对代谢组学的含义,中心任务,研究方法,样品要求,应用及其发展方向进行了简要综述. 系统生物学概念的诞生标志着研究哲学由“还原论”向“整体论”的变化. 系统生物学的中心任务就是要针对生物系统整体 (无论它是生物细胞,多细胞组织,器...对代谢组学的含义,中心任务,研究方法,样品要求,应用及其发展方向进行了简要综述. 系统生物学概念的诞生标志着研究哲学由“还原论”向“整体论”的变化. 系统生物学的中心任务就是要针对生物系统整体 (无论它是生物细胞,多细胞组织,器官还是生物整体),建立定量,普适,整体和可预测 (QUIP) 的认知. 具体而言,系统生物学研究就是要将给定生物系统的基因,转录,蛋白质和代谢水平所发生的事件,相关性及其对所涉及生物过程的意义进行整体性认识. 从而出现了许多的“组”和“组学”的新概念. 但是现已提出的一百多个“组”和“组学”,可以大体归纳为“基因组”/“基因组学”,“转录组”/“转录组学”,“蛋白质组”/“蛋白质组学”和“代谢组”/“代谢组学”四个方面. 显而易见,DNA,mRNA 以及蛋白质的存在为生物过程的发生提供了物质基础 (但这个过程有可能不发生!),而代谢物质所反映的是已经发生了的生物学事件. 因此代谢组学是对一个生物系统进行全面认识的不可缺少的一部分,是全局系统生物学 (global systems biology) 的重要基础,也是系统生物学的一个重要组成部分. 在现有的英文表述中,代谢组学同时存在两个不同的词汇和概念,即metabonomics 和 metabolomics. 尽管前者多用在动物系统而后者多用于植物和微生物系统,但这些概念的本质从他们的定义中能够得到较细致的了解. Metabonomics 的最初定义是就生物系统对生理和病理刺激以及基因改变的代谢应答的定量测定(“the quantitative measurement of the multi-parametric metabolic response of living systems to pathophysiological stimuli or geneticmodifications”). 我们认为这个定义现在可以更广泛地表述为:代谢组学是关于定量描述生物内源性代谢物质的整体及其对内因和外因变化应答规律的科学 (“Metabonomics is the branch of science concerned with the quantitative understandings of themetabolite complement of integrated living systems and its dynamic responses to the changes of both endogenous factors (such asphysiology and development) and exogenous factors (such as environmental factors and xenobiotics).”). 其中心任务包括 (1) 对内源性代谢物质的整体及其动态变化规律进行检测,量化和编录,(2) 确定此变化规律和生物过程的有机联系. Metabolomics 存在多个定义,但其精髓是:对一个生物系统的细胞在给定时间和给定条件下所有小分子代谢物质的定量分析(the quantitativemeasurement of all low molecular weight metabolites in an organism's cells at a specified time under specific environmentalconditions). 因此,metabolomics 可以译作“代谢物组学”. 不难看出,前者是对生物系统进行的整体和动态的认识 (不仅关心代谢物质的整体也关注其动态变化规律),而后者强调分析而且是个静态的认识概念. 因此可以认为,metabolomics 是metabonomics 的一个组成部分 (参看定义). 近年又有人提出了“dynamic metabolomics”的概念,这个概念所表达的含义十分接近“metabonomics”本身的含义. 所以,可以预见,随着这门新兴学科的发展和更深入讨论,这两个概念必将趋向一致. 因此我们建议,在中文表述中将“代谢组学”一词和英文中的 metabonomics 相对应,以避免不必要的混淆和争议. 就细胞系统而言,不仅存在细胞自身的代谢物质组成问题,存在细胞之间代谢物质交换的问题,也存在代谢过程所发生的位点问题. 因此,简单地分析代谢物质的总组成 (即代谢组) 缺乏“整体论”所要求的全面性,其意义有一定局限. 代谢组学属于全局系统生物学 (Global systems biology) 研究方法,便于对复杂体系的整体进行认识. 譬如,一个正常工作的人体包括“人体”本身和与之共同进化而来且共生的消化道微生物群体 (或称菌群),孤立地研究“人体”本身的基因,转录子以及蛋白质当然可以为人们认识人体生物学提供重要信息,但无法提供使人体正常工作不可缺少的菌群的信息. 人体血液和尿液的代谢组却携带着包括菌群在内的每一个细胞的信息,因此代谢组学方法对研究如人体这样复杂的进化杂合体十分有效. 正因如此,代谢组学已经广泛地应用到了包括药物研发,分子生理学,分子病理学,基因功能组学,营养学,环境科学等重要领域. 在代谢组学诞生的过去 6 年里,有关代谢组学的研究论文和专利以指数的形式逐年增长. 可以预见,这门新兴学科将应用到更为广泛的领域.展开更多
Objective:To establish the prevalence and associated risk factors of Schistosoma mansoni(S.mansoni) infection among schoolchildren at a village in Wolaita Zone.Sothern Ethiopia,Methods:A cross-sectional study was carr...Objective:To establish the prevalence and associated risk factors of Schistosoma mansoni(S.mansoni) infection among schoolchildren at a village in Wolaita Zone.Sothern Ethiopia,Methods:A cross-sectional study was carried out among primary schoolchildren.A total of 384 randomly selected study subjects provided stool samples for parasitological examination by Kato-Katz and Formalin-Ether concentration techniques.Secondary parasitological data were obtained from Health Center Laboratory to see the previous history of.S.mansoni infection in the area.Statistical analysis was performed using SPSS software version 16.Results:From the total children examined.85.4% were found positive for at least one helminth infection.S.mansoni infection(81.3% ) was the most prevalent and the prevalence of STH was 32% ..Moderate and heavy infection intensities were only observed in S,mansoni infections.The overall heavy intensity of infection was 56.4% .Contact to Bisarc stream was the most important factor for S.mansoni infection(OR 3.9) followed by herding cattle near the stream(OR2.527).Males were twice more likely to get the infection than females(OR 1.923).Analysis of secondary parasitological data showed that S.mansoni infection was a leading helminthic infection over the past years.Conclusions:The present study found a higher intensity and prevalence of S.mansoni infection in a rural village of Wolaita Zone.Therefore,appropriate integrated control and prevention measures need to be implemented in the study area.展开更多
BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in ...BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.展开更多
Clinicians can provide a means to better distribute the pressure around the foot, and can also correct the biomechanics of the foot by using a customized shoe insole. If detected early enough, orthopedic insoles can c...Clinicians can provide a means to better distribute the pressure around the foot, and can also correct the biomechanics of the foot by using a customized shoe insole. If detected early enough, orthopedic insoles can correct or prevent further complications. In this study the 3 Dimensional (D) model of the foot was used to fabricate a customized orthosis. The Computed Tomography (CT) images of patient’s foot having no muscle weakness and joint restriction were acquired. The gray intensities corresponding to the bones of the foot from the CT images were 3 dimensionally reconstructed. The 3D model of the foot was then imported into the CAD Software. Boolean operations were carried out in between the 3D foot model and a solid rectangular surface to create a customized foot orthosis. The exact contours and shape of the subject’s foot was acquired using the computerized method of fabricating an orthosis. The novel idea described in this study support, automating the process of designing a customized orthosis with the impression got from the 3 dimensionally modeled feet, thereby reducing the modeling time considerably. The simple technique used in this process will help in giving comfort and stability to the patient’s feet while walking.展开更多
Biodegradable metals as electrodes, interconnectors, and device conductors are essential components in the emergence of transient electronics, either for passive implants or active electronic devices, especially in th...Biodegradable metals as electrodes, interconnectors, and device conductors are essential components in the emergence of transient electronics, either for passive implants or active electronic devices, especially in the fields of biomedical electronics. Magnesium and its alloys are strong candidates for biodegradable and implantable conducting materials because of their high conductivity and biocompatibility, in addition to their well-understood dissolution behavior. One critical drawback of Mg and its alloys is their considerably high dissolution rates originating from their low anodic potential, which disturbs the compatibility to biomedical applications. Herein, we introduce a single-phase thin film of a Mg-Zn binary alloy formed by sputtering, which enhances the corrosion resistance of the device electrode, and verify its applicability in biodegradable electronics. The formation of a homogeneous solid solution of single-phase Mg-3Zn was confirmed through X-ray diffraction and transmission electron microscopy. In addition, the dissolution behavior and chemistry was also investigated in various biological fluids by considering the effect of different ion species. Micro-tensile tests showed that the Mg-3Zn alloy electrode exhibited an enhanced yield strain and elongation in relation to a pure Mg electrode. Cell viability test revealed the high biocompatibility rate of the Mg-3Zn binary alloy thin film. Finally, the fabrication of a wireless heater demonstrated the integrability of biodegradable electrodes and highlighted the ability to prolong the lifecycle of thermotherapy-relevant electronics by enhancing the dissolution resistance of the Mg alloy.展开更多
Iron can contribute to the pathogenesis and progression of multiple sclerosis（MS） due to its accumulation in the human brain.We focus on the thalamus as an information transmitter between various subcortical and cor...Iron can contribute to the pathogenesis and progression of multiple sclerosis（MS） due to its accumulation in the human brain.We focus on the thalamus as an information transmitter between various subcortical and cortical areas.Thalamic iron seems to follow different rules than iron in other deep gray matter structures and its relation to the clinical outcomes of MS is still indistinct.In our study,we investigated a connection between thalamic iron and patients＇ disability and course of the disease.The presence of paramagnetic substances in the tissues was tracked by T2＊ quantification.Twenty-eight subjects with definite MS and 15 age-matched healthy controls underwent MRI examination with a focus on gradient echo sequence.We observed a non-monotonous course of T2＊ values with age in healthy controls.Furthermore,T2＊ distribution in MS patients was significantly wider than that of age matched healthy volunteers（P〈 0.001）.A strong significant correlation was demonstrated between T2＊ distribution spread and the expanded disability status scale（EDSS）（left thalamus：P〈0.00005;right thalamus：P〈0.005）,and multiple sclerosis severity scale（MSSS）（left thalamus：P〈0.05;right thalamus：P〈0.005）.The paramagnetic iron distribution in the thalamus in MS was not uniform and this inhomogeneity may be considered as an indicator of thalamic neurodegeneration in MS.展开更多
EMR2 is an EGF-like module containing mucin-like hormone receptor-2 precursor, a G-protein coupled receptor （G-PCR）. Mutation in EMR2 causes complicated disorders like polycystic kidney disease （PKD）. The structur...EMR2 is an EGF-like module containing mucin-like hormone receptor-2 precursor, a G-protein coupled receptor （G-PCR）. Mutation in EMR2 causes complicated disorders like polycystic kidney disease （PKD）. The structure of EMR2 shows that the fifth domain is comprised of EGF-TM7 helices. Functional assignment of EMR2 by support vector machine （SVM） revealed that along with transporter activity, several novel functions are predicted. A twenty amino acid sequence ＂MGGRVFLVFLAFCVWLTLPG＂ acts as the signal peptide responsible for post- translational transport. Eight amino acids are involved in N-glycosylation sites and two cleavage sites are LeuS17 and SerS18 in EMR2. The residue Arg241 is responsible for interaction with glycosaminoglycan and chondroitin sulfate. On the basis of structure, function and ligand binding sites, competitive EMR2 inhibitors designed may decrease the rate of human diseases like Usher＇s syndrome, bilateral frontoparietal polymicrogyria and PKD.展开更多
Purpose:The purpose of this study was to compare the coordination between the trunk and the pelvis during a sustained asymmetric repetitive lifting task between a group with a history of low back pain(LBP;HBP) and a g...Purpose:The purpose of this study was to compare the coordination between the trunk and the pelvis during a sustained asymmetric repetitive lifting task between a group with a history of low back pain(LBP;HBP) and a group with no history of LBP(NBP).Methods:Volunteers lifted a 11-kg box from ankle height in front to a shelf 45° off-center at waist height,and lowered it to the start position at12 cycles/min for 10 min.Lifting side was alternated during the trial.Continuous relative phase was used to calculate coordination between the pelvis and trunk rotation at the beginning(Min 1),middle(Min 5),and end of the bout(Min 9).Results:While there were no main effects for group,a significant interaction between time and group indicated that,in the frontal plane,the NBP group coordination was more anti-phase toward the end of the bout,with no such differences for the HBP group.Analysis of sagittal-axial(bend and twist) coordination revealed the HBP group coordination was more in-phase at the end of the bout over the entire cycle and for the lifting phase alone,with no such differences for the NBP group.Conclusion:Differences between groups demonstrate residual consequences of LBP in an occupational scenario,even though the HBP group was pain-free for >6 months prior to data collection.More in-phase coordination in the HBP group may represent a coordination pattern analogous to'guarded gait' which has been observed in other studies,and may lend insight as to why these individuals are at increased risk for re-injury.展开更多
1|INTRODUCTION Langya Henipavirus(LayV)is a zoonotic virus that has recently re‐emerged in Eastern China.There is limited data available on the global prevalence,mortality,and morbidity of LayV.The majority of cases ...1|INTRODUCTION Langya Henipavirus(LayV)is a zoonotic virus that has recently re‐emerged in Eastern China.There is limited data available on the global prevalence,mortality,and morbidity of LayV.The majority of cases have been reported in two provinces in China(Shandong and Henan).Between 2018 and 2022,35 individuals were diagnosed with the LayV infection in these regions.This novel ribonucleic acid virus attacks animals(including goats,dogs,and shrews)and can potentially spread to humans.The Henipavirus genus is a Paramyxoviridae family member that can be spread through animalhuman contact with no established human‐to‐human transmission yet[1].展开更多
Substrates or encapsulants in soft and stretchable formats are key components for transient,bioresorbable electronic systems;however,elastomeric polymers with desired mechanical and biochemical properties are very lim...Substrates or encapsulants in soft and stretchable formats are key components for transient,bioresorbable electronic systems;however,elastomeric polymers with desired mechanical and biochemical properties are very limited compared to nontransient counterparts.Here,we introduce a bioresorbable elastomer,poly(glycolide-co-ε-caprolactone)(PGCL),that contains excellent material properties including high elongation-at-break(<1300%),resilience and toughness,and tunable dissolution behaviors.Exploitation of PGCLs as polymer matrices,in combination with conducing polymers,yields stretchable,conductive composites for degradable interconnects,sensors,and actuators,which can reliably function under external strains.Integration of device components with wireless modules demonstrates elastic,transient electronic suture system with on-demand drug delivery for rapid recovery of postsurgical wounds in soft,time-dynamic tissues.展开更多
Due to typesetting mistake,Hanul Min was missed to be denoted as a corresponding author in the article.The type-setter apologizes for this.The original article has been corrected.Open Access This article is licensed u...Due to typesetting mistake,Hanul Min was missed to be denoted as a corresponding author in the article.The type-setter apologizes for this.The original article has been corrected.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.展开更多
Medical stents are vital for treating vascular complications and restoring blood flow in millions of patients.Despite its widespread effectiveness,restenosis,driven by the complex interplay of cellular responses,remai...Medical stents are vital for treating vascular complications and restoring blood flow in millions of patients.Despite its widespread effectiveness,restenosis,driven by the complex interplay of cellular responses,remains a concern.This study investigated the reactions of vascular cells to nano/microscale wrinkle(nano-W and micro-W)patterns created on laser-textured nitinol(NiTi)surfaces by adjusting laser processing parameters,such as spot overlap ratio and line overlap ratio.Evaluation of topographical effects on endothelial and smooth muscle cells(SMCs)revealed diverse morphologies,proliferation rates,and gene expressions.Notably,microscale wrinkle patterns exhibited reduced monocyte adhesion and inflammation-related gene expression,demon-strating their potential applications in mitigating vascular complications after stent insertion.Additionally,an ex vivo metatarsal assay was utilized to bridge the gap between in vitro and in vivo studies,demonstrating enhanced angiogenesis on laser-textured NiTi surfaces.Laser-textured NiTi exhibits a guided formation process,empha-sizing their potential to promote swift endothelialization.These findings underscore the efficacy of laser texturing for tailored cellular interactions on metallic surfaces and offer valuable insights into optimizing biocompatibility and controlling cellular responses,which may pave the way for innovative advances in vascular care and contribute to the ongoing improvement of stent insertion.展开更多
Photodynamic therapy(PDT)induces tumor cell pyroptosis,a form of programmed cell death that triggers antitumor immunity.However,high glucose metabolism and hypoxic conditions in the tumor microenvironment(TME)limit PD...Photodynamic therapy(PDT)induces tumor cell pyroptosis,a form of programmed cell death that triggers antitumor immunity.However,high glucose metabolism and hypoxic conditions in the tumor microenvironment(TME)limit PDT efficiency and impair effector cell function.Here,we propose a cancer metabolic reprogramming-enabling photoresponsive nanoproteolysis-targeting chimera(Nano-PROTAC;NanoTAC),derived from the supramolecular self-assembly of drug conjugates that bridge a PROTAC targeting hexokinaseⅡ(HK2)and a photosensitizer via a biomarker-cleavable linker.In a triple-negative breast cancer(TNBC)model,NanoTAC initially silences PROTAC activity and accumulates in tumor regions,where it undergoes linker cleavage in response to enzymatic biomarkers.Upon photoirradiation,PDT-induced pyroptotic cell death promotes the release of tumor-associated antigens(TAAs)and damage-associated molecular patterns(DAMPs)to drive the cancer-immunity cycle.Concurrently,targeted protein degradation(TPD)via PROTACs counteracts glucose and oxygen consumption in the TME,ultimately potentiating pyroptosis-mediated photoimmunotherapy.This combination therapy achieves a high rate of complete regression in primary TNBC and confers adaptive immunity to prevent metastasis and recurrence.Our study presents a rationally designed nanomedicine that integrates PDT and PROTACs,shedding light on strategies for more effective cancer immunotherapy.展开更多
In light of the burgeoning successes of cancer immunotherapy,glioblastoma(GBM)remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity.Thus,identifying promising the...In light of the burgeoning successes of cancer immunotherapy,glioblastoma(GBM)remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity.Thus,identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge.Here we describe photodynamic protein tyrosine phosphatase 1B(PTP1B)proteolysis mediated by a proteolysis-targeting chimera(PROTAC)nanoassembly.The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B(Cat B)-cleavable peptide,which spontaneously forms nanoassemblies due to intermolecularπ-πstack-ing interactions.In GBM models,PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier(BBB),triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage.Upon laser irradiation,photodynamic therapy(PDT)synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death(ICD)in tumor cells.Subsequently,persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers,reinvigorating their function-ality.These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cellmediated antitumor immunity as well as protective immunity,completely eradicating the primary GBM and preventing its recurrence.Overall,our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.展开更多
Pressure ulcers remain a persistent challenge in healthcare,particularly for individuals with limited mobility or compromised sensation.Early detection is critical to prevent ischemic damage leading to necrosis,infect...Pressure ulcers remain a persistent challenge in healthcare,particularly for individuals with limited mobility or compromised sensation.Early detection is critical to prevent ischemic damage leading to necrosis,infections,and prolonged hospital stays.Conventional sensing technologies that integrate into the mattress,while effective in gathering data on pressure distributions,are restricted to stationary environments,and they can miss significant periods when patients leave their beds or shift positions.Furthermore,these systems do not offer consistent information on the specific spatial distribution of pressure across the body,because the sensors integrate with the mattress and not the body.Recent research establishes capabilities in soft,skin-interfaced wireless alternatives,but in designs that require specialized processes and materials that might not scale effectively for practical production and use.Here,we present a wireless,skin-integrated pressure monitoring system that mounts on the skin,in anatomically matched forms and with soft mechanical interfaces,for continuous data collection.This platform,built on manufacturable components and designs,features an array of soft,elastomer-encapsulated pressure sensors that minimize discomfort,with wireless communications and an independent power management system to enable operation across diverse healthcare settings,including homes,outpatient facilities,and operating rooms,all without physical tethers.Additionally,an external alarm satellite device delivers vibratory and visual alerts if predefined pressure thresholds are exceeded,guiding caregivers or patients to take timely action.Experimental and finite element analysis support the design principles,and deployments on patients in hospital settings illustrate modes for practical use.展开更多
In regenerative medicine,extracellular vesicles(EVs)possess the potential to repair injured cells by delivering modulatory factors.However,the therapeutic effect of EVs in large-scale tissue defects,which are subject ...In regenerative medicine,extracellular vesicles(EVs)possess the potential to repair injured cells by delivering modulatory factors.However,the therapeutic effect of EVs in large-scale tissue defects,which are subject to prolonged timelines for tissue architecture and functional restoration,remains poorly understood.In this study,we introduce EVs and cell-tethering hybrid hydrogels composed of tyramine-conjugated gelatin(GelTA)that can be in-situ crosslinked with EVs derived from human induced pluripotent stem cell-derived myofibers(hiPSC-myofibers)and hiPSC-muscle precursor cells.This hybrid hydrogel sustains the release of EVs and provides a beneficial nano-topography and mechanical properties for creating a favorable extracellular matrix.Secreted EVs from the hiPSC-myofibers contain specific microRNAs,potentially improving myogenesis and angiogenesis.Herein,we demonstrate increased myogenic markers and fusion/differentiation indexes through the combina-tory effects of EVs and integrin-mediated adhesions in the 3D matrix.Furthermore,we observe a unique impact of EVs,which aid in maintaining the viability and phenotype of myofibers under harsh environments.The hybrid hydrogel in-situ crosslinked with hiPSCs and EVs is facilely used to fabricate large-scale muscle constructs by the stacking of micro-patterned hydrogel domains.Later,we confirmed a combinational effect,whereby muscle tissue regeneration and functional restoration were improved,via an in vivo murine volumetric muscle loss model.展开更多
The musculoskeletal system,which is vital for movement,support,and protection,can be impaired by disorders such as osteoporosis,osteoarthritis,and muscular dystrophy.This review focuses on the advances in tissue engin...The musculoskeletal system,which is vital for movement,support,and protection,can be impaired by disorders such as osteoporosis,osteoarthritis,and muscular dystrophy.This review focuses on the advances in tissue engineering and regenerative medicine,specifically aimed at alleviating these disorders.It explores the roles of cell therapy,particularly Mesenchymal Stem Cells(MSCs)and Adipose-Derived Stem Cells(ADSCs),biomaterials,and biomolecules/external stimulations in fostering bone and muscle regeneration.The current research underscores the potential of MSCs and ADSCs despite the persistent challenges of cell scarcity,inconsistent outcomes,and safety concerns.Moreover,integrating exogenous materials such as scaffolds and external stimuli like electrical stimulation and growth factors shows promise in enhancing musculoskeletal regeneration.This review emphasizes the need for comprehensive studies and adopting innovative techniques together to refine and advance these multi-therapeutic strategies,ultimately benefiting patients with musculoskeletal disorders.展开更多
Source apportionment of particulate matter （PM10） measurements taken in Delhi, India between January 2013 and June 2014 was carried out using two receptor models, principal component analysis with absolute principal...Source apportionment of particulate matter （PM10） measurements taken in Delhi, India between January 2013 and June 2014 was carried out using two receptor models, principal component analysis with absolute principal component scores （PCA/APCS） and UNMIX. The results were compared with previous estimates generated using the positive matrix factorization （PMF） receptor model to investigate each model＇s source-apportioning capability. All models used the PM10 chemical composition （organic carbon （OC）, elemental carbon （EC）, water soluble inorganic ions （WSIC）, and trace elements） for source apportionment. The average PM10 concentration during the study period was 249.7±103.9 μg/m3 （range： 61.4-584.8 μg/m3）. The UNMIX model resolved five sources （soil dust （SD）, vehicular emissions （VE）, secondary aerosols （SA）, a mixed source of biomass burning （BB） and sea salt （SS）, and industrial emissions （IE））. The PCA/APCS model also resolved five sources, two of which also included mixed sources （SD, VE, SD＋SS, （SA＋BB＋SS） and 1E）. The PMF analysis differentiated seven individual sources （SD, VE, SA, BB, SS, IE, and fossil fuel combustion （FFC））. All models identified the main sources contributing to PM10 emissions and reconfirmed that VE, SA, BB, and SD were the dominant contributors in Delhi.展开更多
文摘对代谢组学的含义,中心任务,研究方法,样品要求,应用及其发展方向进行了简要综述. 系统生物学概念的诞生标志着研究哲学由“还原论”向“整体论”的变化. 系统生物学的中心任务就是要针对生物系统整体 (无论它是生物细胞,多细胞组织,器官还是生物整体),建立定量,普适,整体和可预测 (QUIP) 的认知. 具体而言,系统生物学研究就是要将给定生物系统的基因,转录,蛋白质和代谢水平所发生的事件,相关性及其对所涉及生物过程的意义进行整体性认识. 从而出现了许多的“组”和“组学”的新概念. 但是现已提出的一百多个“组”和“组学”,可以大体归纳为“基因组”/“基因组学”,“转录组”/“转录组学”,“蛋白质组”/“蛋白质组学”和“代谢组”/“代谢组学”四个方面. 显而易见,DNA,mRNA 以及蛋白质的存在为生物过程的发生提供了物质基础 (但这个过程有可能不发生!),而代谢物质所反映的是已经发生了的生物学事件. 因此代谢组学是对一个生物系统进行全面认识的不可缺少的一部分,是全局系统生物学 (global systems biology) 的重要基础,也是系统生物学的一个重要组成部分. 在现有的英文表述中,代谢组学同时存在两个不同的词汇和概念,即metabonomics 和 metabolomics. 尽管前者多用在动物系统而后者多用于植物和微生物系统,但这些概念的本质从他们的定义中能够得到较细致的了解. Metabonomics 的最初定义是就生物系统对生理和病理刺激以及基因改变的代谢应答的定量测定(“the quantitative measurement of the multi-parametric metabolic response of living systems to pathophysiological stimuli or geneticmodifications”). 我们认为这个定义现在可以更广泛地表述为:代谢组学是关于定量描述生物内源性代谢物质的整体及其对内因和外因变化应答规律的科学 (“Metabonomics is the branch of science concerned with the quantitative understandings of themetabolite complement of integrated living systems and its dynamic responses to the changes of both endogenous factors (such asphysiology and development) and exogenous factors (such as environmental factors and xenobiotics).”). 其中心任务包括 (1) 对内源性代谢物质的整体及其动态变化规律进行检测,量化和编录,(2) 确定此变化规律和生物过程的有机联系. Metabolomics 存在多个定义,但其精髓是:对一个生物系统的细胞在给定时间和给定条件下所有小分子代谢物质的定量分析(the quantitativemeasurement of all low molecular weight metabolites in an organism's cells at a specified time under specific environmentalconditions). 因此,metabolomics 可以译作“代谢物组学”. 不难看出,前者是对生物系统进行的整体和动态的认识 (不仅关心代谢物质的整体也关注其动态变化规律),而后者强调分析而且是个静态的认识概念. 因此可以认为,metabolomics 是metabonomics 的一个组成部分 (参看定义). 近年又有人提出了“dynamic metabolomics”的概念,这个概念所表达的含义十分接近“metabonomics”本身的含义. 所以,可以预见,随着这门新兴学科的发展和更深入讨论,这两个概念必将趋向一致. 因此我们建议,在中文表述中将“代谢组学”一词和英文中的 metabonomics 相对应,以避免不必要的混淆和争议. 就细胞系统而言,不仅存在细胞自身的代谢物质组成问题,存在细胞之间代谢物质交换的问题,也存在代谢过程所发生的位点问题. 因此,简单地分析代谢物质的总组成 (即代谢组) 缺乏“整体论”所要求的全面性,其意义有一定局限. 代谢组学属于全局系统生物学 (Global systems biology) 研究方法,便于对复杂体系的整体进行认识. 譬如,一个正常工作的人体包括“人体”本身和与之共同进化而来且共生的消化道微生物群体 (或称菌群),孤立地研究“人体”本身的基因,转录子以及蛋白质当然可以为人们认识人体生物学提供重要信息,但无法提供使人体正常工作不可缺少的菌群的信息. 人体血液和尿液的代谢组却携带着包括菌群在内的每一个细胞的信息,因此代谢组学方法对研究如人体这样复杂的进化杂合体十分有效. 正因如此,代谢组学已经广泛地应用到了包括药物研发,分子生理学,分子病理学,基因功能组学,营养学,环境科学等重要领域. 在代谢组学诞生的过去 6 年里,有关代谢组学的研究论文和专利以指数的形式逐年增长. 可以预见,这门新兴学科将应用到更为广泛的领域.
基金supported in part by NIH/NIBIB grant EB011785,the Ministry of Science and Innovation(New Zealand),a seed grant from Wake Forest Institute for Regenerative Medicine
文摘Objective:To establish the prevalence and associated risk factors of Schistosoma mansoni(S.mansoni) infection among schoolchildren at a village in Wolaita Zone.Sothern Ethiopia,Methods:A cross-sectional study was carried out among primary schoolchildren.A total of 384 randomly selected study subjects provided stool samples for parasitological examination by Kato-Katz and Formalin-Ether concentration techniques.Secondary parasitological data were obtained from Health Center Laboratory to see the previous history of.S.mansoni infection in the area.Statistical analysis was performed using SPSS software version 16.Results:From the total children examined.85.4% were found positive for at least one helminth infection.S.mansoni infection(81.3% ) was the most prevalent and the prevalence of STH was 32% ..Moderate and heavy infection intensities were only observed in S,mansoni infections.The overall heavy intensity of infection was 56.4% .Contact to Bisarc stream was the most important factor for S.mansoni infection(OR 3.9) followed by herding cattle near the stream(OR2.527).Males were twice more likely to get the infection than females(OR 1.923).Analysis of secondary parasitological data showed that S.mansoni infection was a leading helminthic infection over the past years.Conclusions:The present study found a higher intensity and prevalence of S.mansoni infection in a rural village of Wolaita Zone.Therefore,appropriate integrated control and prevention measures need to be implemented in the study area.
文摘BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
文摘Clinicians can provide a means to better distribute the pressure around the foot, and can also correct the biomechanics of the foot by using a customized shoe insole. If detected early enough, orthopedic insoles can correct or prevent further complications. In this study the 3 Dimensional (D) model of the foot was used to fabricate a customized orthosis. The Computed Tomography (CT) images of patient’s foot having no muscle weakness and joint restriction were acquired. The gray intensities corresponding to the bones of the foot from the CT images were 3 dimensionally reconstructed. The 3D model of the foot was then imported into the CAD Software. Boolean operations were carried out in between the 3D foot model and a solid rectangular surface to create a customized foot orthosis. The exact contours and shape of the subject’s foot was acquired using the computerized method of fabricating an orthosis. The novel idea described in this study support, automating the process of designing a customized orthosis with the impression got from the 3 dimensionally modeled feet, thereby reducing the modeling time considerably. The simple technique used in this process will help in giving comfort and stability to the patient’s feet while walking.
基金supported by the Renewable Energy Technology Development (Develop technology to enhance reliability and durability for parts of hydrogen storage tank system) (2022303004020B) grant funded by the Korea Energy Technology Evaluation Planning (KETEP)the Ministry of Science and ICT (Development Project for Emerging Research Instruments Technology),(Project Number: (2022)ERIC)06_1Commercialization Promotion Agency for R&D Outcomes (COMPA)。
文摘Biodegradable metals as electrodes, interconnectors, and device conductors are essential components in the emergence of transient electronics, either for passive implants or active electronic devices, especially in the fields of biomedical electronics. Magnesium and its alloys are strong candidates for biodegradable and implantable conducting materials because of their high conductivity and biocompatibility, in addition to their well-understood dissolution behavior. One critical drawback of Mg and its alloys is their considerably high dissolution rates originating from their low anodic potential, which disturbs the compatibility to biomedical applications. Herein, we introduce a single-phase thin film of a Mg-Zn binary alloy formed by sputtering, which enhances the corrosion resistance of the device electrode, and verify its applicability in biodegradable electronics. The formation of a homogeneous solid solution of single-phase Mg-3Zn was confirmed through X-ray diffraction and transmission electron microscopy. In addition, the dissolution behavior and chemistry was also investigated in various biological fluids by considering the effect of different ion species. Micro-tensile tests showed that the Mg-3Zn alloy electrode exhibited an enhanced yield strain and elongation in relation to a pure Mg electrode. Cell viability test revealed the high biocompatibility rate of the Mg-3Zn binary alloy thin film. Finally, the fabrication of a wireless heater demonstrated the integrability of biodegradable electrodes and highlighted the ability to prolong the lifecycle of thermotherapy-relevant electronics by enhancing the dissolution resistance of the Mg alloy.
基金supported in part by grants of The Slovak Research and Development Agency under the contract No.APVV-14-0088ITMS 26220220187 and VEGA 1/0287/16
文摘Iron can contribute to the pathogenesis and progression of multiple sclerosis（MS） due to its accumulation in the human brain.We focus on the thalamus as an information transmitter between various subcortical and cortical areas.Thalamic iron seems to follow different rules than iron in other deep gray matter structures and its relation to the clinical outcomes of MS is still indistinct.In our study,we investigated a connection between thalamic iron and patients＇ disability and course of the disease.The presence of paramagnetic substances in the tissues was tracked by T2＊ quantification.Twenty-eight subjects with definite MS and 15 age-matched healthy controls underwent MRI examination with a focus on gradient echo sequence.We observed a non-monotonous course of T2＊ values with age in healthy controls.Furthermore,T2＊ distribution in MS patients was significantly wider than that of age matched healthy volunteers（P〈 0.001）.A strong significant correlation was demonstrated between T2＊ distribution spread and the expanded disability status scale（EDSS）（left thalamus：P〈0.00005;right thalamus：P〈0.005）,and multiple sclerosis severity scale（MSSS）（left thalamus：P〈0.05;right thalamus：P〈0.005）.The paramagnetic iron distribution in the thalamus in MS was not uniform and this inhomogeneity may be considered as an indicator of thalamic neurodegeneration in MS.
基金supported by the project "Establishment of Biomedical Informatics Center at RMRIRMS,Patan" by ICMR (Govt. of India),New Delhi
文摘EMR2 is an EGF-like module containing mucin-like hormone receptor-2 precursor, a G-protein coupled receptor （G-PCR）. Mutation in EMR2 causes complicated disorders like polycystic kidney disease （PKD）. The structure of EMR2 shows that the fifth domain is comprised of EGF-TM7 helices. Functional assignment of EMR2 by support vector machine （SVM） revealed that along with transporter activity, several novel functions are predicted. A twenty amino acid sequence ＂MGGRVFLVFLAFCVWLTLPG＂ acts as the signal peptide responsible for post- translational transport. Eight amino acids are involved in N-glycosylation sites and two cleavage sites are LeuS17 and SerS18 in EMR2. The residue Arg241 is responsible for interaction with glycosaminoglycan and chondroitin sulfate. On the basis of structure, function and ligand binding sites, competitive EMR2 inhibitors designed may decrease the rate of human diseases like Usher＇s syndrome, bilateral frontoparietal polymicrogyria and PKD.
文摘Purpose:The purpose of this study was to compare the coordination between the trunk and the pelvis during a sustained asymmetric repetitive lifting task between a group with a history of low back pain(LBP;HBP) and a group with no history of LBP(NBP).Methods:Volunteers lifted a 11-kg box from ankle height in front to a shelf 45° off-center at waist height,and lowered it to the start position at12 cycles/min for 10 min.Lifting side was alternated during the trial.Continuous relative phase was used to calculate coordination between the pelvis and trunk rotation at the beginning(Min 1),middle(Min 5),and end of the bout(Min 9).Results:While there were no main effects for group,a significant interaction between time and group indicated that,in the frontal plane,the NBP group coordination was more anti-phase toward the end of the bout,with no such differences for the HBP group.Analysis of sagittal-axial(bend and twist) coordination revealed the HBP group coordination was more in-phase at the end of the bout over the entire cycle and for the lifting phase alone,with no such differences for the NBP group.Conclusion:Differences between groups demonstrate residual consequences of LBP in an occupational scenario,even though the HBP group was pain-free for >6 months prior to data collection.More in-phase coordination in the HBP group may represent a coordination pattern analogous to'guarded gait' which has been observed in other studies,and may lend insight as to why these individuals are at increased risk for re-injury.
文摘1|INTRODUCTION Langya Henipavirus(LayV)is a zoonotic virus that has recently re‐emerged in Eastern China.There is limited data available on the global prevalence,mortality,and morbidity of LayV.The majority of cases have been reported in two provinces in China(Shandong and Henan).Between 2018 and 2022,35 individuals were diagnosed with the LayV infection in these regions.This novel ribonucleic acid virus attacks animals(including goats,dogs,and shrews)and can potentially spread to humans.The Henipavirus genus is a Paramyxoviridae family member that can be spread through animalhuman contact with no established human‐to‐human transmission yet[1].
基金supported by the KIST Institutional Program (Project No.2E32501-23-106)the KU-KIST Graduate School of Converging Science and Technology Program+3 种基金the National Research Foundation of Korea (NRF) grant funded by the Korean government (the Ministry of Science, ICT, MSIT) (RS-2022-00165524)the development of technologies for electroceuticals of the National Research Foundataion (NRF) funded by the Korean government (MSIT) (RS-2023-00220534)the Ministry of Science and ICT (MSIT), Korea, under the ICT Creative Consilience program (IITP-2023-2020-0-01819) supervised by the IITP (Institute for Information and Communications Technology Planning and Evaluation)Start up Pioneering in Research and Innovation(SPRINT) through the Commercialization Promotion Agency for R&D Outcomes(COMPA) grant funded by the Korea government(Ministry of Science and ICT) (1711198921)
文摘Substrates or encapsulants in soft and stretchable formats are key components for transient,bioresorbable electronic systems;however,elastomeric polymers with desired mechanical and biochemical properties are very limited compared to nontransient counterparts.Here,we introduce a bioresorbable elastomer,poly(glycolide-co-ε-caprolactone)(PGCL),that contains excellent material properties including high elongation-at-break(<1300%),resilience and toughness,and tunable dissolution behaviors.Exploitation of PGCLs as polymer matrices,in combination with conducing polymers,yields stretchable,conductive composites for degradable interconnects,sensors,and actuators,which can reliably function under external strains.Integration of device components with wireless modules demonstrates elastic,transient electronic suture system with on-demand drug delivery for rapid recovery of postsurgical wounds in soft,time-dynamic tissues.
文摘Due to typesetting mistake,Hanul Min was missed to be denoted as a corresponding author in the article.The type-setter apologizes for this.The original article has been corrected.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.
基金supported by a KIST project[2E32351,2E33122,2V09840-23-P023]the KU-KIST Graduate School of Converging Science and Technology Program+4 种基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)[grant number RS-2023-00302145]supported by the Bio-cluster Industry Capacity Enhance-ment Project of Jeonbuk Technopark(JBTP)supported by the Korea Medical Device Development Fund grant funded by the Korean government(the Ministry of Science and ICT,the Ministry of Trade,Industry and Energy,the Ministry of Health&Wel-fare,and the Ministry of Food and Drug Safety)(NTIS Number:9991007189)supported by the Ministry of Trade,Industry,and Energy(MOTIE)of Korea through project No.P0022331supervised by the Korea Institute for Advance-ment of Technology(KIAT).
文摘Medical stents are vital for treating vascular complications and restoring blood flow in millions of patients.Despite its widespread effectiveness,restenosis,driven by the complex interplay of cellular responses,remains a concern.This study investigated the reactions of vascular cells to nano/microscale wrinkle(nano-W and micro-W)patterns created on laser-textured nitinol(NiTi)surfaces by adjusting laser processing parameters,such as spot overlap ratio and line overlap ratio.Evaluation of topographical effects on endothelial and smooth muscle cells(SMCs)revealed diverse morphologies,proliferation rates,and gene expressions.Notably,microscale wrinkle patterns exhibited reduced monocyte adhesion and inflammation-related gene expression,demon-strating their potential applications in mitigating vascular complications after stent insertion.Additionally,an ex vivo metatarsal assay was utilized to bridge the gap between in vitro and in vivo studies,demonstrating enhanced angiogenesis on laser-textured NiTi surfaces.Laser-textured NiTi exhibits a guided formation process,empha-sizing their potential to promote swift endothelialization.These findings underscore the efficacy of laser texturing for tailored cellular interactions on metallic surfaces and offer valuable insights into optimizing biocompatibility and controlling cellular responses,which may pave the way for innovative advances in vascular care and contribute to the ongoing improvement of stent insertion.
基金supported by grants from the National Research Foundation(NRF)of Korea,funded by the Ministry of Science(RS-2025-02219039,RS-2025-02217286,RS-2024-00351420,RS-2024-00405287,RS-2024-00463774,and RS-2021-NR061836)the Intramural Research Program of KIST.
文摘Photodynamic therapy(PDT)induces tumor cell pyroptosis,a form of programmed cell death that triggers antitumor immunity.However,high glucose metabolism and hypoxic conditions in the tumor microenvironment(TME)limit PDT efficiency and impair effector cell function.Here,we propose a cancer metabolic reprogramming-enabling photoresponsive nanoproteolysis-targeting chimera(Nano-PROTAC;NanoTAC),derived from the supramolecular self-assembly of drug conjugates that bridge a PROTAC targeting hexokinaseⅡ(HK2)and a photosensitizer via a biomarker-cleavable linker.In a triple-negative breast cancer(TNBC)model,NanoTAC initially silences PROTAC activity and accumulates in tumor regions,where it undergoes linker cleavage in response to enzymatic biomarkers.Upon photoirradiation,PDT-induced pyroptotic cell death promotes the release of tumor-associated antigens(TAAs)and damage-associated molecular patterns(DAMPs)to drive the cancer-immunity cycle.Concurrently,targeted protein degradation(TPD)via PROTACs counteracts glucose and oxygen consumption in the TME,ultimately potentiating pyroptosis-mediated photoimmunotherapy.This combination therapy achieves a high rate of complete regression in primary TNBC and confers adaptive immunity to prevent metastasis and recurrence.Our study presents a rationally designed nanomedicine that integrates PDT and PROTACs,shedding light on strategies for more effective cancer immunotherapy.
基金supported by grants from the National Research Foundation(NRF)of Korea,funded by the Ministry of Science(RS-2025-02219039,RS-2021-NR061836,RS-202400343156,NRF-2022R1A2C2006861,RS-2024-00463774,RS2022-NR068161 and RS-2024-00405287)the Intramural Research Program of KIST.
文摘In light of the burgeoning successes of cancer immunotherapy,glioblastoma(GBM)remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity.Thus,identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge.Here we describe photodynamic protein tyrosine phosphatase 1B(PTP1B)proteolysis mediated by a proteolysis-targeting chimera(PROTAC)nanoassembly.The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B(Cat B)-cleavable peptide,which spontaneously forms nanoassemblies due to intermolecularπ-πstack-ing interactions.In GBM models,PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier(BBB),triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage.Upon laser irradiation,photodynamic therapy(PDT)synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death(ICD)in tumor cells.Subsequently,persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers,reinvigorating their function-ality.These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cellmediated antitumor immunity as well as protective immunity,completely eradicating the primary GBM and preventing its recurrence.Overall,our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.
基金supported by the Querrey Simpson Institute for Bioelectronics at Northwestern University.S.Y.acknowledges support from the National Research Foundation of Korea(NRF)grant(No.RS-2025-23525124)funded by the Korea government(MSIT)+4 种基金the BK21 FOUR program(Digital Anti-aging Convergence Research Group,Inje University)support from the National NaturalScience Foundation of China(12202241)support from the National Research Foundation of Korea(NRF)grant(Nos.RS-2022-NR072054 and RS-2020-NR049568)the Institute of Information&Communications Technology Planning&Evaluation(IITP)under the Graduate School of Artificial Intelligence Semiconductor(IITP-2025-RS-2023-00256472)grantfunded by the Korea government(MSIT),and the BK21 FOUR program(Connected AI Education&Research Program for Industry and Society Innovation,KAIST EE,No.4120200113769).
文摘Pressure ulcers remain a persistent challenge in healthcare,particularly for individuals with limited mobility or compromised sensation.Early detection is critical to prevent ischemic damage leading to necrosis,infections,and prolonged hospital stays.Conventional sensing technologies that integrate into the mattress,while effective in gathering data on pressure distributions,are restricted to stationary environments,and they can miss significant periods when patients leave their beds or shift positions.Furthermore,these systems do not offer consistent information on the specific spatial distribution of pressure across the body,because the sensors integrate with the mattress and not the body.Recent research establishes capabilities in soft,skin-interfaced wireless alternatives,but in designs that require specialized processes and materials that might not scale effectively for practical production and use.Here,we present a wireless,skin-integrated pressure monitoring system that mounts on the skin,in anatomically matched forms and with soft mechanical interfaces,for continuous data collection.This platform,built on manufacturable components and designs,features an array of soft,elastomer-encapsulated pressure sensors that minimize discomfort,with wireless communications and an independent power management system to enable operation across diverse healthcare settings,including homes,outpatient facilities,and operating rooms,all without physical tethers.Additionally,an external alarm satellite device delivers vibratory and visual alerts if predefined pressure thresholds are exceeded,guiding caregivers or patients to take timely action.Experimental and finite element analysis support the design principles,and deployments on patients in hospital settings illustrate modes for practical use.
基金funded by the National Institutes of Health(R01AR077132)AHA collaborative award(944227)+3 种基金the Gillian Reny Stepping Strong Center for Trauma Innovationpartially supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2021R1A6A3A14039720)supporting Jiseong Kim and Jieun Jeon by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Minstry of Health&Welfare,Republic of Korea(HI19C0757)partially funded by the Deanship of Scientific Research(DSR)at King Abdulaziz University,Jeddah,under Grant No.RG-22-135-39.
文摘In regenerative medicine,extracellular vesicles(EVs)possess the potential to repair injured cells by delivering modulatory factors.However,the therapeutic effect of EVs in large-scale tissue defects,which are subject to prolonged timelines for tissue architecture and functional restoration,remains poorly understood.In this study,we introduce EVs and cell-tethering hybrid hydrogels composed of tyramine-conjugated gelatin(GelTA)that can be in-situ crosslinked with EVs derived from human induced pluripotent stem cell-derived myofibers(hiPSC-myofibers)and hiPSC-muscle precursor cells.This hybrid hydrogel sustains the release of EVs and provides a beneficial nano-topography and mechanical properties for creating a favorable extracellular matrix.Secreted EVs from the hiPSC-myofibers contain specific microRNAs,potentially improving myogenesis and angiogenesis.Herein,we demonstrate increased myogenic markers and fusion/differentiation indexes through the combina-tory effects of EVs and integrin-mediated adhesions in the 3D matrix.Furthermore,we observe a unique impact of EVs,which aid in maintaining the viability and phenotype of myofibers under harsh environments.The hybrid hydrogel in-situ crosslinked with hiPSCs and EVs is facilely used to fabricate large-scale muscle constructs by the stacking of micro-patterned hydrogel domains.Later,we confirmed a combinational effect,whereby muscle tissue regeneration and functional restoration were improved,via an in vivo murine volumetric muscle loss model.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)[NRF-2021K1A3A1A74095929,RS-2023-00302145,NRF-2021R1A2C2092375]the KIST project[grant number 2E33151,2E33122]the KUKIST Graduate School of Converging Science and Technology Program.Figures were created using BioRender.com.
文摘The musculoskeletal system,which is vital for movement,support,and protection,can be impaired by disorders such as osteoporosis,osteoarthritis,and muscular dystrophy.This review focuses on the advances in tissue engineering and regenerative medicine,specifically aimed at alleviating these disorders.It explores the roles of cell therapy,particularly Mesenchymal Stem Cells(MSCs)and Adipose-Derived Stem Cells(ADSCs),biomaterials,and biomolecules/external stimulations in fostering bone and muscle regeneration.The current research underscores the potential of MSCs and ADSCs despite the persistent challenges of cell scarcity,inconsistent outcomes,and safety concerns.Moreover,integrating exogenous materials such as scaffolds and external stimuli like electrical stimulation and growth factors shows promise in enhancing musculoskeletal regeneration.This review emphasizes the need for comprehensive studies and adopting innovative techniques together to refine and advance these multi-therapeutic strategies,ultimately benefiting patients with musculoskeletal disorders.
文摘Source apportionment of particulate matter （PM10） measurements taken in Delhi, India between January 2013 and June 2014 was carried out using two receptor models, principal component analysis with absolute principal component scores （PCA/APCS） and UNMIX. The results were compared with previous estimates generated using the positive matrix factorization （PMF） receptor model to investigate each model＇s source-apportioning capability. All models used the PM10 chemical composition （organic carbon （OC）, elemental carbon （EC）, water soluble inorganic ions （WSIC）, and trace elements） for source apportionment. The average PM10 concentration during the study period was 249.7±103.9 μg/m3 （range： 61.4-584.8 μg/m3）. The UNMIX model resolved five sources （soil dust （SD）, vehicular emissions （VE）, secondary aerosols （SA）, a mixed source of biomass burning （BB） and sea salt （SS）, and industrial emissions （IE））. The PCA/APCS model also resolved five sources, two of which also included mixed sources （SD, VE, SD＋SS, （SA＋BB＋SS） and 1E）. The PMF analysis differentiated seven individual sources （SD, VE, SA, BB, SS, IE, and fossil fuel combustion （FFC））. All models identified the main sources contributing to PM10 emissions and reconfirmed that VE, SA, BB, and SD were the dominant contributors in Delhi.
