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Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 69-85页

作者： Noehyun Myung Hyun-wook kang Department of Biomedical Engineering Ulsan National Institute of Science and Technology(UNIST)Ulju-gun 44919South Korea

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

关键词： Dose-dense chemotherapy Triple-negative breast cancer 3D printing Pulsatile release Local drug delivery systems

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

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Neural Regeneration Research 2024年第7期19卷 1584-1592页

作者： Jong Mi Park Masoud Rahmati sang Chul Lee Jae Il Shin Yong wook Kim Department and Research Institute of Rehabilitation Medicine Yonsei University College of MedicineSeoulSouth Korea Department of Physical Education and Sport Sciences Faculty of Literature and Human SciencesLorestan UniversityKhoramabadIran Department of Pediatrics Yonsei University College of MedicineSeoulSouth Korea

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgro

关键词： animal animal experimentation mesenchymal stem cells models Parkinson’s disease stem cell transplantation

Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

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Nano-Micro Letters 2024年第4期16卷 269-292页

作者： Moon Sung kang Yeuni Yu Rowoon Park Hye Jin Heo Seok Hyun Lee Suck Won Hong Yun Hak Kim Dong‑wook Han Department of Cogno‑Mechatronics Engineering College of Nanoscience and NanotechnologyPusan National UniversityBusan 46241Republic of Korea Medical Research Institute School of MedicinePusan National UniversityYangsan 50612Republic of Korea Department of Anatomy School of MedicinePusan National UniversityYangsan 50612Republic of Korea Engineering Research Center for Color‑Modulated Extra‑Sensory Perception Technology Pusan National UniversityBusan 46241Republic of Korea Department of Biomedical Informatics School of MedicinePusan National UniversityYangsan 50612Republic of Korea Periodontal Disease Signaling Network Research Center and Dental and Life Science Institute School of DentistryPusan National UniversityYangsan 50612Republic of Korea BIO‑IT Fusion Technology Research Institute Pusan National UniversityBusan 46241Republic of Korea Present Address:Osstem Implant Inc. Seoul 07789Republic of Korea

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

关键词： Ti_(3)C_(2)T_(x)MXene nanoparticle Ternary nanofibrous matrices Myogenesis Regeneration of volumetric muscle loss Next generation sequencing

Optimizing intrinsic cocatalyst activity and light absorption efficiency for efficient hydrogen evolution of 1D/2D ReS_(2)-CdS photocatalysts via control of ReS_(2)nanosheet layer growth

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Journal of Materials Science & Technology 2024年第1期168卷 103-113页

作者： Ghufran Aulia Bin Azizar Jong wook Hong Department of Chemistry University of UlsanUlsan 44610Korea

The visible-light-driven hydrogen evolution is extremely important,but the poor charge transfer capa-bility,a sluggish evolution rate of hydrogen,and severe photo-corrosion make photocatalytic hydrogen evolution impractical.In this study,we present 1D/2D ReS_(2)-CdS hybrid nanorods for photocatalytic hy-drogen evolution,comprised of a ReS_(2)nanosheet layer grown on CdS nanorods.We found that precise control of the contents of the ReS_(2)nanosheet layer allows for manipulating the electronic structure of Re in the ReS_(2)-CdS hybrid nanorods.The ReS_(2)-CdS hybrid nanorods with optimal ReS_(2)nanosheet layer content dramatically improve photocatalytic hydrogen evolution activity.Notably,photocatalytic hydro-gen evolution activity(64.93 mmol g^(−1)h^(−1))of ReS_(2)-CdS hybrid nanorods with ReS_(2)nanosheet layers(Re/Cd atomic ratio of 0.051)is approximately 136 times higher than that of pure CdS nanorods under visible light irradiation.Furthermore,intimated coupling of the ReS_(2)nanosheet layer with CdS nanorods reduced the surface trap-site of the CdS nanorods,resulting in enhanced photocatalytic stability.The de-tailed optical and electrical investigations demonstrate that the optimal ReS_(2)nanosheet layer contents in the ReS_(2)-CdS hybrid nanorods can provide improved charge transfer capability,catalytic activity,and light absorption efficiency.This study sheds light on the development of photocatalysts for highly efficient photocatalytic hydrogen evolution.

关键词： Photocatalyst Hydrogen evolution reaction ReS_(2)-CdS heterostructure Control of ReS_(2)nanosheet layer growth Optimization of cocatalyst activity and light absorption

Extracellular vesicles for neural regeneration after spinal cord injury

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Neural Regeneration Research 2024年第3期19卷 491-492页

作者： Young-Ju Lim wook-Tae Park Gun Woo Lee Department of Orthopedic Surgery Yeungnam University Medical CenterYeungnam University College of MedicineDaeguKorea

What is spinal cord injury:Spinal cord injury(SCI)is the damage to the structure of the bundles of cells and nerves that communicate signals from the brain to the body and extremities.The pathology of SCI includes both primary and secondary injuries(Morales et al.,2016).Physical forces such as compression,shearing,contusion,and tearing are major causes of primary injury in SCI.There are two main processes in primary injury:acute and subacute.The acute phase includes traumatic disruption of axons and hemorrhage of the blood vessels around the spinal cord.Hemorrhagic injury to the vessels can lead to increased edema within the neural and cord tissues,susceptibility to infiltration by microglia and astrocytes,excitotoxicity,and demyelination.Similarly,disruption of the blood-spinal cord barrier results in the release of inflammatory cytokines from specific cells and vessels.

关键词： acute injuries nerves

In-situ isothermal aging TEM analysis of a micro Cu/ENIG/Sn solder joint for flexible interconnects

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Journal of Materials Science & Technology 2024年第2期169卷 42-52页

作者： Jinhong Liu Jianhao Xu Kyung-wook Paik Peng He Shuye Zhang State Key Laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin150001China Department of materials science and engineering KAIST291 Daehak-roYuseong-guDaejeon305-338Republic of Korea

Sn/ENIG has recently been used in flexible interconnects to form a more stable micron-sized metallurgical joint,due to high power capability which causes solder joints to heat up to 200℃.However,Cu_(6)Sn_(5)which is critical for a microelectronic interconnection,will go through a phase transition at temperatures between 186 and 189℃.This research conducted an in-situ TEM study of a micro Cu/ENIG/Sn solder joint under isothermal aging test and proposed a model to illustrate the mechanism of the microstructural evolution.The results showed that part of the Sn solder reacted with Cu diffused from the electrode to formη´-Cu_(6)Sn_(5)during the ultrasonic bonding process,while the rest of Sn was left and enriched in a region in the solder joint.But the enriched Sn quickly diffused to both sides when the temperature reached 100℃,reacting with the ENIG coating and Cu to form(Ni_(x)Cu_(1-x))_(3)Sn_(4),AuSn_(4),and Cu_(6)Sn_(5)IMCs.After entering the heat preservation process,the diffusion of Cu from the electrode to the joint became more intense,resulting in the formation of Cu_(3)Sn.The scallop-type Cu_(6)Sn_(5)and the seahorse-type Cu_(3)Sn constituted a typical two-layered structure in the solder joint.Most importantly,the transition betweenηandη’was captured near the phase transition temperature for Cu_(6)Sn_(5)during both the heating and cooling process,which was accompanied by a volume shifting,and the transition process was further studied.This research is expected to serve as a reference for the service of micro Cu/ENIG/Sn solder joints in the electronic industry.

关键词： In-situ TEM observation Isothermal aging Micro Cu/ENIG/Sn solder joint Cu_(6)Sn_(5)phase transition

Transparent high-performance piezoceramics through pressureless sintering

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Journal of Advanced Ceramics 2024年第5期13卷 561-567页

作者： Hye-Lim Yu Woo-Seok kang Ju-Hyeon Lee Temesgen Tadeyos Zate Young-Jin Lee Bo-Kun Koo Dong-Jin Shin Min-Soo Kim Soon-Jong Jeong Young Ghyu Ahn wook Jo Department of Material Science and Engineering Ulsan National Institute of Science and TechnologyUlsan 44919Republic of Korea Energy Conversion Research Center Korea Electrotechnology Research InstituteChangwon 51543Republic of Korea MLCC Development Team Component Biz.UnitSamsung Electro-Mechanics Co.Ltd.Suwon 16674Republic of Korea

Piezoelectricity offers an electromechanical coupling that is widely utilized in transducer applications.There has been a consistent demand for transparent piezoelectric materials for optoelectrical applications.Therefore,despite the inherent tradeoff between the transparency and the piezoelectricity,numerous strategies have been explored to develop the transparent piezoelectric materials.Nonetheless,the most transparent piezoelectric materials developed to date is either a single crystal or materials that achieve transparency via hot-press sintering,limiting its industrial applicability.Therefore,we introduce a novel piezoelectric material that ensures transparency through co-doping and pressureless sintering of polycrystalline ceramics.In this study,we employed a compositional optimization approach to enhance the synergistic effect between the transparency and the piezoelectric properties of 0.71Pb(Mg_(1/3)Nb_(2/3))O_(3)–0.29PbTiO_(3)(PMN–0.29PT)ceramics.By utilizing the tape casting process for mass production and large-area manufacturing,our Pb_(0.913)La_(0.0145)Sm_(0.0145)(Mg_(1/3)Nb_(2/3))_(0.71)Ti_(0.29)O_(3)(TP2.9)ceramics exhibited over 60%transparency and large piezoelectric coefficient(d33)of 1104 pC/N.This material holds considerable promise for a wide range of industrial applications in both the optical and electronic domains.

关键词： piezoelectric ceramics transparency pressureless sintering co-doping tape casting

Pedicled abdominal flap using deep inferior epigastric artery perforators for forearm reconstruction: A case report

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World Journal of Clinical Cases 2024年第4期12卷 828-834页

作者： Jae Hyung Jeon Kyung wook Kim Hong Bae Jeon Department of Plastic and Reconstructive Surgery Dankook University HospitalCheonan 31116ChungnamSouth Korea Department of Orthopaedic Surgery Dankook University HospitalDankook University College of MedicineCheonan 31116ChungnamSouth Korea Department of Plastic and Reconstructive Surgery Dankook University HospitalDankook University College of MedicineCheonan 31116ChungnamSouth Korea

BACKGROUND Pedicled abdominal flaps are a widely used surgical technique for forearm reconstruction in patients with soft tissue defects.However,some drawbacks include restricted flap size,partial flap loss,and donor-site morbidity.To address these concerns,we present a case of a pedicled abdominal flap using the deep inferior epigastric artery perforators(DIEP)for forearm reconstruction in a patient with a large soft tissue defect.CASE SUMMARY A 46-year-old male patient was admitted to our hospital with forearm injury caused by a pressing machine.A 15 cm×10 cm soft tissue defect with complete rupture of the ulnar side structures of the forearm was found.One week after orthopedic management of the neurovascular injury and fractures using the first stage of Masquelet technique,the patient was referred to the plastic and recon-structive surgery department for wound coverage.Surgical debridement and negative-pressure wound therapy revealed a 20 cm×15 cm soft tissue defect.A pedicle abdominal flap with the DIEP was used to cover the defect.Three weeks later,the flap was detached from the abdomen,and the abdominal defect was directly closed.Subsequently,the second stage of Masquelet technique was performed at the fracture site at week 10.Finally,all donor and recipient sites healed without complications,such as flap dehiscence,infection,hematoma,or necrosis.Fracture site osteosynthesis was achieved without complications.CONCLUSION Pedicled abdominal flap using the DIEP provides a reliable option for forearm reconstruction in patients with large soft tissue defects.

关键词： Forearm injury Open fracture reduction Perforator flap Deep inferior epigastric artery perforators Case report

Prevalence and risk factors of wound complications after transtibial amputation in patients with diabetic foot

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World Journal of Diabetes 2024年第4期15卷 629-637页

作者： Young Uk Park Seong Hyuk Eim Young wook Seo Department of Orthopedic Surgery Ajou University School of MedicineAjou University HospitalSuwon 16499South Korea

BACKGROUND Diabetic foot(DMF)complications are common and are increasing in incidence.Risk factors related to wound complications are yet to be established after transtibial amputation under the diagnosis of DMF infection.AIM To analyze the prognosis and risk factors related to wound complications after transtibial amputation in patients with diabetes.METHODS This retrospective cohort study included seventy-two patients with DMF complications who underwent transtibial amputation between April 2014 and March 2023.The groups were categorized based on the occurrence of wound complications,and we compared demographic data between the complication group and the non-complication group to analyze risk factors.Moreover,a multivariate logistic regression analysis was performed to identify risk factors.RESULTS The average follow-up period was 36.2 months.Among the 72 cases,31(43.1%)had wound complications.Of these,12 cases(16.7%)received further treatment,such as debridement,soft tissue stump revision,and re-amputation at the proximal level.In a group that required further management due to wound complications after transtibial amputation,the hemoglobin A1c(HbA1c)level was 9.32,while the other group that did not require any treatment had a 7.54 HbA1c level.The prevalence of a history of kidney transplantation with wound complications after transtibial amputation surgery in DMF patients was significantly greater than in cases without wound complications(P=0.02).Other factors did not show significant differences.CONCLUSION Approximately 43.1%of the patients with transtibial amputation surgery experienced wound complications,and 16.7%required additional surgical treatment.High HbA1c levels and kidney transplant history are risk factors for postoperative wound complications.

关键词： Diabetic foot Transtibial amputation Wound complications Risk factor