Collagen,the main component of mammal skin,has been traditionally used in leather manufacturing for thousands of years due to its diverse physicochemical properties.Collagen is the most abundant protein in mammals and the main component of the extracellular matrix(ECM).The properties of collagen also make it an ideal building block for the engineering of materials for a range of biomedical applications.Reproductive medicine,especially human fertility preservation strategies and reproductive organ regeneration,has attracted significant attention in recent years as it is key in resolving the growing social concern over aging populations worldwide.Collagen-based biomaterials such as collagen hydrogels,decellularized ECM(dECM),and bioengineering techniques including collagen-based 3D bio-printing have facilitated the engineering of reproductive tissues.This review summarizes the recent progress in apply-ing collagen-based biomaterials in reproductive.Furthermore,we discuss the prospects of collagen-based materials for engineering artificial reproductive tissues,hormone replacement therapy,and reproductive organ reconstruction,aiming to inspire new thoughts and advancements in engineered reproductive tissues research.
Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.
Lu ShiHongling TianPeng WangLing LiZhaoqi ZhangJiayu ZhangYong Zhao
Nowadays cloud architecture is widely applied on the internet.New malware aiming at the privacy data stealing or crypto currency mining is threatening the security of cloud platforms.In view of the problems with existing application behavior monitoring methods such as coarse-grained analysis,high performance overhead and lack of applicability,this paper proposes a new fine-grained binary program monitoring and analysis method based on multiple system level components,which is used to detect the possible privacy leakage of applications installed on cloud platforms.It can be used online in cloud platform environments for fine-grained automated analysis of target programs,ensuring the stability and continuity of program execution.We combine the external interception and internal instrumentation and design a variety of optimization schemes to further reduce the impact of fine-grained analysis on the performance of target programs,enabling it to be employed in actual environments.The experimental results show that the proposed method is feasible and can achieve the acceptable analysis performance while consuming a small amount of system resources.The optimization schemes can go beyond traditional dynamic instrumentation methods with better analytical performance and can be more applicable to online analysis on cloud platforms.
It is believed that the adaptive immune system responds to nonself according to its specificity and memory properties,whereas the innate immune system lacks adaptive characteristics.The specificity of the adaptive immune response is based on irreversible changes in the DNA sequence by retroposons encoding site-specific recombinases,which generate unlimited numbers of receptors to allow B lymphocytes and T lymphocytes to specifically recognize antigens.
Cisplatin(CDDP)-induced ototoxicity is one of the common adverse effects of cisplatin chemotherapy.Thus far,effective approaches for attenuating hearing loss are unavailable in clinical practice.Mitochondrial biogenesis acts as a master element of mitochondrial health and is necessary for mitochondrial quality control.The current study examined whether mitochondrial biogenesis is involved in CDDP-induced ototoxicity.Herein,we showed that CDDP damaged mitochondrial function and caused death of House Ear Institute-Organ of Corti 1(HEI-OC1)cells by impairing mitochondrial biogenesis.Moreover,overexpression of peroxisome proliferatoractivated receptor-g coactivator-1a,a key factor in mitochondrial biogenesis,promoted mitochondrial biogenesis in HEI-OC1 cells and protected them against CDDP-induced cytotoxicity.These findings suggest that mitochondrial biogenesis is involved in the pathology of CDDP cytotoxicity of HEI-OC1 cells,and activation of peroxisome proliferator-activated receptor-g coactivator-1a can be considered a potential therapeutic strategy to attenuate CDDP-mediated ototoxicity.
It is believed that the adaptive immune system responds to nonself entities with its specificity and memory properties.In contrast,the innate immune system lacks adaptive characteristics.Whether innate immune cells can generate adaptive immune features has always been an unanswered question.
Xenogeneic thymus transplantation can efficiently induce specific immune tolerance to donor antigens in athymic recipients. However, many nude mice suffer from autoimmune diseases （AID） for over 10 weeks after xenogeneic thymus transplantation. CD4^＋CD25^＋Foxp3^＋ regulatory T （Treg） cells were recently determined to play a pivotal role in keeping immune tolerance in humans and mice. Thus, we investigated this subpopulation of Treg cells in the periphery of pig thymus-grafted nude mice suffering from AID. Our results showed that the expression of Foxp3, CTLA-4 and GITR on mouse CD4^＋CD25^＋ T cells and the ratio of CD4^＋CD25^＋Foxp3^＋ Treg cells to CD4^＋ T cells were significantly decreased in the periphery of pig thymus-grafted nude mice suffering from AID, compared with healthy pig or mouse thymus-grafted nude mice. Furthermore, mouse CD4^＋CD25^＋ T cells in pig thymus-grafted nude mice suffering from AID showed more severe deficiency in immunosuppressive function compared with the counterpart in xenogeneic pig or syngeneic thymus-grafted nude mice without AID. Thus, the decreased frequency, altered phenotype and functional deficiency of mouse CD4^＋CD25^＋ Treg cells in pig thymus-grafted nude mice may contribute to the development of AID in this model.
Neutrophils are heterogeneous with distinct subsets,and can switch phenotypes to exert regulatory functions on immunity.We herein demonstrate that IL-23-treated neutrophils selectively produce IL-17A,IL-17F and IL-22,and display a distinct gene expression profile in contrast to resting and lipopolysaccharide-treated neutrophils.IL-17+neutrophils are present in the colons of mice with dextran sulfate sodium-induced colitis.Adoptive transfer of IL-23-treated neutrophils significantly promotes pathogenesis in this model.IL-23 induces neutrophil polarization through STAT3-dependent RORγt and BATF pathways.Thus,IL-23-induced neutrophil polarization expresses a unique cytokine-producing profile,which may contribute to IL-23-mediated inflammatory diseases.
CD4^(+)CD25^(+) T regulatory(Treg)cells are critical in inducing and maintaining immunological self-tolerance as well as transplant tolerance.The effect of low doses of whole-body irradiation(WBI)on CD41CD251Foxp31 Treg cells has not been determined.The proportion,phenotypes and function of CD4^(+)CD25^(+) Treg cells were investigated 0.5,5 and 15 days after euthymic,thymectomized or allogeneic bone marrow transplanted C57BL/6 mice received 2-Gy c-rays of WBI.The 2-Gy WBI significantly enhanced the ratios of CD41CD251 Treg cells and CD4^(+)CD25^(+)Foxp3^(+) Treg cells to CD41 T cells in peripheral blood,lymph nodes,spleens and thymi of mice.The CD41CD251 Treg cells of the WBI-treated mice showed immunosuppressive activities on the immune response of CD4^(+)CD25^(+) T effector cells to alloantigens or mitogens as efficiently as the control mice.Furthermore,2-Gy c-ray WBI significantly increased the percentage of CD4^(+)CD25^(+)Foxp3^(+) Treg cells in the periphery of either thymectomized mice or allogeneic bone marrow transplanted mice.The in vitro assay showed that ionizing irradiation induced less cell death in CD4^(+)CD25^(+)Foxp3^(+) Treg cells than in CD4^(+)CD25^(+) T cells.Thus,a low dose of WBI could significantly enhance the level of functional CD41CD251Foxp31 Treg cells in the periphery of naive or immunized mice.The enhanced proportion of CD41CD251Foxp31 Treg cells in the periphery by a low dose of WBI may make hosts more susceptible to immune tolerance induction.
