Cancer patients in China navigate a complex and uneven insurance landscape,making plan choice critical for equitable financial protection.This study conducts a structured narrative review(2010-2025)of the Web of Scien...Cancer patients in China navigate a complex and uneven insurance landscape,making plan choice critical for equitable financial protection.This study conducts a structured narrative review(2010-2025)of the Web of Science,PubMed,CNKI,and Wanfang databases,focusing on empirical research on insurance plan choice,enrollment,or switching among cancer patients and their households in China.Two reviewers independently screened studies and extracted information on key determinants and identification strategies.The evidence converges on five main determinants:insurance literacy,health knowledge,prior coverage,financial capability,and policy promotion intensity(PPI).However,most studies are cross-sectional and descriptive,with inconsistent operationalization of determinants,weak or absent mediation tests for PPI,and limited coverage of rural,elderly,and low-literacy populations.Building on these gaps,we synthesize an evidence map,propose an operational PPI index,and highlight quasi-experimental opportunities(such as staggered NRDL updates and variation in local publicity efforts)to identify mechanisms and inform more inclusive,patient-centered insurance design in China.展开更多
The vectorial evolution of light polarization can reveal the microstructure and anisotropy of a medium beyond what can be obtained from measuring light intensity alone.However,polarization imaging in reflection geomet...The vectorial evolution of light polarization can reveal the microstructure and anisotropy of a medium beyond what can be obtained from measuring light intensity alone.However,polarization imaging in reflection geometry,which is ubiquitous and often preferred in diverse applications,has often suffered from poor and even incorrect characterization of anisotropic media.We present reciprocal polarization imaging of complex media in reflection geometry with the reciprocal polar decomposition of backscattering Mueller matrices enforcing reciprocity.We demonstrate that reciprocal polarization imaging of complex chiral and anisotropic media ac-curately quantifies their anisotropic properties in reflection geometry,whereas traditional approaches encounter difficulties and produce inferior and often erroneous results from the violation of reciprocity.In particular,reciprocal polarization imaging provides a consistent characterization of complex media of different thicknesses,accurately measures the optical activity and glucose concentration of turbid media in reflection,and discriminates between cancerous and normal tissue with even stronger contrast than forward measurement.Reciprocal polarization imaging promises broad applications of polarization optics ranging from remote sensing to bio-medicine in reflection geometries,especially in in vivo biomedical imaging,where reflection is the only feasible geometry.展开更多
Foliar resorption is a principal nutrient conservation mechanism in terrestrial vegetation that could be sensitive to ongoing changes in climate and atmospheric nitrogen(N)deposition.We quantified N resorption in nort...Foliar resorption is a principal nutrient conservation mechanism in terrestrial vegetation that could be sensitive to ongoing changes in climate and atmospheric nitrogen(N)deposition.We quantified N resorption in northern hardwood forests along an elevation gradient of decreasing temperature and increasing soil N availability to evaluate how this critical nutrient cycling process can be expected to respond to global and regional environmental changes.Foliar N resorption proficiency(NRP)increased significantly at lower elevations for both sugar maple and American beech,the dominant species in these forests.Foliar N resorption efficiency(NRE)also decreased with increasing elevation,but only in one year.Both species exhibited strong negative relationships between NRP and soil N availability.Thus,we anticipate that with climate warming and decreasing N inputs,northern hardwood forests can be expected to exhibit stronger N conservation via foliar resorption.Both species also exhibited strong correlations between resorption efficiency of N and C,but resorption of both elements was much greater for beech than sugar maple,suggesting contrasting mechanisms of nutrient conservation between these two widespread species.展开更多
Cancer is a formidable andmultifaceted disease driven by genetic aberrations and metabolic disruptions.Around 19% of cancer-related deaths worldwide are attributable to lung and colon cancer,which is also the top caus...Cancer is a formidable andmultifaceted disease driven by genetic aberrations and metabolic disruptions.Around 19% of cancer-related deaths worldwide are attributable to lung and colon cancer,which is also the top cause of death worldwide.The malignancy has a terrible 5-year survival rate of 19%.Early diagnosis is critical for improving treatment outcomes and survival rates.The study aims to create a computer-aided diagnosis(CAD)that accurately diagnoses lung disease by classifying histopathological images.It uses a publicly accessible dataset that includes 15,000 images of benign,malignant,and squamous cell carcinomas in the lung.In addition,this research employs multiscale processing to extract relevant image features and conducts a comprehensive comparative analysis using four Convolutional Neural Network(CNN)based on pre-trained models such as AlexNet,VGG(Visual Geometry Group)16,ResNet-50,and VGG19,after hyper-tuning these models by optimizing factors such as batch size,learning rate,and epochs.The proposed(CNN+VGG19)model achieves the highest accuracy of 99.04%.This outstanding performance demonstrates the potential of the CAD system in accurately classifying lung cancer histopathological images.This study contributes significantly to the creation of a more precise CNN-based model for lung cancer identification,giving researchers and medical professionals in this vital sector a useful tool using advanced deep learning techniques and publicly available datasets.展开更多
We report new material of the zalambdalestid,Zhangolestes jilinensis,from the Quantou Formation(lower Upper Cretaceous,Cenomanian to Turonian),Gongzhuling City,Jilin Province,NE China.Using micro-CT-scan,the material ...We report new material of the zalambdalestid,Zhangolestes jilinensis,from the Quantou Formation(lower Upper Cretaceous,Cenomanian to Turonian),Gongzhuling City,Jilin Province,NE China.Using micro-CT-scan,the material is shown to include dentocranial and postcranial elements recovered from the same matrix block containing the holotype specimen.The CT-images also show the labial and internal structures of the holotype fragment of the lower jaw of Z.jilinensis.Based on the preservation,relative size,and tooth wear,the new material and the holotype lower jaw likely belong to the same individual animal,whereas the hypodigm mandibular fragment assigned to Z.jilinensis in the original study is thought now to belong to a different individual,potentially representing a different species,which,if true,would increase the eutherian diversity in the Late Cretaceous Changchunsaurus Fauna.Furthermore,the new CT-images show that the incisor morphology is diverse within zalambdalestids and probably evolved independently from the enlarged incisors in placental mammals,such as Glires.展开更多
以3.5PbO.96.5B2O3(m o l%)玻璃作为研究对象,着重研究其在不同重力条件下的分相现象。该部分讨论了2个落塔实验试样发生分相的重力条件,同时分析了试样的相组成和试样成分的不均匀性。结果发现,该成分玻璃发生分相后形成的富硼相和富...以3.5PbO.96.5B2O3(m o l%)玻璃作为研究对象,着重研究其在不同重力条件下的分相现象。该部分讨论了2个落塔实验试样发生分相的重力条件,同时分析了试样的相组成和试样成分的不均匀性。结果发现,该成分玻璃发生分相后形成的富硼相和富铅相都是玻璃相。分相在高重力阶段发生的试样其成分均匀性最差,原因在于富硼相和富铅相间存在较大的密度差。展开更多
DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs...DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.展开更多
The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau＇s functions in microtubule assembly and stabilization...The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau＇s functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications： hyperphosphorylation, ubiquitination, glycation, glycosytation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifications can alter tau＇s biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and propose a mechanism of neurodegeneration.展开更多
Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been onl...Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.展开更多
Angiotensin II （Angll） is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases. Subcutaneous infusion of Angll into mice induces the development of...Angiotensin II （Angll） is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases. Subcutaneous infusion of Angll into mice induces the development of abdominal aortic aneurysms （AAAs）. Like human AAAs, Angll-induced AAA tissues exhibit progressive changes and considerable heterogeneity. This complex pathology provides an impediment to the quantification of aneurysmal tissue composition by biochemical and immunostaining techniques. Therefore, while the mouse model of Angll-induced AAAs provides a salutary approach to studying the mechanisms of the evolution of AAAs in humans, meaningful interpretation of mechanisms requires consideration of the heterogeneous nature of the diseased tissue.展开更多
The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in ...The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research suggests that oxytocin effects may depend on cell type, concentration of the hormone, its interactions with other hormones in the microenvironment, and the precise localization of its receptor on the cell membrane. Future research is needed to further elucidate the involvement of oxytocin in cancer, and whether it could be a clinical cancer biomarker or therapeutic target.展开更多
Vascular depression(VD)as defined by magnetic resonance imaging(MRI)has been proposed as a unique subtype of late-life depression.The VD hypothesis posits that cerebrovascular disease,as characterized by the presence ...Vascular depression(VD)as defined by magnetic resonance imaging(MRI)has been proposed as a unique subtype of late-life depression.The VD hypothesis posits that cerebrovascular disease,as characterized by the presence of MRIdefined white matter hyperintensities,contributes to and increases the risk for depression in older adults.VD is also accompanied by cognitive impairment and poor antidepressant treatment response.The VD diagnosis relies on MRI findings and yet this clinical entity is largely unfamiliar to neuroradiologists and is rarely,if ever,discussed in radiology journals.The primary purpose of this review is to introduce the MRI-defined VD construct to the neuroradiology community.Case reports are highlighted in order to illustrate the profile of VD in terms of radiological,clinical,and neuropsychological findings.A secondary purpose is to elucidate and elaborate on the measurement of cerebrovascular disease through visual rating scales and semi-and fully-automated volumetric methods.These methods are crucial for determining whether lesion burden or lesion severity is the dominant pathological contributor to VD.Additionally,these rating methods have implications for the growing field of computer assisted diagnosis.Since VD has been found to have a profile that is distinct from other types of late-life depression,neuroradiologists,in conjunction with psychiatrists and psychologists,should consider VD in diagnosis and treatment planning.展开更多
The kernel energy method(KEM) has been shown to provide fast and accurate molecular energy calculations for molecules at their equilibrium geometries.KEM breaks a molecule into smaller subsets,called kernels,for the p...The kernel energy method(KEM) has been shown to provide fast and accurate molecular energy calculations for molecules at their equilibrium geometries.KEM breaks a molecule into smaller subsets,called kernels,for the purposes of calculation.The results from the kernels are summed according to an expression characteristic of KEM to obtain the full molecule energy.A generalization of the kernel expansion to density matrices provides the full molecule density matrix and orbitals.In this study,the kernel expansion for the density matrix is examined in the context of density functional theory(DFT) Kohn-Sham(KS) calculations.A kernel expansion for the one-body density matrix analogous to the kernel expansion for energy is defined,and is then converted into a normalizedprojector by using the Clinton algorithm.Such normalized projectors are factorizable into linear combination of atomic orbitals(LCAO) matrices that deliver full-molecule Kohn-Sham molecular orbitals in the atomic orbital basis.Both straightforward KEM energies and energies from a normalized,idempotent density matrix obtained from a density matrix kernel expansion to which the Clinton algorithm has been applied are compared to reference energies obtained from calculations on the full system without any kernel expansion.Calculations were performed both for a simple proof-of-concept system consisting of three atoms in a linear configuration and for a water cluster consisting of twelve water molecules.In the case of the proof-of-concept system,calculations were performed using the STO-3 G and6-31 G(d,p) bases over a range of atomic separations,some very far from equilibrium.The water cluster was calculated in the 6-31 G(d,p) basis at an equilibrium geometry.The normalized projector density energies are more accurate than the straightforward KEM energy results in nearly all cases.In the case of the water cluster,the energy of the normalized projector is approximately four times more accurate than the straightforward KEM energy result.The KS density matrices of this study are applicable to quantum crystallography.展开更多
Flaviviruses, ss(+) RNA viruses, include many of mankind's most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to ...Flaviviruses, ss(+) RNA viruses, include many of mankind's most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic(Bax-mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches for activating these pathways. Infection can lead to necrosis if viral load is extremely high or to other types of cell death if routes to apoptosis are blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In this case the autophagy temporarily spares the infected cell, allowing a longer period of reproduction for the virus, and the autophagy further protects the cell against other stresses such as those caused by reactive oxygen species. Several of the viral proteins have been shown to induce apoptosis or autophagy on their own, independent of the presence of other viral proteins. Given the versatility of these viruses to adapt to and manipulate the metabolism, and thus to control the survival of, the infected cells, we need to understand much better how the specific viral proteins affect the pathways to apoptosis and autophagy. Only in this manner will we be able to minimize the pathology that they cause.展开更多
文摘Cancer patients in China navigate a complex and uneven insurance landscape,making plan choice critical for equitable financial protection.This study conducts a structured narrative review(2010-2025)of the Web of Science,PubMed,CNKI,and Wanfang databases,focusing on empirical research on insurance plan choice,enrollment,or switching among cancer patients and their households in China.Two reviewers independently screened studies and extracted information on key determinants and identification strategies.The evidence converges on five main determinants:insurance literacy,health knowledge,prior coverage,financial capability,and policy promotion intensity(PPI).However,most studies are cross-sectional and descriptive,with inconsistent operationalization of determinants,weak or absent mediation tests for PPI,and limited coverage of rural,elderly,and low-literacy populations.Building on these gaps,we synthesize an evidence map,propose an operational PPI index,and highlight quasi-experimental opportunities(such as staggered NRDL updates and variation in local publicity efforts)to identify mechanisms and inform more inclusive,patient-centered insurance design in China.
基金upported by the Natural Science Foundation of Zhejiang Province(Grant No.LZ16H180002)the National Natural Science Foundation of China(Grant No.61905181)+1 种基金the Wenzhou Municipal Science and Technology Bureau(Grant No.ZS2017022)the National Science Foundation of the U.S.(Grant No.1607664).
文摘The vectorial evolution of light polarization can reveal the microstructure and anisotropy of a medium beyond what can be obtained from measuring light intensity alone.However,polarization imaging in reflection geometry,which is ubiquitous and often preferred in diverse applications,has often suffered from poor and even incorrect characterization of anisotropic media.We present reciprocal polarization imaging of complex media in reflection geometry with the reciprocal polar decomposition of backscattering Mueller matrices enforcing reciprocity.We demonstrate that reciprocal polarization imaging of complex chiral and anisotropic media ac-curately quantifies their anisotropic properties in reflection geometry,whereas traditional approaches encounter difficulties and produce inferior and often erroneous results from the violation of reciprocity.In particular,reciprocal polarization imaging provides a consistent characterization of complex media of different thicknesses,accurately measures the optical activity and glucose concentration of turbid media in reflection,and discriminates between cancerous and normal tissue with even stronger contrast than forward measurement.Reciprocal polarization imaging promises broad applications of polarization optics ranging from remote sensing to bio-medicine in reflection geometries,especially in in vivo biomedical imaging,where reflection is the only feasible geometry.
基金National Science Foundation supported this research through the Long Term Ecological Research(LTER)Grant to Hubbard Brook(NSF DEB1114804,1637685,and 2224545)by the project grant(NSF DEB,2020397).
文摘Foliar resorption is a principal nutrient conservation mechanism in terrestrial vegetation that could be sensitive to ongoing changes in climate and atmospheric nitrogen(N)deposition.We quantified N resorption in northern hardwood forests along an elevation gradient of decreasing temperature and increasing soil N availability to evaluate how this critical nutrient cycling process can be expected to respond to global and regional environmental changes.Foliar N resorption proficiency(NRP)increased significantly at lower elevations for both sugar maple and American beech,the dominant species in these forests.Foliar N resorption efficiency(NRE)also decreased with increasing elevation,but only in one year.Both species exhibited strong negative relationships between NRP and soil N availability.Thus,we anticipate that with climate warming and decreasing N inputs,northern hardwood forests can be expected to exhibit stronger N conservation via foliar resorption.Both species also exhibited strong correlations between resorption efficiency of N and C,but resorption of both elements was much greater for beech than sugar maple,suggesting contrasting mechanisms of nutrient conservation between these two widespread species.
文摘Cancer is a formidable andmultifaceted disease driven by genetic aberrations and metabolic disruptions.Around 19% of cancer-related deaths worldwide are attributable to lung and colon cancer,which is also the top cause of death worldwide.The malignancy has a terrible 5-year survival rate of 19%.Early diagnosis is critical for improving treatment outcomes and survival rates.The study aims to create a computer-aided diagnosis(CAD)that accurately diagnoses lung disease by classifying histopathological images.It uses a publicly accessible dataset that includes 15,000 images of benign,malignant,and squamous cell carcinomas in the lung.In addition,this research employs multiscale processing to extract relevant image features and conducts a comprehensive comparative analysis using four Convolutional Neural Network(CNN)based on pre-trained models such as AlexNet,VGG(Visual Geometry Group)16,ResNet-50,and VGG19,after hyper-tuning these models by optimizing factors such as batch size,learning rate,and epochs.The proposed(CNN+VGG19)model achieves the highest accuracy of 99.04%.This outstanding performance demonstrates the potential of the CAD system in accurately classifying lung cancer histopathological images.This study contributes significantly to the creation of a more precise CNN-based model for lung cancer identification,giving researchers and medical professionals in this vital sector a useful tool using advanced deep learning techniques and publicly available datasets.
基金supported by the National Natural Science Foundation of China(Grant Nos.42122010,42072017)the Youth Innovation Promotion Association CAS(Y2023017)+1 种基金the National Mineral Rock and Fossil Specimens Resource Center(NCSTI-RMF20240203)China Geological Survey(DD20230221)。
文摘We report new material of the zalambdalestid,Zhangolestes jilinensis,from the Quantou Formation(lower Upper Cretaceous,Cenomanian to Turonian),Gongzhuling City,Jilin Province,NE China.Using micro-CT-scan,the material is shown to include dentocranial and postcranial elements recovered from the same matrix block containing the holotype specimen.The CT-images also show the labial and internal structures of the holotype fragment of the lower jaw of Z.jilinensis.Based on the preservation,relative size,and tooth wear,the new material and the holotype lower jaw likely belong to the same individual animal,whereas the hypodigm mandibular fragment assigned to Z.jilinensis in the original study is thought now to belong to a different individual,potentially representing a different species,which,if true,would increase the eutherian diversity in the Late Cretaceous Changchunsaurus Fauna.Furthermore,the new CT-images show that the incisor morphology is diverse within zalambdalestids and probably evolved independently from the enlarged incisors in placental mammals,such as Glires.
文摘以3.5PbO.96.5B2O3(m o l%)玻璃作为研究对象,着重研究其在不同重力条件下的分相现象。该部分讨论了2个落塔实验试样发生分相的重力条件,同时分析了试样的相组成和试样成分的不均匀性。结果发现,该成分玻璃发生分相后形成的富硼相和富铅相都是玻璃相。分相在高重力阶段发生的试样其成分均匀性最差,原因在于富硼相和富铅相间存在较大的密度差。
文摘DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
基金supported in part by an NIH grant(R15AG034524-01)an Alzheimer’s Association(Chicago,IL)grant(IIRG-09-133206)a Brooklyn Home for the Aged Man grant for the support of developing Alzheimer research at CSI
文摘The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau＇s functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications： hyperphosphorylation, ubiquitination, glycation, glycosytation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifications can alter tau＇s biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and propose a mechanism of neurodegeneration.
文摘Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.
基金Project (Nos. HL062846 and HL80100) supported by the National Institutes of Health of the United States of America
文摘Angiotensin II （Angll） is the primary bioactive peptide of the renin angiotensin system that plays a critical role in many cardiovascular diseases. Subcutaneous infusion of Angll into mice induces the development of abdominal aortic aneurysms （AAAs）. Like human AAAs, Angll-induced AAA tissues exhibit progressive changes and considerable heterogeneity. This complex pathology provides an impediment to the quantification of aneurysmal tissue composition by biochemical and immunostaining techniques. Therefore, while the mouse model of Angll-induced AAAs provides a salutary approach to studying the mechanisms of the evolution of AAAs in humans, meaningful interpretation of mechanisms requires consideration of the heterogeneous nature of the diseased tissue.
文摘The neuropeptide hormone oxytocin, which is released from the posterior pituitary gland, is involved in a number of physiological processes. Understanding of its effects is gradually increasing due to new research in this area. While mostly recognized as a reproductive system hormone, oxytocin also regulates other organ systems such as the brain and cardiovascular system. Recently, research has focused on unraveling its involvement in cancer, and emerging evidence suggests a potential role for oxytocin as a cancer biomarker. This review summarizes observations linking oxytocin and cancer, with a special emphasis on prostate cancer, where it may promote cell proliferation. Research suggests that oxytocin effects may depend on cell type, concentration of the hormone, its interactions with other hormones in the microenvironment, and the precise localization of its receptor on the cell membrane. Future research is needed to further elucidate the involvement of oxytocin in cancer, and whether it could be a clinical cancer biomarker or therapeutic target.
文摘Vascular depression(VD)as defined by magnetic resonance imaging(MRI)has been proposed as a unique subtype of late-life depression.The VD hypothesis posits that cerebrovascular disease,as characterized by the presence of MRIdefined white matter hyperintensities,contributes to and increases the risk for depression in older adults.VD is also accompanied by cognitive impairment and poor antidepressant treatment response.The VD diagnosis relies on MRI findings and yet this clinical entity is largely unfamiliar to neuroradiologists and is rarely,if ever,discussed in radiology journals.The primary purpose of this review is to introduce the MRI-defined VD construct to the neuroradiology community.Case reports are highlighted in order to illustrate the profile of VD in terms of radiological,clinical,and neuropsychological findings.A secondary purpose is to elucidate and elaborate on the measurement of cerebrovascular disease through visual rating scales and semi-and fully-automated volumetric methods.These methods are crucial for determining whether lesion burden or lesion severity is the dominant pathological contributor to VD.Additionally,these rating methods have implications for the growing field of computer assisted diagnosis.Since VD has been found to have a profile that is distinct from other types of late-life depression,neuroradiologists,in conjunction with psychiatrists and psychologists,should consider VD in diagnosis and treatment planning.
文摘The kernel energy method(KEM) has been shown to provide fast and accurate molecular energy calculations for molecules at their equilibrium geometries.KEM breaks a molecule into smaller subsets,called kernels,for the purposes of calculation.The results from the kernels are summed according to an expression characteristic of KEM to obtain the full molecule energy.A generalization of the kernel expansion to density matrices provides the full molecule density matrix and orbitals.In this study,the kernel expansion for the density matrix is examined in the context of density functional theory(DFT) Kohn-Sham(KS) calculations.A kernel expansion for the one-body density matrix analogous to the kernel expansion for energy is defined,and is then converted into a normalizedprojector by using the Clinton algorithm.Such normalized projectors are factorizable into linear combination of atomic orbitals(LCAO) matrices that deliver full-molecule Kohn-Sham molecular orbitals in the atomic orbital basis.Both straightforward KEM energies and energies from a normalized,idempotent density matrix obtained from a density matrix kernel expansion to which the Clinton algorithm has been applied are compared to reference energies obtained from calculations on the full system without any kernel expansion.Calculations were performed both for a simple proof-of-concept system consisting of three atoms in a linear configuration and for a water cluster consisting of twelve water molecules.In the case of the proof-of-concept system,calculations were performed using the STO-3 G and6-31 G(d,p) bases over a range of atomic separations,some very far from equilibrium.The water cluster was calculated in the 6-31 G(d,p) basis at an equilibrium geometry.The normalized projector density energies are more accurate than the straightforward KEM energy results in nearly all cases.In the case of the water cluster,the energy of the normalized projector is approximately four times more accurate than the straightforward KEM energy result.The KS density matrices of this study are applicable to quantum crystallography.
基金Supported by NIAID NIH grant to Zakeri Z,No.1R15AIO94351-01the NIH NIGMS(MARC-USTAR),No.T 34 GM070387
文摘Flaviviruses, ss(+) RNA viruses, include many of mankind's most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic(Bax-mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches for activating these pathways. Infection can lead to necrosis if viral load is extremely high or to other types of cell death if routes to apoptosis are blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In this case the autophagy temporarily spares the infected cell, allowing a longer period of reproduction for the virus, and the autophagy further protects the cell against other stresses such as those caused by reactive oxygen species. Several of the viral proteins have been shown to induce apoptosis or autophagy on their own, independent of the presence of other viral proteins. Given the versatility of these viruses to adapt to and manipulate the metabolism, and thus to control the survival of, the infected cells, we need to understand much better how the specific viral proteins affect the pathways to apoptosis and autophagy. Only in this manner will we be able to minimize the pathology that they cause.
