查看更多>>摘要：Molecular luminescent materials with optical waveguide have wide application prospects in light-emitting diodes,sensors,and logic gates.However,the majority of traditional optical waveguide systems are based on brittle molecular crystals,which limited the fabrication,transportation,storage,and adaptation of flexible devices under diverse application situations.To date,the design and synthesis of photofunctional materials with high flexibility,novel optical waveguide,and multi-port color-tunable emission in the same solid-state system remain an open challenge.Here,we have constructed new types of zero-dimensional organic metal halides(Au-4-dimethylaminopyridine[DMAP]and In-DMAP)with a rarely high elasticity and rather low loss coefficients for optical waveguide.Theoretical calculations on the intermolecular interactions showed that the high elasticity of 2 molecular crystalline materials was original from their herringbone structure and slip plane.Based on one-dimensional flexible microrods of 2 crystals and the 2-dimensional microplate of the Mn-DMAP,heterojunctions with multi-color and space-resolved optical waveguides have been fabricated.The formation mechanism of heterojunctions is based on the surface selective growth on account of the low lattice mismatch ratio between contacting crystal planes.Therefore,this work describes the first attempt to the design of metal-halide-based crystal heterojunctions with high flexibility and optical waveguide,expanding the prospects of traditional luminescent materials for smart optical devices,such as logic gates and multiplexers.
查看更多>>摘要：Background:Hepatic ischemia-reperfusion injury(HIRI)stands as an unavoidable complication arising from liver surgery,profoundly intertwined with its prognosis.The role of lysine methyltransferase SET domain bifurcated 1(SETDB1)in HIRI remains elusive,despite its confirmation as a potential therapeutic target for diverse diseases.Here,we investigated the mechanism by which SETDB1 regulated HIRI.Methods:RNA sequencing data were used to identify the expression and potential targets of SETDB1 through bioinformatics analysis.To elucidate the impact of SETDB1 on HIRI,both an in vivo model of HIRI in mice and an in vitro model of hepatocyte hypoxia/reoxygenation were established.Biochemical and histological analyses were used to investigate the influence of SETDB1 on liver damage mediated by HIRI.Chromatin immunoprecipitation and coimmunoprecipitation were implemented to explore the in-depth mechanism of SETDB1 regulating HIRI.Results:We confirmed that hepatocellular SETDB1 was up-regulated during HIRI and had a close correlation with HIRI-related inflammation and apoptosis.Moreover,inhibition of SETDB1 could mitigate HIRI-induced liver damage,inflammation,and apoptosis.Through our comprehensive mechanistic investigation,we revealed that SETDB1 interacts with apoptosis-signal-regulating kinase 1(ASK1)and facilitates the methylation of its lysine residues.Inhibition of SETDB1 resulted in reduced phosphorylation of ASK1,leading to a marked suppression of downstream c-Jun N-terminal kinase(JNK)/p38 signaling pathway activation.The therapeutic effect on inflammation and apoptosis achieved through SETDB1 inhibition was nullified by the restoration of JNK/p38 signaling activation through ASK1 overexpression.Conclusions:The findings from our study indicate that SETDB1 mediates lysine methylation of ASK1 and modulates the activation of the ASK1-JNK/p38 pathway,thus involved in HIRI-induced inflammation and apoptosis.These results suggest that SETDB1 holds promise as a potential therapeutic target for mitigating HIRI.
查看更多>>摘要：Shape memory polymers(SMPs)and their composites(SMPCs)are smart materials that can be stably deformed and then return to their original shape under external stimulation,thus having a memory of their shape.Three-dimensional(3D)printing is an advanced technology for fabricating products using a digital software tool.Four-dimensional(4D)printing is a new generation of additive manufacturing technology that combines shape memory materials and 3D printing technology.Currently,4D-printed SMPs and SMPCs are gaining considerable research attention and are finding use in various fields,including biomedical science.This review introduces SMPs,SMPCs,and 4D printing technologies,highlighting several special 4D-printed structures.It summarizes the recent research progress of 4D-printed SMPs and SMPCs in various fields,with particular emphasis on biomedical applications.Additionally,it presents an overview of the challenges and development prospects of 4D-printed SMPs and SMPCs and provides a preliminary discussion and useful reference for the research and application of 4D-printed SMPs and SMPCs.
查看更多>>摘要：Brown adipose tissue(BAT)is the major site of non-shivering thermogenesis and crucial for systemic metabolism.Under chronic cold exposures and high-fat diet challenges,BAT undergoes robust remodeling to adapt to physiological demands.However,whether and how BAT regenerates after acute injuries are poorly understood.Here,we established a novel BAT injury and regeneration model(BAT-IR)in mice and performed single-cell RNA sequencing(scRNA-seq)and bulk RNA-seq to determine cellular and transcriptomic dynamics during BAT-IR.We further defined distinct fibro-adipogenic and myeloid progenitor populations contributing to BAT regeneration.Cell trajectory and gene expression analyses uncovered the involvement of MAPK,Wnt,and Hedgehog(Hh)signaling pathways in BAT regeneration.We confirmed the role of Hh signaling in BAT development through Myf5Cre-mediated conditional knockout(cKO)of the Sufu gene to activate Hh signaling in BAT and muscle progenitors.Our BAT-IR model therefore provides a paradigm to identify conserved cellular and molecular mechanisms underlying BAT development and remodeling.
查看更多>>摘要：Metallic lithium represents a promising anode candidate to be utilized in future high-energy lithium batteries.However,the undesirable dendrite growth and fragile solid-electrolyte interphase(SEI)pose critical challenge for pursuing further practical application.In contrast to traditional approaches of using inert/lithiophilicity coating,here,we demonstrate a reverse strategy of introducing a highly conductive and lithophobic carbon fabric(CF)scaffold on lithium foil to guide a favorable nucleation site of lithium far away from the anode/separator interface.The CF scaffold with high conductivity can couple with inner electric field for achieving a uniform distribution of the lithium-ion flux,while the lithophobic feature offers the condition to guide the preferred deposition of lithium onto the underlying lithium foil,which greatly reduces the risk of dendrite-induced short circuits.Moreover,the SEI immersed in the CF scaffold is well supported by CF fibers and therefore exhibits extremely high stability during charge-discharge cycles.As a result,the lithium/CF anodes show＞2,000-h stable cycling at 0.5 mA cm-2.Lithium metal batteries equipped with our lithium/CF anode deliver a high capacity retention of～99.99％per cycle,i.e.,retain～97.3％capacity after 200 cycles.The unique interface-regulation strategy is versatile for various conductive scaffolds(e.g.,ultrathin and ultralight conductive fabrics),exhibiting high superiority for highly safe lithium metal batteries.
查看更多>>摘要：Fluid intelligence is a cognitive domain that encompasses general reasoning,pattern recognition,and problem-solving abilities independent of task-specific experience.Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development,lifelong health,and well-being.One approach to address this challenge is to map the network of correlations between intelligence and other constructs.In the current study,we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence.Our results revealed novel common genetic loci(SH2B1,TUFM,ATP2A1,and FOXO3)underlying the association between fluid intelligence and body metabolism.Surprisingly,we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume.Consistently,selective genetic ablation of Sh2b1 in the mouse hippocampus,particularly in inhibitory neurons,but not in excitatory neurons,significantly impaired working memory,short-term novel object recognition memory,and behavioral flexibility,but not spatial learning and memory,mirroring the human intellectual performance.Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase(ERK)signaling,whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment.Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.
查看更多>>摘要：Jade is most valued in Chinese culture since ancient times.For unearthed jade artifacts,the alteration color resulting from weathering effects and human activities provides information for cultural heritage conservation,archaeology,and history.Currently,the noninvasive 3-dimensional characterization of jade artifacts with high chemical and spatial resolution remains challenging.In this work,we applied femtosecond pump-probe microscopy and second harmonic generation microscopy techniques to study the black alteration of an ancient jade artifact of the late Spring and Autumn period(546 to 476 BC).The direct cause of the"mercury alteration"phenomena was discovered to be the conversion of metacinnabar from buried cinnabar in the tomb.Furthermore,a 3-dimensional optical reconstruction of the black alteration was achieved,providing a high-resolution method for analyzing the blackening mechanism without the need of sample damage.Our approach opens up new opportunities to extract microscopic spatiochemical information for a broad range of alteration colors in jade artifacts.
查看更多>>摘要：Living tissues often have anisotropic and heterogeneous organizations,in which developmental processes are coordinated by cells and extracellular matrix modeling.Cells have the capability of modeling matrix in long distance;however,the biophysical mechanism is largely unknown.We investigated the dynamic remodeling of collagen I(COL)fibril matrix by cell contraction with designed patterns of cell clusters.By considering cell dynamic contractions,our molecular dynamics simulations predicted the anisotropic patterns of the observed COL bundling in experiments with various geometrical patterns without spatial limitation.The pattern of COL bundling was closely related to the dynamic remodeling of fibril under cell active contraction.We showed that cell cytoskeletal integrity(actin filaments and microtubules),actomyosin contractions,and endoplasmic reticulum calcium channels acting as force generations and transductions were essential for fiber bundling inductions,and membrane mechanosensory components integrin and Piezo played critical roles as well.This study revealed the underlying mechanisms of the cell mechanics-induced matrix remodeling in large scales and the associated cellular mechanism and should provide important guidelines for tissue engineering in potential biomedical applications.
Laura García-MendívilMaría Pérez-ZabalzaAntoni Oliver-GelabertJosé María Vallejo-Gil...
417-432页
查看更多>>摘要：Connexin 43(CX43)is one of the major components of gap junctions,the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle.There is limited information on the histological changes of CX43 with age and their effect on electrophysiology,especially in humans.Here,we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling.We assessed its quantity,degree of lateralization,and spatial heterogeneity together with fibrotic deposition.We observed no significant age-related remodeling of CX43.Only spatial heterogeneity increased slightly with age,and this increase was better explained by biological age than by chronological age.Importantly,we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content,in contrast to animal species.We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity,action potential duration,and arrhythmogenicity.We found that larger amounts of fibrosis were associated with the highest arrhythmic risk,with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity.These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population.In conclusion,our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife,but highlight its potential as a proarrhythmic factor at the individual level,especially when combined with increased fibrosis.
查看更多>>摘要：T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains constrained.The objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor CD8+T cells using the TRAMP-C1 prostate cancer and B16F10 melanoma model.To achieve this,we generated an Irf4GFPDTR mouse strain and discovered that CD8+tumor-infiltrating lymphocytes(TILs)expressing high levels of IRF4.GFP exhibited a more differentiated PD-1high cell phenotype.By administering diphtheria toxin to tumor-bearing Irf4GFP-DTR mice,we partially depleted IRF4.GFP+TILs and observed an accelerated tumor growth.To specifically explore the function of IRF4 in antitumor CD8+T cells,we conducted 3 adoptive cell therapy(ACT)models.Firstly,depleting IRF4.GFP+CD8+TILs derived from ACT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor progression.Secondly,deleting the Irf4 gene in antitumor CD8+T cells used for ACT led to a reduction in the frequency and effector differentiation of CD8+TILs,completely abolishing the antitumor effects of ACT.Lastly,we performed a temporal deletion of the Irf4 gene in antitumor CD8+T cells during ACT,starting from 20 days after tumor implantation,which significantly compromised tumor control.Therefore,sustained expression of IRF4 is essential for maintaining CD8+T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.
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