Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
In this study,we present the development of a cryobioink designed to fabricate anisotropic scaffolds that support both neural and muscle cell-alignment.Given the critical role of cellular organization in nerve fibers ...In this study,we present the development of a cryobioink designed to fabricate anisotropic scaffolds that support both neural and muscle cell-alignment.Given the critical role of cellular organization in nerve fibers and neuromuscular junctions,we employed a vertical cryobioprinting-enabled ice-templating technique to create scaffolds with aligned microchannels.These channels facilitated cell-alignment,which is important in modeling neural and neuromuscular tissues.By integrating hyaluronic acid-methacrylate(HAMA)with gelatin methacryloyl and the necessary cryoprotective agent melezitose,we showcased that the cryobioink could preserve cell viability during freezing/thawing processes,even at low temperatures employed during cryobioprinting.We optimized HAMA concentration to enhance neural cell viability and alignment,and successfully constructed anisotropic scaffolds featuring distinct sections that contained muscle and neural cells,establishing a model for neuromuscular junctions.The resulting models provide a versatile platform for studying nerve fibers and neuromuscular dysfunctions,offering potential advancements in neural regeneration research.展开更多
Soft-tissue motion introduces significant challenges in robotic teleoperation,especially in medical scenarios where precise target tracking is critical.Latency across sensing,computation,and actuation chains leads to ...Soft-tissue motion introduces significant challenges in robotic teleoperation,especially in medical scenarios where precise target tracking is critical.Latency across sensing,computation,and actuation chains leads to degraded tracking performance,particularly around high-acceleration segments and trajectory inflection points.This study investigates machine learning-based predictive compensation for latency mitigation in soft-tissue tracking.Three models—autoregressive(AR),long short-term memory(LSTM),and temporal convolutional network(TCN)—were implemented and evaluated on both synthetic and real datasets.By aligning the prediction horizon with the end-to-end system delay,we demonstrate that prediction-based compensation significantly reduces tracking errors.Among the models,TCN achieved superior robustness and accuracy on complex motion patterns,particularly in multi-step prediction tasks,and exhibited better latency–horizon compatibility.The results suggest that TCN is a promising candidate for real-time latency compensation in teleoperated robotic systems involving dynamic soft-tissue interaction.展开更多
Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid ...Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid and nutrient components between the adipose tissue of Bamei pigs and commercial pigs are still unclear.The study employed UPLC-MS/MS to quantify the composition of lipids and metabolites in the backfat of both Bamei and Large White pigs.A total of 428 lipids and 193 metabolites were significantly different between the 2 groups.Specifically,Bamei pig backfat exhibited altered levels of various lipids and metabolites that may potentially contribute to nutritional and flavor differences,including unsaturated triglycerides,free fatty acids,medium-chain triglycerides,essential amino acids,vitamins and antioxidants,while maintaining reduced cholesterol levels.Furthermore,we delved into the molecular mechanisms underlying these nutritional differences by analyzing significantly different 431 m RNAs and 865 proteins and integrating the regulatory network of protein-metabolite-lipid pathway.Importantly,in the pyruvate metabolic pathway of Bamei pigs,the bioprocess of lactate production was inhibited but the acetyl-Co A production was activated,suggesting the possibility that energy allocation favors the biogenesis of lipid precursors.These findings may contribute to guiding industrial food producers in enhancing the quality of lard at the genetic and molecular levels.展开更多
The esophagus is a tubular organ essential for maintaining normal eating function in humans.However,the replacement of the esophagus remains challenging in clinical settings.Although tissue engineering scaffolds are a...The esophagus is a tubular organ essential for maintaining normal eating function in humans.However,the replacement of the esophagus remains challenging in clinical settings.Although tissue engineering scaffolds are a promising alternative solution,their fabrication is difficult due to the complex structure and function of the esophagus.This review describes the existing fabrication methods for esophageal tubular scaffolds,including decellularization,casting,electrospinning,three dimensional(3 D)bioprinting,and pin-frogging.Also discussed are the stimulation cues of the fabricated esophageal tubular scaffold that induce esophageal muscle and epithelial cells.Finally,this review emphasizes three important concerns for esophageal tubular scaffolds:leakage and porosity,elasticity and proliferation of smooth muscle cells,and biocompatibility and structural fidelity of biomaterials.展开更多
Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated ...Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.展开更多
Microwave ablation(MWA)is a minimally invasive technique for treating hepatic tumors,necessitating precise monitoring to ensure treatment efficacy and minimize damage to surrounding tissues.This study explores the pot...Microwave ablation(MWA)is a minimally invasive technique for treating hepatic tumors,necessitating precise monitoring to ensure treatment efficacy and minimize damage to surrounding tissues.This study explores the potential of photoacoustic imaging(PAI)in monitoring MWA by examining ex vivo porcine liver tissues.In this study,a comprehensive analysis of photoacoustic signals was performed to compare the main lobe width(MLW)between ablated and normal regions in porcine liver tissue.Histological staining with succinate dehydrogenase(SDH)and shear wave elastography(SWE)were employed to validate the changes in tissue elasticity after ablation.The analysis demonstrated a notable reduction in the MLW of the average A-lines in ablated tissues compared to nonablated regions(p<0.01).This reduction,attributed to increased tissue density and enhanced elasticity,indicates accelerated sound propagation in thermally ablated areas,which then serves as a critical parameter for mapping tissue characteristics.The reconstruction of the MLW distribution successfully delineated the ablated regions,and was consistent with the results of SDH staining and SWE.In addition,MLW-based imaging exhibited higher spatial resolution compared to SWE.Incorporating MLW analysis into PAI may be a promising strategy to improve the accuracy and effectiveness of MWA monitoring in clinical settings.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminog...Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.展开更多
Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain cha...Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain characteristics with the nodules themselves.In this study,a silicotic rat model was established via a single intratracheal in-stillation of a 50 mg/mL silica suspension.Pulmonary anatomical and pathological examinations revealed that silica deposition induced severe alterations in both the nodular and perinodular tissues.Subsequently,pseudo-targeted metabolomics analysis revealed that abnormally elevated ornithine levels were closely associated with the progression of silicosis,from normal to perinodular and finally to nodular tissues.Immunofluorescent stain-ing demonstrated that,in addition to M2 macrophages,silica exposure increased the protein levels of ARG1 in epithelial cells,a finding further confirmed by in vitro experiments using A549 and BEAS-2B cells.Moreover,accumulated ornithine induced epithelial-mesenchymal transition in vitro,increased extracellular matrix expres-sion in NIH 3T3 fibroblasts,and enhanced TGF-β1 levels in RAW264.7 cells.Co-exposure to ornithine and silica significantly induced the aberrant expression of fibrosis-associated proteins compared to silica exposure alone,characterized by increased levels of FN and𝛼-SMA,as well as decreased E-cad expression.These findings sug-gest that silica exposure up-regulates ARG1 in various cells,leading to ornithine accumulation,which in turn accelerates the progression of fibrosis.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention...BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention for its role in influencing their function,accessibility,and readiness for clinical use.AIM To identify the most suitable adipose source for MSC isolation and expansion for further applications.METHODS We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method.The MSCs were examined for their expansion using population doubling time,differentiation capacity using multilineage differentiation induction,surface markers using flow cytometry,and stability of chromosomes using the karyotyping method.Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.RESULTS MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2.All adipose-derived MSCs(AD-MSCs)exhibited the typical elongated,spindle-shaped morphology and comparable proliferation rate.They expressed positive surface markers(cluster of differentiation 73[CD73]:>97%,CD90:>98%,and CD105:>95%),and negative markers(<1%).All MSCs expressed similar levels of stemness genes(octamer-binding transcription factor 4,SRY-box 2,Krüppel-like factor,and MYC),colonyforming,and trilineage differentiation potential.Karyotyping analysis revealed normal chromosomal patterns in all samples,except one sample exhibiting a polymorphism(1qh+).Furthermore,the growth factors and cytokines of hepatocyte growth factor,vascular endothelial growth factor A,interleukin 6(IL-6),and IL-8 were detected in all AD-MSC conditioned media;but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs,respectively.CONCLUSION These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences,which are suitable for further expansion and various clinical applications.展开更多
We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)with...We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)within 10 min.Unlike conventional methods,sTED minimizes cell loss and enhances reproducibility,achieving>90%cell viability in mouse tissues and>60%in human tumors,with 1.5×10^(4)-2.5×10^(4)cells/mg yield from mouse liver.Tailored for biopsies and ultrasmall samples,sTED addresses critical standardization challenges in organoid-based research.展开更多
The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechani...The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechanical properties.Recent advances have increasingly revealed the beneficial impact of bioelectrical microenvironments on cellular behaviors,tissue regeneration,and therapeutic efficacy for excitable tissues.This review aims to unveil the mechanisms by which electrical microenvironments enhance the regeneration and functionality of excitable cells and tissues,considering both endogenous electrical cues from electroactive biomaterials and exogenous electrical stimuli from external electronic systems.We explore the synergistic effects of these electrical microenvironments,combined with structural and mechanical guidance,on the regeneration of excitable tissues using tissue engineering scaffolds.Additionally,the emergence of micro/nanoscale bioelectronics has significantly broadened this field,facilitating intimate interactions between implantable bioelectronics and excitable tissues across cellular,tissue,and organ levels.These interactions enable precise data acquisition and localized modulation of cell and tissue functionalities through intricately designed electronic components according to physiological needs.The integration of tissue engineering and bioelectronics promises optimal outcomes,highlighting a growing trend in developing living tissue construct-bioelectronic hybrids for restoring and monitoring damaged excitable tissues.Furthermore,we envision critical challenges in engineering the next-generation hybrids,focusing on integrated fabrication strategies,the development of ionic conductive biomaterials,and their convergence with biosensors.展开更多
Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significa...Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significant challenges in terms of safety and scalability for clinical applications.An alternative strategy involves the direct generation of organoids from readily available tissues.Herein,we report the generation of functional organoids representing all three germ layers from human adult adipose tissue without single-cell processing steps.Specifically,by employing a specialized suspension culture system,we have developed reaggregated microfat(RMF)tissues,which differentiated into mesodermal bone marrow organoids capable of reconstituting human normal hematopoiesis in immunodeficient mice,endodermal insulin-producing organoids that reversed hyperglycemia in streptozotocin(STZ)-induced diabetic mice,and ectodermal nervous-like tissues resembling neurons and neuroglial cells.These findings therefore highlight the potential of human adipose tissue as a safe,scalable,and clinically viable source for organoid-based regenerative therapies.展开更多
The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.T...The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.展开更多
The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infan...The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.展开更多
Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the...Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the stromal vascular fraction(SVF)and adipose-derived stem cells(ASCs)have gained considerable attention due to their potent regenerative and immunomodulatory capacities.SVF is a heterogeneous mixture of cells,whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion.Together,these cell populations(SVF and ASCs)are described as“living drugs”,as they are viable and act as dynamic biological agents within the body.Unlike conventional medicines,living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules,including cytokines,growth factors,and extracellular vesicles.These secreted factors can modulate the surrounding microenvironment,enhance tissue repair,and regulate immune responses.Such paracrine mechanisms often play a more significant role than direct cell replacement,making living drugs versatile tools for regenerative medicine.This review provides a comprehensive overview of SVF and ASCs as living drugs.It discusses their cellular composition,mechanisms of action,methods of isolation,and the regenerative biomolecules they secrete.Furthermore,it explores current and emerging clinical applications,challenges,and future innovations.展开更多
Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects....Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects.In this special issue,Bin Li’s team outlines the latest advances in minimally invasive implantable biomaterials for bone regeneration and different methods of achieving osteogenesis,with a focus on bioceramics and polymer materials and their applications in bone healing,vertebral augmenta-tion,implant fixation,tumor treatment of bone,and treatment of infections related to bone defects.Xinquan Jiang’s team constructs a novel photo-responsive multifunctional polyetheretherketone(PEEK)-based implant material(sPEEK/BP/E7)through the self-assembly of black phosphorus(BP)nanoplatelets,bioinspired poly-dopamine(PDA),and the biologically active short peptide E7 on sPEEK.The material exhibits effective osteogenic effects and good sterilization performance,providing a new idea for clinical application.展开更多
Tissue expansion is a widely utilized technique in plastic and reconstructive surgery;however,the biological mechanisms underlying the skin response remain poorly understood.We propose that tissue fluidity,the transit...Tissue expansion is a widely utilized technique in plastic and reconstructive surgery;however,the biological mechanisms underlying the skin response remain poorly understood.We propose that tissue fluidity,the transition of tissue from a solid-like state to a fluid-like state,plays a pivotal role in enabling the reorganization of the epidermal structure and cellular spatial order,which is essential for effective tissue expansion.Drawing parallels between fluidity in materials science and biological systems,we suggest that the fluid-like behavior in the skin may be critical for mechanical adaptability.Understanding the influence of tissue fluidity may open pathways for modulating this process,potentially enhancing tissue expansion efficiency,reducing procedural duration,and improving clinical outcomes.This perspective highlights the importance of investigating the biological dynamics of tissue fluidity and exploring the potential for targeted manipulation of fluidity-related pathways to optimize tissue expansion.Such advancements could profoundly affect regenerative and reconstructive surgical practices.展开更多
Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and infl...Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.展开更多
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金support from the National Institutes of Technology(R21EB030257,R01EB028143,R01HL153857,R01HL166522,R01CA282451,R56EB034702)National Science Foundation(CBET-EBMS-1936105,CISE-IIS-2225698)+1 种基金Chan Zuckerberg Initiative(2022316712,2024-347836)the Brigham Research Institute.
文摘In this study,we present the development of a cryobioink designed to fabricate anisotropic scaffolds that support both neural and muscle cell-alignment.Given the critical role of cellular organization in nerve fibers and neuromuscular junctions,we employed a vertical cryobioprinting-enabled ice-templating technique to create scaffolds with aligned microchannels.These channels facilitated cell-alignment,which is important in modeling neural and neuromuscular tissues.By integrating hyaluronic acid-methacrylate(HAMA)with gelatin methacryloyl and the necessary cryoprotective agent melezitose,we showcased that the cryobioink could preserve cell viability during freezing/thawing processes,even at low temperatures employed during cryobioprinting.We optimized HAMA concentration to enhance neural cell viability and alignment,and successfully constructed anisotropic scaffolds featuring distinct sections that contained muscle and neural cells,establishing a model for neuromuscular junctions.The resulting models provide a versatile platform for studying nerve fibers and neuromuscular dysfunctions,offering potential advancements in neural regeneration research.
基金Support by Sichuan Science and Technology Program[2023YFSY0026,2023YFH0004]Guangzhou Huashang University[2024HSZD01,HS2023JYSZH01].
文摘Soft-tissue motion introduces significant challenges in robotic teleoperation,especially in medical scenarios where precise target tracking is critical.Latency across sensing,computation,and actuation chains leads to degraded tracking performance,particularly around high-acceleration segments and trajectory inflection points.This study investigates machine learning-based predictive compensation for latency mitigation in soft-tissue tracking.Three models—autoregressive(AR),long short-term memory(LSTM),and temporal convolutional network(TCN)—were implemented and evaluated on both synthetic and real datasets.By aligning the prediction horizon with the end-to-end system delay,we demonstrate that prediction-based compensation significantly reduces tracking errors.Among the models,TCN achieved superior robustness and accuracy on complex motion patterns,particularly in multi-step prediction tasks,and exhibited better latency–horizon compatibility.The results suggest that TCN is a promising candidate for real-time latency compensation in teleoperated robotic systems involving dynamic soft-tissue interaction.
基金supported by the National Key Research and Development Program of China(2021YFF1000602)the National Natural Science Foundations(32202642)the earmarked fund for CARS-35-PIG.
文摘Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid and nutrient components between the adipose tissue of Bamei pigs and commercial pigs are still unclear.The study employed UPLC-MS/MS to quantify the composition of lipids and metabolites in the backfat of both Bamei and Large White pigs.A total of 428 lipids and 193 metabolites were significantly different between the 2 groups.Specifically,Bamei pig backfat exhibited altered levels of various lipids and metabolites that may potentially contribute to nutritional and flavor differences,including unsaturated triglycerides,free fatty acids,medium-chain triglycerides,essential amino acids,vitamins and antioxidants,while maintaining reduced cholesterol levels.Furthermore,we delved into the molecular mechanisms underlying these nutritional differences by analyzing significantly different 431 m RNAs and 865 proteins and integrating the regulatory network of protein-metabolite-lipid pathway.Importantly,in the pyruvate metabolic pathway of Bamei pigs,the bioprocess of lactate production was inhibited but the acetyl-Co A production was activated,suggesting the possibility that energy allocation favors the biogenesis of lipid precursors.These findings may contribute to guiding industrial food producers in enhancing the quality of lard at the genetic and molecular levels.
基金support from the National Natural Science Foundation of China(No.82472440)Hubei Provincial Natural Science Foundation of China(No.2023AFB141)+1 种基金the National Medical Products Administration Key Laboratory for Dental Materials(No.PKUSS20240401)the Cross-Research Support Program from Huazhong University of Science and Technology。
文摘The esophagus is a tubular organ essential for maintaining normal eating function in humans.However,the replacement of the esophagus remains challenging in clinical settings.Although tissue engineering scaffolds are a promising alternative solution,their fabrication is difficult due to the complex structure and function of the esophagus.This review describes the existing fabrication methods for esophageal tubular scaffolds,including decellularization,casting,electrospinning,three dimensional(3 D)bioprinting,and pin-frogging.Also discussed are the stimulation cues of the fabricated esophageal tubular scaffold that induce esophageal muscle and epithelial cells.Finally,this review emphasizes three important concerns for esophageal tubular scaffolds:leakage and porosity,elasticity and proliferation of smooth muscle cells,and biocompatibility and structural fidelity of biomaterials.
基金supported by FWO(Fonds voor Wetenschappelijk Onderzoek),grant number G07562NFWO(to BB)。
文摘Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.
基金supported by the National Natural Science Foundation of China(82427808,61875085)the Jiangsu Provincial University Natural Science Foundation(25KJB413004)+1 种基金the Nanjing Health Science and Technology Development Foundation(ZKX24043)the Fundamental Research Funds for the Central Universities(NJ2024029).
文摘Microwave ablation(MWA)is a minimally invasive technique for treating hepatic tumors,necessitating precise monitoring to ensure treatment efficacy and minimize damage to surrounding tissues.This study explores the potential of photoacoustic imaging(PAI)in monitoring MWA by examining ex vivo porcine liver tissues.In this study,a comprehensive analysis of photoacoustic signals was performed to compare the main lobe width(MLW)between ablated and normal regions in porcine liver tissue.Histological staining with succinate dehydrogenase(SDH)and shear wave elastography(SWE)were employed to validate the changes in tissue elasticity after ablation.The analysis demonstrated a notable reduction in the MLW of the average A-lines in ablated tissues compared to nonablated regions(p<0.01).This reduction,attributed to increased tissue density and enhanced elasticity,indicates accelerated sound propagation in thermally ablated areas,which then serves as a critical parameter for mapping tissue characteristics.The reconstruction of the MLW distribution successfully delineated the ablated regions,and was consistent with the results of SDH staining and SWE.In addition,MLW-based imaging exhibited higher spatial resolution compared to SWE.Incorporating MLW analysis into PAI may be a promising strategy to improve the accuracy and effectiveness of MWA monitoring in clinical settings.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金supported by the National Natural Science Foundation of China,Nos.92148206,82071330(both to ZT)a grant from the Major Program of Hubei Province,No.2023BAA005(to ZT)+1 种基金a grant from the Key Research and Discovery Program of Hubei Province,No.2021BCA109(to ZT)the Research Foundation of Tongji Hospital,No.2022B37(to PZ)。
文摘Recombinant tissue plasminogen activator is commonly used for hematoma evacuation in minimally invasive surgery following intracerebral hemorrhage.However,during minimally invasive surgery,recombinant tissue plasminogen activator may come into contact with brain tissue.Therefore,a thorough assessment of its safety is required.In this study,we established a mouse model of intracerebral hemorrhage induced by type VII collagenase.We observed that the administration of recombinant tissue plasminogen activator without hematoma aspiration significantly improved the neurological function of mice with intracerebral hemorrhage,reduced pathological damage,and lowered the levels of apoptosis and autophagy in the tissue surrounding the hematoma.In an in vitro model of intracerebral hemorrhage using primary cortical neurons induced by hemin,the administration of recombinant tissue plasminogen activator suppressed neuronal apoptosis,autophagy,and endoplasmic reticulum stress.Transcriptome sequencing analysis revealed that recombinant tissue plasminogen activator upregulated the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway in neurons.Moreover,the phosphoinositide 3-kinase inhibitor LY294002 abrogated the neuroprotective effects of recombinant tissue plasminogen activator in inhibiting excessive apoptosis,autophagy,and endoplasmic reticulum stress.Furthermore,to specify the domain of recombinant tissue plasminogen activator responsible for its neuroprotective effects,various inhibitors were used to target distinct domains.It has been revealed that the epidermal growth factor receptor inhibitor AG-1478 reversed the effect of recombinant tissue plasminogen activator on the phosphoinositide 3-kinase/RAC-alpha serine/threonineprotein kinase/mammalian target of rapamycin pathway.These findings suggest that recombinant tissue plasminogen activator exerts a direct neuroprotective effect on neurons following intracerebral hemorrhage,possibly through activation of the phosphoinositide 3-kinase/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin pathway.
基金supported by the National Natural Science Foundation of China(No.81973466)the National Administration of Traditional Chinese Medicine Youth Qihuang Scholars Support Project,and the Program of Graduate Innovation Research in Shanxi Province(No.2023KY019).
文摘Silicosis is one of the most serious and prevalent occupational diseases globally,characterized by typical silicotic nodules and fibrosis.Recent studies suggest that the perinodular zone of the lung shares certain characteristics with the nodules themselves.In this study,a silicotic rat model was established via a single intratracheal in-stillation of a 50 mg/mL silica suspension.Pulmonary anatomical and pathological examinations revealed that silica deposition induced severe alterations in both the nodular and perinodular tissues.Subsequently,pseudo-targeted metabolomics analysis revealed that abnormally elevated ornithine levels were closely associated with the progression of silicosis,from normal to perinodular and finally to nodular tissues.Immunofluorescent stain-ing demonstrated that,in addition to M2 macrophages,silica exposure increased the protein levels of ARG1 in epithelial cells,a finding further confirmed by in vitro experiments using A549 and BEAS-2B cells.Moreover,accumulated ornithine induced epithelial-mesenchymal transition in vitro,increased extracellular matrix expres-sion in NIH 3T3 fibroblasts,and enhanced TGF-β1 levels in RAW264.7 cells.Co-exposure to ornithine and silica significantly induced the aberrant expression of fibrosis-associated proteins compared to silica exposure alone,characterized by increased levels of FN and𝛼-SMA,as well as decreased E-cad expression.These findings sug-gest that silica exposure up-regulates ARG1 in various cells,leading to ornithine accumulation,which in turn accelerates the progression of fibrosis.
文摘BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention for its role in influencing their function,accessibility,and readiness for clinical use.AIM To identify the most suitable adipose source for MSC isolation and expansion for further applications.METHODS We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method.The MSCs were examined for their expansion using population doubling time,differentiation capacity using multilineage differentiation induction,surface markers using flow cytometry,and stability of chromosomes using the karyotyping method.Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.RESULTS MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2.All adipose-derived MSCs(AD-MSCs)exhibited the typical elongated,spindle-shaped morphology and comparable proliferation rate.They expressed positive surface markers(cluster of differentiation 73[CD73]:>97%,CD90:>98%,and CD105:>95%),and negative markers(<1%).All MSCs expressed similar levels of stemness genes(octamer-binding transcription factor 4,SRY-box 2,Krüppel-like factor,and MYC),colonyforming,and trilineage differentiation potential.Karyotyping analysis revealed normal chromosomal patterns in all samples,except one sample exhibiting a polymorphism(1qh+).Furthermore,the growth factors and cytokines of hepatocyte growth factor,vascular endothelial growth factor A,interleukin 6(IL-6),and IL-8 were detected in all AD-MSC conditioned media;but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs,respectively.CONCLUSION These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences,which are suitable for further expansion and various clinical applications.
基金supported by the National Natural Science Foundation of China(Nos.32371470 and 82341019)the Department of Science and Technology of Guangdong Province(No.2023B0909020003).
文摘We developed a small-tissue extraction device(sTED),an automated system that integrates 1-min mechanical dissociation and enzymatic digestion to extract viable primary cells from ultrasmall tissue samples(5-20 mg)within 10 min.Unlike conventional methods,sTED minimizes cell loss and enhances reproducibility,achieving>90%cell viability in mouse tissues and>60%in human tumors,with 1.5×10^(4)-2.5×10^(4)cells/mg yield from mouse liver.Tailored for biopsies and ultrasmall samples,sTED addresses critical standardization challenges in organoid-based research.
基金financially supported by the National Natural Science Foundation of China(Nos.52125501,52405325)the Key Research Project of Shaanxi Province(Nos.2021LLRH-08,2024SF2-GJHX-34)+5 种基金the Program for Innovation Team of Shaanxi Province(No.2023-CX-TD17)the Postdoctoral Fellowship Program of CPSF(No.GZB20230573)the Postdoctoral Project of Shaanxi Province(No.2023BSHYDZZ30)the Basic Research Program of Natural Science in Shaanxi Province(No.2021JQ-906)the China Postdoctoral Science Foundationthe Fundamental Research Funds for the Central Universities。
文摘The inherent complexities of excitable cardiac,nervous,and skeletal muscle tissues pose great challenges in constructing artificial counterparts that closely resemble their natural bioelectrical,structural,and mechanical properties.Recent advances have increasingly revealed the beneficial impact of bioelectrical microenvironments on cellular behaviors,tissue regeneration,and therapeutic efficacy for excitable tissues.This review aims to unveil the mechanisms by which electrical microenvironments enhance the regeneration and functionality of excitable cells and tissues,considering both endogenous electrical cues from electroactive biomaterials and exogenous electrical stimuli from external electronic systems.We explore the synergistic effects of these electrical microenvironments,combined with structural and mechanical guidance,on the regeneration of excitable tissues using tissue engineering scaffolds.Additionally,the emergence of micro/nanoscale bioelectronics has significantly broadened this field,facilitating intimate interactions between implantable bioelectronics and excitable tissues across cellular,tissue,and organ levels.These interactions enable precise data acquisition and localized modulation of cell and tissue functionalities through intricately designed electronic components according to physiological needs.The integration of tissue engineering and bioelectronics promises optimal outcomes,highlighting a growing trend in developing living tissue construct-bioelectronic hybrids for restoring and monitoring damaged excitable tissues.Furthermore,we envision critical challenges in engineering the next-generation hybrids,focusing on integrated fabrication strategies,the development of ionic conductive biomaterials,and their convergence with biosensors.
基金supported by the National Natural Science Foundation of China(82372535 to Ru-Lin Huang and 82361138568 to Qingfeng Li)the Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by Science and Technology Commission of Shanghai Municipality(22MC1940300)the Shanghai Plastic Surgery Research Center of Shanghai Priority Research Center(2023ZZ02023)。
文摘Current organoid-generation strategies rely predominantly on intricate in vitro manipulations of dissociated stem cells,including isolation,expansion,and genetic modification.However,these approaches present significant challenges in terms of safety and scalability for clinical applications.An alternative strategy involves the direct generation of organoids from readily available tissues.Herein,we report the generation of functional organoids representing all three germ layers from human adult adipose tissue without single-cell processing steps.Specifically,by employing a specialized suspension culture system,we have developed reaggregated microfat(RMF)tissues,which differentiated into mesodermal bone marrow organoids capable of reconstituting human normal hematopoiesis in immunodeficient mice,endodermal insulin-producing organoids that reversed hyperglycemia in streptozotocin(STZ)-induced diabetic mice,and ectodermal nervous-like tissues resembling neurons and neuroglial cells.These findings therefore highlight the potential of human adipose tissue as a safe,scalable,and clinically viable source for organoid-based regenerative therapies.
基金supported by the National Natural Science Foundation of China(Grant No.52473121,52403370 and 52221006)Fundamental Research Funds for the Central Universities(buctrc202020,buctrc202312).
文摘The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.
文摘The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.
文摘Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the stromal vascular fraction(SVF)and adipose-derived stem cells(ASCs)have gained considerable attention due to their potent regenerative and immunomodulatory capacities.SVF is a heterogeneous mixture of cells,whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion.Together,these cell populations(SVF and ASCs)are described as“living drugs”,as they are viable and act as dynamic biological agents within the body.Unlike conventional medicines,living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules,including cytokines,growth factors,and extracellular vesicles.These secreted factors can modulate the surrounding microenvironment,enhance tissue repair,and regulate immune responses.Such paracrine mechanisms often play a more significant role than direct cell replacement,making living drugs versatile tools for regenerative medicine.This review provides a comprehensive overview of SVF and ASCs as living drugs.It discusses their cellular composition,mechanisms of action,methods of isolation,and the regenerative biomolecules they secrete.Furthermore,it explores current and emerging clinical applications,challenges,and future innovations.
文摘Tissue engineering and regenera-tive medicine have shown signifi-cant potential for repairing and regenerating damaged tissues and can be used to provide personalized treatment plans,with broad applica-tion prospects.In this special issue,Bin Li’s team outlines the latest advances in minimally invasive implantable biomaterials for bone regeneration and different methods of achieving osteogenesis,with a focus on bioceramics and polymer materials and their applications in bone healing,vertebral augmenta-tion,implant fixation,tumor treatment of bone,and treatment of infections related to bone defects.Xinquan Jiang’s team constructs a novel photo-responsive multifunctional polyetheretherketone(PEEK)-based implant material(sPEEK/BP/E7)through the self-assembly of black phosphorus(BP)nanoplatelets,bioinspired poly-dopamine(PDA),and the biologically active short peptide E7 on sPEEK.The material exhibits effective osteogenic effects and good sterilization performance,providing a new idea for clinical application.
基金supported by the National Natural Science Foundation of China(grant nos.82102343 and 82372536)the Shanghai Municipal Health Commission Health Industry Clinical Research Special Program(grant no.20244Y0031)the Shanghai“Rising Stars of Medical Talents”Youth Development Program(Youth Medical Talents-Specialist Program).
文摘Tissue expansion is a widely utilized technique in plastic and reconstructive surgery;however,the biological mechanisms underlying the skin response remain poorly understood.We propose that tissue fluidity,the transition of tissue from a solid-like state to a fluid-like state,plays a pivotal role in enabling the reorganization of the epidermal structure and cellular spatial order,which is essential for effective tissue expansion.Drawing parallels between fluidity in materials science and biological systems,we suggest that the fluid-like behavior in the skin may be critical for mechanical adaptability.Understanding the influence of tissue fluidity may open pathways for modulating this process,potentially enhancing tissue expansion efficiency,reducing procedural duration,and improving clinical outcomes.This perspective highlights the importance of investigating the biological dynamics of tissue fluidity and exploring the potential for targeted manipulation of fluidity-related pathways to optimize tissue expansion.Such advancements could profoundly affect regenerative and reconstructive surgical practices.
基金supported by grants from National Natural Science Foundation of China(32125038)National Key Research and Development Program of China(grant number 2023YFD1801100 and 2023YFD1800804)+1 种基金the Key Research and Development Program of the Xinjiang Uygur Autonomous Region(No.2024B02016)the 2115 Talent Development Program of China Agricultural University.
文摘Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.
