Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume respon...Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.展开更多
Tomato is one of the most essential vegetable crops worldwide,with the highest annual production rate of all agricultural staples(Kimura and Sinha,2008).Long-term domestication of tomatoes has led to the selection of ...Tomato is one of the most essential vegetable crops worldwide,with the highest annual production rate of all agricultural staples(Kimura and Sinha,2008).Long-term domestication of tomatoes has led to the selection of favorable agronomic traits that often come at the expense of stress resistance.To identify potential genetic targets for improved stress tolerance,whole-genome sequencing(WGS)has been applied to wild and cultivated accessions.展开更多
BACKGROUND Macrophages play a crucial role in the tumor microenvironment,displaying remarkable plasticity that allows them to either suppress or promote tumor progression.Their polarization into M1 or M2 phenotypes co...BACKGROUND Macrophages play a crucial role in the tumor microenvironment,displaying remarkable plasticity that allows them to either suppress or promote tumor progression.Their polarization into M1 or M2 phenotypes could have significant prognostic implications,and manipulating this polarization may offer a novel approach to controlling colorectal neoplasms.AIM To evaluate the infiltration rates of M1 and M2 macrophages in colorectal neoplasia,specifically comparing cases with and without metalloproteinase mutations.Additionally,it sought to explore potential prognostic factors as-sociated with the disease.展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To ad...Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.展开更多
Chirality,a common phenomenon in nature,appears in structures ranging from galaxies and condensed matter to atomic nuclei.There is a persistent demand for new,high-precision methods to detect chiral structures,particu...Chirality,a common phenomenon in nature,appears in structures ranging from galaxies and condensed matter to atomic nuclei.There is a persistent demand for new,high-precision methods to detect chiral structures,particularly at the microscale.Here,we propose a novel method,vortex Mössbauer spectroscopy,for probing chiral structures.By leveraging the orbital angular momentum carried by vortex beams,this approach achieves high precision in detecting chiral structures at scales ranging from nanometers to hundreds of nanometers.Our simulation shows the ratio of characteristic lines in the Mössbauer spectra of ^(57)Fe under vortex beams exhibits differences of up to four orders of magnitude for atomic structures with different arrangements.Additionally,simulations reveal the response of ^(229m)Th chiral structures to vortex beams with opposite angular momenta differs by approximately 49-fold.These significant spectral variations indicate that this new vortex Mössbauer probe holds great potential for investigating the microscopic chiral structures and interactions of matter.展开更多
The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regul...The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.展开更多
The phenotypes of the adenine-to-guanine transition at position 3243 of mitochondrial DNA(m.3243A>G)are highly variable,with different symptoms observed in different patients.These include mitochondrial encephalomy...The phenotypes of the adenine-to-guanine transition at position 3243 of mitochondrial DNA(m.3243A>G)are highly variable,with different symptoms observed in different patients.These include mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episodes(MELAS);maternally inherited diabetes and deafness syndrome(MIDD);other syndromic conditions;or non-syndromic mitochondrial disorders.Renal involvement associated with this mutation generally manifests as subnephrotic proteinuria,progressive deterioration of kidney function,and increased morbidity.The retinopathies linked to the m.3243A>G mutation have heterogeneous presentations,characterized by variable degrees of retinal pigment epithelium(RPE)atrophy and hyperpigmentation at the posterior pole.As a severe phenotype of the m.3243A>G mutation,MELAS combined with focal and segmental glomerulosclerosis(FSGS)is rare.We herein firstly reported in detail the ophthalmic manifestations of a patient with this condition.Additionally,we reviewed the literature on fundus,ophthalmic electrophysiology,and optical coherence tomography(OCT)findings related to the m.3243A>G mutation.展开更多
Ensuring digital media security through robust image watermarking is essential to prevent unauthorized distribution,tampering,and copyright infringement.This study introduces a novel hybrid watermarking framework that...Ensuring digital media security through robust image watermarking is essential to prevent unauthorized distribution,tampering,and copyright infringement.This study introduces a novel hybrid watermarking framework that integrates Discrete Wavelet Transform(DWT),Redundant Discrete Wavelet Transform(RDWT),and Möbius Transformations(MT),with optimization of transformation parameters achieved via a Genetic Algorithm(GA).By combining frequency and spatial domain techniques,the proposed method significantly enhances both the imper-ceptibility and robustness of watermark embedding.The approach leverages DWT and RDWT for multi-resolution decomposition,enabling watermark insertion in frequency subbands that balance visibility and resistance to attacks.RDWT,in particular,offers shift-invariance,which improves performance under geometric transformations.Möbius transformations are employed for spatial manipulation,providing conformal mapping and spatial dispersion that fortify watermark resilience against rotation,scaling,and translation.The GA dynamically optimizes the Möbius parameters,selecting configurations that maximize robustness metrics such as Peak Signal-to-Noise Ratio(PSNR),Structural Similarity Index Measure(SSIM),Bit Error Rate(BER),and Normalized Cross-Correlation(NCC).Extensive experiments conducted on medical and standard benchmark images demonstrate the efficacy of the proposed RDWT-MT scheme.Results show that PSNR exceeds 68 dB,SSIM approaches 1.0,and BER remains at 0.0000,indicating excellent imperceptibility and perfect watermark recovery.Moreover,the method exhibits exceptional resilience to a wide range of image processing attacks,including Gaussian noise,JPEG compression,histogram equalization,and cropping,achieving NCC values close to or equal to 1.0.Comparative evaluations with state-of-the-art watermarking techniques highlight the superiority of the proposed method in terms of robustness,fidelity,and computational efficiency.The hybrid framework ensures secure,adaptive watermark embedding,making it highly suitable for applications in digital rights management,content authentication,and medical image protection.The integration of spatial and frequency domain features with evolutionary optimization presents a promising direction for future watermarking technologies.展开更多
Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accou...Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.展开更多
Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have groupe...Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have grouped these two cell types together based on similarities in structure and function,an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes.In this study,we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury.Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury,gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed.Regarding macrophages,our findings highlighted abundant communication with other cells,including fibroblasts and neurons.Both pro-inflammatory and neuroprotective effects of macrophages were also identified;the pro-inflammatory effect may be related to integrin β2(Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway.These findings were validated by in vivo experiments.This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury,and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regiona...[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regional production trial utilizing C.violaceum strain CMS1,which was sourced from a semi-wild population in Langzhong,Sichuan Province,as the experimental material.In contrast,C.violaceum CMS2,derived from a cultivated population in Langzhong,Sichuan Province,along with a mixed population of C.violaceum cultispecies from the same region,served as the control material.Through a comparative analysis of phenological periods,agronomic traits,yield,and quality,a novel cultivar,‘Chengming No.1’,was ultimately selected and developed based on its superior comprehensive evaluation.[Results]In the phenological period survey conducted as part of a two-year comparative study,the CMS1 strain exhibited a shorter growth cycle compared to others.Furthermore,the agronomic characteristics of the CMS1 strain were superior to those of both CMS2 and CK.The average yields of CMS1,CMS2,and CK in the 2019 cultivar comparison test and yield trial were 468.88,448.52,and 422.15 kg/667 m 2,respectively.This resulted in an average yield increase of 11.07%for CMS1 compared to CK and 6.25%for CMS2 compared to CK.The average yields of CMS1,CMS2,and CK in the 2020 cultivar comparison test and yield trial were 482.69,467.54,and 436.82 kg/667 m 2,respectively.CMS1 exhibited an average yield increase of 10.50%compared to CK,while CMS2 demonstrated an average yield increase of 7.03%relative to CK.Furthermore,the average yield of CMS1 per 667 m 2 achieved a statistically significant level compared to CK in both years of the study.In multiple-point comparison and yield trials conducted in 2019 and 2020,the CMS1 strain exhibited a total ash content of 15.30%,an acid-insoluble ash content of 1.30%,a moisture content of 10.80%,and water-soluble extract amounting to 11.40%.All of the indicators conformed to the criteria established by the Sichuan Standards for Chinese Medicinal Materials(2010 Edition).[Conclusions]The CMS1 strain successfully passed the field technical appraisal for the novel cultivar of C.violaceum in 2021.This cultivar is characterized by high yield,excellent quality,and stable traits.In 2022,it received validation from the Sichuan Provincial Committee for the Certification of Non-Staple Crop Varieties and was officially named‘Chengming No.1’(CRY 2022002).This cultivar demonstrates significant potential for widespread cultivation.展开更多
The use of an alternative magnetic field during vacuum arc remelting(VAR)can have significant effects on the primary carbide and mechanical properties of M50-bearing steel.The solidification structure and the primary ...The use of an alternative magnetic field during vacuum arc remelting(VAR)can have significant effects on the primary carbide and mechanical properties of M50-bearing steel.The solidification structure and the primary carbide morphology of the VAR ingot were analyzed by optical microscopy and scanning electron microscopy.Characterization and analysis of the growth direction of primary carbides were conducted using high-resolution rapid electron backscatter diffraction.Solute elements segregation was analyzed using an electron probe microanalyzer.FLUENT was utilized to conduct numerical simulations to validate the experimental findings and elucidate the underlying mechanism.Compared to traditional VAR,magnetic-controlled VAR generates a horizontal circulation,which makes a shallower and flatter molten pool and a more even temperature distribution.In the time dimension,the local solidification time is shortened,and the concentration of solute elements will be alleviated.In the spatial dimension,the secondary dendrite arm spacing decreases,alleviating the degree of inter-dendritic segregation.Consequently,the possibility of forming a segregation diminishes.Both aspects promote the even distribution of solute atoms,resulting in less segregation and hindering the development of primary carbide.This leads to the refinement of primary carbide size and its uniform distribution.The magnetic-controlled vacuum arc melting not only refines the dendritic structure in the M50 ingot,causing it to expand more axially along the ingot,but also refines primary carbides and improves tensile and wear-resistant mechanical properties.展开更多
Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investiga...Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina.We first showed that two types of quiescent MG(resting MG1 and MG2)reside in the uninjured retina.Following retinal injury,resting MG1 transitioned into an activated state expressing known reprogramming genes,while resting MG2 gave rise to rod progenitors.We further showed that retinal microglia can be categorized into three subtypes(microglia-1,microglia-2,and proliferative)and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury.Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG,with many interactions shared among different immune cell types.Finally,we showed that inflammation activated Jak1–Stat3 signaling in MG,promoting their transition from a resting to an activated state.Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair,and may provide valuable insights into future mammalian retina regeneration.展开更多
BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds pre...BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds present significant therapeutic challenges,requiring novel strategies to improve healing outcomes.AIM To investigate the potential of fetal dermal mesenchymal stem cells(FDMSCs)in enhancing wound healing through modulation of macrophage polarization,specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.METHODS FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization.Flow cytometry,quantitative reverse transcriptase polymerase chain reaction,and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model.Statistical analysis was performed using GraphPad Prism.RESULTS FDMSCs induced macrophage polarization from the M1 to M2 phenotype,as demonstrated by a reduction in proinflammatory markers(inducible nitric oxide synthase,interleukin-6)and an increase in anti-inflammatory markers[mannose receptor(CD206),arginase-1]in co-cultured RAW264.7 macrophages.These shifts were confirmed by flow cytometry.In an acute skin wound model,FDMSC-treated mice exhibited faster wound healing,enhanced collagen deposition,and improved vascular regeneration compared to controls.Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.CONCLUSION FDMSCs effectively modulate macrophage polarization from M1 to M2,reduce inflammation,and enhance tissue repair,demonstrating their potential as an immunomodulatory strategy in wound healing.These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.展开更多
Dispatched by the Chinese government,a multidisciplinary team of 30 researchers collaborated with a team from Myanmar to conduct a 14-day on-site investigation.The work encompassed seismic intensity assessments,field ...Dispatched by the Chinese government,a multidisciplinary team of 30 researchers collaborated with a team from Myanmar to conduct a 14-day on-site investigation.The work encompassed seismic intensity assessments,field surveys,and loss evaluations.The paper focuses on the intensity distribution and structural damage characteristics of the 2025 M7.9 Myanmar earthquake,yielding the following key findings.(1)The seismogenic fault rupture propagated in a nearly N-S direction,with a surface rupture length of approximately 450 km.The seismic impact zone exhibited an elongated N-S distribution and a shorter E-W span,distributed like a belt around the seismogenic fault.(2)Within the seismic impact zones,existing buildings comprised five primary structural types,with timber(bamboo)structures constituting the largest proportion(≈80%in rural areas,≈50%in urban areas).The relatively low disaster losses and casualties were primarily attributable to the good seismic performance and low damage ratio of timber(bamboo)structures across varying intensity zones.(3)An anomalous zone of intensityⅨwas located at the boundary between intensityⅥandⅦregions in Nay Pyi Taw.Here,ridge topography combined with soft soil layers significantly amplified ground motion,exacerbating structural damage.(4)Directional effects of ground motion were observed,with the structural damage phenomena and peak ground acceleration(PGA)values in the N-S direction exceeding those in the E-W direction.This validates that the maximum PGA distribution of strike-slip fault earthquakes aligns with the fault strike.The research is expected to provide technical support for post-disaster reconstruction planning,site selection,and disaster mitigation strategies in Myanmar.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
基金supported by the National Natural Science Foundation of China,No.31930068National Key Research and Development Program of China,Nos.2018YFA0107302 and 2021YFA1101203(all to HX).
文摘Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased states.In lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored functionality.Conversely,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various technologies.Advancements in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice.Nevertheless,there remain issues that hinder improving reprogramming efficiency and maturity.Thus,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming strategies.This review describes recent progress in relatively successful Müller glia reprogramming strategies.It also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.
基金supported by grants from the Shanghai Agriculture Applied Technology Development Program(2021-02-08-00-12-F00792)Projects of International Cooperation and Exchanges NSFC(3201101910).
文摘Tomato is one of the most essential vegetable crops worldwide,with the highest annual production rate of all agricultural staples(Kimura and Sinha,2008).Long-term domestication of tomatoes has led to the selection of favorable agronomic traits that often come at the expense of stress resistance.To identify potential genetic targets for improved stress tolerance,whole-genome sequencing(WGS)has been applied to wild and cultivated accessions.
文摘BACKGROUND Macrophages play a crucial role in the tumor microenvironment,displaying remarkable plasticity that allows them to either suppress or promote tumor progression.Their polarization into M1 or M2 phenotypes could have significant prognostic implications,and manipulating this polarization may offer a novel approach to controlling colorectal neoplasms.AIM To evaluate the infiltration rates of M1 and M2 macrophages in colorectal neoplasia,specifically comparing cases with and without metalloproteinase mutations.Additionally,it sought to explore potential prognostic factors as-sociated with the disease.
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
基金supported by the Macao Science and Technology Development Fund (FDCT 0148/2022/A3 and 0019/2024/RIA1)the National Natural Science Foundation of China (No. 81572979)
文摘Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.
基金supported in part by the National Key R&D Program(Grant No.2023YFA1606900)the National Natural Science Foundation of China(Grant No.12235003)。
文摘Chirality,a common phenomenon in nature,appears in structures ranging from galaxies and condensed matter to atomic nuclei.There is a persistent demand for new,high-precision methods to detect chiral structures,particularly at the microscale.Here,we propose a novel method,vortex Mössbauer spectroscopy,for probing chiral structures.By leveraging the orbital angular momentum carried by vortex beams,this approach achieves high precision in detecting chiral structures at scales ranging from nanometers to hundreds of nanometers.Our simulation shows the ratio of characteristic lines in the Mössbauer spectra of ^(57)Fe under vortex beams exhibits differences of up to four orders of magnitude for atomic structures with different arrangements.Additionally,simulations reveal the response of ^(229m)Th chiral structures to vortex beams with opposite angular momenta differs by approximately 49-fold.These significant spectral variations indicate that this new vortex Mössbauer probe holds great potential for investigating the microscopic chiral structures and interactions of matter.
基金supported by grants from Simons Foundation (SFARI 479754),CIHR (PJT-180565)the Scottish Rite Charitable Foundation of Canada (to YL)funding from the Canada Research Chairs program。
文摘The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.
基金Supported by the Clinical Research Plan of SHDC(No.SHDC2020CR6029).
文摘The phenotypes of the adenine-to-guanine transition at position 3243 of mitochondrial DNA(m.3243A>G)are highly variable,with different symptoms observed in different patients.These include mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episodes(MELAS);maternally inherited diabetes and deafness syndrome(MIDD);other syndromic conditions;or non-syndromic mitochondrial disorders.Renal involvement associated with this mutation generally manifests as subnephrotic proteinuria,progressive deterioration of kidney function,and increased morbidity.The retinopathies linked to the m.3243A>G mutation have heterogeneous presentations,characterized by variable degrees of retinal pigment epithelium(RPE)atrophy and hyperpigmentation at the posterior pole.As a severe phenotype of the m.3243A>G mutation,MELAS combined with focal and segmental glomerulosclerosis(FSGS)is rare.We herein firstly reported in detail the ophthalmic manifestations of a patient with this condition.Additionally,we reviewed the literature on fundus,ophthalmic electrophysiology,and optical coherence tomography(OCT)findings related to the m.3243A>G mutation.
文摘Ensuring digital media security through robust image watermarking is essential to prevent unauthorized distribution,tampering,and copyright infringement.This study introduces a novel hybrid watermarking framework that integrates Discrete Wavelet Transform(DWT),Redundant Discrete Wavelet Transform(RDWT),and Möbius Transformations(MT),with optimization of transformation parameters achieved via a Genetic Algorithm(GA).By combining frequency and spatial domain techniques,the proposed method significantly enhances both the imper-ceptibility and robustness of watermark embedding.The approach leverages DWT and RDWT for multi-resolution decomposition,enabling watermark insertion in frequency subbands that balance visibility and resistance to attacks.RDWT,in particular,offers shift-invariance,which improves performance under geometric transformations.Möbius transformations are employed for spatial manipulation,providing conformal mapping and spatial dispersion that fortify watermark resilience against rotation,scaling,and translation.The GA dynamically optimizes the Möbius parameters,selecting configurations that maximize robustness metrics such as Peak Signal-to-Noise Ratio(PSNR),Structural Similarity Index Measure(SSIM),Bit Error Rate(BER),and Normalized Cross-Correlation(NCC).Extensive experiments conducted on medical and standard benchmark images demonstrate the efficacy of the proposed RDWT-MT scheme.Results show that PSNR exceeds 68 dB,SSIM approaches 1.0,and BER remains at 0.0000,indicating excellent imperceptibility and perfect watermark recovery.Moreover,the method exhibits exceptional resilience to a wide range of image processing attacks,including Gaussian noise,JPEG compression,histogram equalization,and cropping,achieving NCC values close to or equal to 1.0.Comparative evaluations with state-of-the-art watermarking techniques highlight the superiority of the proposed method in terms of robustness,fidelity,and computational efficiency.The hybrid framework ensures secure,adaptive watermark embedding,making it highly suitable for applications in digital rights management,content authentication,and medical image protection.The integration of spatial and frequency domain features with evolutionary optimization presents a promising direction for future watermarking technologies.
文摘Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.
文摘Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response,with resident microglia and infiltrating macrophages playing pivotal roles.While previous studies have grouped these two cell types together based on similarities in structure and function,an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes.In this study,we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury.Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury,gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed.Regarding macrophages,our findings highlighted abundant communication with other cells,including fibroblasts and neurons.Both pro-inflammatory and neuroprotective effects of macrophages were also identified;the pro-inflammatory effect may be related to integrin β2(Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway.These findings were validated by in vivo experiments.This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury,and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金Supported by Sichuan Innovation Team Project of China Agricultural Industry Research System(SCCXTD-2023-19)Key R&D Project of Sichuan Provincial Department of Science and Technology(2022YFS0592)Sichuan Provincial Science and Technology Innovation Seedling Project(MZGC20230119,MZGC20230126).
文摘[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regional production trial utilizing C.violaceum strain CMS1,which was sourced from a semi-wild population in Langzhong,Sichuan Province,as the experimental material.In contrast,C.violaceum CMS2,derived from a cultivated population in Langzhong,Sichuan Province,along with a mixed population of C.violaceum cultispecies from the same region,served as the control material.Through a comparative analysis of phenological periods,agronomic traits,yield,and quality,a novel cultivar,‘Chengming No.1’,was ultimately selected and developed based on its superior comprehensive evaluation.[Results]In the phenological period survey conducted as part of a two-year comparative study,the CMS1 strain exhibited a shorter growth cycle compared to others.Furthermore,the agronomic characteristics of the CMS1 strain were superior to those of both CMS2 and CK.The average yields of CMS1,CMS2,and CK in the 2019 cultivar comparison test and yield trial were 468.88,448.52,and 422.15 kg/667 m 2,respectively.This resulted in an average yield increase of 11.07%for CMS1 compared to CK and 6.25%for CMS2 compared to CK.The average yields of CMS1,CMS2,and CK in the 2020 cultivar comparison test and yield trial were 482.69,467.54,and 436.82 kg/667 m 2,respectively.CMS1 exhibited an average yield increase of 10.50%compared to CK,while CMS2 demonstrated an average yield increase of 7.03%relative to CK.Furthermore,the average yield of CMS1 per 667 m 2 achieved a statistically significant level compared to CK in both years of the study.In multiple-point comparison and yield trials conducted in 2019 and 2020,the CMS1 strain exhibited a total ash content of 15.30%,an acid-insoluble ash content of 1.30%,a moisture content of 10.80%,and water-soluble extract amounting to 11.40%.All of the indicators conformed to the criteria established by the Sichuan Standards for Chinese Medicinal Materials(2010 Edition).[Conclusions]The CMS1 strain successfully passed the field technical appraisal for the novel cultivar of C.violaceum in 2021.This cultivar is characterized by high yield,excellent quality,and stable traits.In 2022,it received validation from the Sichuan Provincial Committee for the Certification of Non-Staple Crop Varieties and was officially named‘Chengming No.1’(CRY 2022002).This cultivar demonstrates significant potential for widespread cultivation.
基金supported by the National Natural Science Foundation of China(Grant numbers 52204347,52274385,52004156,51904184,and 52204392)the National Key Research and Development Program of China(Grant number 2022YFC2904900)+1 种基金the Science and Technology Commission of Shanghai Municipality(13JC14025000,15520711000)the Shi Changxu Innovation Center for Advanced Materials(SCXKFJJ202204).
文摘The use of an alternative magnetic field during vacuum arc remelting(VAR)can have significant effects on the primary carbide and mechanical properties of M50-bearing steel.The solidification structure and the primary carbide morphology of the VAR ingot were analyzed by optical microscopy and scanning electron microscopy.Characterization and analysis of the growth direction of primary carbides were conducted using high-resolution rapid electron backscatter diffraction.Solute elements segregation was analyzed using an electron probe microanalyzer.FLUENT was utilized to conduct numerical simulations to validate the experimental findings and elucidate the underlying mechanism.Compared to traditional VAR,magnetic-controlled VAR generates a horizontal circulation,which makes a shallower and flatter molten pool and a more even temperature distribution.In the time dimension,the local solidification time is shortened,and the concentration of solute elements will be alleviated.In the spatial dimension,the secondary dendrite arm spacing decreases,alleviating the degree of inter-dendritic segregation.Consequently,the possibility of forming a segregation diminishes.Both aspects promote the even distribution of solute atoms,resulting in less segregation and hindering the development of primary carbide.This leads to the refinement of primary carbide size and its uniform distribution.The magnetic-controlled vacuum arc melting not only refines the dendritic structure in the M50 ingot,causing it to expand more axially along the ingot,but also refines primary carbides and improves tensile and wear-resistant mechanical properties.
基金supported by the National Natural Science Foundation of China,Nos.81970820(to HX),31771644(to JL),31930068(to JL),82371176(to JL),81801331(to LC)National Key Research and Development Project of China.Nos.2017YFA0104100(to JL),2017YFA0701304(to HX)+1 种基金Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)Talent Introduction Plan,No.KYPT202204(to LC)the Fundamental Research Funds for the Central Universities,No.22120230292(to JL)。
文摘Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina.We first showed that two types of quiescent MG(resting MG1 and MG2)reside in the uninjured retina.Following retinal injury,resting MG1 transitioned into an activated state expressing known reprogramming genes,while resting MG2 gave rise to rod progenitors.We further showed that retinal microglia can be categorized into three subtypes(microglia-1,microglia-2,and proliferative)and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury.Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG,with many interactions shared among different immune cell types.Finally,we showed that inflammation activated Jak1–Stat3 signaling in MG,promoting their transition from a resting to an activated state.Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair,and may provide valuable insights into future mammalian retina regeneration.
基金National Natural Science Foundation of China,No.81873934and Jinan Science and Technology Planning Project,No.202225065.
文摘BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds present significant therapeutic challenges,requiring novel strategies to improve healing outcomes.AIM To investigate the potential of fetal dermal mesenchymal stem cells(FDMSCs)in enhancing wound healing through modulation of macrophage polarization,specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.METHODS FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization.Flow cytometry,quantitative reverse transcriptase polymerase chain reaction,and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model.Statistical analysis was performed using GraphPad Prism.RESULTS FDMSCs induced macrophage polarization from the M1 to M2 phenotype,as demonstrated by a reduction in proinflammatory markers(inducible nitric oxide synthase,interleukin-6)and an increase in anti-inflammatory markers[mannose receptor(CD206),arginase-1]in co-cultured RAW264.7 macrophages.These shifts were confirmed by flow cytometry.In an acute skin wound model,FDMSC-treated mice exhibited faster wound healing,enhanced collagen deposition,and improved vascular regeneration compared to controls.Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.CONCLUSION FDMSCs effectively modulate macrophage polarization from M1 to M2,reduce inflammation,and enhance tissue repair,demonstrating their potential as an immunomodulatory strategy in wound healing.These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.
基金National Natural Science Foundation of China under Grant No.U2239252National Natural Science Foundation of China under Grant No.52279128Natural Science Foundation of Heilongjiang Province of China under Grant No.YQ2022E013。
文摘Dispatched by the Chinese government,a multidisciplinary team of 30 researchers collaborated with a team from Myanmar to conduct a 14-day on-site investigation.The work encompassed seismic intensity assessments,field surveys,and loss evaluations.The paper focuses on the intensity distribution and structural damage characteristics of the 2025 M7.9 Myanmar earthquake,yielding the following key findings.(1)The seismogenic fault rupture propagated in a nearly N-S direction,with a surface rupture length of approximately 450 km.The seismic impact zone exhibited an elongated N-S distribution and a shorter E-W span,distributed like a belt around the seismogenic fault.(2)Within the seismic impact zones,existing buildings comprised five primary structural types,with timber(bamboo)structures constituting the largest proportion(≈80%in rural areas,≈50%in urban areas).The relatively low disaster losses and casualties were primarily attributable to the good seismic performance and low damage ratio of timber(bamboo)structures across varying intensity zones.(3)An anomalous zone of intensityⅨwas located at the boundary between intensityⅥandⅦregions in Nay Pyi Taw.Here,ridge topography combined with soft soil layers significantly amplified ground motion,exacerbating structural damage.(4)Directional effects of ground motion were observed,with the structural damage phenomena and peak ground acceleration(PGA)values in the N-S direction exceeding those in the E-W direction.This validates that the maximum PGA distribution of strike-slip fault earthquakes aligns with the fault strike.The research is expected to provide technical support for post-disaster reconstruction planning,site selection,and disaster mitigation strategies in Myanmar.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
