Hypoxia is one of the major environmental stressors,frequently resulting in serious yield losses for maricultured large yellow croaker(Larimichthys crocea).We know that pyroptosis contributes to tissue damage under hy...Hypoxia is one of the major environmental stressors,frequently resulting in serious yield losses for maricultured large yellow croaker(Larimichthys crocea).We know that pyroptosis contributes to tissue damage under hypoxic conditions.However,whether GSDMEs-mediated pyroptosis is involved in hypoxia-induced tissue damage in fish remains unclear.In the present study,two Lcgsdme genes,Lcgsdmea/b,were cloned and characterized from the large yellow croaker.Both genes contain a conserved N-terminalpore-forming domain,a C-terminal auto-inhibitory domain,and a flexible hinge region.After hypoxia stress,the expression of Lcgsdmea/b transcripts and proteins in the liver were significantly higher than in unstressed fish.The proteins of LcGSDMEa/b could be cleaved under hypoxic conditions.Compared to LcGSDMEb,the expression of LeGSDMEa was higher in both mRNA and protein levels,thus exhibiting a stronger response during hypoxia stress.Furthermore,after 48 h of hypoxia stress,approximately 65%liver cells exhibited abnormalities,with pyroptosis being detected using a transmission electron microscope.TUNEI/LeGSDMEa double staining assay revealed a high expression of LcGSDMEa in the dead cells.We observed a significant up-regulation of pyroptosis pathway genes(asc,caspase-3)and pro-inflammatory cytokine genes(il-1β,il-18).After simultaneous knockdown of Legsdmea/b in vivo,the liver exhibited better health compared to the control group,with less cell swelling and vacuolation.Taken together,these findings demonstrate that hypoxia stress could activate LcGSDMEa/b and induce pyroptosis in the liver of large yellow croakers,thereby contributing to tissue damage.Our study improves the understanding of hypoxia-induced tissue damage in fish,and provides new clues for protecting fish against hypoxia-induced damage.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
Objective:To observe the pharmaceutical effect of Chinese drugs for activating blood circulation (Xiongshao Capsule,XSC,芎芍胶囊)and for activating blood circulation and detoxification(Xiongshao Capsule and Huangl...Objective:To observe the pharmaceutical effect of Chinese drugs for activating blood circulation (Xiongshao Capsule,XSC,芎芍胶囊)and for activating blood circulation and detoxification(Xiongshao Capsule and Huanglian Capsule,XSHLC,黄连胶囊)in terms of the indices of thrombosis,inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats.Methods:Fifty Wistar rats were randomly divided into the sham operation group,the model group,the Simvastatin group(SG),the activating blood circulation(ABC)group,and the activating blood circulation and detoxifying(ABCD)group,with 10 rats in each group.Simvastatin(1.8 mg/kg),XSC(0.135 g/kg)and XSHLC(0.135 g/kg)were administered to Simvastatin,ABC and ABCD group by gastrogavage,and an equal volume of normal saline was given to the sham operation group and the model group.After 2 weeks of successive medication,the rats in the model and all drug therapy groups were made into experimental carotid artery thrombosis model.The serum levels of matrix metalloproteinases(MMP-9),tissue inhibitors to metalloproteinase(TIMP-1),granule membrane protein-140(GMP-140),tissue-type plasminogen activator(t-PA),high-sensitivity C-reactive protein(hs-CRP) and interleukin-6(IL-6)were detected with enzyme-linked immunoassay 24 h later.Results:Compared with the model group,the levels of serum GMP-140,hs-CRP,IL-6 and MMP-9 were significantly decreased,and the level of t-PA was significantly increased in the ABC and ABCD group(P〈0.05),while the level of serum hs-CRP in ABCD group decreased significantly compared with that in the ABC group(P〈0.05).Conclusions:Chinese drugs both for activating blood circulation and for activating blood circulation and detoxifying have good effects on regulating indices of thrombosis,inflammatory reaction and tissue damage in experimental carotid artery thrombosis rats.The effect of activating blood circulation and detoxifying drugs on regulating the level of serum hs-CRP is superior to that of activating blood circulation drug alone.展开更多
Broiler chicks are fast-growing and susceptible to dietary selenium(Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male c...Broiler chicks are fast-growing and susceptible to dietary selenium(Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male chicks(n=6 cages/diet, 6 chicks/cage) were fed with a Se-deficient diet(Se-Def, 0.047 mg Se/kg) or the Se-Def+0.3 mg Se/kg(Control, 0.345 mg Se/kg) for 6weeks. The serum, liver, pancreas, spleen, heart, and pectoral muscle of the broilers were collected at week 6 to assay for Se concentration, histopathology, serum metabolome, and tissue transcriptome. Compared with the Control group, Se deficiency induced growth retardation and histopathological lesions and reduced Se concentration in the five organs. Integrated transcriptomics and metabolomics analysis revealed that dysregulation of immune and redox homeostasis related biological processes and pathways contributed to Se deficiency-induced multiple tissue damage in the broilers. Meanwhile, four metabolites in the serum, daidzein, epinephrine, L-aspartic acid and 5-hydroxyindoleacetic acid, interacted with differentially expressed genes with antioxidative effects and immunity among all the five organs, which contributed to the metabolic diseases induced by Se deficiency. Overall, this study systematically elucidated the underlying molecular mechanisms in the pathogenesis of Se deficiency-related diseases, which provides a better understanding of the significance of Se-mediated heath in animals.展开更多
The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bon...The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.展开更多
For years,the study of senescent cells resembled a molecular guessing game.Researchers knew these dormant cells played paradoxical roles-some secreting inflammatory signals that accelerated tissue damage,others releas...For years,the study of senescent cells resembled a molecular guessing game.Researchers knew these dormant cells played paradoxical roles-some secreting inflammatory signals that accelerated tissue damage,others releasing factors to restrain it.Yet traditional tools could only lump all senescent cells into a single category.This blindness persisted until 2024,when Dr.ZHOU Bin’s team at the Shanghai Institute of Biochemistry and Cell Biology(SIBCB).展开更多
AIM: To evaluate the protective effects on kidney tissue of frequently used intravenous anesthetics (ketamine, propofol, thiopental, and fentanyl) in rats with obstructive jaundice.
Ultra-high dose rate flash radiotherapy(FLASH-RT)has attracted wide attention in the field of radiotherapy in recent years.For FLASH-RT,radiation is delivered at a very high dose rate[usually thousands of times compar...Ultra-high dose rate flash radiotherapy(FLASH-RT)has attracted wide attention in the field of radiotherapy in recent years.For FLASH-RT,radiation is delivered at a very high dose rate[usually thousands of times compared with conventional radiotherapy(CONV-RT)]in an extremely short time.This novel irradiation technique shows a protective effect on normal tissues,also known as the flash effect.At the same time,FLASH-RT is comparable to CONV-RT in terms of tumorkilling efficacy.As basic research dedicates to uncover the mechanisms by which FLASH-RT reduces radiation-induced normal tissue damage,clinical trials of FLASH-RT have been gradually conducted worldwide.This article systematically reviews the evidence of the feasibility and safety of FLASH-RT in clinical practice and offers insights into the future translation of this technology in clinic.展开更多
Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens.This study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiol...Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens.This study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiologi-cal characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction.A total of 24074-week-old Hy-line Brown laying hens were selected and allocated to a high(HBS,44.83±1.31 N)or low(LBS,24.43±0.57 N)eggshell breaking strength group.Results A decreased thickness,weight and weight ratio of eggshells were observed in the LBS,accompanied with ultrastructural deterioration and total Ca reduction.Bone quality was negatively correlated with eggshell quality,marked with enhanced structures and increased components in the LBS.In the LBS,the mammillary knobs and effective layer grew slowly.At the initiation stage of eggshell calcification,a total of 130 differentially expressed genes(DEGs,122 upregulated and 8 downregulated)were identified in the uterus of hens in the LBS relative to those in the HBS.These DEGs were relevant to apoptosis due to the cellular Ca overload.Higher values of p62 protein level,caspase-8 activity,Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the LBS.TUNEL assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the LBS.Although few DEGs were identified at the growth stage,similar uterine tissue damages were also observed in the LBS.The expressions of runt-related transcription factor 2 and osteocal-cin were upregulated in humeri of the LBS.Enlarged diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the HBS.Conclusion The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages,which could affect eggshell calcification and lead to a weak ultrastructure.Impaired uterine Ca transport may result in reduced femoral bone resorption and increased humeral bone formation to maintain a higher mineral and bone quality in the LBS.展开更多
The aim of this study was to evaluate the effectiveness of BM (basement membrane) and SIS (small intestine submucosa) composite extracellular matrix staple line reinforcement in surgical procedures through finite elem...The aim of this study was to evaluate the effectiveness of BM (basement membrane) and SIS (small intestine submucosa) composite extracellular matrix staple line reinforcement in surgical procedures through finite element modelling simulations and leak-proof performance experiments. The mechanical analyses of soft tissues with and without staple line reinforcement were performed by establishing finite element models of three tissues, namely, stomach, intestine and lungs, under the use scenarios of different anastomosis staple models;and the leak-proof performance of the staple line reinforcement was evaluated by simulating leak-proof experiments of gastric incision margins, intestinal sections, and lung incision margins in vitro. The results showed that the equivalent average stresses of the staple line reinforcement were increased by 20 kPa-68 kPa in gastric and intestinal tissues, and 8 kPa-22 kPa in lung tissues. and that the BM and SIS composite extracellular matrix staple line reinforcement could strengthen the anastomotic structure, and at the same time disperse the high stresses of the anastomosed tissues, which could effectively reduce the postoperative complications such as anastomotic bleeding and anastomotic leakage, and provide a safer and more effective optimized design for surgical mechanical anastomosis. It can effectively reduce postoperative complications such as anastomotic bleeding and anastomotic leakage, and provide a safer and more effective optimized design for surgical mechanical anastomosis.展开更多
Objective: To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods: Rats were exposed to wa...Objective: To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods: Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin (range 0.8‐1 μg per 1 cm 2 ) for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results: Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury (increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death). Increased numbers of proliferating cell nuclear antigen (PCNA + ) cells indicated reparative processes in injured skin. Infiltration of CD3 + cells (T lymphocytes) along with the increased production of tumor necrosis factor‐α (TNF‐α) by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion: Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.展开更多
AIM: To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats. METHODS: Thirty male Wistar rats weighing 200-250 g were used. Ischemia was ...AIM: To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats. METHODS: Thirty male Wistar rats weighing 200-250 g were used. Ischemia was induced by ob-structing blood flow in 25% of the total small intesti-nal length (ileum) with a vascular clamp for 45 min, after which either 60 min or 24 h of reperfusion was allowed. Rats were either anesthetized with pento-barbital sodium (50 mg/kg) or ketamine (100 mg/kg). Control groups received sham surgery. After 60 min of reperfusion, the intestine was examined for mor-phological alterations, and after 24 h intestinal basic electrical rhythm (BER) frequency was calculated, and intestinal transit determined in all groups. RESULTS: The intestinal mucosa in rats that were anesthetized with ketamine showed moderate altera-tions such as epithelial lifting, while ulceration and hemorrhage was observed in rats that received pento-barbital sodium after 60 min of reperfusion. Quantita-tive analysis of structural damage using the Chiu scaleshowed significantly less injury in rats that received ketamine than in rats that did not (2.35 ± 1.14 vs 4.58 ± 0.50, P < 0.0001). The distance traveled by a mark-er, expressed as percentage of total intestinal length, in rats that received pentobarbital sodium was 20% ± 2% in comparison with 25.9% ± 1.64% in rats that re-ceived ketamine (P = 0.017). BER was not statistically different between groups. CONCLUSION: Our results show that ketamine anesthesia is associated with diminished intestinal injury and abolishes the intestinal transit delay induced by ischemia/reperfusion.展开更多
BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects o...BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects of enhanced external counterpulsation(EECP)in con-junction with atorvastatin on cognitive function,neurotransmitter levels,and the repair of brain tissue damage in patients with cognitive impairment due to stroke.METHODS In this retrospective study,data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group(n=30)and a control group(n=30)according to the different nursing methods applied.Patients in the treatment group received EECP in addition to atorvastatin,while those in the control group received atorvastatin alone.Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and activities of daily living(ADL)scale scores were compared between the two groups.Additionally,the two groups were compared in terms of serum acetylcholine(ACh),acetylcholin-esterase(AChE),nitric oxide(NO),endothelin-1(ET-1),β2-microglobulin(β2-MG),glial fibrillary acidic protein(GFAP),and visinin-like protein 1(VILIP-1)in the serum.Blood flow measurements from the anterior cerebral artery(ACA),middle cerebral artery(MCA)and posterior cerebral artery(PCA)were compared between the two groups before and after treatment,and the pulsatility index(PI)and resistance index(RI)of each artery were determined.RESULTS MMSE,MoCA,and ADL scores all improved in both groups following treatment,with the study group showing more improvement than the control group(P<0.05).After treatment,there were statistically significant increases in both ACh and NO levels,whereas decreases occurred in AChE,ET-1,β2-MG,VILIP-1,and GFAP,levels and the PI and RI of the left-ACA,right-ACA,left-MCA,right-MCA,left-PCA,and right-PCA.The study group showed greater gains in all metrics than the control group(P<0.05).CONCLUSION EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function,neurotransmitter levels,and brain tissue damage status of patients.展开更多
Synchrotron radiation(SR) X-ray has significant potential for medical applications. However, the mechanisms underlying the effects of SR X-ray on biological tissues remain unclear. Because increasing evidence has indi...Synchrotron radiation(SR) X-ray has significant potential for medical applications. However, the mechanisms underlying the effects of SR X-ray on biological tissues remain unclear. Because increasing evidence has indicated critical roles of cluster of differentiation 38(CD38) in various cellular functions and cell survival, in this study we used rodent testes as a model to determine the effects of SR X-ray irradiation on the CD38 level of the testes. We found that SR X-ray irradiation led to a significant increase in the CD38 level of rodent testes one day after the irradiation. In contrast, the SR X-ray irradiation did not produce a significant increase in the CD38 level of the testes from the rats that were administered with the antioxidant N-acetyl cysteine, thus suggesting that oxidative stress plays a significant role in the SR X-ray irradiation-induced increase in the CD38 levels. Our study has also provided evidence suggesting that poly(ADP-ribose) polymerase(PARP) activity is not involved in the SR X-ray irradiation-produced effect on the CD38 levels. Collectively, this study has provided first in vivo evidence indicating that CD38 levels can be increased by ionizing radiation, in which oxidative stress plays an important role. Because oxidative stress occurs in ionizing radiation as well as such diseases as cerebral ischemia and Parkinson's disease, oxidative stress may produce pathological effects by inducing increased CD38 levels.展开更多
The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related ...The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.展开更多
Non-specific arm pain is a special clinical condition that can occur in work-related activities that involve maintaining a static position for prolonged periods or repetitive and frequent movements of the hand or enti...Non-specific arm pain is a special clinical condition that can occur in work-related activities that involve maintaining a static position for prolonged periods or repetitive and frequent movements of the hand or entire arm. Such activities include typing on a keyboard, maneuvering a computer mouse, playing musical instruments (such as piano and guitar) and many forms of manual labor. The pain is dull and diffuse; It is localized in the forearm or in the hand but quickly can expand to the entire extremity. Non-specific arm pain is the most frequent type of work-related pain after lower-back pain. It thus has important socio-economic significance as a major cause of absence from work. The designation of "non-specific" originates from the fact that it has no obvious signs of tissue damage, unlike the "specific" pain accompanying carpal tunnel syndrome, tenosinovitis de Quervain, or lateral epicondylitis. Suggested causes of the pain include microtrauma of soft tissue followed by an inflammatory reaction, ischemia, fatigue, hyper-sensitization of nociceptors, focal dystonia of the hand and/or psychological stress. Treatment consists of application of NSAIDs, physical modalities, stretching and aerobic exercises. Prevention focuses on ergonomic modification during manual labor or work on a computer.展开更多
Regenerative medicine has rapidly developed over the past decade and created new opportunities to repair or replace tissue or organ function lost because of congenital defects, age, diseases, or serious damage (Cheng...Regenerative medicine has rapidly developed over the past decade and created new opportunities to repair or replace tissue or organ function lost because of congenital defects, age, diseases, or serious damage (Cheng et al., 2016a; Cheng et al., 2016b). Regenerative medicine strategies in- clude the transplantation of bioactive factors, stem cells, or biomaterials, even the induced regeneration in a de novo, depending on the application (Fu, 2014a; Huang and Fu, 2014). However, there are several limitations to the use of regenerative medicine in the clinic with respect to using stem cells and biomaterials.展开更多
Objective To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal(4-HNE),thioredoxin(Trx),thioredoxin reductase(TrxR)and the sctivities of Trx and TrxR,and to explore the...Objective To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal(4-HNE),thioredoxin(Trx),thioredoxin reductase(TrxR)and the sctivities of Trx and TrxR,and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models.Methods展开更多
Lubrication is an important prerequisite and foundation for the organism to protect biological tissues from mechanical friction damage and to maintain their normal life functions[1,2].After mechanical friction trauma,...Lubrication is an important prerequisite and foundation for the organism to protect biological tissues from mechanical friction damage and to maintain their normal life functions[1,2].After mechanical friction trauma,the lubrication matrix repairs damaged tissue by protecting the host from external impact and promotes the restoration of lubrication balance in the body.The process of lubrication typically unfolds in a series of events,beginning with a rapid response phase where lubricating fluids flow within the organism,reducing wear between tissues.This is followed by a gradual transition into a lubrication phase involving various lubrication mechanisms,such as fluid lubrication(The load is fully sustained by lubricant due to viscous forces in the space or gap between the components that are moving in relation to another object,while preventing solid-to-solid contact),boundary lubrication(The load is carried by surface high points rather than by lubricant),hydration lubrication(Hydration layers are tightly bound by the surrounding charges,allowing them to withstand significant pressure without being displaced,while also being able to quickly relax,resulting in a fluid-like response to shear forces),and mixed lubrication(This regime exists between full film lubrication and boundary lubrication,where the lubricant film generated is inadequate to fully separate the surfaces in contact,yet the hydrodynamic effect is significant)[3-5].Thus,lubrication plays a vital role in protecting living beings.However,if this well-coordinated wear reduction process is disrupted,lubrication can become uncontrolled or deteriorate,potentially leading to a range of lubrication-related diseases,including osteoarthritis,tendon adhesion,intervertebral disc degeneration,femoral head necrosis,cardiovascular blockages,tooth wear,and implant infections[1].展开更多
Cellular reprograming offers an opportunity to convert one somatic cell type into another,providing promising potential for disease modeling and regenerative medicine.This cell fate conversion can be achieved using li...Cellular reprograming offers an opportunity to convert one somatic cell type into another,providing promising potential for disease modeling and regenerative medicine.This cell fate conversion can be achieved using lineage-specific transcription factors,microRNAs or combinations of small molecules.A better understanding of how cell fate conversion is regulated will provide novel insights for precise manipulation of reprogramming,paving the way for developing novel strategies to regenerate the damaged tissue.展开更多
基金supported by grants from the National Key Research and Development Program of China(2022YFD2401001)Central Public-interest Scientific Institution Basal Research Fund,CAFS(NO.2023TD81 and NO.20603022023018)China Agriculture Research System(CARS47-G19).
文摘Hypoxia is one of the major environmental stressors,frequently resulting in serious yield losses for maricultured large yellow croaker(Larimichthys crocea).We know that pyroptosis contributes to tissue damage under hypoxic conditions.However,whether GSDMEs-mediated pyroptosis is involved in hypoxia-induced tissue damage in fish remains unclear.In the present study,two Lcgsdme genes,Lcgsdmea/b,were cloned and characterized from the large yellow croaker.Both genes contain a conserved N-terminalpore-forming domain,a C-terminal auto-inhibitory domain,and a flexible hinge region.After hypoxia stress,the expression of Lcgsdmea/b transcripts and proteins in the liver were significantly higher than in unstressed fish.The proteins of LcGSDMEa/b could be cleaved under hypoxic conditions.Compared to LcGSDMEb,the expression of LeGSDMEa was higher in both mRNA and protein levels,thus exhibiting a stronger response during hypoxia stress.Furthermore,after 48 h of hypoxia stress,approximately 65%liver cells exhibited abnormalities,with pyroptosis being detected using a transmission electron microscope.TUNEI/LeGSDMEa double staining assay revealed a high expression of LcGSDMEa in the dead cells.We observed a significant up-regulation of pyroptosis pathway genes(asc,caspase-3)and pro-inflammatory cytokine genes(il-1β,il-18).After simultaneous knockdown of Legsdmea/b in vivo,the liver exhibited better health compared to the control group,with less cell swelling and vacuolation.Taken together,these findings demonstrate that hypoxia stress could activate LcGSDMEa/b and induce pyroptosis in the liver of large yellow croakers,thereby contributing to tissue damage.Our study improves the understanding of hypoxia-induced tissue damage in fish,and provides new clues for protecting fish against hypoxia-induced damage.
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 National Basic Research Program of China(No. 2006CB504803)
文摘Objective:To observe the pharmaceutical effect of Chinese drugs for activating blood circulation (Xiongshao Capsule,XSC,芎芍胶囊)and for activating blood circulation and detoxification(Xiongshao Capsule and Huanglian Capsule,XSHLC,黄连胶囊)in terms of the indices of thrombosis,inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats.Methods:Fifty Wistar rats were randomly divided into the sham operation group,the model group,the Simvastatin group(SG),the activating blood circulation(ABC)group,and the activating blood circulation and detoxifying(ABCD)group,with 10 rats in each group.Simvastatin(1.8 mg/kg),XSC(0.135 g/kg)and XSHLC(0.135 g/kg)were administered to Simvastatin,ABC and ABCD group by gastrogavage,and an equal volume of normal saline was given to the sham operation group and the model group.After 2 weeks of successive medication,the rats in the model and all drug therapy groups were made into experimental carotid artery thrombosis model.The serum levels of matrix metalloproteinases(MMP-9),tissue inhibitors to metalloproteinase(TIMP-1),granule membrane protein-140(GMP-140),tissue-type plasminogen activator(t-PA),high-sensitivity C-reactive protein(hs-CRP) and interleukin-6(IL-6)were detected with enzyme-linked immunoassay 24 h later.Results:Compared with the model group,the levels of serum GMP-140,hs-CRP,IL-6 and MMP-9 were significantly decreased,and the level of t-PA was significantly increased in the ABC and ABCD group(P〈0.05),while the level of serum hs-CRP in ABCD group decreased significantly compared with that in the ABC group(P〈0.05).Conclusions:Chinese drugs both for activating blood circulation and for activating blood circulation and detoxifying have good effects on regulating indices of thrombosis,inflammatory reaction and tissue damage in experimental carotid artery thrombosis rats.The effect of activating blood circulation and detoxifying drugs on regulating the level of serum hs-CRP is superior to that of activating blood circulation drug alone.
基金supported by the National Natural Science Foundation of China (32102588)the Top-notch Young Talent Supporting Program to LHSBeijing Deyuanshun Biological Technology Co.,Ltd。
文摘Broiler chicks are fast-growing and susceptible to dietary selenium(Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male chicks(n=6 cages/diet, 6 chicks/cage) were fed with a Se-deficient diet(Se-Def, 0.047 mg Se/kg) or the Se-Def+0.3 mg Se/kg(Control, 0.345 mg Se/kg) for 6weeks. The serum, liver, pancreas, spleen, heart, and pectoral muscle of the broilers were collected at week 6 to assay for Se concentration, histopathology, serum metabolome, and tissue transcriptome. Compared with the Control group, Se deficiency induced growth retardation and histopathological lesions and reduced Se concentration in the five organs. Integrated transcriptomics and metabolomics analysis revealed that dysregulation of immune and redox homeostasis related biological processes and pathways contributed to Se deficiency-induced multiple tissue damage in the broilers. Meanwhile, four metabolites in the serum, daidzein, epinephrine, L-aspartic acid and 5-hydroxyindoleacetic acid, interacted with differentially expressed genes with antioxidative effects and immunity among all the five organs, which contributed to the metabolic diseases induced by Se deficiency. Overall, this study systematically elucidated the underlying molecular mechanisms in the pathogenesis of Se deficiency-related diseases, which provides a better understanding of the significance of Se-mediated heath in animals.
基金Supported by the National Key Research and Development Program of China,No.2023YFC2508806Key Research and Development Project in Henan Province,No.231111310500+4 种基金Young Elite Scientists Sponsorship Program by CAST,No.2021-QNRC2-A06Scientific Research Project of Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation,No.ZYYC2023ZDYouth Science Award Project of the Provincial-Level Joint Fund for Science and Technology Research and Development Project in Henan Province,No.225200810084Special Project on Training Top Talents in Traditional Chinese Medicine in Henan Province,No.2022ZYBJ242023 Hunan University of Chinese Medicine Postgraduate Innovation Project,No.2023CX64。
文摘The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.
文摘For years,the study of senescent cells resembled a molecular guessing game.Researchers knew these dormant cells played paradoxical roles-some secreting inflammatory signals that accelerated tissue damage,others releasing factors to restrain it.Yet traditional tools could only lump all senescent cells into a single category.This blindness persisted until 2024,when Dr.ZHOU Bin’s team at the Shanghai Institute of Biochemistry and Cell Biology(SIBCB).
文摘AIM: To evaluate the protective effects on kidney tissue of frequently used intravenous anesthetics (ketamine, propofol, thiopental, and fentanyl) in rats with obstructive jaundice.
文摘Ultra-high dose rate flash radiotherapy(FLASH-RT)has attracted wide attention in the field of radiotherapy in recent years.For FLASH-RT,radiation is delivered at a very high dose rate[usually thousands of times compared with conventional radiotherapy(CONV-RT)]in an extremely short time.This novel irradiation technique shows a protective effect on normal tissues,also known as the flash effect.At the same time,FLASH-RT is comparable to CONV-RT in terms of tumorkilling efficacy.As basic research dedicates to uncover the mechanisms by which FLASH-RT reduces radiation-induced normal tissue damage,clinical trials of FLASH-RT have been gradually conducted worldwide.This article systematically reviews the evidence of the feasibility and safety of FLASH-RT in clinical practice and offers insights into the future translation of this technology in clinic.
基金This study was supported by the National Natural Science Foundation of China(32172743)China Agriculture Research System(CARS-40)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS.
文摘Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens.This study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiologi-cal characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction.A total of 24074-week-old Hy-line Brown laying hens were selected and allocated to a high(HBS,44.83±1.31 N)or low(LBS,24.43±0.57 N)eggshell breaking strength group.Results A decreased thickness,weight and weight ratio of eggshells were observed in the LBS,accompanied with ultrastructural deterioration and total Ca reduction.Bone quality was negatively correlated with eggshell quality,marked with enhanced structures and increased components in the LBS.In the LBS,the mammillary knobs and effective layer grew slowly.At the initiation stage of eggshell calcification,a total of 130 differentially expressed genes(DEGs,122 upregulated and 8 downregulated)were identified in the uterus of hens in the LBS relative to those in the HBS.These DEGs were relevant to apoptosis due to the cellular Ca overload.Higher values of p62 protein level,caspase-8 activity,Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the LBS.TUNEL assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the LBS.Although few DEGs were identified at the growth stage,similar uterine tissue damages were also observed in the LBS.The expressions of runt-related transcription factor 2 and osteocal-cin were upregulated in humeri of the LBS.Enlarged diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the HBS.Conclusion The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages,which could affect eggshell calcification and lead to a weak ultrastructure.Impaired uterine Ca transport may result in reduced femoral bone resorption and increased humeral bone formation to maintain a higher mineral and bone quality in the LBS.
文摘The aim of this study was to evaluate the effectiveness of BM (basement membrane) and SIS (small intestine submucosa) composite extracellular matrix staple line reinforcement in surgical procedures through finite element modelling simulations and leak-proof performance experiments. The mechanical analyses of soft tissues with and without staple line reinforcement were performed by establishing finite element models of three tissues, namely, stomach, intestine and lungs, under the use scenarios of different anastomosis staple models;and the leak-proof performance of the staple line reinforcement was evaluated by simulating leak-proof experiments of gastric incision margins, intestinal sections, and lung incision margins in vitro. The results showed that the equivalent average stresses of the staple line reinforcement were increased by 20 kPa-68 kPa in gastric and intestinal tissues, and 8 kPa-22 kPa in lung tissues. and that the BM and SIS composite extracellular matrix staple line reinforcement could strengthen the anastomotic structure, and at the same time disperse the high stresses of the anastomosed tissues, which could effectively reduce the postoperative complications such as anastomotic bleeding and anastomotic leakage, and provide a safer and more effective optimized design for surgical mechanical anastomosis. It can effectively reduce postoperative complications such as anastomotic bleeding and anastomotic leakage, and provide a safer and more effective optimized design for surgical mechanical anastomosis.
基金supported by the Ministry of Science and Technological Development of the Republic of Serbia, Grant # 143038
文摘Objective: To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods: Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin (range 0.8‐1 μg per 1 cm 2 ) for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results: Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury (increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death). Increased numbers of proliferating cell nuclear antigen (PCNA + ) cells indicated reparative processes in injured skin. Infiltration of CD3 + cells (T lymphocytes) along with the increased production of tumor necrosis factor‐α (TNF‐α) by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion: Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.
文摘AIM: To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats. METHODS: Thirty male Wistar rats weighing 200-250 g were used. Ischemia was induced by ob-structing blood flow in 25% of the total small intesti-nal length (ileum) with a vascular clamp for 45 min, after which either 60 min or 24 h of reperfusion was allowed. Rats were either anesthetized with pento-barbital sodium (50 mg/kg) or ketamine (100 mg/kg). Control groups received sham surgery. After 60 min of reperfusion, the intestine was examined for mor-phological alterations, and after 24 h intestinal basic electrical rhythm (BER) frequency was calculated, and intestinal transit determined in all groups. RESULTS: The intestinal mucosa in rats that were anesthetized with ketamine showed moderate altera-tions such as epithelial lifting, while ulceration and hemorrhage was observed in rats that received pento-barbital sodium after 60 min of reperfusion. Quantita-tive analysis of structural damage using the Chiu scaleshowed significantly less injury in rats that received ketamine than in rats that did not (2.35 ± 1.14 vs 4.58 ± 0.50, P < 0.0001). The distance traveled by a mark-er, expressed as percentage of total intestinal length, in rats that received pentobarbital sodium was 20% ± 2% in comparison with 25.9% ± 1.64% in rats that re-ceived ketamine (P = 0.017). BER was not statistically different between groups. CONCLUSION: Our results show that ketamine anesthesia is associated with diminished intestinal injury and abolishes the intestinal transit delay induced by ischemia/reperfusion.
基金This study was approved by the Ethics Committee of Shengjing Hospital of China Medical University.
文摘BACKGROUND Cerebral apoplexy patients are prone to cognitive impairment,and it is very important to choose appropriate treatment methods to improve their cognitive impairment after stroke.AIM To evaluate the effects of enhanced external counterpulsation(EECP)in con-junction with atorvastatin on cognitive function,neurotransmitter levels,and the repair of brain tissue damage in patients with cognitive impairment due to stroke.METHODS In this retrospective study,data from 60 patients with poststroke cognitive impairment due to stroke who were treated in our hospital from February 2021 to July 2022 were analyzed and divided into a treatment group(n=30)and a control group(n=30)according to the different nursing methods applied.Patients in the treatment group received EECP in addition to atorvastatin,while those in the control group received atorvastatin alone.Mini-Mental State Examination(MMSE),Montreal Cognitive Assessment(MoCA)and activities of daily living(ADL)scale scores were compared between the two groups.Additionally,the two groups were compared in terms of serum acetylcholine(ACh),acetylcholin-esterase(AChE),nitric oxide(NO),endothelin-1(ET-1),β2-microglobulin(β2-MG),glial fibrillary acidic protein(GFAP),and visinin-like protein 1(VILIP-1)in the serum.Blood flow measurements from the anterior cerebral artery(ACA),middle cerebral artery(MCA)and posterior cerebral artery(PCA)were compared between the two groups before and after treatment,and the pulsatility index(PI)and resistance index(RI)of each artery were determined.RESULTS MMSE,MoCA,and ADL scores all improved in both groups following treatment,with the study group showing more improvement than the control group(P<0.05).After treatment,there were statistically significant increases in both ACh and NO levels,whereas decreases occurred in AChE,ET-1,β2-MG,VILIP-1,and GFAP,levels and the PI and RI of the left-ACA,right-ACA,left-MCA,right-MCA,left-PCA,and right-PCA.The study group showed greater gains in all metrics than the control group(P<0.05).CONCLUSION EECP combined with atorvastatin is effective in the treatment of cognitive impairment after stroke and can effectively improve the cognitive function,neurotransmitter levels,and brain tissue damage status of patients.
基金the National Basic Research Program (973) of China(No.2010CB834306)the National Natural Science Foundation of China(No.81171098)
文摘Synchrotron radiation(SR) X-ray has significant potential for medical applications. However, the mechanisms underlying the effects of SR X-ray on biological tissues remain unclear. Because increasing evidence has indicated critical roles of cluster of differentiation 38(CD38) in various cellular functions and cell survival, in this study we used rodent testes as a model to determine the effects of SR X-ray irradiation on the CD38 level of the testes. We found that SR X-ray irradiation led to a significant increase in the CD38 level of rodent testes one day after the irradiation. In contrast, the SR X-ray irradiation did not produce a significant increase in the CD38 level of the testes from the rats that were administered with the antioxidant N-acetyl cysteine, thus suggesting that oxidative stress plays a significant role in the SR X-ray irradiation-induced increase in the CD38 levels. Our study has also provided evidence suggesting that poly(ADP-ribose) polymerase(PARP) activity is not involved in the SR X-ray irradiation-produced effect on the CD38 levels. Collectively, this study has provided first in vivo evidence indicating that CD38 levels can be increased by ionizing radiation, in which oxidative stress plays an important role. Because oxidative stress occurs in ionizing radiation as well as such diseases as cerebral ischemia and Parkinson's disease, oxidative stress may produce pathological effects by inducing increased CD38 levels.
文摘The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of na?ve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by antiinflammatory(M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to agerelated diseases. Underlying biochemical and metabolic studies will open nutritional treatment.
文摘Non-specific arm pain is a special clinical condition that can occur in work-related activities that involve maintaining a static position for prolonged periods or repetitive and frequent movements of the hand or entire arm. Such activities include typing on a keyboard, maneuvering a computer mouse, playing musical instruments (such as piano and guitar) and many forms of manual labor. The pain is dull and diffuse; It is localized in the forearm or in the hand but quickly can expand to the entire extremity. Non-specific arm pain is the most frequent type of work-related pain after lower-back pain. It thus has important socio-economic significance as a major cause of absence from work. The designation of "non-specific" originates from the fact that it has no obvious signs of tissue damage, unlike the "specific" pain accompanying carpal tunnel syndrome, tenosinovitis de Quervain, or lateral epicondylitis. Suggested causes of the pain include microtrauma of soft tissue followed by an inflammatory reaction, ischemia, fatigue, hyper-sensitization of nociceptors, focal dystonia of the hand and/or psychological stress. Treatment consists of application of NSAIDs, physical modalities, stretching and aerobic exercises. Prevention focuses on ergonomic modification during manual labor or work on a computer.
基金supported in part by the National Nature Science Foundation of China (81121004, 81230041, 81171798, 81171812, 81272105, 81671924)the National Basic Science and Development Programme (2012CB518105)the National Science and Technology Major Project (2011ZXJ07104B-03B)
文摘Regenerative medicine has rapidly developed over the past decade and created new opportunities to repair or replace tissue or organ function lost because of congenital defects, age, diseases, or serious damage (Cheng et al., 2016a; Cheng et al., 2016b). Regenerative medicine strategies in- clude the transplantation of bioactive factors, stem cells, or biomaterials, even the induced regeneration in a de novo, depending on the application (Fu, 2014a; Huang and Fu, 2014). However, there are several limitations to the use of regenerative medicine in the clinic with respect to using stem cells and biomaterials.
文摘Objective To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal(4-HNE),thioredoxin(Trx),thioredoxin reductase(TrxR)and the sctivities of Trx and TrxR,and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models.Methods
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0500700)the National Natural Science Foundation of China(52305206)the Shanghai Pujiang Programme(23PJD056)。
文摘Lubrication is an important prerequisite and foundation for the organism to protect biological tissues from mechanical friction damage and to maintain their normal life functions[1,2].After mechanical friction trauma,the lubrication matrix repairs damaged tissue by protecting the host from external impact and promotes the restoration of lubrication balance in the body.The process of lubrication typically unfolds in a series of events,beginning with a rapid response phase where lubricating fluids flow within the organism,reducing wear between tissues.This is followed by a gradual transition into a lubrication phase involving various lubrication mechanisms,such as fluid lubrication(The load is fully sustained by lubricant due to viscous forces in the space or gap between the components that are moving in relation to another object,while preventing solid-to-solid contact),boundary lubrication(The load is carried by surface high points rather than by lubricant),hydration lubrication(Hydration layers are tightly bound by the surrounding charges,allowing them to withstand significant pressure without being displaced,while also being able to quickly relax,resulting in a fluid-like response to shear forces),and mixed lubrication(This regime exists between full film lubrication and boundary lubrication,where the lubricant film generated is inadequate to fully separate the surfaces in contact,yet the hydrodynamic effect is significant)[3-5].Thus,lubrication plays a vital role in protecting living beings.However,if this well-coordinated wear reduction process is disrupted,lubrication can become uncontrolled or deteriorate,potentially leading to a range of lubrication-related diseases,including osteoarthritis,tendon adhesion,intervertebral disc degeneration,femoral head necrosis,cardiovascular blockages,tooth wear,and implant infections[1].
文摘Cellular reprograming offers an opportunity to convert one somatic cell type into another,providing promising potential for disease modeling and regenerative medicine.This cell fate conversion can be achieved using lineage-specific transcription factors,microRNAs or combinations of small molecules.A better understanding of how cell fate conversion is regulated will provide novel insights for precise manipulation of reprogramming,paving the way for developing novel strategies to regenerate the damaged tissue.