Background:Goat milk is very similar to human milk in terms of its abundant nutrients and ease of digestion.To derive greater economic benefit,farmers require more female offspring(does);however,the buck-to-doe offspr...Background:Goat milk is very similar to human milk in terms of its abundant nutrients and ease of digestion.To derive greater economic benefit,farmers require more female offspring(does);however,the buck-to-doe offspring sex ratio is approximately 50%.At present,artificial insemination after the separation of X/Y sperm using flow cytometry is the primary means of controlling the sex of livestock offspring.However,flow cytometry has not been successfully utilised for the separation of X/Y sperm aimed at sexing control in dairy goats.Results:In this study,a novel,simple goat sperm sexing technology that activates the toll-like receptor 7/8(TLR7/8),thereby inhibiting X-sperm motility,was investigated.Our results showed that the TLR7/8 coding goat Xchromosome was expressed in approximately 50%of round spermatids in the testis and sperm,as measured from cross-sections of the epididymis and ejaculate,respectively.Importantly,TLR7/8 was located at the tail of the Xsperm.Upon TLR7/8 activation,phosphorylated forms of glycogen synthase kinaseα/β(GSK3α/β)and nuclear factor kappa-B(NF-κB)were detected in the X-sperm,causing reduced mitochondrial activity,ATP levels,and sperm motility.High-motility Y-sperm segregated to the upper layer and the low-motility X-sperm,to the lower layer.Following in vitro fertilisation using the TLR7/8-activated sperm from the lower layer,80.52±6.75%of the embryos were XX females.The TLR7/8-activated sperm were subsequently used for in vivo embryo production via the superovulatory response;nine embryos were collected from the uterus of two does that conceived.Eight of these were XX embryos,and one was an XY embryo.Conclusions:Our study reveals a novel TLR7/8 signalling mechanism that affects X-sperm motility via the GSK3α/β-hexokinase pathway;this technique could be used to facilitate the efficient production of sexed dairy goat embryos.展开更多
Location-based services have become an important part of the daily life.Fingerprint localization has been put forward to overcome the shortcomings of the traditional positioning algorithms in indoor scenario and rich ...Location-based services have become an important part of the daily life.Fingerprint localization has been put forward to overcome the shortcomings of the traditional positioning algorithms in indoor scenario and rich scattering environment.In this paper,a single-site multiple-input multiple-output(MIMO)orthogonal frequency division multiplexing(OFDM)system is modeled,from which an angle delay channel power matrix(ADCPM)is extracted.Considering the changing environment,auto encoders are used to generate new fingerprints based on ADCPM fingerprints to improve the robustness of the fingerprints.When the scattering environment has changed beyond a certain extent,the robustness will not be able to make up for the positioning error.Under this circumstance,an updating of the fingerprint database is imperative.A new fingerprint database updating algorithm which combines a new clustering method and an updating rule based on probability is proposed.Simulation results show the desirable performance of the proposed methods.展开更多
CD4^(+)T cells,particularly IL-17-secreting helper CD4^(+)T cells,play a central role in the inflammatory processes underlying autoimmune disorders.Eukaryotic Elongation Factor 2 Kinase(eEF2K)is pivotal in CD8^(+)T ce...CD4^(+)T cells,particularly IL-17-secreting helper CD4^(+)T cells,play a central role in the inflammatory processes underlying autoimmune disorders.Eukaryotic Elongation Factor 2 Kinase(eEF2K)is pivotal in CD8^(+)T cells and has important implications in vascular dysfunction and inflammation-related diseases such as hypertension.However,its specific immunological role in CD4^(+)T cell activities and related inflammatory diseases remains elusive.Our investigation has uncovered that the deficiency of eEF2K disrupts the survival and proliferation of CD4^(+)T cells,impairs their ability to secrete cytokines.Notably,this dysregulation leads to heightened production of pro-inflammatory cytokine IL-17,fosters a pro-inflammatory microenvironment in the absence of eEF2K in CD4^(+)T cells.Furthermore,the absence of eEF2K in CD4^(+)T cells is linked to increased metabolic activity and mitochondrial bioenergetics.We have shown that eEF2K regulates mitochondrial function and CD4^(+)T cell activity through the upregulation of the transcription factor,signal transducer and activator of transcription 3(STAT3).Crucially,the deficiency of eEF2K exacerbates the severity of inflammation-related diseases,including rheumatoid arthritis,multiple sclerosis,and ulcerative colitis.Strikingly,the use of C188-9,a small molecule targeting STAT3,mitigates colitis in a murine immunodeficiency model receiving eEF2K knockout(KO)CD4^(+)T cells.These findings emphasize the pivotal role of eEF2K in controlling the function and metabolism of CD4^(+)T cells and its indispensable involvement in inflammation-related diseases.Manipulating eEF2K represents a promising avenue for novel therapeutic approaches in the treatment of inflammation-related disorders.展开更多
基金supported by Xiamen University Malaysia Research Fund (XMUMRF/2019-C3/IENG/0013)financial assistance and faculty start-up grants/supports from Xiamen University~~
基金This research was supported by the National Natural Science Foundation of China(31672425)Shaanxi Province Key R&D Program(2018ZDXM-NY-043,2020ZDLNY02–04).
文摘Background:Goat milk is very similar to human milk in terms of its abundant nutrients and ease of digestion.To derive greater economic benefit,farmers require more female offspring(does);however,the buck-to-doe offspring sex ratio is approximately 50%.At present,artificial insemination after the separation of X/Y sperm using flow cytometry is the primary means of controlling the sex of livestock offspring.However,flow cytometry has not been successfully utilised for the separation of X/Y sperm aimed at sexing control in dairy goats.Results:In this study,a novel,simple goat sperm sexing technology that activates the toll-like receptor 7/8(TLR7/8),thereby inhibiting X-sperm motility,was investigated.Our results showed that the TLR7/8 coding goat Xchromosome was expressed in approximately 50%of round spermatids in the testis and sperm,as measured from cross-sections of the epididymis and ejaculate,respectively.Importantly,TLR7/8 was located at the tail of the Xsperm.Upon TLR7/8 activation,phosphorylated forms of glycogen synthase kinaseα/β(GSK3α/β)and nuclear factor kappa-B(NF-κB)were detected in the X-sperm,causing reduced mitochondrial activity,ATP levels,and sperm motility.High-motility Y-sperm segregated to the upper layer and the low-motility X-sperm,to the lower layer.Following in vitro fertilisation using the TLR7/8-activated sperm from the lower layer,80.52±6.75%of the embryos were XX females.The TLR7/8-activated sperm were subsequently used for in vivo embryo production via the superovulatory response;nine embryos were collected from the uterus of two does that conceived.Eight of these were XX embryos,and one was an XY embryo.Conclusions:Our study reveals a novel TLR7/8 signalling mechanism that affects X-sperm motility via the GSK3α/β-hexokinase pathway;this technique could be used to facilitate the efficient production of sexed dairy goat embryos.
基金supported by Jiangsu Province Key Research and Development Program(BE2018704)Technical Innovation Project of The Ministry of Public Security(20170001)+1 种基金Fundamental Research Funds for the Central Universities(2242022k30001)National Science Foundation of China(CN)(Grant No.61871111).
文摘Location-based services have become an important part of the daily life.Fingerprint localization has been put forward to overcome the shortcomings of the traditional positioning algorithms in indoor scenario and rich scattering environment.In this paper,a single-site multiple-input multiple-output(MIMO)orthogonal frequency division multiplexing(OFDM)system is modeled,from which an angle delay channel power matrix(ADCPM)is extracted.Considering the changing environment,auto encoders are used to generate new fingerprints based on ADCPM fingerprints to improve the robustness of the fingerprints.When the scattering environment has changed beyond a certain extent,the robustness will not be able to make up for the positioning error.Under this circumstance,an updating of the fingerprint database is imperative.A new fingerprint database updating algorithm which combines a new clustering method and an updating rule based on probability is proposed.Simulation results show the desirable performance of the proposed methods.
文摘CD4^(+)T cells,particularly IL-17-secreting helper CD4^(+)T cells,play a central role in the inflammatory processes underlying autoimmune disorders.Eukaryotic Elongation Factor 2 Kinase(eEF2K)is pivotal in CD8^(+)T cells and has important implications in vascular dysfunction and inflammation-related diseases such as hypertension.However,its specific immunological role in CD4^(+)T cell activities and related inflammatory diseases remains elusive.Our investigation has uncovered that the deficiency of eEF2K disrupts the survival and proliferation of CD4^(+)T cells,impairs their ability to secrete cytokines.Notably,this dysregulation leads to heightened production of pro-inflammatory cytokine IL-17,fosters a pro-inflammatory microenvironment in the absence of eEF2K in CD4^(+)T cells.Furthermore,the absence of eEF2K in CD4^(+)T cells is linked to increased metabolic activity and mitochondrial bioenergetics.We have shown that eEF2K regulates mitochondrial function and CD4^(+)T cell activity through the upregulation of the transcription factor,signal transducer and activator of transcription 3(STAT3).Crucially,the deficiency of eEF2K exacerbates the severity of inflammation-related diseases,including rheumatoid arthritis,multiple sclerosis,and ulcerative colitis.Strikingly,the use of C188-9,a small molecule targeting STAT3,mitigates colitis in a murine immunodeficiency model receiving eEF2K knockout(KO)CD4^(+)T cells.These findings emphasize the pivotal role of eEF2K in controlling the function and metabolism of CD4^(+)T cells and its indispensable involvement in inflammation-related diseases.Manipulating eEF2K represents a promising avenue for novel therapeutic approaches in the treatment of inflammation-related disorders.
