PD-L1 blockade for locally advanced lung cancer

Nano Research 2023年第4期16卷 5300-5310页

作者： Yang Liu william N.Crowe Lulu wang w.jeffrey petty Amyn A.Habib Dawen Zhao Department of Biomedical Engineering Wake Forest University School of MedicineWinston-SalemNC 27157USA Department of Medicine Section on Hematology and OncologyWake Forest University School of MedicineWinston-SalemNC 27157USA Department of Neurology University of Texas Southwestern Medical Center and VA North Texas Medical CenterDallasTX 75390USA Department of Cancer Biology Wake Forest University School of MedicineWinston-SalemNC 27157USA

Despite therapeutic advancements,the prognosis of locally advanced non-small cell lung cancer(LANSCLC),which has invaded multiple lobes or the other lung and intrapulmonary lymph nodes,remains poor.The emergence of immunotherapy with immune checkpoint blockade(ICB)is transforming cancer treatment.However,only a fraction of lung cancer patients benefit from ICB.Significant clinical evidence suggests that the proinflammatory tumor microenvironment(TME)and programmed death-ligand 1(PD-L1)expression correlate positively with response to the PD-1/PD-L1 blockade.we report here a liposomal nanoparticle loaded with cyclic dinucleotide and aerosolized(AeroNP-CDN)for inhalation delivery to deep-seated lung tumors and target CDN to activate stimulators of interferon(IFN)genes in macrophages and dendritic cells(DCs).Using a mouse model that recapitulates the clinical LANSCLC,we show that AeroNP-CDN efficiently mitigates the immunosuppressive TME by reprogramming tumor-associated macrophage from the M2 to M1 phenotype,activating DCs for effective tumor antigen presentation and increasing tumor-infiltrating CD8+T cells for adaptive anticancer immunity.Intriguingly,activation of interferons by AeroNP-CDN also led to increased PD-L1 expression in lung tumors,which,however,set a stage for response to anti-PD-L1 treatment.Indeed,anti-PD-L1 antibody-mediated blockade of IFNs-induced immune inhibitory PD-1/PD-L1 signaling further prolonged the survival of the LANSCLC-bearing mice.Importantly,AeroNP-CDN alone or combination immunotherapy was safe without local or systemic immunotoxicity.In conclusion,this study demonstrates a potential nano-immunotherapy strategy for LANSCLC,and mechanistic insights into the evolution of adaptive immune resistance provide a rational combination immunotherapy to overcome it.

关键词： locally advanced non-small cell lung cancer(LANSCLC) nanoparticle immunotherapeutic aerosol inhalation stimulator of interferon genes programmed death 1/programmed death-ligand 1(PD-1/PD-L1)blockade

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Protein-activated atomic layer deposition for robust crude-oil-repellent hierarchical nano-armored membranes

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Science Bulletin 2024年第2期69卷 218-226页

作者： Xiaobin Yang Pan Sun Yajie wen Anil U.Mane jeffrey w.Elam Jun Ma Shaomin Liu Seth B.Darling Lu Shao MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage State Key Laboratory of Urban Water Resource and EnvironmentSchool of Chemistry and Chemical EngineeringHarbin Institute of TechnologyHarbin 150001China Chemical Sciences and Engineering Division Argonne National LaboratoryLemont IL 60439USA Applied Materials Division Argonne National LaboratoryLemont IL 60439USA Advanced Materials for Energy-water Systems Energy Frontier Research Center Argonne National LaboratoryLemont IL 60439USA Pritzker School of Molecular Engineering University of ChicagoChicago IL 60637USA Department of Physics University of Ilinois at ChicagoChicago IL 60607USA School of Environment Harbin Institute of TechnologyHarbin 150090China wA School of Mines:Minerals Energy and Chemical EngineeringCurtin UniversityPerth WA 6845Australia

Atomic layer deposition(ALD)offers unique capabilities to fabricate atomically engineered porous materials with precise pore tuning and multi-functionalization for diverse applications like advanced membrane separations towards sustainable energy-water systems.However,current ALD technique is inhibited on most non-polar polymeric membranes due to lack of accessible nucleation sites.Here,we report a facile method to efficiently promote ALD coating on hydrophobic surface of polymeric membranes via novel protein activation/sensitization.As a proof of concept,TiO2 ALD-coated membranes activated by bovine serum albumin exhibit remarkable superhydrophilicity,ultralow underwater crude oil adhesion,and robust tolerance to rigorous environments including acid,alkali,saline,and ethanol.Most importantly,excellent cyclable crude oil-in-water emulsion separation performance can be achieved.The mechanism for activation/sensitization is rooted in reactivity for a particular set of amino acids.Furthermore,the universality of protein-sensitized ALD is demonstrated using common egg white,promising numerous potential usages in biomedical engineering,environmental remediation,lowcarbon manufacturing,catalysis,and beyond.

关键词： Membrane separation Atomic layer deposition water treatment Antifouling

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New insights on the high-corrosion resistance of UHP Mg-Ge alloys tested in a simulated physiological environment

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Journal of Magnesium and Alloys 2024年第3期12卷 1026-1044页

作者： Ting Liu Xingrui Chen jeffrey Venezuela Yuan wang Zhiming Shi wenyi Chen Matthew Dargusch Centre for Advanced Materials Processing and Manufacturing(AMPAM) School of Mechanical and Mining Engineeringthe University of QueenslandBrisbaneQLD 4072Australia CSIRO Mineral Resources 1 Technology CourtPullenvaleQLD 4069Australia

UHP Mg-Ge alloys was recently found to provide excellent corrosion resistance.This paper provides new insights on the mechanism of improved corrosion resistance of UHP Mg-Ge alloys in Hanks’solution.The studied UHP Mg-0.5Ge and UHP Mg-1Ge alloys showed superior corrosion resistance compared to UHP Mg and wE43,with the Mg-1Ge exhibiting the best corrosion performance.The exceptional corrosion resistance of the UHP alloy is attributed to(i)Mg_(2)Ge’s ability to suppress cathodic kinetics,(ii)Ge’s capability to accelerate the formation of a highly passive layer,and the(iii)low amounts of corrosion-accelerating impurities.

关键词： UHP Mg-Ge alloy Cathodic kinetics suppression Biodegradable metals In vitro corrosion Magnesium corrosion.

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Supplementation of vitamin E or a botanical extract as antioxidants to improve growth performance and health of growing pigs housed under thermoneutral or heat-stressed conditions

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1101-1118页

作者： Ysenia V.Silva‑Guillen Consuelo Arellano jeffrey wiegert R.Dean Boyd Gabriela E.Martinez Eric van Heugten Department of Animal Science North Carolina State UniversityRaleighNC 27695USA Department of Statistics North Carolina State UniversityRaleighNC 27695USA Department of Animal Science Texas A&M UniversityCollege StationTX 77843USA Animal Nutrition Research LLCAlvatonKY 42122USA.

Background Heat stress has severe negative consequences on performance and health of pigs,leading to significant economic losses.The objective of this study was to investigate the effects of supplemental vitamin E and a botanical extract in feed or drinking water on growth performance,intestinal health,and oxidative and immune status in grow-ing pigs housed under heat stress conditions.Methods Duplicate experiments were conducted,each using 64 crossbred pigs with an initial body weight of 50.7±3.8 and 43.9±3.6 kg and age of 13-week and 12-week,respectively.Pigs(n=128)were housed individually and assigned within weight blocks and sex to a 2×4 factorial arrangement consisting of 2 environments(thermo-neutral(21.2℃)or heat-stressed(30.9℃))and 4 supplementation treatments(control diet;control+100 IU/L of D-α-tocopherol in water;control+200 IU/kg of DL-α-tocopheryl-acetate in feed;or control+400 mg/kg of a botanical extract in feed).Results Heat stress for 28 d reduced(P≤0.001)final body weight,average daily gain,and average daily feed intake(-7.4 kg,-26.7%,and-25.4%,respectively)but no effects of supplementation were detected(P>0.05).Serum vitamin E increased(Pwith vitamin E supplementation in water and in feed(1.64 vs.3.59 and 1.64 vs.3.24),but not for the botanical extract(1.64 vs.1.67 mg/kg)and was greater when supplemented in water vs.feed(P=0.002).Liver vitamin E increased(Pwith vitamin E supplementations in water(3.9 vs.31.8)and feed(3.9 vs.18.0),but not with the botanical extract(3.9 vs.4.9 mg/kg).Serum malondialdehyde was reduced with heat stress on d 2,but increased on d 28(interaction,Pwas greater(Pwas reduced(P=0.037)in the jejunum under heat stress,but increased in the ileum when vitamin E was supplemented in feed and water under heat stress(interaction,P=0.04).Tumor necrosis factor-αin jejunum and ileum mucosa decreased by heat stress(Pwas reduced by vitamin E sup-plementations under heat

关键词： Botanical extract Growing pigs Heat stress Immune status Oxidative status Tocopherol water

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Chemotherapy-induced small extracellular vesicles prime the pre-metastatic niche to accelerate neuroblastoma metastasis

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Genes & Diseases 2024年第4期11卷 65-68页

作者： Carson A.wills Xiaoming Liu Longgui Chen Yuanjun Zhao Zhenqiu Liu Vladimir S.Spiegelman jeffrey Sundstrom Hong-Gang wang Department of Pediatrics Division of Pediatric Hematology and OncologyThe Pennsylvania State University Collegeof MedicinePA 17033USA Department of Ophthalmology The Pennsylvania State University College of MedicinePA 17033USA Department of Public Health Sciences The Pennsylvania StateUniversityCollegeofMedicinePA 17033USA

Neuroblastoma is the most common extracranial solid tumor in children,accounting for more than 10%of cancerrelated deaths in this population.The standard of care for patients diagnosed with medium-to high-risk neurobl... 详细信息

关键词： neuroblastoma metastatic metastasis

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Advances in ground heat exchangers for space heating and cooling:Review and perspectives

Energy and Built Environment

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Energy and Built Environment 2024年第2期5卷 255-269页

作者： Ping Cui weibo Yang wenke Zhang Ke Zhu jeffrey D.Spitler Mingzhi Yu School of Thermal Engineering Shandong Jianzhu UniversityJinanShandong 250101China College of Electrical Energy and Power EngineeringYangzhou UniversityYangzhouJiangsu 225127China Department of Mechanical Engineering Oklahoma State UniversityStillwaterOKUSA

As a renewable energy source,geothermal energy has been widely used to provide space heating and cooling for buildings.The thermal performance of ground heat exchanger(GHE)is significant for the operating efficiency of the ground source heat pump(GSHP)systems.This paper presents a comprehensive review of developments and advances of three kinds of GHE,including vertical borehole GHE(VBGHE),Pile GHE(PGHE),and deep borehole GHE(DBGHE)which are currently popular in larger GSHP systems.Firstly,analytical models proposed to ana-lyze heat transfer process of VBGHE with different geological conditions are summarized,such as homogenous or heterogeneous ground,with or without groundwater advection.Numerical and short-time step models and measures to improve GHE thermal performance are also reviewed.Secondly,a summary of research advances in PGHE is provided,which includes the heat transfer models of PGHE,the effects of geometric structure,oper-ation modes,pile spacing,use of phase change material(PCM),thermal properties of PCM,thermo-mechanical behavior and/or thermal performance of PGHE.The effects of groundwater flow direction and velocity on PGHE are also summarized in brief.Lastly,models of three kinds of DBGHEs,i.e.,deep coaxial GHE(DCGHE),deep U-bend GHE(DUGHE)and super-long gravity heat pipe(SLGHP),are reviewed.The physical bases of the dif-ferent analytical models are elaborated and also their advantages and disadvantages are described.Advances in numerical modelling and improving numerical model calculation speed of DCBHE,DCBHE array,and DUBHE are summarized.The review provides a meaningful reference for the further study of GHEs.

关键词： Vertical borehole ground heat exchanger Pile ground heat exchanger Deep borehole ground heat exchanger Modelling

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Treadmill training in Parkinson's disease:possible role of prefrontal modifications in the improved cortical-subcortical network function

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Neural Regeneration Research 2024年第2期19卷 407-408页

作者： Hao Ding Amgad Droby Abdul Rauf Anwar jeffrey M.Hausdorff Bahman Nasseroleslami Anat Mirelman Inbal Maidan Muthuraman Muthuraman Department of Neurology University Hospital WürzburgWürzburgGermany Academic Unit of Neurology Trinity College Dublinthe University of DublinDublinIreland Department of Neurology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Sagol School of Neuroscience Tel Aviv UniversityTel AvivIsrael Biomedical Engineering Centre UET Lahore(KSK Campus)LahorePakistan Laboratory for Early Markers of Neurodegeneration(LEMON) Center for the Study of MovementCognitionand Mobility(CMCM)Neurological InstituteTel Aviv Sourasky Medical CenterTel AvivIsrael Department of Physical Therapy Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Rush Alzheimer’s Disease Center and Department of Orthopaedic Surgery Rush University Medical CenterChicagoILUSA

Parkinson’s disease(PD)is a complex neurodegenerative disorder characterized by a range of motor symptoms such as bradykinesia,resting tremor,rigidity,and postural instability,as well as non-motor symptoms,such as de... 详细信息

关键词： rigidity fatigue

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多样化二氧化碳去除方法下交通部门使用氢能的潜在效益和权衡

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Science Bulletin 2024年第1期69卷 34-39页

作者：刘海峰 jeffrey Dankwa Ampah Sandylove Afrane Humphrey Adun 金超尧命发 State Key Laboratory of Engines Tianjin UniversityTianjin 300072China School of Environmental Science and Engineering Tianjin UniversityTianjin 300072China Energy Systems Engineering Department Cyprus International UniversityHaspolat-Lefkosa Mersin 10Turkey

Climate change remains arguably one of the most important issues facing the world in the 21st century.According to the Paris Agreement,the world should strive to limit global mean temperature change by 2100 to below 1.5-2℃above pre-industrial levels[1].To achieve this goal,global net carbon dioxide(CO_(2))emissions should reach zero no later than 2050 for the realization of the1.5℃target and 2070 for the 2℃target,respectively[2].Since the introduction of this global commitment,several mitigation options have been proposed to achieve the climate goal.

关键词：潜在效益 global climate

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Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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world Journal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： jeffrey A Lowell Michael J Farber Keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States Preclinical Studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).while current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy

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A medium chain fatty acid, 6-hydroxyhexanoic acid (6-HHA), protects against obesity and insulin resistance

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1892-1894页

作者： Sara C.Sebag Meihua Hao Qingwen Qian Chawin Upara Qiong Ding Min Zhu jeffrey A.Banas Huojun Cao Liu Hong Ling Yang Department of Anatomy and Cell Biology University of Iowa Carver College of MedicineIowa CityIA 52242USA Fraternal Order of Eagles Diabetes Research Center University of Iowa Carver College of MedicineIowa CityIA 52242USA Pappajohn Biomedical Institute University of Iowa Carver College of MedicineIowa CityIA 52242USA Iowa Institute for Oral Health Research University of Iowa College of DentistryIowa CityIA 52242USA

To the Editor,Obesity,one of the most serious health concerns worldwide,exacerbates periodontitis pathogenesis and reduces the effectiveness of treatments1.Conversely,periodontitis-associated inflammation disrupts systemic lipid and glucose homeostasis,the major risk factors for developing obesity-associated pathologies1.Accumulated studies have demonstrated that certain supplemental dietary lipids such as dietary polyunsaturated fatty acids,have beneficial outcomes for diabetic and obese patients.In addition to dietary lipid supply,the oral and gut microbiota produce fatty acids(FAs)which provide the host with essential nutrients and aid in defense against pathogens.Hydroxyhexanoic medium chain FAs(MCFAs;6–12 carbons)are bacterial-derived lipids shown to have anti-inflammatory and insulin sensitization effects in diverse cell types such as hepatocytes2.However,whether and to what extent oral microbiota-produced MCFAs may ameliorate obesity-associated metabolic dysfunction are largely unknown.

关键词： obesity dietary lipids

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