Barrier tissues such as the endothelium are critical in the regulation of mass transfer throughout the body.Trans-endothelium/epithelium electrical resistance(TEER)is an important bioelectrical measurement technique t...Barrier tissues such as the endothelium are critical in the regulation of mass transfer throughout the body.Trans-endothelium/epithelium electrical resistance(TEER)is an important bioelectrical measurement technique to monitor barrier integrity.Although available on the market,TEER sensors are usually expensive and bulky and do not allow customization around experimental setups like specific microfluidic settings.We recently reported a customizable TEER sensor built on Arduino.In this paper,we significantly advanced a new generation of TEER sensors characterized by 1)a large dynamic range of 242-11,880Ω·cm^(2) with high accuracy(>95%),which covers common needs for TEER studies,2)a coupling three-dimensional(3D)-printed microfluidic system enabling modular cell integration and flow-based barrier studies,3)customizable on-off cycles to significantly reduce cell exposure to the current,and 4)automated continuous measurements with customizable intervals.With this sensor system,we investigated how doxorubicin could impair the endothelium layer’s permeability,at a 1-min interval for 24 h.Endothelium toxicity is a new research direction under cardiotoxicity,with many aspects unknown.We found that a clinically relevant dosage did not change the endothelium integrity significantly until approximately 16 h of treatment,after that,the TEER started to drop(showing higher permeability),followed by a slight restoration of its barrier integrity.With an excess dosage(2.5μM),the TEER started to drop significantly after 5 h and did not show recovery afterward,indicating endothelium toxicity.Overall,we report a new TEER sensor that can monitor continuous drug toxicity on barrier tissues.The customizable features make it translational for various other studies,such as personalized dosage determination on stem cell-derived tissue barriers,and transient barrier permeability variations under diseased conditions.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
The decreasing of hazard ratio for cancer incidence (HRCVD) in the range of twenty native tissues (lung, liver, brain, hematologic, neuroendocrine renal, pancreas, lymphoid, bladder, colon, lip-oral-head-neck, leukocy...The decreasing of hazard ratio for cancer incidence (HRCVD) in the range of twenty native tissues (lung, liver, brain, hematologic, neuroendocrine renal, pancreas, lymphoid, bladder, colon, lip-oral-head-neck, leukocytic, rectum and anus, thyroid, soft tissue, prostate, skin, ovarian, breast, uterine) as much, as decreasing of the level of cardiovascular pathology (CVD) in the host before malignization, have been described by C.F. Bell et al. in 2023. Earlier, in 2022, the decreasing of 5-year mortality from cancer in similar range of tissues discussed by us as the inverse dependence from the content of stem CD34 markers in tissues before malignization, with example of population in England. In present article we investigate the interrelation between both data more thoroughly, using accessible and more representative populations level of the data. The analysis shows that high level of HRCVD is able to predicts only high cancer death for tissue sites in the beginning of the range, being applied to the referent data of cancer cases and deaths in estimated population of USA 2024. Along with this, an increasing the content of CD34 stem marker in the native tissues of the same range was favorite for increasing of cancer’s cases at the end of the range, diminishing, in parallel, the signs of vasculo-endothelial pathology, i.e. HR CVD. Thus, the cases (incidence) of cancer depend directly rather from content of CD34, which preexisted in native sites, than that from HRCVD. Further analysis shows that CD34 content averaged over twenty cites dominates over that CD2 marker of total T-cells more than 7 times, in oppose to their ratio in the blood. The enhancement of stem CD34 marker in the range of tissues is accompanied by unidirectional rising of its maturing derivatives, vasculo-endothelial CD31 and total T-cells CD2 markers, which contents relate positively to increasing of cancer death in US population 2024. The increase of CD34 decreases cancer mortality (death: cases) in sites, but indirectly, rather due to enhancement of the denominator. The high HRCVD (more than 1.0) in range of 20 tissues, concerns of those of them, which have had highest mitotic activity (by Ki67), but lowest “stemness” (by CD34), “vascularity” (by CD31), cancer’s incidence (cases) and the worse results of therapy. Oppositely, the normal tissue with lowest HRCVD (below 1.0) and Ki67, but highest CD34, CD31, and cancer incidence (cases) are more sensitive to treatment. Thus, the residential hematopoietic “stemness” in native tissues acts as natural protectors for cardio-vascular system and promoter for cancer incidence in them. The steady and irreversible exhaustion of current regenerative resource (CRR) of BM, which assumed by us as a product of CD34 number and average telomeres length, manifests itself in acceleration of non-malignant CVD and deceleration of malignancy in population +70 (in term the death per 105), according to data extracted from WHO Mortality Database. The similar deficit of CD34 arises artificially during cytotoxic treatment of cancer, when rapid waste of local CRR forces malignant cells to search more “stemness” cites. The competition between malignant and native tissues of the host for scanty CRR seems to be the most important factor for evaluation and prediction of prevalence, curability, and long-term results in oncology.展开更多
Physiological and pathological processes such as embryonic development and tumor progression involve complicated interplay of mechanical,chemical,and biological factors cross a wealth of spatial and temporal scales.In...Physiological and pathological processes such as embryonic development and tumor progression involve complicated interplay of mechanical,chemical,and biological factors cross a wealth of spatial and temporal scales.In this paper,we review some recent advances in the field of mechano-chemo-biological coupling theories in biological tissues and cells,and their applications in cancer,immunological,and other diseases.Key issues in the mechano-chemo-biological modeling of specific dynamic processes of cells and tissues are discussed.A mechano-chemo-biological growth theory is introduced,which interrogates the mechanical,chemical,and biological coupling mechanisms underpinning the growth,remodeling and degradation of tissues such as tumors.The mechano-chemo-biological instabilities of cells and tissues are systematically analyzed,with particular attention to those induced by coupled mechano-chemo-biological mechanisms.Furthermore,we provide a mechano-chemo-biological multiscale computational framework to investigate the dynamic processes of cells and tissues,for example,the migration and metastasis of cancer cells.Besides,we discuss some recent theoretical and experimental findings in the mechano-chemo-biological dynamics of collective cells.Finally,perspectives and clinical applications of the mechanochemo-biological theories of cells and tissues are proposed.展开更多
Smoking is a well-established risk factor for periodontitis,yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood.Recent advances in spatial transcriptomics have enabl...Smoking is a well-established risk factor for periodontitis,yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood.Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution,offering new opportunities to investigate these mechanisms.In this study,we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals,including those with periodontitis,those with smoking-associated periodontitis,and healthy controls.Our analysis revealed that smoking disrupts the epithelial barrier integrity,induces fibroblast alterations,and dysregulates fibroblast–epithelial cell communication,thereby exacerbating periodontitis.The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact,which further promotes the progression of smoking-induced periodontal disease.Importantly,we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype,alleviated epithelial inflammation,and reduced alveolar bone resorption.These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial–macrophage interaction as a therapeutic strategy.Furthermore,this study establishes an essential information resource for investigating the effects of smoking on periodontitis,providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.展开更多
Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune resp...Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune response,and QTL mapping data to illustrate the interactions between pathogen and host immune system,will be an effective tool for identification of disease resistance genes in pigs.The immune system of an organism is the source of disease resistance in livestock,consisting of various immune tissues,as well as the immune cells and cytokines they produced.However,comprehensive systematic studies on transcriptome of porcine immune tissues are still rare.Poly(I:C),as a viral mimic,is commonly used to study immune responses of the body during viral infections,and serves as a valuable tool for investigating immune mechanisms in swine.Results WGCNA analysis identified core immune genes across six immune tissues(bone marrow,jejunum,lymph node,PBMC,spleen,thymus)in Landrace pigs,which are also crucial for the development of PBMCs.The examination of the changes in the proportion of immune cells during three developmental stages(1-month-old,4-month-old,7-month-old)shows a shift from innate immunity to humoral immunity.By integrating different epigenetic genomics datasets,we identified several core immune genes and their causal variants,including IFI44,IFIT5,EIF2AK2 and others,which are closely related to immune development and response.Functional validation studies reveal that the IFI44 gene acts as a negative regulator of the antiviral response;its inhibition effect significantly reduced Poly(I:C)-induced cell necrosis,while enhancing apoptosis to combat viral infections.Conclusion Our study elucidated the fundamental transcriptional program in porcine immune tissues and the immunodynamics underlying development of PBMCs,identifying many core immune genes,including IFI44,which plays a critical negative regulator role in the antiviral response,providing valuable insights for breeding programs aimed at enhancing pig disease resistance.展开更多
The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales hav...The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales have been employed to characterize the mechanical behavior of soft tissues,which is essential for developing accurate tissue simulants and numerical models.This review comprehensively explores the mechanical properties of soft tissues,examining experimental methods,mechanical models,numerical simulations,and the progress in materials that mimic the mechanical performance of soft tissues.Finally,it reviews the damage and protection of human tissues under kinetic impacts,anticipating the future construction of soft tissue surrogate targets.The aim is to provide a systematic theoretical foundation and the latest advancements in the field,addressing the design,preparation,and quantitative modeling of biomimetic materials,thereby promoting the in-depth development of soft tissue mechanics and its applications.展开更多
Our gosl was to develop and experimentally validate a polarization-interferene method for phsae scanning of laser speckle fields generated by diffuse layers of birefringent biological tissues.This method isolates and ...Our gosl was to develop and experimentally validate a polarization-interferene method for phsae scanning of laser speckle fields generated by diffuse layers of birefringent biological tissues.This method isolates and uses new diagnostic parameters related to the"phsse WAvEs of local depolarization".We combined polarization-interferenæregistration with phase scanning of complex amplitude distributions in diffuse Laser speckle fields to detect phase waves of local depolarization in birefringent fibrillar networks of biological tisue and messure their modulation depth.This eppгоsch led to the discovery of new criteria for differentiating verious necrotic changes in diffuse histological samples of myocardial tisue from decmsed individuals with"ischemic heart disase(IHD)--cute coronary insufficiency(ACT)",even in the presænce of a high level of depolarized bckground.To evaluate the degree of necrotic changes in the optical anisotropy of difuse myocardial Layers,a new quantitative parameter--modulation depth of local depolarization wave fluctustions-has been proposed.Using this approsch,for the first time,differentiation of diffuse myocardial samples from decessed individuals with IHD and ACI was achieved witha very good 90.45%and outstanding aocuracy of 95.2%.展开更多
Spinal cord injury presents a significant challenge in regenerative medicine due to the complex and deli-cate nature of neural tissue repair.This study aims to design a conductive hydrogel embedded with magnetic MgFe_...Spinal cord injury presents a significant challenge in regenerative medicine due to the complex and deli-cate nature of neural tissue repair.This study aims to design a conductive hydrogel embedded with magnetic MgFe_(2)O_(4) nanoparticles to establish a bioelectrically active and spatially stable microenvironment that promotes spinal cord regeneration through computational analysis(BIOVIA Materials Studio).Hydrogels,known for their biocompatibility and extracellular matrix-mimicking properties,support essential cellular behaviors such as adhesion,proliferation,and migration.The integration of MgFe_(2)O_(4) nanoparticles imparts both electrical conductivity and magnetic responsiveness,enabling controlled transmission of electrical signals that are crucial for guiding cellular processes like differentiation and directed migration.Furthermore,the hydrogel acts as a delivery medium,facilitating the adsorption of MgFe_(2)O_(4) nanoparticles onto spinal tissue through strong Van der Waals and intramolecular interactions.The computational simulations revealed a robust adsorption profile,with a binding distance of 20.180Åand a cumulative adsorption energy of 2740.42 kcal/mol,indicating stable nanoparticle-tissue interactions.Pressure-dependent sorption analysis further demonstrated that reduced pressure conditions enhance adsorption strength,promoting tighter material-tissue integration.The adverse Van der Waals energy and increased intramolecular energy observed under these conditions underscore the importance of optimized adsorption settings for functional tissue interface formation.Altogether,the conductive hydrogel-MgFe_(2)O_(4) composite system offers a promising therapeutic platform by combining structural support,electrical stimulation,and magnetic guidance,thereby enhancing cell-material interactions and fostering an environment conducive to spinal cord tissue repair.展开更多
Bioprinting is a revolutionary technology within the field of tissue engineering that enables the precise fabrication of three-dimensional(3D)tissue constructs.It combines the principles of engineering and biology to ...Bioprinting is a revolutionary technology within the field of tissue engineering that enables the precise fabrication of three-dimensional(3D)tissue constructs.It combines the principles of engineering and biology to create structures that closely mimic the complexity of native human tissues,facilitating advancements in regenerative medicine and personalized healthcare.This review paper systematically explores the challenges and design requirements in the fabrication of 3D biomimetic tissue constructs,emphasizing the need for advanced bioprinting strategies.Achieving biomimicry involves creating 3D anatomically relevant structures,biomimetic microenvironments,and vascularization.The focus is on overcoming existing bottlenecks through advancements in both fabrication techniques and bio-inks.Future directions in bioprinting are outlined,including multi-modal bioprinting systems,in-situ bioprinting,and the integration of machine learning into bioprinting processes.The critical role of bio-inks and printing methodologies in influencing cell viability is highlighted,providing insights into strategies for enhancing cellular functionality throughout the bioprinting process.Furthermore,the paper addresses post-fabrication considerations,particularly in accelerating tissue maturation,as a pivotal component for advancing the clinical applicability of bioprinted tissues.By navigating through the challenges,innovations,and prospects of advanced bioprinting strategies,this review highlights the transformative impact on tissue engineering.Pushing the boundaries of technological capabilities,these strategies hold the promise of groundbreaking advancements in regenerative medicine and personalized healthcare.Ultimately,the integration of these advanced techniques into bioprinting processes will pave the way for the development of more highly biomimetic and functional bioprinted tissues.展开更多
Characterization of the distribution and accurate counting of RNA molecules in the context of tissues is necessary to understand their complexity and heterogeneity.Single-molecule fluorescence in situ hybridization re...Characterization of the distribution and accurate counting of RNA molecules in the context of tissues is necessary to understand their complexity and heterogeneity.Single-molecule fluorescence in situ hybridization reveals the abundance and distribution of RNA and resolves different cell types in complex tissues.Especially,off-target binding and nonspecific adsorption of probes are prone to producing nonspecific amplification.Herein,we present highly de-noising amplified imaging,which leverages a sitespecific cleavage-amplifying design to achieve accurate counting of RNA in tissues.Our method avoids adding probe as primer,decreases nonspecific spots of single cells from 7 to nearly zero,and enables RNA imaging in uncleared tissue sections with nearly zero noise.We demonstrate the efficacy of this method on various thickness of mouse tissue sections.We envision this approach will serve as a tool to revealing the information content from patient samples for biomedical purpose.展开更多
Tendon and ligament injuries represent a major orthopedic challenge with limited effective regenerative options.In an original research study by Yang et al de-veloped a tissue engineering approach combining aligned na...Tendon and ligament injuries represent a major orthopedic challenge with limited effective regenerative options.In an original research study by Yang et al de-veloped a tissue engineering approach combining aligned nanofiber scaffolds with cyclic uniaxial stretching to promote tenogenic differentiation in bone marrow-derived mesenchymal stem cells.Their results provide critical insight into how structural and mechanical cues can synergize to generate ligament-like tissue in vitro.This editorial contextualizes their findings within the broader field of ligament regeneration and highlights the translational potential of their strategy.展开更多
[Objective] The aim was to learn the resistance of different tissues and organs of transgenic cotton to Spodoptera exigua （Hbner）. [Method] Flowers,the 1st,the 3rd,the 6th and the 14th leaves from the top of 33B,GK1...[Objective] The aim was to learn the resistance of different tissues and organs of transgenic cotton to Spodoptera exigua （Hbner）. [Method] Flowers,the 1st,the 3rd,the 6th and the 14th leaves from the top of 33B,GK12 and SGK321 were used to feed S. exigua neonates respectively. Survival larvae and dead ones were counted on the 3rd,the 7th,the 10th,the 16th and the 19th day; meanwhile,the pupae amount was recorded,and the pupae weight was measured at the 24th h after pupation. [Result] The survival curves,pupation rates and pupae weights of S. exigua feeding on different tissues of transgenic cotton were not significantly different from those of S. exigua feeding on the corresponding tissues of conventional cotton; pupation rate of S. exigua feeding on different leaves of the same cotton variety were not significantly different from each other,but all higher than that of S. exigua feeding on the flowers of that cotton; and there were no differences among pupation weights of S. exigua feeding on different leaves or flowers of the same cotton variety. [Conclusion] Transgenic cotton showed weak resistance to S. exigua. Hence,in the transgenic cotton fields,more attention should be paid to occurrence trend of S. exigua and its control.展开更多
It has been hypothesized that under iron stress high ferric chelate reductase (FCR) activity in the absorptive root of plants tolerant to iron_deficiency will be induced and result in subsequent Fe 2+ transport a...It has been hypothesized that under iron stress high ferric chelate reductase (FCR) activity in the absorptive root of plants tolerant to iron_deficiency will be induced and result in subsequent Fe 2+ transport across the plasmalemma. The activity of FCR and expression of FCR gene (FRO2) in Citrus junos Sieb. ex Tanaka tolerant to iron_deficiency and Poncirus trifoliata (L.) Raf. susceptible to iron_deficiency were determined to elucidate the physiological difference which causes the different tolerance of the two citrus rootstocks to iron stress. The activity of FCR was detectable in excised roots and was stimulated about 20_times in C. junos and only about 3_times in P. trifoliata under iron deficiency for four weeks. The FRO2 of Arabidopsis was used as a probe, the tissue print technique was used to ascertain the expression of the FCR gene in C. junos and P. trifoliata under iron stress. High_level transcripts were observed in the absorptive root, young green stem as well as new leaf of C. junos under iron stress for two weeks, and the transcripts were accumulated only slightly in P. trifoliata at the same time. The results showed that the obvious increase of FCR activity was an important reason for the tolerance of C. junos to iron_deficiency, and the regulation of FCR activity seemed to be at the transcriptional level, and the expression of FRO2 occurred in the root, stem and leaf.展开更多
Leaves from three_year_old solar greenhouse nectarine trees ( Prunus persica L. var. nectarina Ait. “Zao Hong Yan”) were used as materials in this study. It was the first time that the ultrastructural charact...Leaves from three_year_old solar greenhouse nectarine trees ( Prunus persica L. var. nectarina Ait. “Zao Hong Yan”) were used as materials in this study. It was the first time that the ultrastructural characteristics of phloem tissues of source leaves were observed and compared in normal and weak light intensities using the transmission electron microscopy. Results showed that the average diameters of companion cells (CC) and sieve elements (SE) of all kinds of veins were bigger in normal than that in weak light intensity, indicating that light could influence the cell development and growth. Dense cytoplasm with abundant mitochondria, endoplasmic reticulums, multivesicular bodies, vesicles and plastids were observed in normal light intensity. On the contrary, CC with small vacuolar structures and few mitochondrias, endoplasmic reticulums were shown in weak light. Misalignment of grana thylakoid margins of nectarine leaves also was seen in weak light. The sieve pores of SEs were obstructed in weak light. Chloroplasts with numerous starch grains and few mitochondrias were noticed in the mesophyll cell (MES) surrounding the bundle sheath in weak light. The storage of starch grains appeared to result from an unbalance between photosynthate production and export of photosynthates. This observation provided a strong support to the point that most leaves export the most of assimilates in the light time. Plasmodesmal densities between SE/CC, CC/PP (phloem parenchyma cell), PP/PP and PP/BSC (bundle_sheath cell) decreased in weak light. Plasmodesmata were observed between CC/SE (NS) (nacreous_walled sieve element), PP/BSC in branch veins in normal light intensity, but not in weak light. Thus apoplasmic pathway may be the main mode of transport of assimilates in weak light, however symplasmic pathway may be the main mode of transport of assimilates in normal light intensity. These results demonstrated that the solar greenhouse nectarine trees could be adapted to the weak light via the ultrastructure variation of phloem tissues of the source leaves.展开更多
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
Amyloid protein aggregation plays a major role in multiple neurodegenerative diseases and is likely the primary driving force for the progression of most of these diseases.Multiple recent studies have highlighted that...Amyloid protein aggregation plays a major role in multiple neurodegenerative diseases and is likely the primary driving force for the progression of most of these diseases.Multiple recent studies have highlighted that the DNAJ homolog subfamily B member 6(DNAJB6)chaperone is particularly interesting,when it comes to preventing amyloidogenic proteins from aggregating.It has been shown that DNAJB6 can prevent the aggregation of polyglutamine-expanded proteins in models of Huntington’s disease.Likewise,it can suppress aggregation ofα-synuclein in models of Parkinson’s disease and other synucleinopathies.Finally,it has been shown that DNAJB6 can block aggregation of multiple additional amyloid proteins involved in Alzheimer’s disease and other tauopathies as well.We believe there is yet much to learn about the protective role of DNAJB6 in the brain,but this focused review summarizes,what we know so far of this chaperone.It describes the biological role of DNAJB6 in the brain and its interaction with Hsp70,with particular emphasis on the studies that show its ability to prevent amyloid protein aggregation in vitro and in vivo.Moreover,recent work on dysregulation of the expression of DNAJB6 in brain clinical tissue is discussed.Finally,we discuss potential therapeutic perspectives as we believe this protein is a promising druggable target.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
基金support from the Maryland Stem Cell Research Fund(MSCRF),USA(Grant No.:2023-MSCRFL-6015).
文摘Barrier tissues such as the endothelium are critical in the regulation of mass transfer throughout the body.Trans-endothelium/epithelium electrical resistance(TEER)is an important bioelectrical measurement technique to monitor barrier integrity.Although available on the market,TEER sensors are usually expensive and bulky and do not allow customization around experimental setups like specific microfluidic settings.We recently reported a customizable TEER sensor built on Arduino.In this paper,we significantly advanced a new generation of TEER sensors characterized by 1)a large dynamic range of 242-11,880Ω·cm^(2) with high accuracy(>95%),which covers common needs for TEER studies,2)a coupling three-dimensional(3D)-printed microfluidic system enabling modular cell integration and flow-based barrier studies,3)customizable on-off cycles to significantly reduce cell exposure to the current,and 4)automated continuous measurements with customizable intervals.With this sensor system,we investigated how doxorubicin could impair the endothelium layer’s permeability,at a 1-min interval for 24 h.Endothelium toxicity is a new research direction under cardiotoxicity,with many aspects unknown.We found that a clinically relevant dosage did not change the endothelium integrity significantly until approximately 16 h of treatment,after that,the TEER started to drop(showing higher permeability),followed by a slight restoration of its barrier integrity.With an excess dosage(2.5μM),the TEER started to drop significantly after 5 h and did not show recovery afterward,indicating endothelium toxicity.Overall,we report a new TEER sensor that can monitor continuous drug toxicity on barrier tissues.The customizable features make it translational for various other studies,such as personalized dosage determination on stem cell-derived tissue barriers,and transient barrier permeability variations under diseased conditions.
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.
文摘The decreasing of hazard ratio for cancer incidence (HRCVD) in the range of twenty native tissues (lung, liver, brain, hematologic, neuroendocrine renal, pancreas, lymphoid, bladder, colon, lip-oral-head-neck, leukocytic, rectum and anus, thyroid, soft tissue, prostate, skin, ovarian, breast, uterine) as much, as decreasing of the level of cardiovascular pathology (CVD) in the host before malignization, have been described by C.F. Bell et al. in 2023. Earlier, in 2022, the decreasing of 5-year mortality from cancer in similar range of tissues discussed by us as the inverse dependence from the content of stem CD34 markers in tissues before malignization, with example of population in England. In present article we investigate the interrelation between both data more thoroughly, using accessible and more representative populations level of the data. The analysis shows that high level of HRCVD is able to predicts only high cancer death for tissue sites in the beginning of the range, being applied to the referent data of cancer cases and deaths in estimated population of USA 2024. Along with this, an increasing the content of CD34 stem marker in the native tissues of the same range was favorite for increasing of cancer’s cases at the end of the range, diminishing, in parallel, the signs of vasculo-endothelial pathology, i.e. HR CVD. Thus, the cases (incidence) of cancer depend directly rather from content of CD34, which preexisted in native sites, than that from HRCVD. Further analysis shows that CD34 content averaged over twenty cites dominates over that CD2 marker of total T-cells more than 7 times, in oppose to their ratio in the blood. The enhancement of stem CD34 marker in the range of tissues is accompanied by unidirectional rising of its maturing derivatives, vasculo-endothelial CD31 and total T-cells CD2 markers, which contents relate positively to increasing of cancer death in US population 2024. The increase of CD34 decreases cancer mortality (death: cases) in sites, but indirectly, rather due to enhancement of the denominator. The high HRCVD (more than 1.0) in range of 20 tissues, concerns of those of them, which have had highest mitotic activity (by Ki67), but lowest “stemness” (by CD34), “vascularity” (by CD31), cancer’s incidence (cases) and the worse results of therapy. Oppositely, the normal tissue with lowest HRCVD (below 1.0) and Ki67, but highest CD34, CD31, and cancer incidence (cases) are more sensitive to treatment. Thus, the residential hematopoietic “stemness” in native tissues acts as natural protectors for cardio-vascular system and promoter for cancer incidence in them. The steady and irreversible exhaustion of current regenerative resource (CRR) of BM, which assumed by us as a product of CD34 number and average telomeres length, manifests itself in acceleration of non-malignant CVD and deceleration of malignancy in population +70 (in term the death per 105), according to data extracted from WHO Mortality Database. The similar deficit of CD34 arises artificially during cytotoxic treatment of cancer, when rapid waste of local CRR forces malignant cells to search more “stemness” cites. The competition between malignant and native tissues of the host for scanty CRR seems to be the most important factor for evaluation and prediction of prevalence, curability, and long-term results in oncology.
基金supported by the National Natural Science Foundation of China(Grant Nos.12032014,T2488101,and 12325209)。
文摘Physiological and pathological processes such as embryonic development and tumor progression involve complicated interplay of mechanical,chemical,and biological factors cross a wealth of spatial and temporal scales.In this paper,we review some recent advances in the field of mechano-chemo-biological coupling theories in biological tissues and cells,and their applications in cancer,immunological,and other diseases.Key issues in the mechano-chemo-biological modeling of specific dynamic processes of cells and tissues are discussed.A mechano-chemo-biological growth theory is introduced,which interrogates the mechanical,chemical,and biological coupling mechanisms underpinning the growth,remodeling and degradation of tissues such as tumors.The mechano-chemo-biological instabilities of cells and tissues are systematically analyzed,with particular attention to those induced by coupled mechano-chemo-biological mechanisms.Furthermore,we provide a mechano-chemo-biological multiscale computational framework to investigate the dynamic processes of cells and tissues,for example,the migration and metastasis of cancer cells.Besides,we discuss some recent theoretical and experimental findings in the mechano-chemo-biological dynamics of collective cells.Finally,perspectives and clinical applications of the mechanochemo-biological theories of cells and tissues are proposed.
基金supported by grants from the National Natural Science Foundation of China(Grant nos.82201011,82370958 and 81870770).
文摘Smoking is a well-established risk factor for periodontitis,yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood.Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution,offering new opportunities to investigate these mechanisms.In this study,we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals,including those with periodontitis,those with smoking-associated periodontitis,and healthy controls.Our analysis revealed that smoking disrupts the epithelial barrier integrity,induces fibroblast alterations,and dysregulates fibroblast–epithelial cell communication,thereby exacerbating periodontitis.The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact,which further promotes the progression of smoking-induced periodontal disease.Importantly,we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype,alleviated epithelial inflammation,and reduced alveolar bone resorption.These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial–macrophage interaction as a therapeutic strategy.Furthermore,this study establishes an essential information resource for investigating the effects of smoking on periodontitis,providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
基金financially supported by the Biological Breeding-National Science and Technology Major Project(No.2023ZD0407106)National Key R&D Program of China(No.2023YFD1300400)Biological Breeding-National Science and Technology Major Project,No.2023ZD0407106,Kai Xing。
文摘Background Viral diseases have profoundly influenced the sustainable development of the swine farming industry.With the development of genomics technology,the combination of transcriptome,genetic variation,immune response,and QTL mapping data to illustrate the interactions between pathogen and host immune system,will be an effective tool for identification of disease resistance genes in pigs.The immune system of an organism is the source of disease resistance in livestock,consisting of various immune tissues,as well as the immune cells and cytokines they produced.However,comprehensive systematic studies on transcriptome of porcine immune tissues are still rare.Poly(I:C),as a viral mimic,is commonly used to study immune responses of the body during viral infections,and serves as a valuable tool for investigating immune mechanisms in swine.Results WGCNA analysis identified core immune genes across six immune tissues(bone marrow,jejunum,lymph node,PBMC,spleen,thymus)in Landrace pigs,which are also crucial for the development of PBMCs.The examination of the changes in the proportion of immune cells during three developmental stages(1-month-old,4-month-old,7-month-old)shows a shift from innate immunity to humoral immunity.By integrating different epigenetic genomics datasets,we identified several core immune genes and their causal variants,including IFI44,IFIT5,EIF2AK2 and others,which are closely related to immune development and response.Functional validation studies reveal that the IFI44 gene acts as a negative regulator of the antiviral response;its inhibition effect significantly reduced Poly(I:C)-induced cell necrosis,while enhancing apoptosis to combat viral infections.Conclusion Our study elucidated the fundamental transcriptional program in porcine immune tissues and the immunodynamics underlying development of PBMCs,identifying many core immune genes,including IFI44,which plays a critical negative regulator role in the antiviral response,providing valuable insights for breeding programs aimed at enhancing pig disease resistance.
基金supported by the National Natural Science Foundation of China(Grant No.U2241273)the Beijing Municipal Natural Science Foundation(Grant No.Z240017)+3 种基金the 111 project(Grant No.B13003)the Fundamental Research Funds for the Central Universitiesthe China Scholarship Councilthe Academic Excellence Foundation of BUAA for PhD Students.
文摘The mechanical properties of biological soft tissues play a critical role in the study of biomechanics and the development of protective measures against human injury.Various testing techniques at different scales have been employed to characterize the mechanical behavior of soft tissues,which is essential for developing accurate tissue simulants and numerical models.This review comprehensively explores the mechanical properties of soft tissues,examining experimental methods,mechanical models,numerical simulations,and the progress in materials that mimic the mechanical performance of soft tissues.Finally,it reviews the damage and protection of human tissues under kinetic impacts,anticipating the future construction of soft tissue surrogate targets.The aim is to provide a systematic theoretical foundation and the latest advancements in the field,addressing the design,preparation,and quantitative modeling of biomimetic materials,thereby promoting the in-depth development of soft tissue mechanics and its applications.
文摘Our gosl was to develop and experimentally validate a polarization-interferene method for phsae scanning of laser speckle fields generated by diffuse layers of birefringent biological tissues.This method isolates and uses new diagnostic parameters related to the"phsse WAvEs of local depolarization".We combined polarization-interferenæregistration with phase scanning of complex amplitude distributions in diffuse Laser speckle fields to detect phase waves of local depolarization in birefringent fibrillar networks of biological tisue and messure their modulation depth.This eppгоsch led to the discovery of new criteria for differentiating verious necrotic changes in diffuse histological samples of myocardial tisue from decmsed individuals with"ischemic heart disase(IHD)--cute coronary insufficiency(ACT)",even in the presænce of a high level of depolarized bckground.To evaluate the degree of necrotic changes in the optical anisotropy of difuse myocardial Layers,a new quantitative parameter--modulation depth of local depolarization wave fluctustions-has been proposed.Using this approsch,for the first time,differentiation of diffuse myocardial samples from decessed individuals with IHD and ACI was achieved witha very good 90.45%and outstanding aocuracy of 95.2%.
基金the“Young Talent Research Grant”:(600-RMC/YTR/5/3(004/2022)Universiti Teknologi Mara(UiTM)for providing the financial support.
文摘Spinal cord injury presents a significant challenge in regenerative medicine due to the complex and deli-cate nature of neural tissue repair.This study aims to design a conductive hydrogel embedded with magnetic MgFe_(2)O_(4) nanoparticles to establish a bioelectrically active and spatially stable microenvironment that promotes spinal cord regeneration through computational analysis(BIOVIA Materials Studio).Hydrogels,known for their biocompatibility and extracellular matrix-mimicking properties,support essential cellular behaviors such as adhesion,proliferation,and migration.The integration of MgFe_(2)O_(4) nanoparticles imparts both electrical conductivity and magnetic responsiveness,enabling controlled transmission of electrical signals that are crucial for guiding cellular processes like differentiation and directed migration.Furthermore,the hydrogel acts as a delivery medium,facilitating the adsorption of MgFe_(2)O_(4) nanoparticles onto spinal tissue through strong Van der Waals and intramolecular interactions.The computational simulations revealed a robust adsorption profile,with a binding distance of 20.180Åand a cumulative adsorption energy of 2740.42 kcal/mol,indicating stable nanoparticle-tissue interactions.Pressure-dependent sorption analysis further demonstrated that reduced pressure conditions enhance adsorption strength,promoting tighter material-tissue integration.The adverse Van der Waals energy and increased intramolecular energy observed under these conditions underscore the importance of optimized adsorption settings for functional tissue interface formation.Altogether,the conductive hydrogel-MgFe_(2)O_(4) composite system offers a promising therapeutic platform by combining structural support,electrical stimulation,and magnetic guidance,thereby enhancing cell-material interactions and fostering an environment conducive to spinal cord tissue repair.
基金support from NTU Presidential Postdoctoral Fellowshipthe support from the National Research Foundation,Singapore,under its NRF Investigatorship(NRFNRFI07-2021-007,Funding Awardee:Wai Yee Yeong)。
文摘Bioprinting is a revolutionary technology within the field of tissue engineering that enables the precise fabrication of three-dimensional(3D)tissue constructs.It combines the principles of engineering and biology to create structures that closely mimic the complexity of native human tissues,facilitating advancements in regenerative medicine and personalized healthcare.This review paper systematically explores the challenges and design requirements in the fabrication of 3D biomimetic tissue constructs,emphasizing the need for advanced bioprinting strategies.Achieving biomimicry involves creating 3D anatomically relevant structures,biomimetic microenvironments,and vascularization.The focus is on overcoming existing bottlenecks through advancements in both fabrication techniques and bio-inks.Future directions in bioprinting are outlined,including multi-modal bioprinting systems,in-situ bioprinting,and the integration of machine learning into bioprinting processes.The critical role of bio-inks and printing methodologies in influencing cell viability is highlighted,providing insights into strategies for enhancing cellular functionality throughout the bioprinting process.Furthermore,the paper addresses post-fabrication considerations,particularly in accelerating tissue maturation,as a pivotal component for advancing the clinical applicability of bioprinted tissues.By navigating through the challenges,innovations,and prospects of advanced bioprinting strategies,this review highlights the transformative impact on tissue engineering.Pushing the boundaries of technological capabilities,these strategies hold the promise of groundbreaking advancements in regenerative medicine and personalized healthcare.Ultimately,the integration of these advanced techniques into bioprinting processes will pave the way for the development of more highly biomimetic and functional bioprinted tissues.
基金supported by the National Natural Science Foundation of China(Nos.22125404,92068118,21874105)the Natural Science Basic Research Program of Shaanxi Province(Nos.2023-JCJQ-13,2020JQ-021)the Innovation Capability Support Program of Shaanxi Province(No.2023-CX-TD-62)。
文摘Characterization of the distribution and accurate counting of RNA molecules in the context of tissues is necessary to understand their complexity and heterogeneity.Single-molecule fluorescence in situ hybridization reveals the abundance and distribution of RNA and resolves different cell types in complex tissues.Especially,off-target binding and nonspecific adsorption of probes are prone to producing nonspecific amplification.Herein,we present highly de-noising amplified imaging,which leverages a sitespecific cleavage-amplifying design to achieve accurate counting of RNA in tissues.Our method avoids adding probe as primer,decreases nonspecific spots of single cells from 7 to nearly zero,and enables RNA imaging in uncleared tissue sections with nearly zero noise.We demonstrate the efficacy of this method on various thickness of mouse tissue sections.We envision this approach will serve as a tool to revealing the information content from patient samples for biomedical purpose.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,No.NRF-2022R1I1A1A01068652.
文摘Tendon and ligament injuries represent a major orthopedic challenge with limited effective regenerative options.In an original research study by Yang et al de-veloped a tissue engineering approach combining aligned nanofiber scaffolds with cyclic uniaxial stretching to promote tenogenic differentiation in bone marrow-derived mesenchymal stem cells.Their results provide critical insight into how structural and mechanical cues can synergize to generate ligament-like tissue in vitro.This editorial contextualizes their findings within the broader field of ligament regeneration and highlights the translational potential of their strategy.
基金Supported by National Transgenic Major Project ( Safe Monitoring Technique of Transgenic Organism 2008ZX08012-004)~~
文摘[Objective] The aim was to learn the resistance of different tissues and organs of transgenic cotton to Spodoptera exigua （Hbner）. [Method] Flowers,the 1st,the 3rd,the 6th and the 14th leaves from the top of 33B,GK12 and SGK321 were used to feed S. exigua neonates respectively. Survival larvae and dead ones were counted on the 3rd,the 7th,the 10th,the 16th and the 19th day; meanwhile,the pupae amount was recorded,and the pupae weight was measured at the 24th h after pupation. [Result] The survival curves,pupation rates and pupae weights of S. exigua feeding on different tissues of transgenic cotton were not significantly different from those of S. exigua feeding on the corresponding tissues of conventional cotton; pupation rate of S. exigua feeding on different leaves of the same cotton variety were not significantly different from each other,but all higher than that of S. exigua feeding on the flowers of that cotton; and there were no differences among pupation weights of S. exigua feeding on different leaves or flowers of the same cotton variety. [Conclusion] Transgenic cotton showed weak resistance to S. exigua. Hence,in the transgenic cotton fields,more attention should be paid to occurrence trend of S. exigua and its control.
文摘It has been hypothesized that under iron stress high ferric chelate reductase (FCR) activity in the absorptive root of plants tolerant to iron_deficiency will be induced and result in subsequent Fe 2+ transport across the plasmalemma. The activity of FCR and expression of FCR gene (FRO2) in Citrus junos Sieb. ex Tanaka tolerant to iron_deficiency and Poncirus trifoliata (L.) Raf. susceptible to iron_deficiency were determined to elucidate the physiological difference which causes the different tolerance of the two citrus rootstocks to iron stress. The activity of FCR was detectable in excised roots and was stimulated about 20_times in C. junos and only about 3_times in P. trifoliata under iron deficiency for four weeks. The FRO2 of Arabidopsis was used as a probe, the tissue print technique was used to ascertain the expression of the FCR gene in C. junos and P. trifoliata under iron stress. High_level transcripts were observed in the absorptive root, young green stem as well as new leaf of C. junos under iron stress for two weeks, and the transcripts were accumulated only slightly in P. trifoliata at the same time. The results showed that the obvious increase of FCR activity was an important reason for the tolerance of C. junos to iron_deficiency, and the regulation of FCR activity seemed to be at the transcriptional level, and the expression of FRO2 occurred in the root, stem and leaf.
文摘Leaves from three_year_old solar greenhouse nectarine trees ( Prunus persica L. var. nectarina Ait. “Zao Hong Yan”) were used as materials in this study. It was the first time that the ultrastructural characteristics of phloem tissues of source leaves were observed and compared in normal and weak light intensities using the transmission electron microscopy. Results showed that the average diameters of companion cells (CC) and sieve elements (SE) of all kinds of veins were bigger in normal than that in weak light intensity, indicating that light could influence the cell development and growth. Dense cytoplasm with abundant mitochondria, endoplasmic reticulums, multivesicular bodies, vesicles and plastids were observed in normal light intensity. On the contrary, CC with small vacuolar structures and few mitochondrias, endoplasmic reticulums were shown in weak light. Misalignment of grana thylakoid margins of nectarine leaves also was seen in weak light. The sieve pores of SEs were obstructed in weak light. Chloroplasts with numerous starch grains and few mitochondrias were noticed in the mesophyll cell (MES) surrounding the bundle sheath in weak light. The storage of starch grains appeared to result from an unbalance between photosynthate production and export of photosynthates. This observation provided a strong support to the point that most leaves export the most of assimilates in the light time. Plasmodesmal densities between SE/CC, CC/PP (phloem parenchyma cell), PP/PP and PP/BSC (bundle_sheath cell) decreased in weak light. Plasmodesmata were observed between CC/SE (NS) (nacreous_walled sieve element), PP/BSC in branch veins in normal light intensity, but not in weak light. Thus apoplasmic pathway may be the main mode of transport of assimilates in weak light, however symplasmic pathway may be the main mode of transport of assimilates in normal light intensity. These results demonstrated that the solar greenhouse nectarine trees could be adapted to the weak light via the ultrastructure variation of phloem tissues of the source leaves.
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.
文摘Amyloid protein aggregation plays a major role in multiple neurodegenerative diseases and is likely the primary driving force for the progression of most of these diseases.Multiple recent studies have highlighted that the DNAJ homolog subfamily B member 6(DNAJB6)chaperone is particularly interesting,when it comes to preventing amyloidogenic proteins from aggregating.It has been shown that DNAJB6 can prevent the aggregation of polyglutamine-expanded proteins in models of Huntington’s disease.Likewise,it can suppress aggregation ofα-synuclein in models of Parkinson’s disease and other synucleinopathies.Finally,it has been shown that DNAJB6 can block aggregation of multiple additional amyloid proteins involved in Alzheimer’s disease and other tauopathies as well.We believe there is yet much to learn about the protective role of DNAJB6 in the brain,but this focused review summarizes,what we know so far of this chaperone.It describes the biological role of DNAJB6 in the brain and its interaction with Hsp70,with particular emphasis on the studies that show its ability to prevent amyloid protein aggregation in vitro and in vivo.Moreover,recent work on dysregulation of the expression of DNAJB6 in brain clinical tissue is discussed.Finally,we discuss potential therapeutic perspectives as we believe this protein is a promising druggable target.
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.
