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Mechanical stretching of 3D hydrogels for neural stem cell differentiation

Bio-Design and Manufacturing 2022年第4期5卷 714-728页

作者： Quanjing Mei ho-yin yuen Xin Zhao Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHung HomHong KongChina

While it is known that mechanical dynamics are influential in neural differentiation for critical processes like neurogenesis or neurodegeneration, studies on neural stem cell therapies usually focus on biochemical interactions rather than mechanical aspects, frequently resulting in low efficacy and unfulfilled potential. Therefore, current studies are attempting to elucidate the effect of mechanical stimulus on neural performance using conventional two-dimensional(2D) planar substrates. Yet, these2D substrates fail to capture the defining three-dimensional(3D) characteristics of the in vivo neural stem cell *** complete this research gap, we synthesized a series of soft and elastic 3D hydrogels to mimic the neural tissue mechanical environment for 3D cell culture, using long-chain polyethylene glycol diacrylate(PEGDA) and gelatin-methacryloyl(Gel MA).By varying the concentration of the polymer, we obtained biomimicking hydrogels with a tensile modulus as low as 10 k Pa and a compressive modulus as low as 0.8 k Pa. The in vitro results demonstrated that Gel MA-PEGDA hydrogels have the high biocompatibility required to support neural cell growth, proliferation, and differentiation, as well as neurite outgrowth. We then studied the effect of mechanical stretching on the behaviors of neural cells and observed that mechanical stretching could significantly enhance neurite extension and axon elongation. In addition, the neurites were more directionally oriented to the stretching direction. Immunocytochemistry and relative gene expression data also suggested that mechanical tension could upregulate the expression of neural differentiation protein and genes, including GFAP and βIII-Tubulin. Overall, this study shows that in addition to the specific mechanical properties of Gel MA-PEGDA that improve neural differentiation towards specific lineages, hydrogel stretching is also a potentially attractive strategy to improve the therapeutic outcomes of neural stem cel

关键词： Mechanical property Tensile stretching Hydrogels Neural differentiation 3D cell culture

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Microcurvature landscapes induce neural stem cell polarity and enhance neural differentiation

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生物设计与制造(英文) 2023年第5期6卷 522-535页

作者： ho-yin yuen Wai-Sze Yip Suet To Xin Zhao Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHung HomKowloonHong Kong SARChina State Key Laboratory of Ultra-Precision Machining Technology Department of Industrial and Systems EngineeringThe Hong Kong Polytechnic UniversityHung HomKowloonHong Kong SARChina

Tissue curvature has long been recognized as an important anatomical parameter that affects intracellular behaviors,and there is emerging interest in applying cell-scale curvature as a designer property to drive cell fates for tissue engineering *** neural cells are known to undergo dramatic and terminal morphological changes during development and curvature-limiting behaviors have been demonstrated in neurite outgrowth studies,there are still crucial gaps in understanding neural cell behaviors,particularly in the context of a three-dimensional(3D)curvature landscape similar to an actual tissue engineering *** this study,we fabricated two substrates of microcurvature(curvature-substrates)that present a smooth and repeating landscape with focuses of either a concave or a convex *** these curvature-substrates,we studied the properties of morphological differentiation in N2a neuroblastoma *** contrast to other studies where two-dimensional(2D)curvature was demonstrated to limit neurite outgrowth,we found that both the concave and convex substrates acted as continuous and uniform mechanical protrusions that significantly enhanced neural polarity and differentiation with few morphological changes in the main cell *** enhanced differentiation was manifested in various properties,including increased neurite length,increased nuclear displacement,and upregulation of various neural *** demonstrating how the micron-scale curvature landscape induces neuronal polarity,we provide further insights into the design of biomaterials utilizing the influence of surface curvature in neural tissue engineering.

关键词： Curvature Neural differentiation Neurite outgrowth Mechanotransduction

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Going below and beyond the surface: Microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration

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Bioactive Materials 2023年第9期27卷 303-326页

作者： Shang Lyu Zhifei Dong Xiaoxiao Xu ho-Pan Bei ho-yin yuen Chung-Wai James Cheung Man-Sang Wong Yong He Xin Zhao Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHung HomHong Kong SARPR China Faculty of Science University of WaterlooWaterlooOntarioCanada State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhouPR China

Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Although microneedles are initially designed to penetrate stratum corneum of skin for transdermal drug delivery, they, recently, have been used to promote wound healing and regeneration of diverse tissues and organs and the results are promising. Despite there are reviews about microneedles, few of them focus on wound healing and tissue regeneration. Here, we review the recent advances of microneedles in this field. We first give an overview of microneedle system in terms of its potential cargos (e.g., small molecules, macromolecules, nucleic acids, nanoparticles, extracellular vesicle, cells), structural designs (e.g., multidrug structures, adhesive structures), material selection, and drug release mechanisms. Then we briefly summarize different microneedle fabrication methods, including their advantages and limitations. We finally summarize the recent progress of microneedle-assisted wound healing and tissue regeneration (e.g., skin, cardiac, bone, tendon, ocular, vascular, oral, hair, spinal cord, and uterine tissues). We expect that our article would serve as a guideline for readers to design their microneedle systems according to different applications, including material selection, drug selection, and structure design, for achieving better healing and regeneration efficacy.

关键词： Microneedles Microfabrication Wound healing Tissue regeneration Drug delivery

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Comparing 11 early warning scores and three shock indices in early sepsis prediction in the emergency department

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World Journal of Emergency Medicine 2024年第4期15卷 273-282页

作者： Rex Pui Kin Lam Zonglin Dai Eric ho yin Lau Carrie yuen Ting Ip ho Ching Chan Lingyun Zhao Tat ChiTsang Matthew Sik hon Tsui Timothy Hudson Rainer Department of Emergency Medicine School of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina School of Public Health Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina Accident and Emergency Department Queen Mary HospitalHong KongChina

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METhoDS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in hong *** primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED *** c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time ***:We analyzed 601 patients,of whom 166(27.6%)developed ***2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary ***,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),*** discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time ***:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

关键词： Sepsis Emergency department Clinical prediction rule Early warning score Shock index

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Characteristics of Emission Non-nulling Pulsars Through Simulation

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Research in Astronomy and Astrophysics 2024年第4期24卷 91-102页

作者： Rai yuen Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Xinjiang Key Laboratory of Radio Astrophysics Chinese Academy of SciencesUrumqi 830011China Key Laboratory of Radio Astronomy Chinese Academy of SciencesNanjing 210008China SIfA School of PhysicsUniversity of SydneySydneyNSW2006Australia

We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar *** from a pulsar is identified as non-nulling if(i)the emission does not cease across the whole pulse profile,and(ii)the emission is ***(i),we adopt a model for switching in the plasma charge density,and emission persists if the charge density is ***(ii),we assume that detectable emission originates from source points where it is emitted tangentially to the magnetic field-line and parallel to the *** find that pulsars exhibiting non-nulling emission possess obliquity angles with an average of 42°.5,and almost half the samples maintain a duty cycle between 0.05 and ***,the pulsar population is not fixed but dependent on the obliquity angle,with the population peaking at 20°.In addition,three evolutionary phases are identified in the pulsar population as the obliquity angle evolves,with the majority of samples having an obliquity angle between 20°and 65°.Our results also suggest that emission from a pulsar may evolve between nulling and non-nulling during its lifetime.

关键词： radiation mechanisms:non thermal stars:neutron (stars:)pulsars:general

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Prostate health index can stratify patients with Prostate Imaging Reporting and Data System score 3 lesions on magnetic resonance imaging to reduce prostate biopsies

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Asian Journal of Andrology 2024年第1期26卷 20-24页

作者： John Shung-Lai Leung Wai-Kit Ma Brian Sze-ho ho Stacia Tsun-Tsun Chun Rong Na Yongle Zhan Chi-yuen Ng Chi-ho Ip Ada Tsui-Lin Ng Yiu-Chung Lam Division of Urology Department of SurgeryQueen Mary HospitalUniversity of Hong KongHong KongChina Division of Urology Department of SurgeryPrincess Margaret HospitalHongKongChina

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance *** with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers(Queen Mary hospital and Princess Margaret hospital,hong Kong,China)between January 2017 and June 2022 were ***-magnetic resonance imaging fusion biopsies were performed after prostate health index *** who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were *** of the 747 patients,47.3%had Prostate Imaging Reporting and Data System score 3 lesions *** detection rate of clinically significant prostate cancer in this group was 15.0%.The cancer detection rates of clinically significant prostate cancer had statistically significant differences:5.3%in prostate health index<25.0,7.4%in prostate health index 25.0-34.9,17.9%in prostate health index 35.0-54.9,and 52.6%in prostate health index≥55.0(P<0.01).Among the patients,26.9%could have avoided a biopsy with a prostate health index<25.0,at the expense of a 5.3%risk of missing clinically significant prostate *** health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 *** could be avoided in patients with low prostate health index,with a small risk of missing clinically significant prostate cancer.

关键词： biopsy fusion biopsy magnetic resonance imaging prostate cancer prostate health index

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Asymptotics for the joint tail probability of bidimensional randomly weighted sums with applications to insurance

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Science China Mathematics 2024年第1期67卷 163-186页

作者： Yang Yang Shaoying Chen Kam Chuen yuen School of Statistics and Data Science Nanjing Audit UniversityNanjing 211815China Department of Statistics and Actuarial Science The University of Hong KongHong Kong 999077China

This paper studies the joint tail behavior of two randomly weighted sums∑_(i=1)^(m)Θ_(i)X_(i)and∑_(j=1)^(n)θ_(j)Y_(j)for some m,n∈N∪{∞},in which the primary random variables{X_(i);i∈N}and{Y_(i);i∈N},respectively,are real-valued,dependent and heavy-tailed,while the random weights{Θi,θi;i∈N}are nonnegative and arbitrarily dependent,but the three sequences{X_(i);i∈N},{Y_(i);i∈N}and{Θ_(i),θ_(i);i∈N}are mutually *** two types of weak dependence assumptions on the heavy-tailed primary random variables and some mild moment conditions on the random weights,we establish some(uniformly)asymptotic formulas for the joint tail probability of the two randomly weighted sums,expressing the insensitivity with respect to the underlying weak dependence *** applications,we consider both discrete-time and continuous-time insurance risk models,and obtain some asymptotic results for ruin probabilities.

关键词： asymptotic joint tail behavior randomly weighted sum heavy-tailed distribution dependence insurance risk model

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Performance in the Fundamentals of Laparoscopic Surgery: Does it reflect global rating scales in the Objective Structured Assessment of Technical Skills in porcine laparoscopic surgery?

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Asian Journal of Urology 2024年第3期11卷 443-449页

作者： ho Yee Tiong Wei Zheng So Jeremy yuen-Chun Teoh Shuji Isotani Gang Zhu Teng Aik Ong Eddie Shu-yin Chan Peggy Sau-Kwan Chu Kittinut Kijvikai Ming Liu Bannakji Lojanapiwat Michael Wong Anthony Chi-Fai Ng Yong Loo Lin School of Medicine Department of SurgeryNational University of SingaporeSingapore S.H.ho Urology Centre Department of SurgeryThe Chinese University of Hong KongHong KongChina Department of Urology Juntendo University Graduate School of MedicineTokyoJapan Department of Urology National University HospitalSingapore Department of Urology Beijing United Family HospitalBeijingChina Department of Surgery University of Malaya Specialist CentreKuala LumpurMalaysia Division of Urology Department of SurgeryTuen Mun HospitalHong Kong Department of Urology Ramathibodi HospitalMahidol UniversitySalayaThailand Department of Urology Beijing HospitalBeijingChina Department of Urology Chiangmai Ram HospitalChiang MaiThailand International Urology Fertility&Gynaecology CentreSingapore

Objective:To correlate the utility of the Fundamentals of Laparoscopic Surgery(FLS)manual skills program with the Objective Structured Assessment of Technical Skills(OSATS)global rating scale in evaluating operative ***:The Asian Urological Surgery Training and Educational Group(AUSTEG)Laparoscopic Upper Tract Surgery Course implemented and validated the FLS program for its usage in laparoscopic surgical ***’basic laparoscopic skills were assessed using three different training models(peg transfer,precision cutting,and intra-corporeal suturing).They also performed live porcine laparoscopic surgery at the same *** surgery skills were assessed by blinded faculty using the OSATS rating ***:From March 2016 to March 2019,a total of 81 certified urologists participated in the course,with a median of 5 years of post-residency *** differences in task time did not reach statistical significance,those with more surgical experience were visibly faster at completing the peg transfer and intra-corporeal suturing FLS ***,they took longer to complete the precision cutting task than participants with less *** OSATS scores correlated weakly with all three FLS tasks(peg transfer time:r=0.331,r^(2)=0.110;precision cutting time:r=0.240,r^(2)=0.058;suturing with intracorporeal knot time:r=0.451,r^(2)=0.203).Conclusion:FLS task parameters did not correlate strongly with OSATS globing rating scale *** FLS task models demonstrated strong validity,it is important to assimilate the inconsistencies when benchmarking technical proficiency against real-life operative competence,as evaluated by FLS and OSATS,respectively.

关键词： TheFundamentalsof Laparoscopic Surgery The Objective Structured Assessment of Technical Skills Laparoscopic training Surgical education Surgical training Urological laparoscopic surgery

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Targeting calcium signaling in Alzheimer’s disease: challenges and promising therapeutic avenues

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Neural Regeneration Research 2024年第3期19卷 501-502页

作者： LinLin Song YongPei Tang Betty yuen Kwan Law Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administration RegionChina

The critical role of calcium dyshomeostasis in the pathogenesis of Alzheimer’s disease(AD):AD is a progressive neurodegenerative disease characterized by cognitive decline,memory impairment,and behavioral *** an estimated 50 million people being affected worldwide,the incidence of AD is constantly increasing *** hallmark of AD is the accumulation of amyloid-beta protein(Aβ)in the form of amyloid plaques and hyperphosphorylated tau protein in the form of neurofibrillary ***,increasing evidence suggests that calcium ion(Ca2+)dysregulation also plays a crucial role in the pathogenesis of AD(Calvo-Rodriguez and Bacskai,2021).As a key second messenger,Ca2+regulates a wide range of cellular processes,including the release of neurotransmitters,gene expression,and cell ***^(2+)also regulates the activity of Calcium/calmodulin-dependent protein kinase II,which is critical for synaptic plasticity,learning,and memory(Kaushik et al.,2022).Alternation in the Ca^(2+)signal is an early event in the pathogenesis of AD,which can lead to synaptic dysfunction,neuronal loss,and cognitive impairment.

关键词： Alzheimer homeostasis globally

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A prospective cohort of men with localized prostate cancer on active surveillance protocol in hong Kong,China:what did we learn?

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Asian Journal of Andrology 2024年第3期26卷 245-249页

作者： Xiaobo Wu Ivan Ching-ho Ko Cindy Yeuk-Lam hong Samuel Chi-Hang Yee Jeremy yuen-Chun Teoh Samson Yun-Sang Chan ho-Man Tam Chi-Kwok Chan Chi-Fai Ng Peter Ka-Fung Chiu SH ho Urology Centre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong KongChina

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH ho Urology Centre,Prince of Wales hospital,hong Kong,*** investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease ***,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 *** study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated *** combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

关键词： active surveillance cohort localized prostate cancer

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