Mammalian spermatogenesis contains three continuous and organized processes, by which spermatogonia undergo mitosis and differentiate to spermatocytes, follow on meiosis to form haploid spermatids and ultimately trans...Mammalian spermatogenesis contains three continuous and organized processes, by which spermatogonia undergo mitosis and differentiate to spermatocytes, follow on meiosis to form haploid spermatids and ultimately transform into spermatozoa. These processes require an accurately, spatially and temporally regulated gene expression patterns. The microRNAs are a novel class of post-transcriptional regulators. Cumulating evidences have demonstrated that microRNAs are expressed in a cell-specific or stage-specific manner during spermatogenesis. In this review, we focus on the roles of microRNAs in spermatogenesis. We highlight that N6-methyladenosine(m6A)is involved in the biogenesis of microRNAs and miRNA regulates the m6A modification on mRNA, and that specific mi RNAs have been exploited as potential biomarkers for the male factor infertility, which will provide insightful understanding of microRNA roles in spermatogenesis.展开更多
Background: Sertoli cells(SCs) create a specialized environment to support and dictate spermatogenesis.MicroRNAs(miRNAs), a kind of ~ 22 nt small noncoding RNAs, have been reported to be highly abundant in mouse SCs a...Background: Sertoli cells(SCs) create a specialized environment to support and dictate spermatogenesis.MicroRNAs(miRNAs), a kind of ~ 22 nt small noncoding RNAs, have been reported to be highly abundant in mouse SCs and play critical roles in spermatogenesis. However, the miRNAs of porcine SCs remain largely unknown.Methods: We isolated porcine SCs and conducted small RNA sequencing. By comparing miRNAs in germ cells, we systematically analyzed the miRNA expression pattern of porcine SCs. We screened the highly enriched SC miRNAs and predicted their functions by Gene Ontology analysis. The dual luciferase assay was used to elucidate the regulation of tumor necrosis factor receptor(TNFR)-associated factor 3(TRAF3) by ssc-miR-149.Results: The analysis showed that 18 miRNAs were highly expressed in SCs and 15 miRNAs were highly expressed in germ cells. These miRNAs were predicted to mediate SC and germ cell functions. In addition, ssc-miR-149 played critical roles in SCs by targeting TRAF3.Conclusion: Our findings provide novel insights into the miRNA expression pattern and their regulatory roles of porcine SCs.展开更多
Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in re...Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.展开更多
A novel method of scheme design is proposed for power shifting transmissions of parallel hybrid electric vehicles(HEVs).First,shift sequences considering the path of power flow and shift logics are analyzed based on t...A novel method of scheme design is proposed for power shifting transmissions of parallel hybrid electric vehicles(HEVs).First,shift sequences considering the path of power flow and shift logics are analyzed based on the graph theory model,abstracted from the degree-of-freedom(DOF)of the schemes.Second,the scheme of gear-pair and shaft,defined as the scheme that ignores the arrangement of synchronizers,is derived from the basic configuration,defined as the scheme of gear-pair and shaft that contains only one of each type of the variable connections,and the numbers of each type of the variable connections.Finally,a multi-parameter scheme,including the arrangement of synchronizers and gear ratios,is designed to optimize the results of synthesis.This method helps to gain a deeper understanding of the systematic design of other fixed gear transmission schemes,such as automated mechanical transmission,dual clutch transmission,and even some novel multi-input transmission.展开更多
Bi-activated photonic materials are promising for various applications in high-capacity telecommunication,tunable laser,and advanced bioimaging and sensing.Although various Bi-doped material candidates have been explo...Bi-activated photonic materials are promising for various applications in high-capacity telecommunication,tunable laser,and advanced bioimaging and sensing.Although various Bi-doped material candidates have been explored,manufacturing of Bi heavily doped fiber with excellent optical activity remains a long-standing challenge.Herein,a novel viscosity evolutional behavior mediated strategy for manufacturing of Bi-doped active fiber with high dopant solubility is proposed.The intrinsic relation among the evolution of Bi,reaction temperature and viscosity of the glass system is established.Importantly,the effective avenue to prevent the undesired deactivation of Bi during fiber drawing by tuning the temperature dependent viscosity evolution is built.By applying the strategy,for the first time we demonstrate the success in fabrication of heavily doped Bi active fiber.Furthermore,the principal fiber amplifier device is constructed and broadband optical signal amplification is realized.Our findings indicate the effectiveness of the proposed temperature dependent viscosity mediated strategy for developing novel photonic active fiber,and they also demonstrate the great potential for application in the next-generation high-capacity telecommunication system.展开更多
As nonlinearity is highly correlated with their geometric dimensions,precise fabrication of optical micro/nanofibers(MNFs)has been a longstanding pursuit.Existing MNFs fabrication systems typically adopt horizontal st...As nonlinearity is highly correlated with their geometric dimensions,precise fabrication of optical micro/nanofibers(MNFs)has been a longstanding pursuit.Existing MNFs fabrication systems typically adopt horizontal structures,which inherently introduce inaccuracy stem from asymmetry between fiber axis/geometry and chaotic environment due to high temperature airflow,vibration,etc.,leading to deviations from the expected fiber morphology,especially for complex-structured MNFs.Here,we propose and manufacture a MNFs fabrication systems,effectively reducing fiber shape deviations during the fabrication process,enabling the fabrication of precise MNFs.To demonstrate the capability of our system in manufacturing precise structure MNFs,we design and fabricate diameter-gradient microfibers with four cascaded structures over a length of approximately 120 mm and a minimum diameter of about 1μm for on-demand nonlinearity to generate supercontinuum spectrum.Eventually,we obtain supercontinuum spectrum covering 1463-1741 nm at the−10 dB level with an efficiency of 264.62 nm∕kW,exhibiting good flatness and enabling efficient spectral broadening.展开更多
The high-speed boundary layer transition directly affects the refined design of the flight vehicle’s aerodynamic and thermal properties.However,current research in this field generally focuses on simplified geometrie...The high-speed boundary layer transition directly affects the refined design of the flight vehicle’s aerodynamic and thermal properties.However,current research in this field generally focuses on simplified geometries,such as cones or flat plates,resulting in a limited understanding of high-speed boundary layer transition in prac-tical vehicle configurations.This study aims to carry out an in-depth investigation of high-speed boundary layer transitions in a fin-cone configuration with a double-cone design.PCB sensors are used to characterize the evolution of instability waves along the streamwise direction on both the leeward and windward sides of the model.Additionally,focused laser differential interferometry(FLDI)is deployed to measure the instability characteristics along the wall-normal direction of the high-speed bound-ary layer.Furthermore,an infrared camera is employed to obtain surface temperatures.In addition to the second-mode instabilities observed on the leeward side,streamwise vortex-induced local peaks on the windward side are also observed with PCB sensors.Infrared images reveal that the thermal characteristics are different between the wind-ward and leeward sides due to transition mechanisms.The study reveals that at simi-lar Reynolds numbers,the area fully developed to turbulence on the windward side is considerably larger than that on the leeward side for the cone region,while the fin region displays different trends.These findings provide invaluable insights for the advancement of aerodynamic and thermal design in high-speed aircraft.展开更多
Spermatogenesis is a continual process that occurs in the testes,in which diploid spermatogonial stem cells(SSCs)differentiate and generate haploid spermatozoa.This highly efficient and intricate process is orchestrat...Spermatogenesis is a continual process that occurs in the testes,in which diploid spermatogonial stem cells(SSCs)differentiate and generate haploid spermatozoa.This highly efficient and intricate process is orchestrated at multiple levels.N^(6)-methyladenosine(m^(6)A),an epigenetic modification prevalent in mRNAs,is implicated in the transcriptional regulation during spermatogenesis.However,the dynamics of m^(6)A modification in non-rodent mammalian species remains unclear.Here,we systematically investigated the profile and role of m^(6)A during spermatogenesis in pigs.By analyzing the transcriptomic distribution of m^(6)A in spermatogonia,spermatocytes,and round spermatids,we identified a globally conserved m^(6)A pattern between porcine and murine genes with spermatogenic function.We found that m^(6)A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators.In addition,transcriptomes in porcine male germ cells could be subjected to the m^(6)A modification.Our data show that m^(6)A plays the regulatory roles during spermatogenesis in pigs,which is similar to that in mice.Illustrations of this point are three genes(SETDB1,FOXO1,and FOXO3)that are crucial to the determination of the fate of SSCs.To the best of our knowledge,this study for the first time uncovers the expression profile and role of m^(6)A during spermatogenesis in large animals and provides insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.展开更多
The domain of industrial biomanufacturing is enthusiastically embracing the concept of Digital Twin,owing to its promises of increased process efficiency and resource utilisation.However,Digital Twin in biomanufacturi...The domain of industrial biomanufacturing is enthusiastically embracing the concept of Digital Twin,owing to its promises of increased process efficiency and resource utilisation.However,Digital Twin in biomanufacturing is not yet clearly defined and this sector of the industry is falling behind the others in terms of its implementation.On the other hand,some of the benefits of Digital Twin seem to overlap with the more established practices of process control and optimization,and the term is vaguely used in different scenarios.In an attempt to clarify this issue,we investigate this overlap for the specific case of fermentation operation,a central step in many biomanufacturing processes.Based on this investigation,a framework built upon a five-step pathway starting from a basic steady-state process model is proposed to develop a fully-fledged Digital Twin.For demonstration purposes,the framework is applied to a bench-scale second-generation ethanol fermentation process as a case study.It is proposed that the success or failure of a fully-fledged Digital Twin implementation is determined by key factors that comprise the role of modelling,human operator actions,and other propositions of economic value.展开更多
基金funded,in part,by the National Basic Research Program of China(973 programNo.2013CB943103)+1 种基金the National Natural Science Foundation of China(No.31272439,No.31230048 and No.31572401)Programs Foundation of Ministry of Education of China(No.20130204110017)
文摘Mammalian spermatogenesis contains three continuous and organized processes, by which spermatogonia undergo mitosis and differentiate to spermatocytes, follow on meiosis to form haploid spermatids and ultimately transform into spermatozoa. These processes require an accurately, spatially and temporally regulated gene expression patterns. The microRNAs are a novel class of post-transcriptional regulators. Cumulating evidences have demonstrated that microRNAs are expressed in a cell-specific or stage-specific manner during spermatogenesis. In this review, we focus on the roles of microRNAs in spermatogenesis. We highlight that N6-methyladenosine(m6A)is involved in the biogenesis of microRNAs and miRNA regulates the m6A modification on mRNA, and that specific mi RNAs have been exploited as potential biomarkers for the male factor infertility, which will provide insightful understanding of microRNA roles in spermatogenesis.
基金supported in part by the National Natural Science Foundation of China (Grant No. 31572401, 31772605) to W.Z。
文摘Background: Sertoli cells(SCs) create a specialized environment to support and dictate spermatogenesis.MicroRNAs(miRNAs), a kind of ~ 22 nt small noncoding RNAs, have been reported to be highly abundant in mouse SCs and play critical roles in spermatogenesis. However, the miRNAs of porcine SCs remain largely unknown.Methods: We isolated porcine SCs and conducted small RNA sequencing. By comparing miRNAs in germ cells, we systematically analyzed the miRNA expression pattern of porcine SCs. We screened the highly enriched SC miRNAs and predicted their functions by Gene Ontology analysis. The dual luciferase assay was used to elucidate the regulation of tumor necrosis factor receptor(TNFR)-associated factor 3(TRAF3) by ssc-miR-149.Results: The analysis showed that 18 miRNAs were highly expressed in SCs and 15 miRNAs were highly expressed in germ cells. These miRNAs were predicted to mediate SC and germ cell functions. In addition, ssc-miR-149 played critical roles in SCs by targeting TRAF3.Conclusion: Our findings provide novel insights into the miRNA expression pattern and their regulatory roles of porcine SCs.
基金supported by the National Natural Science Foun-dation of China(Grant Nos.:32170680 and T2122018)the Natural Science Foundation of Shanghai,China(Grant No.:21ZR1476000)the CAS Youth Innovation Promotion Association,China(Grant No.:Y2022076).
文摘Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.
基金Supported by the National Natural Science Foundation of China(U1764257)。
文摘A novel method of scheme design is proposed for power shifting transmissions of parallel hybrid electric vehicles(HEVs).First,shift sequences considering the path of power flow and shift logics are analyzed based on the graph theory model,abstracted from the degree-of-freedom(DOF)of the schemes.Second,the scheme of gear-pair and shaft,defined as the scheme that ignores the arrangement of synchronizers,is derived from the basic configuration,defined as the scheme of gear-pair and shaft that contains only one of each type of the variable connections,and the numbers of each type of the variable connections.Finally,a multi-parameter scheme,including the arrangement of synchronizers and gear ratios,is designed to optimize the results of synthesis.This method helps to gain a deeper understanding of the systematic design of other fixed gear transmission schemes,such as automated mechanical transmission,dual clutch transmission,and even some novel multi-input transmission.
基金support from the National Key R&D Program of China(2020YFB1805901)the National Science Fund for Distinguished Young Scholars(62125502)+7 种基金the National Natural Science Foundation of China(51972113,52302002 and 62305115)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01X137)Foshan Science and Technology Innovation Project(1920001000052)the Foundation of State Key Laboratory of Reactor System Design Technologythe Large Scientific Facility Open Subject of Songshan Lake,Dongguan,Guangdongthe Research Project supported by State Key Lab of Luminescent Materials and DevicesSouth China University of Technology(Skllmd2023-07)the Sponsored Research Project of Corning Incorporated。
文摘Bi-activated photonic materials are promising for various applications in high-capacity telecommunication,tunable laser,and advanced bioimaging and sensing.Although various Bi-doped material candidates have been explored,manufacturing of Bi heavily doped fiber with excellent optical activity remains a long-standing challenge.Herein,a novel viscosity evolutional behavior mediated strategy for manufacturing of Bi-doped active fiber with high dopant solubility is proposed.The intrinsic relation among the evolution of Bi,reaction temperature and viscosity of the glass system is established.Importantly,the effective avenue to prevent the undesired deactivation of Bi during fiber drawing by tuning the temperature dependent viscosity evolution is built.By applying the strategy,for the first time we demonstrate the success in fabrication of heavily doped Bi active fiber.Furthermore,the principal fiber amplifier device is constructed and broadband optical signal amplification is realized.Our findings indicate the effectiveness of the proposed temperature dependent viscosity mediated strategy for developing novel photonic active fiber,and they also demonstrate the great potential for application in the next-generation high-capacity telecommunication system.
基金supported by the Natural Science Foundation of Zhejiang Province China grant[LR22F050006(YM)]the National Natural Science Foundation of China(NSFC)grant[62222511(YM)]+1 种基金the National Key Research and Development Program of China grant[2023YFF0613000(YM)]the STI 2030-Major Projects grant[2021ZD0200401(YM)].
文摘As nonlinearity is highly correlated with their geometric dimensions,precise fabrication of optical micro/nanofibers(MNFs)has been a longstanding pursuit.Existing MNFs fabrication systems typically adopt horizontal structures,which inherently introduce inaccuracy stem from asymmetry between fiber axis/geometry and chaotic environment due to high temperature airflow,vibration,etc.,leading to deviations from the expected fiber morphology,especially for complex-structured MNFs.Here,we propose and manufacture a MNFs fabrication systems,effectively reducing fiber shape deviations during the fabrication process,enabling the fabrication of precise MNFs.To demonstrate the capability of our system in manufacturing precise structure MNFs,we design and fabricate diameter-gradient microfibers with four cascaded structures over a length of approximately 120 mm and a minimum diameter of about 1μm for on-demand nonlinearity to generate supercontinuum spectrum.Eventually,we obtain supercontinuum spectrum covering 1463-1741 nm at the−10 dB level with an efficiency of 264.62 nm∕kW,exhibiting good flatness and enabling efficient spectral broadening.
基金supported by an Experimental Identification Technology Research Project(No.2022G02000250007).
文摘The high-speed boundary layer transition directly affects the refined design of the flight vehicle’s aerodynamic and thermal properties.However,current research in this field generally focuses on simplified geometries,such as cones or flat plates,resulting in a limited understanding of high-speed boundary layer transition in prac-tical vehicle configurations.This study aims to carry out an in-depth investigation of high-speed boundary layer transitions in a fin-cone configuration with a double-cone design.PCB sensors are used to characterize the evolution of instability waves along the streamwise direction on both the leeward and windward sides of the model.Additionally,focused laser differential interferometry(FLDI)is deployed to measure the instability characteristics along the wall-normal direction of the high-speed bound-ary layer.Furthermore,an infrared camera is employed to obtain surface temperatures.In addition to the second-mode instabilities observed on the leeward side,streamwise vortex-induced local peaks on the windward side are also observed with PCB sensors.Infrared images reveal that the thermal characteristics are different between the wind-ward and leeward sides due to transition mechanisms.The study reveals that at simi-lar Reynolds numbers,the area fully developed to turbulence on the windward side is considerably larger than that on the leeward side for the cone region,while the fin region displays different trends.These findings provide invaluable insights for the advancement of aerodynamic and thermal design in high-speed aircraft.
基金the National Natural Science Foundation of China(Grant No.31572401)to Wenxian Zengthe Research Project of Shaanxi Science and Technology Department(Grant No.2020NY-003)to Tao Zhangthe National Natural Science Foundation of China(Grant No.81703193)to Yinghua Lv.
文摘Spermatogenesis is a continual process that occurs in the testes,in which diploid spermatogonial stem cells(SSCs)differentiate and generate haploid spermatozoa.This highly efficient and intricate process is orchestrated at multiple levels.N^(6)-methyladenosine(m^(6)A),an epigenetic modification prevalent in mRNAs,is implicated in the transcriptional regulation during spermatogenesis.However,the dynamics of m^(6)A modification in non-rodent mammalian species remains unclear.Here,we systematically investigated the profile and role of m^(6)A during spermatogenesis in pigs.By analyzing the transcriptomic distribution of m^(6)A in spermatogonia,spermatocytes,and round spermatids,we identified a globally conserved m^(6)A pattern between porcine and murine genes with spermatogenic function.We found that m^(6)A was enriched in a group of genes that specifically encode the metabolic enzymes and regulators.In addition,transcriptomes in porcine male germ cells could be subjected to the m^(6)A modification.Our data show that m^(6)A plays the regulatory roles during spermatogenesis in pigs,which is similar to that in mice.Illustrations of this point are three genes(SETDB1,FOXO1,and FOXO3)that are crucial to the determination of the fate of SSCs.To the best of our knowledge,this study for the first time uncovers the expression profile and role of m^(6)A during spermatogenesis in large animals and provides insights into the intricate transcriptional regulation underlying the lifelong male fertility in non-rodent mammalian species.
基金The work is funded by the Novo Nordisk Foundation in the frame of the‘Accelerated Innovation in Manufacturing Biologics’(AIMBio)project(Grant number NNF19SA0035474).
文摘The domain of industrial biomanufacturing is enthusiastically embracing the concept of Digital Twin,owing to its promises of increased process efficiency and resource utilisation.However,Digital Twin in biomanufacturing is not yet clearly defined and this sector of the industry is falling behind the others in terms of its implementation.On the other hand,some of the benefits of Digital Twin seem to overlap with the more established practices of process control and optimization,and the term is vaguely used in different scenarios.In an attempt to clarify this issue,we investigate this overlap for the specific case of fermentation operation,a central step in many biomanufacturing processes.Based on this investigation,a framework built upon a five-step pathway starting from a basic steady-state process model is proposed to develop a fully-fledged Digital Twin.For demonstration purposes,the framework is applied to a bench-scale second-generation ethanol fermentation process as a case study.It is proposed that the success or failure of a fully-fledged Digital Twin implementation is determined by key factors that comprise the role of modelling,human operator actions,and other propositions of economic value.
