It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mo...It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.展开更多
N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory lo...N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.展开更多
Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overa...Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.展开更多
Recently,small nucleolar RNAs(snoRNAs)have transcended the genomic“noise”to emerge as pivotal molecular markers due to their essential roles in tumor progression.Substantial evidence indicates a strong association b...Recently,small nucleolar RNAs(snoRNAs)have transcended the genomic“noise”to emerge as pivotal molecular markers due to their essential roles in tumor progression.Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance.Historically,snoRNA research has concentrated on two classical mechanisms:2'-O-ribose methylation and pseudouridylation.This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors,encompassing transcriptional,post-transcriptional,and post-translational regulation.We further discuss the synergistic effect between snoRNA host genes(SNHGs)and snoRNAs in tumor progression.More importantly,snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes.Accordingly,we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.展开更多
The thermoelectric energy conversion technique by employing the Disk-Magnet Electromagnetic Induction (DM-EMI) is examined in detail, and possible applications to heat engines as one of the energy-harvesting technolog...The thermoelectric energy conversion technique by employing the Disk-Magnet Electromagnetic Induction (DM-EMI) is examined in detail, and possible applications to heat engines as one of the energy-harvesting technologies are discussed. The idea is induced by the analysis of thermomechanical dynamics (TMD) for a nonequilibrium irreversible thermodynamic system of heat engines, such as a drinking bird and a low temperature Stirling engine, resulting in thermoelectric energy generation different from conventional heat engines. The current thermoelectric energy conversion with DM-EMI can be applied to wide ranges of machines and temperature differences. The mechanism of DM-EMI energy converter is categorized as the axial flux generator (AFG), which is the reason why the technology is applicable to sensitive thermoelectric conversions. On the other hand, almost all the conventional turbines use the radius flux generator to extract huge electric power, which uses the radial flux generator (RFG). The axial flux generator is helpful for a low mechanoelectric energy conversion and activations of waste heat from macroscopic energy generators such as wind, geothermal, thermal, nuclear power plants and heat-dissipation lines. The technique of DM-EMI will contribute to solving environmental problems to maintain clean and sustainable energy as one of the energy harvesting technologies.展开更多
The new independent solutions of the nonlinear differential equation with time-dependent coefficients (NDE-TC) are discussed, for the first time, by employing experimental device called a drinking bird whose simple ba...The new independent solutions of the nonlinear differential equation with time-dependent coefficients (NDE-TC) are discussed, for the first time, by employing experimental device called a drinking bird whose simple back-and-forth motion develops into water drinking motion. The solution to a drinking bird equation of motion manifests itself the transition from thermodynamic equilibrium to nonequilibrium irreversible states. The independent solution signifying a nonequilibrium thermal state seems to be constructed as if two independent bifurcation solutions are synthesized, and so, the solution is tentatively termed as the bifurcation-integration solution. The bifurcation-integration solution expresses the transition from mechanical and thermodynamic equilibrium to a nonequilibrium irreversible state, which is explicitly shown by the nonlinear differential equation with time-dependent coefficients (NDE-TC). The analysis established a new theoretical approach to nonequilibrium irreversible states, thermomechanical dynamics (TMD). The TMD method enables one to obtain thermodynamically consistent and time-dependent progresses of thermodynamic quantities, by employing the bifurcation-integration solutions of NDE-TC. We hope that the basic properties of bifurcation-integration solutions will be studied and investigated further in mathematics, physics, chemistry and nonlinear sciences in general.展开更多
The traditional thermoelectric energy conversion techniques are explained in detail in terms of the axial flux electromagnetic (AFE) and the radial flux electromagnetic (RFE) inductions, and applications to heat engin...The traditional thermoelectric energy conversion techniques are explained in detail in terms of the axial flux electromagnetic (AFE) and the radial flux electromagnetic (RFE) inductions, and applications to heat engines for the energy-harvesting technologies are discussed. The idea is induced by the analysis of thermomechanical dynamics (TMD) for a nonequilibrium irreversible thermodynamic system of heat engines (a drinking bird, a low temperature Stirling engine), resulting in thermoelectric energy generation different from conventional heat engines. The mechanism of thermoelectric energy conversion can be categorized as the axial flux generator (AFG) and the radial flux generator (RFG). The axial flux generator is helpful for low mechanoelectric energy conversion and activations of waste heat from macroscopic energy generators, such as wind, geothermal, thermal, nuclear power plants and heat-dissipation lines, and the device contributes to solving environmental problems to maintain clean and sustainable energy as one of the energy harvesting technologies.展开更多
基金Israel Cancer Research FoundationSamuel Waxman Cancer Research FoundationCore funding from Tel Aviv University。
文摘It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.
基金supported by the National Institute on Aging(Nos.AG000723 and AG000578)(to VAB)the Fondation Sante(No.19656),Greece 2.0+1 种基金the National Recovery and Resilience Plan’s flagship program TAEDR-0535850the European Research Council(No.101077374-Synapto Mitophagy)(to KP)。
文摘N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY21H080005)the National Natural Science Foundation of China(Nos.81572920 and 82100171).
文摘Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.
基金supported by grants from the National Natural Science Foundation of China(81872905,82272915,and 82073884)the Project of the Fourth Batch of Science and Technology Plan of Liaoning Province,China(Grant No.:2021JH210300133)+3 种基金Science and Technology Innovation Team Project of China Medical University,China(Grant No.:CXTD2022007)the Supporting the Highquality Development of Science and Technology Funding Projects at China Medical University(Grant No.:2022011963-JH2/202)China Postdoctoral Science Foundation(Grant No.:2023MD734246)Liaoning Province Natural Science Foundation Joint Fund(Grant No.:2023-MSLH-396)。
文摘Recently,small nucleolar RNAs(snoRNAs)have transcended the genomic“noise”to emerge as pivotal molecular markers due to their essential roles in tumor progression.Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance.Historically,snoRNA research has concentrated on two classical mechanisms:2'-O-ribose methylation and pseudouridylation.This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors,encompassing transcriptional,post-transcriptional,and post-translational regulation.We further discuss the synergistic effect between snoRNA host genes(SNHGs)and snoRNAs in tumor progression.More importantly,snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes.Accordingly,we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.
文摘The thermoelectric energy conversion technique by employing the Disk-Magnet Electromagnetic Induction (DM-EMI) is examined in detail, and possible applications to heat engines as one of the energy-harvesting technologies are discussed. The idea is induced by the analysis of thermomechanical dynamics (TMD) for a nonequilibrium irreversible thermodynamic system of heat engines, such as a drinking bird and a low temperature Stirling engine, resulting in thermoelectric energy generation different from conventional heat engines. The current thermoelectric energy conversion with DM-EMI can be applied to wide ranges of machines and temperature differences. The mechanism of DM-EMI energy converter is categorized as the axial flux generator (AFG), which is the reason why the technology is applicable to sensitive thermoelectric conversions. On the other hand, almost all the conventional turbines use the radius flux generator to extract huge electric power, which uses the radial flux generator (RFG). The axial flux generator is helpful for a low mechanoelectric energy conversion and activations of waste heat from macroscopic energy generators such as wind, geothermal, thermal, nuclear power plants and heat-dissipation lines. The technique of DM-EMI will contribute to solving environmental problems to maintain clean and sustainable energy as one of the energy harvesting technologies.
文摘The new independent solutions of the nonlinear differential equation with time-dependent coefficients (NDE-TC) are discussed, for the first time, by employing experimental device called a drinking bird whose simple back-and-forth motion develops into water drinking motion. The solution to a drinking bird equation of motion manifests itself the transition from thermodynamic equilibrium to nonequilibrium irreversible states. The independent solution signifying a nonequilibrium thermal state seems to be constructed as if two independent bifurcation solutions are synthesized, and so, the solution is tentatively termed as the bifurcation-integration solution. The bifurcation-integration solution expresses the transition from mechanical and thermodynamic equilibrium to a nonequilibrium irreversible state, which is explicitly shown by the nonlinear differential equation with time-dependent coefficients (NDE-TC). The analysis established a new theoretical approach to nonequilibrium irreversible states, thermomechanical dynamics (TMD). The TMD method enables one to obtain thermodynamically consistent and time-dependent progresses of thermodynamic quantities, by employing the bifurcation-integration solutions of NDE-TC. We hope that the basic properties of bifurcation-integration solutions will be studied and investigated further in mathematics, physics, chemistry and nonlinear sciences in general.
文摘The traditional thermoelectric energy conversion techniques are explained in detail in terms of the axial flux electromagnetic (AFE) and the radial flux electromagnetic (RFE) inductions, and applications to heat engines for the energy-harvesting technologies are discussed. The idea is induced by the analysis of thermomechanical dynamics (TMD) for a nonequilibrium irreversible thermodynamic system of heat engines (a drinking bird, a low temperature Stirling engine), resulting in thermoelectric energy generation different from conventional heat engines. The mechanism of thermoelectric energy conversion can be categorized as the axial flux generator (AFG) and the radial flux generator (RFG). The axial flux generator is helpful for low mechanoelectric energy conversion and activations of waste heat from macroscopic energy generators, such as wind, geothermal, thermal, nuclear power plants and heat-dissipation lines, and the device contributes to solving environmental problems to maintain clean and sustainable energy as one of the energy harvesting technologies.
