Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types,which need to precisely mediated for effective healing post-damage.The concept of osteoimmunology emphasizes the exte...Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types,which need to precisely mediated for effective healing post-damage.The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system.Despite the significant advancements in understanding osteoimmunology,the precise role of dendritic cells(DCs)in this field remains under investigation.As key antigen-presenting cells,DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis.Recent researches have further revealed the potential of DCs to influence the development or acceleration of inflammatory and autoimmune bone disease,as well as their interaction with skeletal cells in the context of bone repair and regeneration.展开更多
Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that pla...Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).展开更多
Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for sign...Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.展开更多
Immunotherapy,particularly immune checkpoint inhibitors(ICIs)programmed death-ligand 1/programmed death-1(PD-L1/PD-1)and cytotoxic T-lymphocyte-associated antigen-4(CTLA-4),has heralded a new era of tumor treatment.Al...Immunotherapy,particularly immune checkpoint inhibitors(ICIs)programmed death-ligand 1/programmed death-1(PD-L1/PD-1)and cytotoxic T-lymphocyte-associated antigen-4(CTLA-4),has heralded a new era of tumor treatment.Although ICIs have clinical benefits,their complex heterogeneity and diverse resistance mechanisms critically limit their efficacy.Neoantigens,arising from tumor-specific alterations,offer novel targets for individualized immunotherapy,because of their high immunogenicity and tumor specificity.In the past decade,neoantigen-based tumor vaccines have been demonstrated to be a promising immunotherapy strategy to prime the tumor-specific immune response.These therapeutic vaccines include peptide vaccines,nucleic acid vaccines,and dendritic cell(DC)vaccines,and are categorized according to the neoantigen source and delivery method.In vivo,neoantigens are processed and presented by antigen-presenting cells(APCs)via the peptide-Major Histocompatibility Complex(pMHC)for T cell recognition,thereby triggering specific immune responses.Because DCs,the most potent APCs,play crucial roles in antitumor immunity,neoantigen-based DC vaccines provide a promising therapeutic strategy.A series of global clinical trials are exploring the safety,feasibility,and efficacy of neoantigen-based DC vaccines in tumors.This review focuses on current progress in clinical research on neoantigen-based DC vaccines in the treatment of solid tumors.展开更多
Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglio...Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.展开更多
BACKGROUND Immunotherapy that employs dendritic cells(DCs)to activate the patient’s im-mune system has emerged as a promising therapeutic strategy to combat cancer;however,effective targeting agents are still limited...BACKGROUND Immunotherapy that employs dendritic cells(DCs)to activate the patient’s im-mune system has emerged as a promising therapeutic strategy to combat cancer;however,effective targeting agents are still limited.Ginsenoside F4,as a rare ginsenoside found in Panax ginseng,exhibits stronger antitumor and immunomo-dulatory activities than primary ginsenosides.However,its therapeutic effects on various diseases remain limited.AIM To investigate the antitumor effect of Ginsenoside F4 and mechanism on the maturation of DCs in colorectal cancer(CRC).METHODS The changes in mature DC markers and cytokines generated after DCs were exposed to F4 were assessed using flow cytometry and enzyme-linked immuno-sorbent assay,respectively.The viability of CRC CT26 cells co-cultured with T lymphocytes was monitored by cell counting kit-8 assay.Furthermore,the histopathological characteristics and immune cell infiltration in tumor tissues of CT26-bearing mice were analyzed by hematoxylin-eosin and immuno-fluorescent staining.The expressions of apoptosis-relative proteins were detected by western blot assay.RESULTS Treatment with F4 promoted the maturation of DCs,elevated the expressions of cluster of differentiation(CD)83 and CD86,increased the secretion of interleukin(IL)-2,IL-10,and IL-12 p70,and upregulated the expressions of phosphorylated phosphoinositide 3-kinase,phosphorylated protein kinase B,and nuclear factor kappa-B(NF-κB)phosphorylated p65 in DCs,which enhanced antigen-specific CD8+T-cell responses.However,these benefits could be reversed by the sphingosine-1-phosphate 1(S1PR1)inhibitor fingolimod hydrochloride.Furthermore,oral administration with F4 inhibited tumor growth and increased DC and CD8+T-cell infiltration in the tumor tissues of CT26-bearing mice.CONCLUSION The results demonstrated that F4 inhibited the growth of CRC by maturing DCs through activating S1PR1-mediated phosphoinositide 3-kinase/protein kinase B and NF-κB pathways,which triggered the antitumor effects of CD8+T cells.Therefore,F4 could serve as an antitumor immunomodulator for CRC treatment.展开更多
Boron adsorbents with high adsorption capacities have long been a focus of research for a long time.This study used small molecular polyols with different hydroxyl groups as functional monomers and as end-capping agen...Boron adsorbents with high adsorption capacities have long been a focus of research for a long time.This study used small molecular polyols with different hydroxyl groups as functional monomers and as end-capping agents,functional dendritic polyurethanes with nano structure were successfully prepared by one-pot method.The single molecule size and surface morphology were characterized by dynamic light scattering,transmission electron microscopy and scanning electron microscopy,and the molecular size in the dry state was 11 to 18 nm.The prepared materials were used as the boron adsorbents,and the effects of pH,time,boron solution concentration and temperature on the adsorption were studied.The results showed that the capacity of adsorbed boron could reach 110-130 mg·g^(-1).Adsorption was a homogeneous monolayer adsorption controlled by chemisorption,and adsorption thermodynamics showed that was a spontaneous endothermic process.Adsorption behavior was best described by the pseudo-second-order kinetic model and the Langmuir isotherm.This study also showed that it was difficult for ortho/meta-hydroxyl groups to chelate with H_(3)BO_(3) and other polyborates,and the chelates mainly had good chelating properties with B(OH)_(4)^(-),and the chelates formed had large steric hindrance.At the same time,increasing the number of hydroxyl groups of functional monomers was beneficial to increase the adsorption capacity of materials.In addition,the cyclic adsorption/desorption experiments showed that DPUs have good cyclic stability.At the same time,the adsorption results of the original salt lake brine showed that other metal ions in the brine had little effect on the adsorption of boron,and the adsorption capacity was as high as52.93 mg·g^(-1),and the maximum adsorption capacity was obtained by Adams-Bohart model to58.80 mg·g^(-1).The outstanding selectivity and adsorption capacity of these materials have broad potential application,and are expected to be used for the efficient adsorption and removal in boroncontaining water bodies.展开更多
Objectives:Professional antigen-presenting cells known as dendritic cells(DCs)assist as a connection between the innate and adaptive components of the immune response.DCs are attractive targets for immunomodulatory dr...Objectives:Professional antigen-presenting cells known as dendritic cells(DCs)assist as a connection between the innate and adaptive components of the immune response.DCs are attractive targets for immunomodulatory drugs because of their crucial function in triggering immunity.This study set out to examine,for the first time,how hibifolin affected mouse bone-marrow derived(BMDCs)dendritic cells,triggered by lipopolysaccharide(LPS)in vitro.Additionally,a mouse model of contact hypersensitivity(CHS)was used to assess its possible therapeutic effects in vivo.Methods:LPS was administered to BMDCs with or without hibifolin.Major Histocompatibility Complex(MHC)class II,cytokine production,and co-stimulatory molecule(CD80,CD86)expression levels were assessed.To evaluate the functional effects on T-cell activation,mixed lymphocyte responses using OVA specific T-cells were conducted.In vivo,immunoregulatory potential of hibifolin was examined using a CHS mouse model sensitized with 2,4-dinitrofluorobenzene(DNFB).Results:Hibifolin significantly reduced the expression of the proinflammatory cytokines TNF-αand IL-6,as well as the costimulatory molecules CD80,CD86,and MHC II induced by LPS,by about 40-50%.These effects were associated with reduced NF-κB and p38-MAPK pathway activity.JNK and ERK phosphorylation levels did not alter significantly.In vitro,BMDCs treated with hibifolin showed a 40%-45%down-regulated capacity to stimulate T-cell propagation and IFN-γrelease.Oral hibifolin treatment in vivo modestly decreased DNFB-induced CHS responses by 30%-40%.Conclusion:Overall,our results offer new insights that by inhibiting NF-κB and p38-MAPK signaling,hibifolin decreases the expression of costimulatory molecules and cytokines,thereby limiting BMDC activation,suppressing T-cell responses,and exerting immunomodulatory effects in the CHS mouse model.展开更多
AIM:To investigate the association between active corneal epithelial dendritic cells(CEDCs)and ocular pain in patients with dry eye disease(DED).METHODS:This cross-sectional study enrolled 67 DED patients,who were div...AIM:To investigate the association between active corneal epithelial dendritic cells(CEDCs)and ocular pain in patients with dry eye disease(DED).METHODS:This cross-sectional study enrolled 67 DED patients,who were divided into two groups based on numerical rating scale(NRS)scores:the mild pain group(n=44)and the moderate-to-severe pain group(n=23).In vivo confocal microscopy(IVCM)was used to image the subbasal layer of the central cornea.Corneal nerve characteristics were analyzed using ACCMetrics software,while CEDCs were quantified manually with Image J software.Regression and correlation analyses were performed to assess the impact of active CEDCs on ocular pain.Additionally,the Luminex method was employed to compare the concentrations of inflammation-related cytokines in tears between patients with≥2 CEDCs and those with<2 CEDCs.Differences in cytokine levels between the two groups were analyzed using Student’s t-test.RESULTS:The study included 44 eyes of 44 patients with mild ocular pain(12 males and 32 females)and 23 eyes of 23 patients with moderate-to-severe ocular pain(3 males and 20 females).The mean age was 36.2±13.5y in the mild pain group and 39.7±12.4y in the moderate to severe pain group.There were no significant differences in age or sex between the two groups(P=0.30;P=0.19).Multivariable regression analysis showed that older age[odds ratio(OR)=1.05,95%confidence interval(CI)1.00–1.11]and a higher number of CEDCs(OR=1.80,95%CI 1.17–2.76)were associated with ocular pain.Patients with≥2 CEDCs had significantly higher tear concentrations of interleukin(IL)-6(P<0.05),IL-8(P<0.05),and tumor necrosis factor(TNF)-α(P<0.05)compared to those with<2 active CEDCs.CONCLUSION:The findings suggest that infiltrating CEDCs in the corneal subbasal layer are a potential risk factor for ocular pain in DED.展开更多
Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate...Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.展开更多
Renewable 2,5-furandicarboxylic acid-based polyesters are one of the most promising materials for achieving plastic replacement in the age of energy and environmental crisis.However,their properties still cannot compe...Renewable 2,5-furandicarboxylic acid-based polyesters are one of the most promising materials for achieving plastic replacement in the age of energy and environmental crisis.However,their properties still cannot compete with those of petrochemical-based plastics,owing to insufficient molecular and/or microstructure designs.Herein,we utilize the Ti_(3)C_(2)T_(x)-based MXene nanosheets for decorating carbon nanotube(CNT)and obtaining the structurally stable and highly dispersed dendritic heterostructured MXene@CNT,that can act as multi-roles,i.e.,polycondensation catalyst,crystal nucleator,and interface enhancer of polyester.The biobased MXene@CNT/polybutylene furandicarboxylate(PBF)(denoted as MCP)nanocomposites are synthesized by the strategy of“in situ catalytic polymerization and hot-pressing”.Benefiting from the multi-scale interactions(i.e.,covalent bonds,hydrogen bonds,and physical interlocks)in hybrid structure,the MCP presents exceptional mechanical strength(≈101 MPa),stiffness(≈3.1 GPa),toughness(≈130 MJ m^(-3)),and barrier properties(e.g.,O_(2)0.0187 barrer,CO_(2)0.0264 barrer,and H2O 1.57×10^(-14) g cm cm^(-2) s Pa)that are higher than most reported bio-based materials and engineering plastics.Moreover,it also displays satisfactory multifunctionality with high reprocessability(90%strength retention after 5 recycling),UV resistance(blocking 85%UVA rays),and solvent-resistant properties.As a state-of-art high-performance and multifunctional material,the novel bio-based MCP nanocomposite offers a more sustainable alternative to petrochemical-based plastics in packaging and engineering material fields.More importantly,our catalysis-interfacial strengthening integration strategy opens a door for designing and constructing high-performance bio-based polyester materials in future.展开更多
The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent stud...The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent studies suggested that RORγt+antigen-presenting cells(APCs),which encompass rare dendritic cell(DC)subsets and type 3 innate lymphoid cells(ILC3s),are key to pTreg induction.Here,we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt.Single-cell RNA sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s.These mice showed a secondary reduction in pTregs,impaired tolerance to oral antigens,and an increase in T helper(Th)2 cells.Conversely,ILC3-deficient mice showed no pTregs or Th2 cell abnormalities.Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s,consistent with their similar phenotypic traits.These findings highlight the role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.展开更多
Naf1(Nef-associated factor 1)is a host protein that interacts with human immunodeficiency virus type 1(HIV-1)Nef protein.We and others have previously demonstrated that Naf1 restricts HIV-1 infection of T-lymphocytes....Naf1(Nef-associated factor 1)is a host protein that interacts with human immunodeficiency virus type 1(HIV-1)Nef protein.We and others have previously demonstrated that Naf1 restricts HIV-1 infection of T-lymphocytes.Myeloid cells are targets for HIV infection,but Naf1 expression in myeloid cells and whether it also regulates HIV infection in these cells are not yet identified.In this study,we found that Naf1 had a higher expression in CD14þmonocytes than in monocyte-derived dendritic cells(MDDCs),and its expression in both types of cells could be induced by HIV-1 gp120 glycoproteins or viral particles.Importantly,the expression of Naf1 restricted HIV-1 infection in monocytes and MDDCs.Functional investigation showed that both the constitutive and the induced expression of Naf1 inhibited NF-κB signaling in MDDCs and reduced the basal level or LPS(Lipopolysaccharide)-stimulated production of cytokines.Moreover,Naf1 reduced the expression of ICAM-1(intercellular cell adhesion molecule-1)on MDDCs and compromised their capacity to prime the activation of resting CD4^(+)T cells in co-culture.In light of the essential role of NF-κB signaling for HIV-1 transcription,Naf1-mediated inhibition of NF-κB signaling may hinder a robust viral replication in MDDCs and help maintain viral persistence.Furthermore,virus-induced Naf1 expression in MDDCs may diminish the cross-talk between DC(dendritic cell)and T cells,hence suppressing the activation of antiviral immune responses.Taken together,we identified the new function of Naf1 in myeloid cells.Those findings may facilitate the understanding for the host restriction of HIV-1 infection in myeloid cells.展开更多
Background:Dendritic cells(DCs)play a pivotal role in antigen presentation and regulating adaptive immune responses in asthma pathophysiology.However,the underlying molecular mechanisms remain incompletely understood....Background:Dendritic cells(DCs)play a pivotal role in antigen presentation and regulating adaptive immune responses in asthma pathophysiology.However,the underlying molecular mechanisms remain incompletely understood.Methods:Bioinformatics analysis of the GSE27011 dataset identified differentially expressed genes associated with pediatric asthma.An ovalbumin(OVA)-induced asthma mouse model and an Rfx5 knockdown model were established.RFX5 expression was assessed in DCs from patients with asthma and asthmatic mouse lung tissues using qRT-PCR,Western blotting,and immunohistochemistry.The regulatory effects of regulatory factor X5(RFX5)on histone deacetylase 2(HDAC2),class II major histocompatibility complex transactivator(CIITA),and major histocompatibility complex class II molecules(MHC II)expression,as well as its influence on lung tissue integrity,airway resistance,cytokine profiles,and immune cell infiltration,were analyzed.Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to explore the interaction between RFX5 and HDAC2.Results:During asthma progression,RFX5 expression was upregulated,while HDAC2 levels were reduced in DCs.Rfx5 knockdown significantly alleviated lung pathology and inflammation,decreased granulocyte and lymphocyte counts,and lowered levels of pro-inflammatory cytokines interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1β(IL-1β).In contrast,the expression of anti-inflammatory cytokines such as interleukin 4(IL-4),interleukin 10(IL-10),interleukin 18(IL-18),and prostaglandin E2(PGE2)was elevated,along with an increase in CIITA and MHC II gene transcription.Further analysis revealed a direct association between HDAC2 and the RFX5 promoter region.Conclusion:During asthma pathogenesis,allergens may upregulate RFX5 expression in DCs,enhancing its interaction with HDAC2,thereby alleviating the HDAC2-mediated effect.This process promotes the transcription of MHC II-associated genes and facilitates antigen presentation,ultimately driving asthma initiation and progression.This study elucidates the role of the RFX5/HDAC2 signaling pathway in the regulation of antigen presentation in pediatric asthma.展开更多
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th...Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.展开更多
Nickel-based single-crystal(SX)superalloys are the key metallic materials of aeroengines.However,thermomechanical deformation always occurs during the directional solidification of SX superalloys,negatively influencin...Nickel-based single-crystal(SX)superalloys are the key metallic materials of aeroengines.However,thermomechanical deformation always occurs during the directional solidification of SX superalloys,negatively influencing the SX structure.Casting deformation is simulated in most of the previous studies,whereas the direct simulation of dendritic thermomechanical deformation has been largely ignored,resulting in a lack of comprehensive understanding of this process.In this study,we systematically investigate dendritic thermomechanical deformation with a model coupled with dendrite growth,fluid flow,and thermomechanical deformation behavior.Results reveal that the dendritic thermomechanical deformation-induced dendrite bending is not randomly distributed but is mainly concentrated on the casting surface.The dendritic thermal stress increases as dendrite grows and accumulates after dendrite bridging.Transverse thermal contraction mainly occurs at the edge of casting in the corner,and axial thermal contraction is larger than transverse contraction.The high-stress region of the primary dendrite trunk is mainly distributed below the dendrite bridging near the solidified part,and the stress along the transverse direction reaches its maximum value on the casting surface.Stress concentrated on the casting surface is mainly attributed to variations in transverse temperature gradients caused by heat dissipation on the lateral mold wall,and inconsistent constraints in the lateral mold walls.展开更多
The liquid Zr_(100-x)V_(x)(x=8.6,16.5,30)alloys were undercooled to the maximum undercooling of 364 K(0.18 T_(L)),405 K(0.21 T_(L)),and 375 K(0.21 T_(L)),respectively,by using electrostatic levitation technique.The Zr...The liquid Zr_(100-x)V_(x)(x=8.6,16.5,30)alloys were undercooled to the maximum undercooling of 364 K(0.18 T_(L)),405 K(0.21 T_(L)),and 375 K(0.21 T_(L)),respectively,by using electrostatic levitation technique.The Zr_(91.4)V_(8.6) and Zr_(83.5)V_(16.5) alloys present only one recalescence during liquid/solid phase transition,while the Zr_(70)V_(30) alloy presents a transformation from two recalescence to one recalescence phenomenon with a critical undercooling of approximately 300 K.According to the LKT/BCT model,the calculated results of the primary β-Zr dendrite growth velocity in undercooled liquid Zr_(91.4)V_(8.6) and Zr_(83.5)V_(16.5) alloys agree well with the experiments.The velocity inflection points at 119 K of Zr_(91.4)V_(8.6) alloy and 201 K of Zr_(83.5)V_(16.5) alloy could be explained by the competition between solutal undercooling control and thermal undercooling control modes.For Zr_(70)V_(30) alloy solidified in the P1 with twice recalescence,a critical second undercooling of 253 K and corresponding undercooling of 65 and 244 K are obtained.When the un-dercooling is in the range of 65-244 K,the second undercooling would be greater than 253 K,and the residual liquid phase would solidify into anomalous eutectic microstructure for Zr_(70)V_(30) alloy.The Vickers hardness of Zr_(100-x)V_(x)(x=8.6,16.5,30)alloys all show a quadratic relationship with undercooling.Under electrostatic levitation condition,the mechanical property of Zr-V alloys could be significantly regulated through solidifying the alloys at different undercoolings.展开更多
The phase-field method is used to study the free dendritic crystal growth under forced convection with hypergravity,the hypergravity term is introduced into the liquid-phase momentum equation to examine the dendritic ...The phase-field method is used to study the free dendritic crystal growth under forced convection with hypergravity,the hypergravity term is introduced into the liquid-phase momentum equation to examine the dendritic growth.The paper focuses on the morphology of dendrite growth as well as the tip radius of the upstream dendritic arm and the average growth velocity of dendrite tips under different hypergravity levels.The results show that the morphology of dendrite changes significantly under represent simulation conditions when the hypergravity reaches 35_(g0),the upstream dendritic arm will bifurcate and the horizontal dendrite arms gradually tilt upwards.This change is mainly caused by the hypergravity and flow changing the temperature field near the dendrite interface.In addition,before the morphology of the dendrite is significantly altered,the radius of the tip of the dendrite upstream arm becomes larger with the increase in hypergravity,and the average growth velocity will increase linearly with it.The morphology of dendritic growth under different hypergravity and the changes in the tip radius along with the average growth velocity of the upstream dendritic tip with hypergravity are given in this paper.Finally,the reasons for these phenomena are analyzed.展开更多
BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and furthe...BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and further research on the underlying pathological mechanisms and appropriate treatments is needed.CASE SUMMARY This study describes a female IDCT patient with bile duct lesions.The strong mimicry of IDCT lesions confused doctors,and consequently,this patient,who had no skin lesions,was first diagnosed with cholangiocarcinoma.Then,she presented with persistent abdominal distension without jaundice.Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination.However,no tumor cells or pathogens were found in the three subsequent ascites analyses.It took 2 years to reach the correct diagnosis,which was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes.However,by then,she was already in a cachexic state.Finally,she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases.CONCLUSION For IDCT patients without skin lesions,early biopsy is the key to obtaining a correct diagnosis.Moreover,the collective management of IDCT patients is important.Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.展开更多
Head and neck cancer(HNC)is a prevalent malignant tumor that is aggressive and frequently resistant to treatment.Immunotherapy,a new approach for treating head and neck tumors,is primarily used in patients with recurr...Head and neck cancer(HNC)is a prevalent malignant tumor that is aggressive and frequently resistant to treatment.Immunotherapy,a new approach for treating head and neck tumors,is primarily used in patients with recurrent or metastatic cancer;however,some patients do not respond well to this treatment or experience significant side effects.Further research is needed to identify better treatment options for head and neck tumors.Dendritic cells(DCs)are pivotal components of the immune system and play a crucial role in initiating and regulating immune responses by presenting antigens to other immune cells.Nonetheless,DCs are frequently suppressed in the tumor immune microenvironment.Immunogenic cell death(ICD)is a form of regulated cell death capable of activating DCs by releasing damage-associated molecular patterns(DAMPs),thus potentially enhancing therapeutic efficacy against HNC.This review summarizes the evidence for the involvement of DCs in the anti-tumor immune response against HNC and their status within the tumor microenvironment.We also outline how DAMPs in ICD can activate DCs and discuss the prospects of ICD-based DC vaccine therapy,with the aim of providing new insights into immunotherapy of patients with HNC.展开更多
基金supported by the“Pioneer and Leading Goose+X”research and development program of Zhejiang Province Science and Technology Department(2024C03193)the National Natural Science Foundation of China(No.82271026)Start-up Fund of Stomatology Hospital,School of Stomatology,Zhejiang University School of Medicine(2023PDF017).
文摘Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types,which need to precisely mediated for effective healing post-damage.The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system.Despite the significant advancements in understanding osteoimmunology,the precise role of dendritic cells(DCs)in this field remains under investigation.As key antigen-presenting cells,DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis.Recent researches have further revealed the potential of DCs to influence the development or acceleration of inflammatory and autoimmune bone disease,as well as their interaction with skeletal cells in the context of bone repair and regeneration.
基金supported by AHA Career Development Award 938683 (to PJD)NIH grant R01MH123700 (to MLD)
文摘Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).
基金supported by the National Natural Science Foundation of China(NSFC/RGC/JRF N_HKU735/21)Research Grant Council of Hong Kong,China(17102120,17108821,17103922,C1024-22GF,C7074-21G)+1 种基金Health and Medical Research Fund(HMRF 09200966)(to CSWL)FRQS Postdoctoral Fellowship(to AHKF).
文摘Dendritic spines are small protrusions along dendrites that contain most of the excitatory synapses in principal neurons,playing a crucial role in neuronal function by creating a compartmentalized environment for signal transduction.The plasticity of spine morphologies provides a tunable handle to regulate calcium signal dynamics,allowing rapid regulation of protein expression necessary to establish and maintain synapses(Cornejo et al.,2022).If excitatory inputs were to be located primarily on dendritic shafts,dendrites would frequently short-circuit,preventing voltage signals from propagating(Cornejo et al.,2022).It is thus not surprising that the structural plasticity of dendritic spines is closely linked to synaptic plasticity and memory formation(Berry and Nedivi,2017).While comprehensive in vitro studies have been conducted,in vivo studies that directly tackle the mechanism of dendritic transport and translation in regulating spine plasticity spatiotemporally are limited.
文摘Immunotherapy,particularly immune checkpoint inhibitors(ICIs)programmed death-ligand 1/programmed death-1(PD-L1/PD-1)and cytotoxic T-lymphocyte-associated antigen-4(CTLA-4),has heralded a new era of tumor treatment.Although ICIs have clinical benefits,their complex heterogeneity and diverse resistance mechanisms critically limit their efficacy.Neoantigens,arising from tumor-specific alterations,offer novel targets for individualized immunotherapy,because of their high immunogenicity and tumor specificity.In the past decade,neoantigen-based tumor vaccines have been demonstrated to be a promising immunotherapy strategy to prime the tumor-specific immune response.These therapeutic vaccines include peptide vaccines,nucleic acid vaccines,and dendritic cell(DC)vaccines,and are categorized according to the neoantigen source and delivery method.In vivo,neoantigens are processed and presented by antigen-presenting cells(APCs)via the peptide-Major Histocompatibility Complex(pMHC)for T cell recognition,thereby triggering specific immune responses.Because DCs,the most potent APCs,play crucial roles in antitumor immunity,neoantigen-based DC vaccines provide a promising therapeutic strategy.A series of global clinical trials are exploring the safety,feasibility,and efficacy of neoantigen-based DC vaccines in tumors.This review focuses on current progress in clinical research on neoantigen-based DC vaccines in the treatment of solid tumors.
基金supported by the National Natural Science Foundation of China,No.82271115(to MY).
文摘Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.
基金Supported by the Science and Technology Project of the Zhejiang Province,No.2020Y.
文摘BACKGROUND Immunotherapy that employs dendritic cells(DCs)to activate the patient’s im-mune system has emerged as a promising therapeutic strategy to combat cancer;however,effective targeting agents are still limited.Ginsenoside F4,as a rare ginsenoside found in Panax ginseng,exhibits stronger antitumor and immunomo-dulatory activities than primary ginsenosides.However,its therapeutic effects on various diseases remain limited.AIM To investigate the antitumor effect of Ginsenoside F4 and mechanism on the maturation of DCs in colorectal cancer(CRC).METHODS The changes in mature DC markers and cytokines generated after DCs were exposed to F4 were assessed using flow cytometry and enzyme-linked immuno-sorbent assay,respectively.The viability of CRC CT26 cells co-cultured with T lymphocytes was monitored by cell counting kit-8 assay.Furthermore,the histopathological characteristics and immune cell infiltration in tumor tissues of CT26-bearing mice were analyzed by hematoxylin-eosin and immuno-fluorescent staining.The expressions of apoptosis-relative proteins were detected by western blot assay.RESULTS Treatment with F4 promoted the maturation of DCs,elevated the expressions of cluster of differentiation(CD)83 and CD86,increased the secretion of interleukin(IL)-2,IL-10,and IL-12 p70,and upregulated the expressions of phosphorylated phosphoinositide 3-kinase,phosphorylated protein kinase B,and nuclear factor kappa-B(NF-κB)phosphorylated p65 in DCs,which enhanced antigen-specific CD8+T-cell responses.However,these benefits could be reversed by the sphingosine-1-phosphate 1(S1PR1)inhibitor fingolimod hydrochloride.Furthermore,oral administration with F4 inhibited tumor growth and increased DC and CD8+T-cell infiltration in the tumor tissues of CT26-bearing mice.CONCLUSION The results demonstrated that F4 inhibited the growth of CRC by maturing DCs through activating S1PR1-mediated phosphoinositide 3-kinase/protein kinase B and NF-κB pathways,which triggered the antitumor effects of CD8+T cells.Therefore,F4 could serve as an antitumor immunomodulator for CRC treatment.
基金financially supported by Applied Basic Research Project of Qinghai province(2023-ZJ-774)。
文摘Boron adsorbents with high adsorption capacities have long been a focus of research for a long time.This study used small molecular polyols with different hydroxyl groups as functional monomers and as end-capping agents,functional dendritic polyurethanes with nano structure were successfully prepared by one-pot method.The single molecule size and surface morphology were characterized by dynamic light scattering,transmission electron microscopy and scanning electron microscopy,and the molecular size in the dry state was 11 to 18 nm.The prepared materials were used as the boron adsorbents,and the effects of pH,time,boron solution concentration and temperature on the adsorption were studied.The results showed that the capacity of adsorbed boron could reach 110-130 mg·g^(-1).Adsorption was a homogeneous monolayer adsorption controlled by chemisorption,and adsorption thermodynamics showed that was a spontaneous endothermic process.Adsorption behavior was best described by the pseudo-second-order kinetic model and the Langmuir isotherm.This study also showed that it was difficult for ortho/meta-hydroxyl groups to chelate with H_(3)BO_(3) and other polyborates,and the chelates mainly had good chelating properties with B(OH)_(4)^(-),and the chelates formed had large steric hindrance.At the same time,increasing the number of hydroxyl groups of functional monomers was beneficial to increase the adsorption capacity of materials.In addition,the cyclic adsorption/desorption experiments showed that DPUs have good cyclic stability.At the same time,the adsorption results of the original salt lake brine showed that other metal ions in the brine had little effect on the adsorption of boron,and the adsorption capacity was as high as52.93 mg·g^(-1),and the maximum adsorption capacity was obtained by Adams-Bohart model to58.80 mg·g^(-1).The outstanding selectivity and adsorption capacity of these materials have broad potential application,and are expected to be used for the efficient adsorption and removal in boroncontaining water bodies.
基金supported by the grant PTVH112-011 from Pingtung Veterans General Hospital.
文摘Objectives:Professional antigen-presenting cells known as dendritic cells(DCs)assist as a connection between the innate and adaptive components of the immune response.DCs are attractive targets for immunomodulatory drugs because of their crucial function in triggering immunity.This study set out to examine,for the first time,how hibifolin affected mouse bone-marrow derived(BMDCs)dendritic cells,triggered by lipopolysaccharide(LPS)in vitro.Additionally,a mouse model of contact hypersensitivity(CHS)was used to assess its possible therapeutic effects in vivo.Methods:LPS was administered to BMDCs with or without hibifolin.Major Histocompatibility Complex(MHC)class II,cytokine production,and co-stimulatory molecule(CD80,CD86)expression levels were assessed.To evaluate the functional effects on T-cell activation,mixed lymphocyte responses using OVA specific T-cells were conducted.In vivo,immunoregulatory potential of hibifolin was examined using a CHS mouse model sensitized with 2,4-dinitrofluorobenzene(DNFB).Results:Hibifolin significantly reduced the expression of the proinflammatory cytokines TNF-αand IL-6,as well as the costimulatory molecules CD80,CD86,and MHC II induced by LPS,by about 40-50%.These effects were associated with reduced NF-κB and p38-MAPK pathway activity.JNK and ERK phosphorylation levels did not alter significantly.In vitro,BMDCs treated with hibifolin showed a 40%-45%down-regulated capacity to stimulate T-cell propagation and IFN-γrelease.Oral hibifolin treatment in vivo modestly decreased DNFB-induced CHS responses by 30%-40%.Conclusion:Overall,our results offer new insights that by inhibiting NF-κB and p38-MAPK signaling,hibifolin decreases the expression of costimulatory molecules and cytokines,thereby limiting BMDC activation,suppressing T-cell responses,and exerting immunomodulatory effects in the CHS mouse model.
基金Supported by the National Natural Science Foundation of China(No.82171022No.81974128).
文摘AIM:To investigate the association between active corneal epithelial dendritic cells(CEDCs)and ocular pain in patients with dry eye disease(DED).METHODS:This cross-sectional study enrolled 67 DED patients,who were divided into two groups based on numerical rating scale(NRS)scores:the mild pain group(n=44)and the moderate-to-severe pain group(n=23).In vivo confocal microscopy(IVCM)was used to image the subbasal layer of the central cornea.Corneal nerve characteristics were analyzed using ACCMetrics software,while CEDCs were quantified manually with Image J software.Regression and correlation analyses were performed to assess the impact of active CEDCs on ocular pain.Additionally,the Luminex method was employed to compare the concentrations of inflammation-related cytokines in tears between patients with≥2 CEDCs and those with<2 CEDCs.Differences in cytokine levels between the two groups were analyzed using Student’s t-test.RESULTS:The study included 44 eyes of 44 patients with mild ocular pain(12 males and 32 females)and 23 eyes of 23 patients with moderate-to-severe ocular pain(3 males and 20 females).The mean age was 36.2±13.5y in the mild pain group and 39.7±12.4y in the moderate to severe pain group.There were no significant differences in age or sex between the two groups(P=0.30;P=0.19).Multivariable regression analysis showed that older age[odds ratio(OR)=1.05,95%confidence interval(CI)1.00–1.11]and a higher number of CEDCs(OR=1.80,95%CI 1.17–2.76)were associated with ocular pain.Patients with≥2 CEDCs had significantly higher tear concentrations of interleukin(IL)-6(P<0.05),IL-8(P<0.05),and tumor necrosis factor(TNF)-α(P<0.05)compared to those with<2 active CEDCs.CONCLUSION:The findings suggest that infiltrating CEDCs in the corneal subbasal layer are a potential risk factor for ocular pain in DED.
基金supported by the Natural Science Foundation of China(32394032,82201699,and 82221001)the Natural Science Foundation of Zhejiang Province(LTGD24H250001)+1 种基金the Kay R&D Program of Shaanxi Province(2023-YBSF-093),the Young Talent Fund of University Association for Science and Technology in Shaanxi(20220306)the Joint Founding Project of Innovation Research Institute,Xijing Hospital(LHJJ24JH02).
文摘Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
基金financial supports from the National Natural Science Foundation of China(Grant No.NSFC52473104)National Key R&D Program of China(Grant No.2022YFC2104500)+3 种基金Zhejiang Provincial Natural Science Foundation of China(Grant No.Y24B040002)Ningbo 2025 Key Scientific Research Programs(Grant No.2022Z160)the China Postdoctoral Science Foundation(Grant No.2023M733601)the Ningbo Natural Science Foundation(Grant No.2023I333&2023J409).
文摘Renewable 2,5-furandicarboxylic acid-based polyesters are one of the most promising materials for achieving plastic replacement in the age of energy and environmental crisis.However,their properties still cannot compete with those of petrochemical-based plastics,owing to insufficient molecular and/or microstructure designs.Herein,we utilize the Ti_(3)C_(2)T_(x)-based MXene nanosheets for decorating carbon nanotube(CNT)and obtaining the structurally stable and highly dispersed dendritic heterostructured MXene@CNT,that can act as multi-roles,i.e.,polycondensation catalyst,crystal nucleator,and interface enhancer of polyester.The biobased MXene@CNT/polybutylene furandicarboxylate(PBF)(denoted as MCP)nanocomposites are synthesized by the strategy of“in situ catalytic polymerization and hot-pressing”.Benefiting from the multi-scale interactions(i.e.,covalent bonds,hydrogen bonds,and physical interlocks)in hybrid structure,the MCP presents exceptional mechanical strength(≈101 MPa),stiffness(≈3.1 GPa),toughness(≈130 MJ m^(-3)),and barrier properties(e.g.,O_(2)0.0187 barrer,CO_(2)0.0264 barrer,and H2O 1.57×10^(-14) g cm cm^(-2) s Pa)that are higher than most reported bio-based materials and engineering plastics.Moreover,it also displays satisfactory multifunctionality with high reprocessability(90%strength retention after 5 recycling),UV resistance(blocking 85%UVA rays),and solvent-resistant properties.As a state-of-art high-performance and multifunctional material,the novel bio-based MCP nanocomposite offers a more sustainable alternative to petrochemical-based plastics in packaging and engineering material fields.More importantly,our catalysis-interfacial strengthening integration strategy opens a door for designing and constructing high-performance bio-based polyester materials in future.
文摘The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent studies suggested that RORγt+antigen-presenting cells(APCs),which encompass rare dendritic cell(DC)subsets and type 3 innate lymphoid cells(ILC3s),are key to pTreg induction.Here,we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt.Single-cell RNA sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s.These mice showed a secondary reduction in pTregs,impaired tolerance to oral antigens,and an increase in T helper(Th)2 cells.Conversely,ILC3-deficient mice showed no pTregs or Th2 cell abnormalities.Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s,consistent with their similar phenotypic traits.These findings highlight the role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.
基金supported by the National Natural Science Foundation of China(82172242)the Natural Science Foundation of Guangdong(2022A1515012053)the projects from Guangzhou Municipal Science and Technology Bureau(2023A04J1075).
文摘Naf1(Nef-associated factor 1)is a host protein that interacts with human immunodeficiency virus type 1(HIV-1)Nef protein.We and others have previously demonstrated that Naf1 restricts HIV-1 infection of T-lymphocytes.Myeloid cells are targets for HIV infection,but Naf1 expression in myeloid cells and whether it also regulates HIV infection in these cells are not yet identified.In this study,we found that Naf1 had a higher expression in CD14þmonocytes than in monocyte-derived dendritic cells(MDDCs),and its expression in both types of cells could be induced by HIV-1 gp120 glycoproteins or viral particles.Importantly,the expression of Naf1 restricted HIV-1 infection in monocytes and MDDCs.Functional investigation showed that both the constitutive and the induced expression of Naf1 inhibited NF-κB signaling in MDDCs and reduced the basal level or LPS(Lipopolysaccharide)-stimulated production of cytokines.Moreover,Naf1 reduced the expression of ICAM-1(intercellular cell adhesion molecule-1)on MDDCs and compromised their capacity to prime the activation of resting CD4^(+)T cells in co-culture.In light of the essential role of NF-κB signaling for HIV-1 transcription,Naf1-mediated inhibition of NF-κB signaling may hinder a robust viral replication in MDDCs and help maintain viral persistence.Furthermore,virus-induced Naf1 expression in MDDCs may diminish the cross-talk between DC(dendritic cell)and T cells,hence suppressing the activation of antiviral immune responses.Taken together,we identified the new function of Naf1 in myeloid cells.Those findings may facilitate the understanding for the host restriction of HIV-1 infection in myeloid cells.
基金supported by the 2021 Jiangxi Provincial Department of Science and Technology Applied Research Cultivation Plan Project(No.20212BAG70005,Yahui Wu)2021 Science and Technology Special Project and Social Development Project in Ji’an City,Jiangxi Province(No.20211-025242,Yahui Wu).
文摘Background:Dendritic cells(DCs)play a pivotal role in antigen presentation and regulating adaptive immune responses in asthma pathophysiology.However,the underlying molecular mechanisms remain incompletely understood.Methods:Bioinformatics analysis of the GSE27011 dataset identified differentially expressed genes associated with pediatric asthma.An ovalbumin(OVA)-induced asthma mouse model and an Rfx5 knockdown model were established.RFX5 expression was assessed in DCs from patients with asthma and asthmatic mouse lung tissues using qRT-PCR,Western blotting,and immunohistochemistry.The regulatory effects of regulatory factor X5(RFX5)on histone deacetylase 2(HDAC2),class II major histocompatibility complex transactivator(CIITA),and major histocompatibility complex class II molecules(MHC II)expression,as well as its influence on lung tissue integrity,airway resistance,cytokine profiles,and immune cell infiltration,were analyzed.Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to explore the interaction between RFX5 and HDAC2.Results:During asthma progression,RFX5 expression was upregulated,while HDAC2 levels were reduced in DCs.Rfx5 knockdown significantly alleviated lung pathology and inflammation,decreased granulocyte and lymphocyte counts,and lowered levels of pro-inflammatory cytokines interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1β(IL-1β).In contrast,the expression of anti-inflammatory cytokines such as interleukin 4(IL-4),interleukin 10(IL-10),interleukin 18(IL-18),and prostaglandin E2(PGE2)was elevated,along with an increase in CIITA and MHC II gene transcription.Further analysis revealed a direct association between HDAC2 and the RFX5 promoter region.Conclusion:During asthma pathogenesis,allergens may upregulate RFX5 expression in DCs,enhancing its interaction with HDAC2,thereby alleviating the HDAC2-mediated effect.This process promotes the transcription of MHC II-associated genes and facilitates antigen presentation,ultimately driving asthma initiation and progression.This study elucidates the role of the RFX5/HDAC2 signaling pathway in the regulation of antigen presentation in pediatric asthma.
基金supported by the National Key Research and Development Program of China,No.2021ZD0202503(to AHT)the National Natural Science Foundation of China,Nos.31872759(to AHT)and 32070707(to CF)+1 种基金Shenzhen Science and Technology Program,No.RCJC20210609104333007(to ZW)Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Fundamental Research Institutions,No.2021SHIBS0002(to ZW).
文摘Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
基金financially sponsored by the National Natural Science Foundation of China(Nos.U2441268 and 52304406)the Natural Science Foundation of Shanghai,China(No.23TS1401900)+2 种基金the Science Foundation of Aeronautics(PSSFA),China(No.2024Z053057002)the Science and Technology Cooperation Program of Shanghai Jiao Tong University in Inner Mongolia Autonomous Region-Action Plan of Shanghai Jiao Tong University for“Revitalizing Inner Mongolia through Science and Technology”,ChinaLuwei Yang would like to thank the financial support from the Chinese Scholarship Council(No.202306230337).
文摘Nickel-based single-crystal(SX)superalloys are the key metallic materials of aeroengines.However,thermomechanical deformation always occurs during the directional solidification of SX superalloys,negatively influencing the SX structure.Casting deformation is simulated in most of the previous studies,whereas the direct simulation of dendritic thermomechanical deformation has been largely ignored,resulting in a lack of comprehensive understanding of this process.In this study,we systematically investigate dendritic thermomechanical deformation with a model coupled with dendrite growth,fluid flow,and thermomechanical deformation behavior.Results reveal that the dendritic thermomechanical deformation-induced dendrite bending is not randomly distributed but is mainly concentrated on the casting surface.The dendritic thermal stress increases as dendrite grows and accumulates after dendrite bridging.Transverse thermal contraction mainly occurs at the edge of casting in the corner,and axial thermal contraction is larger than transverse contraction.The high-stress region of the primary dendrite trunk is mainly distributed below the dendrite bridging near the solidified part,and the stress along the transverse direction reaches its maximum value on the casting surface.Stress concentrated on the casting surface is mainly attributed to variations in transverse temperature gradients caused by heat dissipation on the lateral mold wall,and inconsistent constraints in the lateral mold walls.
基金supported by the National Natural Science Foundation of China(Grant No.52088101)the Space Utilization System of China Manned Space Engineering(Grant No.KJZ-YY-NCL02)+1 种基金the National Key R&D Program of China(Grant No.2021YFA0716301)the Shannxi Key Science and Technology Program(Grant Nos.2023-ZDLGY-36,2024JC-ZDXM-24).
文摘The liquid Zr_(100-x)V_(x)(x=8.6,16.5,30)alloys were undercooled to the maximum undercooling of 364 K(0.18 T_(L)),405 K(0.21 T_(L)),and 375 K(0.21 T_(L)),respectively,by using electrostatic levitation technique.The Zr_(91.4)V_(8.6) and Zr_(83.5)V_(16.5) alloys present only one recalescence during liquid/solid phase transition,while the Zr_(70)V_(30) alloy presents a transformation from two recalescence to one recalescence phenomenon with a critical undercooling of approximately 300 K.According to the LKT/BCT model,the calculated results of the primary β-Zr dendrite growth velocity in undercooled liquid Zr_(91.4)V_(8.6) and Zr_(83.5)V_(16.5) alloys agree well with the experiments.The velocity inflection points at 119 K of Zr_(91.4)V_(8.6) alloy and 201 K of Zr_(83.5)V_(16.5) alloy could be explained by the competition between solutal undercooling control and thermal undercooling control modes.For Zr_(70)V_(30) alloy solidified in the P1 with twice recalescence,a critical second undercooling of 253 K and corresponding undercooling of 65 and 244 K are obtained.When the un-dercooling is in the range of 65-244 K,the second undercooling would be greater than 253 K,and the residual liquid phase would solidify into anomalous eutectic microstructure for Zr_(70)V_(30) alloy.The Vickers hardness of Zr_(100-x)V_(x)(x=8.6,16.5,30)alloys all show a quadratic relationship with undercooling.Under electrostatic levitation condition,the mechanical property of Zr-V alloys could be significantly regulated through solidifying the alloys at different undercoolings.
基金supported by the National Natural Science Foundation of China(Grant No.52588202)。
文摘The phase-field method is used to study the free dendritic crystal growth under forced convection with hypergravity,the hypergravity term is introduced into the liquid-phase momentum equation to examine the dendritic growth.The paper focuses on the morphology of dendrite growth as well as the tip radius of the upstream dendritic arm and the average growth velocity of dendrite tips under different hypergravity levels.The results show that the morphology of dendrite changes significantly under represent simulation conditions when the hypergravity reaches 35_(g0),the upstream dendritic arm will bifurcate and the horizontal dendrite arms gradually tilt upwards.This change is mainly caused by the hypergravity and flow changing the temperature field near the dendrite interface.In addition,before the morphology of the dendrite is significantly altered,the radius of the tip of the dendrite upstream arm becomes larger with the increase in hypergravity,and the average growth velocity will increase linearly with it.The morphology of dendritic growth under different hypergravity and the changes in the tip radius along with the average growth velocity of the upstream dendritic tip with hypergravity are given in this paper.Finally,the reasons for these phenomena are analyzed.
文摘BACKGROUND Indeterminate dendritic cell tumor(IDCT)is a rare tumor of immune cells,and IDCT patients without skin lesions are rarely reported.Therefore,the clinical course in this type of patient is unclear,and further research on the underlying pathological mechanisms and appropriate treatments is needed.CASE SUMMARY This study describes a female IDCT patient with bile duct lesions.The strong mimicry of IDCT lesions confused doctors,and consequently,this patient,who had no skin lesions,was first diagnosed with cholangiocarcinoma.Then,she presented with persistent abdominal distension without jaundice.Enlarged mesenteric lymph nodes along with massive ascites were observed in the subsequent imaging examination.However,no tumor cells or pathogens were found in the three subsequent ascites analyses.It took 2 years to reach the correct diagnosis,which was eventually obtained by performing surgery for biopsy of the patient’s abdominal lymph nodes.However,by then,she was already in a cachexic state.Finally,she received a cycle of cyclophosphamide therapy and was advised to visit a hospital specializing in rare diseases.CONCLUSION For IDCT patients without skin lesions,early biopsy is the key to obtaining a correct diagnosis.Moreover,the collective management of IDCT patients is important.Further histological and molecular biology studies based on human specimens are critical for understanding the pathological mechanism of dendritic cell tumors in the future.
基金supported by the Provincial Science and Technology Plan Project of Sichuan Provincial Department of Science and Technology(2022SNZY001)the Science and Technology Project of Sichuan Provincial Health Commission(Appropriate Technology Base)(2022JDXM021)the Science and Technology Research Project of Sichuan Administration of Traditional Chinese Medicine(2024MS643).
文摘Head and neck cancer(HNC)is a prevalent malignant tumor that is aggressive and frequently resistant to treatment.Immunotherapy,a new approach for treating head and neck tumors,is primarily used in patients with recurrent or metastatic cancer;however,some patients do not respond well to this treatment or experience significant side effects.Further research is needed to identify better treatment options for head and neck tumors.Dendritic cells(DCs)are pivotal components of the immune system and play a crucial role in initiating and regulating immune responses by presenting antigens to other immune cells.Nonetheless,DCs are frequently suppressed in the tumor immune microenvironment.Immunogenic cell death(ICD)is a form of regulated cell death capable of activating DCs by releasing damage-associated molecular patterns(DAMPs),thus potentially enhancing therapeutic efficacy against HNC.This review summarizes the evidence for the involvement of DCs in the anti-tumor immune response against HNC and their status within the tumor microenvironment.We also outline how DAMPs in ICD can activate DCs and discuss the prospects of ICD-based DC vaccine therapy,with the aim of providing new insights into immunotherapy of patients with HNC.
