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Simple and customizable method for fabrication of high-aspect ratio microneedle molds using low-cost 3D printing

Microsystems & Nanoengineering 2019年第1期5卷 250-263页

作者： kevin j.krieger Nicky Bertollo Manita Dangol john T.Sheridan Madeleine M.Lowery Eoin D.O’Cearbhaill UCD Centre for Biomedical Engineering University College DublinBelfieldDublin 4Ireland School of Mechanical&Materials Engineering University College DublinBelfieldDublin 4Ireland School of Electrical&Electronic Engineering University College DublinBelfieldDublin 4Ireland

We present a simple and customizable microneedle mold fabrication technique using a low-cost desktop SLA 3D *** opposed to conventional microneedle fabrication methods,this technique neither requires complex and expensive manufacturing facilities nor expertise in *** most low-cost 3D-printed microneedles to date display low aspect ratios and poor tip sharpness,we show that by introducing a two-step“Print&Fill”mold fabrication method,it is possible to obtain high-aspect ratio sharp needles that are capable of penetrating *** first the effect of varying design input parameters and print settings,it is shown that printed needles are always shorter than *** decreasing input height,needles also begin displaying an increasingly greater than specified needle base *** factors contribute to low aspect ratio needles when attempting to print submillimeter height *** setting input height tall enough,it is possible to print needles with high-aspect ratios and tip radii of 20–40μ*** tip sharpness is smaller than the specified printer ***,high-aspect ratio sharp needle arrays are printed in basins which are backfilled and cured in a second step,leaving sub-millimeter microneedles exposed resulting microneedle arrays which can be used as male *** female master molds are then formed from the fabricated microneedle *** the molds,both carboxymethyl cellulose loaded with rhodamine B as well as polylactic acid microneedle arrays are produced and their quality examined.A skin insertion study is performed to demonstrate the functional capabilities of arrays made from the fabricated *** method can be easily adopted by the microneedle research community for in-house master mold fabrication and parametric optimization of microneedle arrays.

关键词： needle cost printer

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Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

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Neural Regeneration Research 2024年第7期19卷 1548-1552页

作者： Shigeharu Tsuda Mustafa Golam jiamei Hou kevin K.W.Wang Floyd j.Thompson Prodip Bose Brain Rehabilitation Research Center Malcom Randall VA Medical CenterNorth Florida/South Georgia Veterans Health SystemGainesvilleFLUSA Department of Anesthesiology College of MedicineUniversity of FloridaGainesvilleFLUSA Department of Emergency Medicine University of FloridaGainesvilleFLUSA Department of Neuroscience University of FloridaGainesvilleFLUSA Department of Neurology University of FloridaGainesvilleFLUSA

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain *** has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb ***,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in *** three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid *** results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham *** other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically *** results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular *** is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

关键词： balance blood flow cardiovascular system central nervous system epinephrine ischemic damage lumbar spinal cord muscle tone repeated blast spasticity traumatic brain injury

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Weight regain after intragastric balloon for pre-surgical weight loss

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World journal of Gastrointestinal Surgery 2024年第7期16卷 2040-2046页

作者： Danielle Abbitt kevin Choy Alexandra Kovar Teresa S jones Krzysztof j Wikiel Edward L jones Department of Surgery University of ColoradoAuroraCO 80045United States Department of Surgery Rocky Mountain Regional Veteran Affairs Medical CenterAuroraCO 80045United States

BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related *** can place patients at increased risk of operative and postoperative *** intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well *** To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon *** This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective *** outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were *** criteria included those with balloon in place at time of *** Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective *** patients were required to participate in a 12-month weight management program to be eligible for balloon *** surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip *** average age at placement was 53 years±11 years,majority(91%)were *** average duration of intragastric balloon therapy was 186 days±41 *** average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight ***-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss ***-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon *** pat

关键词： Intragastric balloon Weight loss Obesity Bariatric Body mass index

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Multinuclear MR and MRI study of lithium-ion cells using a variable field magnet and a fixed frequency RF probe

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Magnetic Resonance Letters 2024年第1期4卷 10-20页

作者： Andrés Ramírez Aguilera Florin Marica kevin j.Sanders Md Al Raihan C.Adam Dyker Gillian R.Goward Bruce *** UNB MRI Centre Department of PhysicsUniversity of New BrunswickFrederictonNew BrunswickE3B 5A3Canada Department of Chemistry McMaster UniversityHamiltonOntarioL8S 4L8Canada Department of Chemistry University of New BrunswickFrederictonNew BrunswickE3B 5A3Canada

An exploratory multinuclear magnetic resonance(MR)and magnetic resonance imaging(MRI)study was performed on lithium-ion battery cells with ^(7)Li,^(19)F,and ^(1)H measurements.A variable field superconducting magnet with a fixed frequency parallel-plate radiofrequency(RF)probe was employed in the *** magnetic field was changed to set the resonance frequency of each nucleus to the fixed RF probe frequency of 33.7 *** cartridge-like lithium-ion cells,with graphite anodes and LiNi_(0.5)Mn_(0.3)Co_(0.2)O_(2)(NMC)cathodes,were *** cell was pristine,and one was charged to a cell voltage of 4.2 *** results presented demonstrate the great potential of the variable field magnet approach in multinuclear measurement of lithium-ion *** methods open the door for developing faster and simpler methods for detecting,quantifying,and interpreting MR and MRI data from lithium-ion and other batteries.

关键词： Multinuclear MR/MRI Variable field magnet Lithium-ion battery Parallel-plate rf probe

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Epidemiologic investigation of pediatric distal humerus fractures: An American insurance claims database study

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World journal of Orthopedics 2024年第1期15卷 52-60页

作者： Kyle jay Klahs jake E Dertinger Grant T Mello kevin Thapa Alexis B Sandler E'Stephan j jesus Garcia Nata Parnes Department of Orthopaedic Surgery Texas Tech University Health Sciences-El PasoEl PasoTX 79905United States Medical School California Health Sciences University College of Osteopathic MedicineClovisCA 93611United States Undergraduate School Binghampton UniversityVestalNY 13902United States Department of Orthopaedic Surgery William Beaumont Army Medical CenterFort BlissTX 79918United States Department of Orthopaedic Surgery Carthage Area HospitalCarthageNY 13619United States

BACKGROUND Distal humerus elbow fractures are one of the most common traumatic fractures seen in pediatric patients and present as three main types:Supracondylar(SC),lateral condyle(LC),and medial epicondyle(ME)*** To evaluate the epidemiology of pediatric distal humerus fractures(SC,LC,and ME)from an American insurance claims *** A retrospective review was performed on patients 17 years and younger with the ICD 9 and 10 codes for SC,LC and ME fractures based on the IBM Truven MarketScan®Commercial and IBM Truven MarketScan Medicare Supplemental *** from 2015 to 2020 were queried for treatments,patient age,sex,length of hospitalization,and *** A total of 1133 SC,154 LC,and 124 ME fractures were *** fractures had the highest percentage of operation at 83%,followed by LC(78%)and ME fractures(41%).Male patients were,on average,older than female patients for both SC and ME *** In the insurance claims databases used,SC fractures were the most reported,followed by LC fractures,and finally ME *** was identified to be a factor for how a pediatric distal humerus fractures,with patients with SC and LC fractures being younger than those with ME *** peak age per injury per sex was similar to reported historic central tendencies,despite reported trends for younger physiologic development.

关键词： Supracondylar humerus fracture Lateral condyle fracture Medial epicondyle fracture Pediatric elbow Truven Epidemiology

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Pharmacological methods for ovarian function and fertility preservation in women with cancer:A literature review

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Oncology Research 2024年第8期32卷 1309-1322页

作者： ANA S.CVETANOVIC MATTEO LAMBERTINI kevin PUNIE GORANA G.MATOVINA BRKO NIKOLA D.ZIVKOVIC MAjA j.POPOVIC MARIjANA M.MILOVIC KOVACEVIC LAZAR S.POPOVIC Department for Oncology Medical Faculty NisUniversity of NisNis18000Serbia Clinic of Oncology University Clinical Centre NisNis18000Serbia Department of Internal Medicine and Medical Sciences(DiMI) School of MedicineUniversity of GenovaGenova16100Italy Department of Medical Oncology U.O.C Clinica di Oncologia MedicaIRCCS Ospedale Policlinico San MartinoGenova16100Italy Department of General Medical Oncology and Multidisciplinary Breast Centre Leuven Cancer InstituteUniversity Hospitals LeuvenLeuven3001Belgium Department of Medical Oncology Oncology Institute of VojvodinaSremska Kamenica21208Serbia Department for Pathology Medical Faculty NisUniversity of NisNis18000Serbia Center for Pathology University Clinical Centre NisNis18000Serbia Faculty of Medicine University of Novi SadNovi Sad21000Serbia Department of Medical Oncology Institute of Oncology and Radiology SerbiaBelgrade11000Serbia

Oncofertility is an extremely signiﬁcant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but signiﬁcantly contributes to preserving life *** effect of chemotherapy can range from minimal effects to complete ovarian *** data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and *** ovarian suppression by administering a gonadotropin-releasing hormone agonist(GnRHa)during chemotherapy decreases the gonadotoxic effect of chemotherapy,thereby diminishing the chance of developing premature ovarian insufﬁciency(POI).At present,the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian ***,most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer,with a considerably small number of studies on patients with hematological ***,most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk,regardless of the hormone receptor *** addition,studies on hematological malignancies have yielded negative results;nevertheless,theﬁndings must be interpreted with caution owing to numerous *** guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm,oocyte,and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not *** this manuscript,we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data,as well as future perspectives in thisﬁeld

关键词： Gonadotropin-releasing hormone agonists(GnRHa) Fertility preservation Premature ovarian insufficiency(POI) Premenopausal patients

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu kevin Qin jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael j.Lee jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan juan Alec C.Bancroft ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard juhoon Lee Sowmya Ramesh Aaron W.james David Hudson kevin N.Dalby Lin Xu Robert j.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref kevin K.Wang j.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Dynamics of self-hybridized exciton–polaritons in 2D halide perovskites

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Light(Science & Applications) 2024年第1期13卷 13-22页

作者： Surendra B.Anantharaman jason Lynch Christopher E.Stevens Christopher Munley Chentao Li jin Hou Hao Zhang Andrew Torma Thomas Darlington Francis Coen kevin Li Arka Majumdar Pjames Schuck Aditya Mohite Hayk Harutyunyan joshua R.Hendrickson Deep jariwala Department of Electrical and Systems Engineering University of PennsylvaniaPhiladelphiaPA19104USA KBR Inc. BeavercreekOH45431USA Air Force Research Laboratory Sensors DirectorateWright-Patterson Air Force BaseOH45433USA Department of Physics University of WashingtonSeattleWA98195USA Department of Physics Emory UniversityAtlantaGA30322USA Department of Chemical and Biomolecular Engineering Rice UniversityHoustonTX77005USA Department of Materials Science and Nanoengineering Rice UniversityHoustonTX77005USA Applied Physics Program Smalley‐Curl InstituteRice UniversityHoustonTX77005USA Department of Mechanical Engineering Columbia UniversityNew YorkNY10027USA Department of Electrical and Computer Engineering University of WashingtonSeattleWA98195USA

Excitons,bound electron–hole pairs,in two-dimensional hybrid organic inorganic perovskites(2D HOIPs)are capable of forming hybrid light-matter states known as exciton-polaritons(E–Ps)when the excitonic medium is confined in an optical *** the case of 2D HOIPs,they can self-hybridize into E–Ps at specific thicknesses of the HOIP crystals that form a resonant optical cavity with the ***,the fundamental properties of these self-hybridized E–Ps in 2D HOIPs,including their role in ultrafast energy and/or charge transfer at interfaces,remain ***,we demonstrate that>0.5µm thick 2D HOIP crystals on Au substrates are capable of supporting multiple-orders of self-hybridized E–P *** E–Ps have high Q factors(>100)and modulate the optical dispersion for the crystal to enhance sub-gap absorption and *** varying excitation energy and ultrafast measurements,we also confirm energy transfer from higher energy E–Ps to lower energy E–***,we also demonstrate that E–Ps are capable of charge transport and transfer at *** findings provide new insights into charge and energy transfer in E–Ps opening new opportunities towards their manipulation for polaritonic devices.

关键词： charge polar excitation

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