In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electros...In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electrospun Poly(lactic-co-glycolic acid)/Gelatin(PLGA/Gel)membrane incorporated with Vascular Endothelial Growth Fac-tor(VEGF)and hawthorn extract.Functionally,the DP supplies native Extracellular Matrix(ECM)components and mechanical support,while PANINPs provide conductivity.The electrospun PLGA/Gel layer mimics fibrous ECM.It incorporates bioactives,with VEGF promoting pro-angiogenic stimulation and hawthorn extract enhanc-ing anticoagulant activity,as well as increasing surface hydrophilicity.The tissue adhesive ensures the interfacial integrity between the two layers.Decellularization efficiency was confirmed histologically using 4',6-diamidino-2-phenylindole(DAPI)and Hematoxylin-Eosin(H&E)staining.The DP exhibited a DNA content of 115.9±47.8 ng/mg DNA,compared to 982.88±395.42 ng/mg in Native Pericardium(NP).The PANINPs had an average par-ticle size of 104.94±13.7 nm.The conductivity of PANINPs-coated decellularized pericardium was measured to be 9.093±8.6×10-4 S/cm using the four-point probe method.PLGA/Gel membranes containing hawthorn extract(1%,5%,10%,and 15%w/v)and VEGF(0.1μg/mL,0.5μg/mL,and 1μg/mL)were fabricated by electrospinning,result-ing in fiber diameters between 850 and 1200 nm and pore sizes between 14 and 20μm.The anticoagulant efficiency of the membranes containing hawthorn extract reached 430 s in the Activated Partial Thromboplastin Time Assay(aPTT).Mechanical testing revealed a tensile strength of 22.70±6.33 MPa,an elongation of 53.58±10.63%,and Young's modulus of 0.67±0.10 MPa.The scaffold also exhibited over 91%cell viability and excellent cardiomyo-cyte adhesion.The hemolysis ratio was determined to be 0.421±0.191%,which confirms its blood compatibility.Our results indicate that the proposed bilayered scaffold can be a promising candidate for cardiac patch applications.展开更多
Tubulin polymerization-promoting protein family member 3(TPPP3)is a neuronal-specific protein involved in cytoskeletal stability,axonal maintenance,and neuronal survival.Dysregulation of TPPP3 is implicated in neurode...Tubulin polymerization-promoting protein family member 3(TPPP3)is a neuronal-specific protein involved in cytoskeletal stability,axonal maintenance,and neuronal survival.Dysregulation of TPPP3 is implicated in neurodegenerative diseases such as Parkinson’s disease and diabetic retinopathy.Unlike TPPP1,which is oligodendrocyte-specific,TPPP3 was reported to primarily promote neuronal regeneration and serve as a therapeutic target for neurodegenerative diseases such as Parkinson’s disease and glaucoma.Beyond the nervous system,TPPP3 has been linked to oncogenesis and tissue regeneration,suggesting potential roles in tumor suppression and wound healing.This review summarizes neuronal functions of TPPP3,therapeutic opportunities,and future research directions.Understanding the molecular mechanisms underlying function of TPPP3 could provide valuable insights into its therapeutic applications in neuroprotection.展开更多
Shikonin,a naphthoquinone compound derived from the root of Lithospermum erythrorhizon,has been extensively studied for its antibacterial,antioxidant,and anti-inflammatory properties.Increasing evidence highlights its...Shikonin,a naphthoquinone compound derived from the root of Lithospermum erythrorhizon,has been extensively studied for its antibacterial,antioxidant,and anti-inflammatory properties.Increasing evidence highlights its potential in treating inflammation-related diseases.However,its clinical application is hindered by challenges such as poor water solubility,rapid metabolism in vivo,and other limitations.Recent advancements have demonstrated that encapsulating shikonin within nanocarriers can significantly enhance its water solubility and pharmacokinetic profile.Building on this,this perspective paper outlines the current landscape of inflammation treatment,explores the anti-inflammatory mechanisms of shikonin,reviews the latest progress in shikonin-based nanomaterials for anti-inflammatory applications,and discusses the challenges and future directions for the clinical translation of shikonin nanoformulations.展开更多
As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodelin...As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodeling after ischemia reperfusion(I/R)are well suited to a porcine model,but the evolution of that injury and its impact on electrical conductivity or arrhythmia threshold have been difficult to monitor continuously.Multiple electrode telemetry devices may be fitted to the animals but are costly and prone to damage.Implantable telemetry devices are likewise expensive,carry surgical risk,and are often verified only for single use.Here,we report the utilization of the commercially available Fourth Frontier X2 external telemetry device for continuous monitoring of heart rate and rhythm after myocardial I/R injury in pigs,highlighting sustained monitoring across a 7day study.展开更多
Genetic variations are risk factors for neonatal hyperbilirubinemia(NHB),a common cause of infant hospitalization in the first postnatal week,but their contribution and long-term impacts remain unclear.This population...Genetic variations are risk factors for neonatal hyperbilirubinemia(NHB),a common cause of infant hospitalization in the first postnatal week,but their contribution and long-term impacts remain unclear.This population-based multicenter study enrolls 1780 hospitalized NHB newborns and 38,158 genetically screened newborns across 20 hospitals(2019-2022).Excluding cases with clear clinical causes,977 NHB cases are categorized into genetic variation-positive and-negative groups.Results show significantly higher NHB-related gene variants(81.63%vs.65.62%)and positive variation rates(36.29%vs.9.4%)in NHB cases than in the general newborn population(all P<0.001).Among the 977 NHB cases,325(33.3%)have positive variants,with higher rates of severe hyperbilirubinemia(16.9%vs.9.7%,P=0.001),prolonged jaundice(36.3%vs.27.6%,P=0.005),and cholestasis/hypercholanaemia(23.7%vs.14.7%,P<0.001)in the positive group.Cumulative genetic variants in bilirubin metabolism pathways exhibit dosedependent associations with increased risks of complications.Long-term follow-up reveals that UGT1A1 variants prolong jaundice up to one month,while severe SLC10A1 variants cause persistent cholestasis/hypercholanaemia beyond nine months.This large-scale evidence highlights genetic factors as key NHB determinants,with implications for neonatal care protocols to integrate genetic testing and establish longterm surveillance for variant carriers.展开更多
Glioblastoma(GBM)is an aggressive brain tumor with limited treatment options and a dismal prognosis.While immunotherapy has shown promise in treating some solid tumors,the treatment of GBM has been mostly unsuccessful...Glioblastoma(GBM)is an aggressive brain tumor with limited treatment options and a dismal prognosis.While immunotherapy has shown promise in treating some solid tumors,the treatment of GBM has been mostly unsuccessful because of a lack of targetable tumor antigens and high tumor heterogeneity.Here,we report RCAN1-4 as a novel tumor antigen derived from alternative splicing induced by the transcription factor C/EBPβ.Both C/EBPβand RCAN1-4 are highly expressed in GBM and glioma stem cells as mesenchymal subtype hallmarks.We report an immunogenic HLA-A24-specific splicing junction epitope within exon 4 and exon 5 that is unique to RCAN1-4.This epitope was validated for its ability to stimulate T cell responses in HLA-A24^(+)donors and GBM patients,leading us to identify RCAN1-4-reactive T cell receptors(TCRs)for the construction of TCR-engineered T cells(TCR-T cells).Functional studies of TCR-Ts demonstrated the in vitro and in vivo killing of RCAN1-4pos GBM tumor cells,highlighting its potential as an immunotherapeutic target in mesenchymal GBM.展开更多
Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extre...Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.展开更多
Colorectal cancer(CRC)is the most prevalent cancer globally,and its traditional treatment modalities commonly encompass radiation therapy,chemotherapy,surgery and the administration of cytotoxic drugs.Currently,novel ...Colorectal cancer(CRC)is the most prevalent cancer globally,and its traditional treatment modalities commonly encompass radiation therapy,chemotherapy,surgery and the administration of cytotoxic drugs.Currently,novel chemotherapy drugs that combine traditional Chinese medicine(TCM)with herbal extracts exhibit superior comprehensive benefits.Herein,we delved into an article authored by Wang et al,focusing specifically on the pharmacological effects of"Herba Patriniae and Coix seed(HC)"and their targeted mechanisms in combating CRC.From the perspective of TCM philosophy,damp-heat stagnation and toxicity are the cardinal pathogenic factors underlying CRC.HC,renowned for their abilities to antipyretic and enhance diuresis,have demonstrated promising efficacy in preliminary studies for the treatment of CRC.These findings offer potential insights in favor of fostering anti-cancer medications.展开更多
The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical ...The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.展开更多
Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering.The advent of digital light processing(DLP)three-dimensional(3D)bioprinting technique has revolutionized the fabrication of complex ...Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering.The advent of digital light processing(DLP)three-dimensional(3D)bioprinting technique has revolutionized the fabrication of complex 3D structures.By adjusting light exposure,it becomes possible to control the mechanical properties of the structure,a critical factor in modulating cell activities.To better mimic cell densities in real tissues,recent progress has been made in achieving high-cell-density(HCD)printing with high resolution.However,regulating the stiffness in HCD constructs remains challenging.The large volume of cells greatly affects the light-based DLP bioprinting by causing light absorption,reflection,and scattering.Here,we introduce a neural network-based machine learning technique to predict the stiffness of cell-laden hydrogel scaffolds.Using comprehensive mechanical testing data from 3D bioprinted samples,the model was trained to deliver accurate predictions.To address the demand of working with precious and costly cell types,we employed various methods to ensure the generalizability of the model,even with limited datasets.We demonstrated a transfer learning method to achieve good performance for a precious cell type with a reduced amount of data.The chosen method outperformed many other machine learning techniques,offering a reliable and efficient solution for stiffness prediction in cell-laden scaffolds.This breakthrough paves the way for the next generation of precision bioprinting and more customized tissue engineering.展开更多
Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-bli...Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-blind,placebo-controlled trial was conducted at the Third Central Hospital of Tianjin,China from March to December 2023.A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days.Efficacy was assessed through measures such as the total melasma area,reduced melasma area,reduction rate of melasma area,melasma color score,Melasma Area and Severity Index(MASI)score,and traditional Chinese medicine(TCM)symptom score scale.Safety assessments included routine blood and biochemical tests.Results:Participants in both groups were aged 52-63 years,with no significant differences.After the 2-month intervention,the total melasma area decreased in both groups;however,a greater reduction was observed in the test group[462.50 mm^(2)(12.81%)vs.100.00 mm2(3.11%),P<.001].Moreover,LDBG treatment significantly reduced the MASI and melasma color scores in the test group(P<.05).The total TCM symptom evaluation score significantly decreased(test group:6.00 vs.placebo group:7.00,P=.001),with significant relief in symptoms such as improvement in dark lips,nails,and waist soreness in the test group,compared with that in the placebo group(P<.05).Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group(P<.05).Conclusion:LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.展开更多
In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B ...In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.展开更多
Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Hunting...Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and females.The higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with males.Since one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.展开更多
The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monit...The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16℃in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni⁃NTA affinity column.Size⁃exclusion chromatography and SDS⁃PAGE analysis demonstrated that the puri⁃fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD^(+)as a coenzyme to NADP^(+).The optimal temperature and pH of the TeXDH were 40℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26%of the initial enzyme activity,while the divalent metal ions Mg^(2+)or Ca^(2+)could recover the enzyme activity of TeXDH,reaching 103.32%and 110.69%of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn^(2+),Ni^(2+),Cu^(2+),Zn^(2+),Co^(2+),and Cd^(2+)significantly inhibited the activity of TeXDH.ICP⁃MS and molecular doc⁃king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn^(2+)ions and 1 mol/L Mg^(2+)ion.Further⁃more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.展开更多
Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the associat...Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the association between the alga toxinsβ-N-methylamino-L-alanine(BMAA),brevetoxin B,cyanoginosin LR,okadaic acid and neurodegenerative diseases remains inadequately investigated.Therefore,the aim of this study was to elucidate the potential associations.Four sets of differentially expressed genes related with BMAA,brevetoxin B,cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database.Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes,while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway,regulation of amyloid protein formation,inflammatory response and endoplasmic reticulum stress.Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed,revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways.The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases.These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.展开更多
Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge si...Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the bloodbrain barrier.In this study,an exosome-membrane(EM)and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain.Histidine/arginine-linked polyamidoamine(PHR)was used as a carrier.PHR binds to pDNA by electrostatic interaction.The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex.For glioblastoma targeting,T7 peptide was attached to the pDNA/PHR-EM complex.Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM(pDNA/PHREM-T7)had a surface charge of–5 mV and a size of 280 nm.Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHREM.Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo.pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM.As a result,the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups.Therefore,the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.展开更多
Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the bod...Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].展开更多
Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this e...Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.展开更多
In this study,injectable bone graft putty samples were developed using fine and coarse melt-quenched 45S5 bioactive glass(BG)incorporated into a carrier system composed of glycerol and polyethylene glycol(PEG)with dif...In this study,injectable bone graft putty samples were developed using fine and coarse melt-quenched 45S5 bioactive glass(BG)incorporated into a carrier system composed of glycerol and polyethylene glycol(PEG)with different average molecular weights.Selected putty samples were further incorporated with varying amounts of Denosumab(5wt%-10wt%)to investigate its influence on rhe-ological behavior and flow properties using mathematical modeling.All PEG/glycerol/45S5-based putty samples exhibited viscoelastic behavior(storage modulus>loss modulus)and pseudoplastic behavior(n<1),with viscosity values required for optimal flow remaining below 1000 Pa∙s.Both viscosity and thixotropic area increased proportionally with higher BG content and smaller-sized BG particles.All putty samples showed more than 98%injectability through a 12G cannula,suggesting potential clinical suitability.However,injectability decreased with smaller cannulas,dropping to 34.7%-58.3%with a 19G cannula and further decreasing with a 23G cannula at higher BG contents.Incorporation of Denosumab preserved viscoelasticity and injectability but modified the flow behavior,shifting it from pseudo-plastic to more Newtonian with higher Denosumab content,while also reducing viscosity and thixotropic area values.Among all tested samples,putty containing a lower amount of Denosumab and smaller-sized BG exhibited the most suitable combination of injectability and rheological features.All putty samples were well described by both the Power law and Herschel-Bulkley rheological models(coeffi-cient of determination>0.95).This study highlights the influence of Denosumab on flowability and rheological relationships and sug-gests potential improvements in bioactivity through a dual synergistic effect of BG and Denosumab in minimally invasive bone graft sys-tems.展开更多
Submarine pipelines are critical infrastructures for offshore energy transport and communications. Understanding their structural response to near-field explosions is crucial for enhancing their blast resistance and o...Submarine pipelines are critical infrastructures for offshore energy transport and communications. Understanding their structural response to near-field explosions is crucial for enhancing their blast resistance and operational safety. This study presents a computational study on the interaction between explosion-induced bubbles and a seabed-mounted pipeline. A recently developed computational framework is employed, which couples a compressible fluid solver with a finite element structural solver via a partitioned procedure. An embedded boundary method and a level-set method are employed to handle the fluid-structure and gas-liquid interfaces. Using this framework, we analyze the flow field evolution, bubble dynamics, and transient pipe deformation. Two distinct response modes are identified: periodic oscillation under low-pressure loading and downward collapse triggered by high-pressure loading and bubble jet impact. Specifically, under high-pressure conditions, the pipe initially deforms inward, generating a localized high-pressure zone within the concave region. During structural rebound, the trapped fluid is expelled upward, giving rise to a bubble jet. Further parametric studies on the pipe's internal pressure, wall thickness, and support angle reveal several key insights. A higher internal pressure delays structural collapse, and a greater pipe thickness results in more uniform implosion morphologies. The support angle strongly influences the collapse dynamics, with the shortest collapse time occurring at 60 °. These findings offer new insights for the protective design of submarine pipelines.展开更多
文摘In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electrospun Poly(lactic-co-glycolic acid)/Gelatin(PLGA/Gel)membrane incorporated with Vascular Endothelial Growth Fac-tor(VEGF)and hawthorn extract.Functionally,the DP supplies native Extracellular Matrix(ECM)components and mechanical support,while PANINPs provide conductivity.The electrospun PLGA/Gel layer mimics fibrous ECM.It incorporates bioactives,with VEGF promoting pro-angiogenic stimulation and hawthorn extract enhanc-ing anticoagulant activity,as well as increasing surface hydrophilicity.The tissue adhesive ensures the interfacial integrity between the two layers.Decellularization efficiency was confirmed histologically using 4',6-diamidino-2-phenylindole(DAPI)and Hematoxylin-Eosin(H&E)staining.The DP exhibited a DNA content of 115.9±47.8 ng/mg DNA,compared to 982.88±395.42 ng/mg in Native Pericardium(NP).The PANINPs had an average par-ticle size of 104.94±13.7 nm.The conductivity of PANINPs-coated decellularized pericardium was measured to be 9.093±8.6×10-4 S/cm using the four-point probe method.PLGA/Gel membranes containing hawthorn extract(1%,5%,10%,and 15%w/v)and VEGF(0.1μg/mL,0.5μg/mL,and 1μg/mL)were fabricated by electrospinning,result-ing in fiber diameters between 850 and 1200 nm and pore sizes between 14 and 20μm.The anticoagulant efficiency of the membranes containing hawthorn extract reached 430 s in the Activated Partial Thromboplastin Time Assay(aPTT).Mechanical testing revealed a tensile strength of 22.70±6.33 MPa,an elongation of 53.58±10.63%,and Young's modulus of 0.67±0.10 MPa.The scaffold also exhibited over 91%cell viability and excellent cardiomyo-cyte adhesion.The hemolysis ratio was determined to be 0.421±0.191%,which confirms its blood compatibility.Our results indicate that the proposed bilayered scaffold can be a promising candidate for cardiac patch applications.
基金supported by NIH Core Grants P30-EY008098,the Eye and Ear Foundation of Pittsburgh,and unrestricted grants from Research to Prevent Blindness,New York,NY,USA(to KCC).
文摘Tubulin polymerization-promoting protein family member 3(TPPP3)is a neuronal-specific protein involved in cytoskeletal stability,axonal maintenance,and neuronal survival.Dysregulation of TPPP3 is implicated in neurodegenerative diseases such as Parkinson’s disease and diabetic retinopathy.Unlike TPPP1,which is oligodendrocyte-specific,TPPP3 was reported to primarily promote neuronal regeneration and serve as a therapeutic target for neurodegenerative diseases such as Parkinson’s disease and glaucoma.Beyond the nervous system,TPPP3 has been linked to oncogenesis and tissue regeneration,suggesting potential roles in tumor suppression and wound healing.This review summarizes neuronal functions of TPPP3,therapeutic opportunities,and future research directions.Understanding the molecular mechanisms underlying function of TPPP3 could provide valuable insights into its therapeutic applications in neuroprotection.
基金supported by the National Natural Science Foundation of China(82373393),Xinjiang Uygur Autonomous Region“Tianchi Yingcai”Project(2023TCYCQNBS02)Xinjiang Uygur Autonomous Region Colleges and Universities Basic Research Operating Expenses Scientific Research Project(XJEDU2022P106).
文摘Shikonin,a naphthoquinone compound derived from the root of Lithospermum erythrorhizon,has been extensively studied for its antibacterial,antioxidant,and anti-inflammatory properties.Increasing evidence highlights its potential in treating inflammation-related diseases.However,its clinical application is hindered by challenges such as poor water solubility,rapid metabolism in vivo,and other limitations.Recent advancements have demonstrated that encapsulating shikonin within nanocarriers can significantly enhance its water solubility and pharmacokinetic profile.Building on this,this perspective paper outlines the current landscape of inflammation treatment,explores the anti-inflammatory mechanisms of shikonin,reviews the latest progress in shikonin-based nanomaterials for anti-inflammatory applications,and discusses the challenges and future directions for the clinical translation of shikonin nanoformulations.
基金College of Graduate Studies,Medical University of South Carolina,Grant/Award Number:SCTR 2305National Heart,Lung,and Blood Institute,Grant/Award Number:1U01HL169361-01NIH:NCATS,Grant/Award Number:UL1TR001450。
文摘As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodeling after ischemia reperfusion(I/R)are well suited to a porcine model,but the evolution of that injury and its impact on electrical conductivity or arrhythmia threshold have been difficult to monitor continuously.Multiple electrode telemetry devices may be fitted to the animals but are costly and prone to damage.Implantable telemetry devices are likewise expensive,carry surgical risk,and are often verified only for single use.Here,we report the utilization of the commercially available Fourth Frontier X2 external telemetry device for continuous monitoring of heart rate and rhythm after myocardial I/R injury in pigs,highlighting sustained monitoring across a 7day study.
基金supported by the Guangzhou Science and Technology Plan Project(2024B03J0191)to Hu Haothe Research Projects of the Sixth Affiliated Hospital,Sun Yat-sen University(No.2023-053 and No.2023-063)to Hu Hao.
文摘Genetic variations are risk factors for neonatal hyperbilirubinemia(NHB),a common cause of infant hospitalization in the first postnatal week,but their contribution and long-term impacts remain unclear.This population-based multicenter study enrolls 1780 hospitalized NHB newborns and 38,158 genetically screened newborns across 20 hospitals(2019-2022).Excluding cases with clear clinical causes,977 NHB cases are categorized into genetic variation-positive and-negative groups.Results show significantly higher NHB-related gene variants(81.63%vs.65.62%)and positive variation rates(36.29%vs.9.4%)in NHB cases than in the general newborn population(all P<0.001).Among the 977 NHB cases,325(33.3%)have positive variants,with higher rates of severe hyperbilirubinemia(16.9%vs.9.7%,P=0.001),prolonged jaundice(36.3%vs.27.6%,P=0.005),and cholestasis/hypercholanaemia(23.7%vs.14.7%,P<0.001)in the positive group.Cumulative genetic variants in bilirubin metabolism pathways exhibit dosedependent associations with increased risks of complications.Long-term follow-up reveals that UGT1A1 variants prolong jaundice up to one month,while severe SLC10A1 variants cause persistent cholestasis/hypercholanaemia beyond nine months.This large-scale evidence highlights genetic factors as key NHB determinants,with implications for neonatal care protocols to integrate genetic testing and establish longterm surveillance for variant carriers.
基金supported by the Botha-Chan Research Fund,the Office of the Assistant Secretary of Defense for Health Affairs through award no.HT9425-24-1-0623(I.R.)the Brain Tumor Funders'Collaborative,the Ellie Kavalieros DIPG Research Fund+6 种基金the UPMC Children’s Hospital of Pittsburgh Foundation(G.K.,I.R.)the Children’s Brain Tumor Network(I.F.P.),a stipend from the Central South University Xiangya School of Medicine and University of Pittsburgh(Z.X.)by grant NS117742 from the National Institute of Health(T.G.F.)support from the Jesse H.&Mary Jones Gibbs Endowed Chair(T.G.F)supported in part by the University of Pittsburgh Center for Research Computing,RRID:SCR_022735through NIH award number S10OD028483Work performed in the UPMC Hillman Cancer Center Tissue and Research Pathology Services Shared Resource Facility and the services and instruments used in this project were supported,in part,by the University of Pittsburgh and the NCI of the NIH under Award Number P30CA047904.
文摘Glioblastoma(GBM)is an aggressive brain tumor with limited treatment options and a dismal prognosis.While immunotherapy has shown promise in treating some solid tumors,the treatment of GBM has been mostly unsuccessful because of a lack of targetable tumor antigens and high tumor heterogeneity.Here,we report RCAN1-4 as a novel tumor antigen derived from alternative splicing induced by the transcription factor C/EBPβ.Both C/EBPβand RCAN1-4 are highly expressed in GBM and glioma stem cells as mesenchymal subtype hallmarks.We report an immunogenic HLA-A24-specific splicing junction epitope within exon 4 and exon 5 that is unique to RCAN1-4.This epitope was validated for its ability to stimulate T cell responses in HLA-A24^(+)donors and GBM patients,leading us to identify RCAN1-4-reactive T cell receptors(TCRs)for the construction of TCR-engineered T cells(TCR-T cells).Functional studies of TCR-Ts demonstrated the in vitro and in vivo killing of RCAN1-4pos GBM tumor cells,highlighting its potential as an immunotherapeutic target in mesenchymal GBM.
基金supported by the NIH grant(RO1 NS118066)the Blazer Foundation(to XJL)。
文摘Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.
基金National Natural Science Foundation of China,No.81970529The Natural Science Foundation of Jilin Province,No.20230508074RC and No.YDZJ202401218ZYTS.
文摘Colorectal cancer(CRC)is the most prevalent cancer globally,and its traditional treatment modalities commonly encompass radiation therapy,chemotherapy,surgery and the administration of cytotoxic drugs.Currently,novel chemotherapy drugs that combine traditional Chinese medicine(TCM)with herbal extracts exhibit superior comprehensive benefits.Herein,we delved into an article authored by Wang et al,focusing specifically on the pharmacological effects of"Herba Patriniae and Coix seed(HC)"and their targeted mechanisms in combating CRC.From the perspective of TCM philosophy,damp-heat stagnation and toxicity are the cardinal pathogenic factors underlying CRC.HC,renowned for their abilities to antipyretic and enhance diuresis,have demonstrated promising efficacy in preliminary studies for the treatment of CRC.These findings offer potential insights in favor of fostering anti-cancer medications.
基金support of the National Natural Science Foundation of China(Grant No.52205593)Shaanxi Natural Science Foundation Project(2024JC-YBMS-711).
文摘The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.
基金supported in part by the National Institutes of Health(Nos.R01HD112026 and R21ES034455)National Science Foundation(NSF,Nos.2135720 and 2223669)performed at San Diego Nanotechnology Infrastructure(SDNI)of UCSD,a member of the National Nanotechnology Coordinated Infrastructure(NNCI),which is supported by NSF(Grant No.ECCS-2025752).
文摘Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering.The advent of digital light processing(DLP)three-dimensional(3D)bioprinting technique has revolutionized the fabrication of complex 3D structures.By adjusting light exposure,it becomes possible to control the mechanical properties of the structure,a critical factor in modulating cell activities.To better mimic cell densities in real tissues,recent progress has been made in achieving high-cell-density(HCD)printing with high resolution.However,regulating the stiffness in HCD constructs remains challenging.The large volume of cells greatly affects the light-based DLP bioprinting by causing light absorption,reflection,and scattering.Here,we introduce a neural network-based machine learning technique to predict the stiffness of cell-laden hydrogel scaffolds.Using comprehensive mechanical testing data from 3D bioprinted samples,the model was trained to deliver accurate predictions.To address the demand of working with precious and costly cell types,we employed various methods to ensure the generalizability of the model,even with limited datasets.We demonstrated a transfer learning method to achieve good performance for a precious cell type with a reduced amount of data.The chosen method outperformed many other machine learning techniques,offering a reliable and efficient solution for stiffness prediction in cell-laden scaffolds.This breakthrough paves the way for the next generation of precision bioprinting and more customized tissue engineering.
基金funded by the National Key Research and Development Plan of the Traditional Chinese Medicine Modernization Research Key Project(2018YFC1706800).
文摘Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-blind,placebo-controlled trial was conducted at the Third Central Hospital of Tianjin,China from March to December 2023.A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days.Efficacy was assessed through measures such as the total melasma area,reduced melasma area,reduction rate of melasma area,melasma color score,Melasma Area and Severity Index(MASI)score,and traditional Chinese medicine(TCM)symptom score scale.Safety assessments included routine blood and biochemical tests.Results:Participants in both groups were aged 52-63 years,with no significant differences.After the 2-month intervention,the total melasma area decreased in both groups;however,a greater reduction was observed in the test group[462.50 mm^(2)(12.81%)vs.100.00 mm2(3.11%),P<.001].Moreover,LDBG treatment significantly reduced the MASI and melasma color scores in the test group(P<.05).The total TCM symptom evaluation score significantly decreased(test group:6.00 vs.placebo group:7.00,P=.001),with significant relief in symptoms such as improvement in dark lips,nails,and waist soreness in the test group,compared with that in the placebo group(P<.05).Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group(P<.05).Conclusion:LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.
基金Supported by the Natural Science Foundation of China,No.81970529the Natural Science Foundation of Jilin Province,No.20230508074RC and No.YDZJ202401218ZYTS.
文摘In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.
基金supported by NIH/NICHD RO1HD109157supported by his American Heart AssociationAward Career Development Award (932980)National Science Foundation CAREER award (NSF2401215)
文摘Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and females.The higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with males.Since one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.
基金湖南省教育厅基金优秀青年项目(No.22B0482)湖南科技大学博士启动基金(No.E51992 and E51993)资助。
文摘The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16℃in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni⁃NTA affinity column.Size⁃exclusion chromatography and SDS⁃PAGE analysis demonstrated that the puri⁃fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD^(+)as a coenzyme to NADP^(+).The optimal temperature and pH of the TeXDH were 40℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26%of the initial enzyme activity,while the divalent metal ions Mg^(2+)or Ca^(2+)could recover the enzyme activity of TeXDH,reaching 103.32%and 110.69%of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn^(2+),Ni^(2+),Cu^(2+),Zn^(2+),Co^(2+),and Cd^(2+)significantly inhibited the activity of TeXDH.ICP⁃MS and molecular doc⁃king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn^(2+)ions and 1 mol/L Mg^(2+)ion.Further⁃more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.
基金supported by the Natural Science Foundation of Shandong province(Nos.ZR2019MH048 and ZR2022QC149)the Double First-class Disciplines Construction Fund Project from Harbin Institute of Technology at Weihai(No.2023SYLHY18)Weihai Science and Technology Development Program。
文摘Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the association between the alga toxinsβ-N-methylamino-L-alanine(BMAA),brevetoxin B,cyanoginosin LR,okadaic acid and neurodegenerative diseases remains inadequately investigated.Therefore,the aim of this study was to elucidate the potential associations.Four sets of differentially expressed genes related with BMAA,brevetoxin B,cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database.Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes,while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway,regulation of amyloid protein formation,inflammatory response and endoplasmic reticulum stress.Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed,revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways.The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases.These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.
基金supported by the Individual Basic Science&Engineering Research Program(NRF-2022R1A2B5B01001920)through the National Research Foundation,funded by the Ministry of Science and ICT in Korea.
文摘Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the bloodbrain barrier.In this study,an exosome-membrane(EM)and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain.Histidine/arginine-linked polyamidoamine(PHR)was used as a carrier.PHR binds to pDNA by electrostatic interaction.The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex.For glioblastoma targeting,T7 peptide was attached to the pDNA/PHR-EM complex.Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM(pDNA/PHREM-T7)had a surface charge of–5 mV and a size of 280 nm.Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHREM.Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo.pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM.As a result,the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups.Therefore,the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.
基金supported by the Sichuan Science and Technology Program(2022NSFSC1936)Doctoral Scientific Research Start-up Foundation of China West Normal University(412984).
文摘Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].
基金support from Fonds de Recherche du Québec Santé(FRQS,grant no.281271)support from FRQS doctoral award #304367funding from CFI,Rheolution Inc.,and Investissement Québec.
文摘Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.
基金supported by Yildiz Technical University Scientific Research Projects Coordination Unit under project number FBA-2023-5377support from the Scientific and Technological Research Council of Turkey(TUBITAK)under the BIDEB/2211-A National PhD Scholarship Program and 2250-Performance-Based Scholarships Program for PhD.
文摘In this study,injectable bone graft putty samples were developed using fine and coarse melt-quenched 45S5 bioactive glass(BG)incorporated into a carrier system composed of glycerol and polyethylene glycol(PEG)with different average molecular weights.Selected putty samples were further incorporated with varying amounts of Denosumab(5wt%-10wt%)to investigate its influence on rhe-ological behavior and flow properties using mathematical modeling.All PEG/glycerol/45S5-based putty samples exhibited viscoelastic behavior(storage modulus>loss modulus)and pseudoplastic behavior(n<1),with viscosity values required for optimal flow remaining below 1000 Pa∙s.Both viscosity and thixotropic area increased proportionally with higher BG content and smaller-sized BG particles.All putty samples showed more than 98%injectability through a 12G cannula,suggesting potential clinical suitability.However,injectability decreased with smaller cannulas,dropping to 34.7%-58.3%with a 19G cannula and further decreasing with a 23G cannula at higher BG contents.Incorporation of Denosumab preserved viscoelasticity and injectability but modified the flow behavior,shifting it from pseudo-plastic to more Newtonian with higher Denosumab content,while also reducing viscosity and thixotropic area values.Among all tested samples,putty containing a lower amount of Denosumab and smaller-sized BG exhibited the most suitable combination of injectability and rheological features.All putty samples were well described by both the Power law and Herschel-Bulkley rheological models(coeffi-cient of determination>0.95).This study highlights the influence of Denosumab on flowability and rheological relationships and sug-gests potential improvements in bioactivity through a dual synergistic effect of BG and Denosumab in minimally invasive bone graft sys-tems.
基金supported by the National Key R&D Program of China(Grant No.2024YFC3013200)the Shenzhen Peacock Plan(Grant No.QD2023006C).
文摘Submarine pipelines are critical infrastructures for offshore energy transport and communications. Understanding their structural response to near-field explosions is crucial for enhancing their blast resistance and operational safety. This study presents a computational study on the interaction between explosion-induced bubbles and a seabed-mounted pipeline. A recently developed computational framework is employed, which couples a compressible fluid solver with a finite element structural solver via a partitioned procedure. An embedded boundary method and a level-set method are employed to handle the fluid-structure and gas-liquid interfaces. Using this framework, we analyze the flow field evolution, bubble dynamics, and transient pipe deformation. Two distinct response modes are identified: periodic oscillation under low-pressure loading and downward collapse triggered by high-pressure loading and bubble jet impact. Specifically, under high-pressure conditions, the pipe initially deforms inward, generating a localized high-pressure zone within the concave region. During structural rebound, the trapped fluid is expelled upward, giving rise to a bubble jet. Further parametric studies on the pipe's internal pressure, wall thickness, and support angle reveal several key insights. A higher internal pressure delays structural collapse, and a greater pipe thickness results in more uniform implosion morphologies. The support angle strongly influences the collapse dynamics, with the shortest collapse time occurring at 60 °. These findings offer new insights for the protective design of submarine pipelines.
