Lysosomal acid lipase （LAL） cleaves cholesteryl esters （CE） and triglycerides （TG） to generate cholesterol and free fatty acid in lysosomes of cells. The down-stream metabolic products of fatty acids are ligands...Lysosomal acid lipase （LAL） cleaves cholesteryl esters （CE） and triglycerides （TG） to generate cholesterol and free fatty acid in lysosomes of cells. The down-stream metabolic products of fatty acids are ligands for activation of peroxisome proliferator-activated re-ceptor gamma （PPARγ）. Accumulation of CEs and TGs is resulted from lack of functional LAL in lysosomes of cells, especially in myeloid cells. One characteristic phenotype in LAL knock-out （ lal-/- ） mice is systemic elevation of myeloid-derived suppressive cells （MDSCs）. MDSCs infltrate into multiple distal organs, alter T cell development, and suppress T cell proliferation and lym-phokine production in lal-/- mice, which lead to severe pathogeneses in multiple organs. The gene transcrip-tional profle analysis in MDSCs from the bone marrow has identified multiple defects responsible for MDSCs malformation and malfunction in lal-/- mice, including G protein signaling, cell cycles, glycolysis metabolism, mitochondrial bioenergetics, mTOR pathway etc. In a sep-arate gene transcriptional profle analysis in the lung of lal-/- mice, matrix metalloproteinase 12 （MMP12） and apoptosis inhibitor 6 （Api6） are highly overexpressed due to lack of ligand synthesis for PPARγ. PPARγ nega-tively regulates MMP12 and Api6. Blocking the PPAR signaling by overexpression of a dominant negative PPARγ （dnPPARγ） form, or overexpressing MMP12 or Api6 in myeloid or lung epithelial cells in inducible transgenic mouse models results in elevated MDSCs and infammation-induced tumorigenesis. These stud-ies demonstrate that LAL and its downstream effectors are critical for MDSCs development, differentiation and malfunction.展开更多
We give two results about Harnack type inequalities.First,on Riemannian surfaces,we have an estimate of type sup+inf.The second result concern the solutions of prescribed scalar curvature equation on the unit ball of ...We give two results about Harnack type inequalities.First,on Riemannian surfaces,we have an estimate of type sup+inf.The second result concern the solutions of prescribed scalar curvature equation on the unit ball of Rn with Dirichlet condition.Next,we give an inequality of type(supK^u)^2s-1×infπu≤c for positive solutions of△u=V u^5 onΩbelong toR^3,where K is a compact set ofΩand V is s-Holderian,s∈]-1/2,1].For the case s=1/2 andΩ=S3,we prove that,if minΩu〉m〉0(for some particular constant m〉0),and the H¨olderian constant A of V tends to 0(in certain meaning),we have the uniform boundedness of the supremum of the solutions of the previous equation on any compact set ofΩ.展开更多
Mild cognitive impairment (MCI) can be regarded as a non-demented transitional stage during the development of Alzheimer’s disease. Early recognition of this stage might increase the chance of prevention by early tre...Mild cognitive impairment (MCI) can be regarded as a non-demented transitional stage during the development of Alzheimer’s disease. Early recognition of this stage might increase the chance of prevention by early treatment. Within a pilot study, two plant-derived preparations and mixtures thereof were tested successfully in subjects suffering from MCI. A combination of Sideritis scardica and Bacopa monnieri extract (memoLoges<sup>®</sup>) was chosen now for a repetitive dosing during 4 weeks. Thirty-two subjects aged 50 to 80 years and suffering from MCI (having a DemTect questionnaire score between 8 and 13) were recruited for intake of 2 capsules of the preparation per day. Quantitative EEG recording during relaxation and concomitant performance of three 5 minutes lasting psychometric tests (d2-concentration test, arithmetic calculation test and memory test) was achieved at the first day and one day after the last repetitive intake. Seventeen channels of EEG and one channel EOG (for artefact rejection) were recorded. After frequency analysis (FFT) current source density was calculated as reported earlier. One, two and three hours after intake of the herbal extract or placebo the whole procedure was repeated. Brain imaging was achieved by conversion of numerical values of spectral EEG power into spectral colors and additive color mixture according to RGB as used in TV settings. Intake of memoLoges<sup>®</sup> induced a trend of improvement of performance in psychometric testing (all three tests). During relaxation quantitative assessment of EEG data revealed attenuation of delta and theta spectral power in frontal brain as likewise reported in the presence of the Alzheimer drug rivastigmine, bringing the spectrum back to “normality”. During mental work memoLoges<sup>®</sup> induced statistically significant increases of beta power. Since MCI subjects produce less beta power in comparison to healthy subjects, this increase must likewise be seen as a positive effect pointing to a healthier spectrum.展开更多
In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunct...In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8<sup>+</sup> T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.展开更多
The endemic South African succulent plant Sceletium tortuosum (L.) N.E. Br., family Mesembryathemaceae, is known as kanna in Nama, kougoed in Afrikaans, and sceletium in English. The plant has been used as a tea and a...The endemic South African succulent plant Sceletium tortuosum (L.) N.E. Br., family Mesembryathemaceae, is known as kanna in Nama, kougoed in Afrikaans, and sceletium in English. The plant has been used as a tea and as a masticatory for millennia by indigenous San hunter-gatherers and Nama pastoralists for endurance and well-being. It has been reported that the plant “gives strength to their limbs, and takes away pain, and makes their memory strong”. The current investigation aimed at the psychophysiological characterization of 25.0 and 50.0 mg of a special extract marketed as Zembrin<sup>®</sup> in comparison to placebo using a new methodology called “EnkephaloVision”. This combination of EEG Neurocode-Tracking and Eye-Tracking allows for concomitant analysis of time epochs of only 364 ms duration. Spectral EEG analysis during cognitive and emotional challenges revealed statistically significant increases of delta (p < 0.01 during arithmetic calculation and watching a boring animal video) and theta spectral power (p < 0.10 during these same challenges) in the presence of Zembrin<sup>®</sup> within the frontal brain. It is these same increases of slow waves in the frontal brain that are described in the literature during performance of mental tests. This indicates a positive effect of Zembrin<sup>®</sup> on the electrical activity of the brain during cognitive processing. In addition, alpha1 and alpha2 spectral power in the frontal brain was increased during several challenges including brain teasing, arithmetic calculations and performance of a memory test. From the literature, increases of spectral alpha1 power indicate a greater degree of calmness and may represent decreased depressive symptoms, while increases in alpha2 waves have been related to memory. Beta2 waves increased during mental performance in the presence of the higher dosage of Zembrin<sup>®</sup> in parietal, occipital and temporal brain regions. In comparison to placebo, Zembrin<sup>®</sup> induced frequency changes in the brain, which have been related to enhanced attention and memory. These results may represent a positive action of Zembrin<sup>®</sup> on cognitive and emotional processes in the brain.展开更多
基金Supported by National Institutes of Health,No.CA138759,CA152099,to Yan CHL087001,to Du H,and HL-061803 and HL-067862 to Yan C and Du H
文摘Lysosomal acid lipase （LAL） cleaves cholesteryl esters （CE） and triglycerides （TG） to generate cholesterol and free fatty acid in lysosomes of cells. The down-stream metabolic products of fatty acids are ligands for activation of peroxisome proliferator-activated re-ceptor gamma （PPARγ）. Accumulation of CEs and TGs is resulted from lack of functional LAL in lysosomes of cells, especially in myeloid cells. One characteristic phenotype in LAL knock-out （ lal-/- ） mice is systemic elevation of myeloid-derived suppressive cells （MDSCs）. MDSCs infltrate into multiple distal organs, alter T cell development, and suppress T cell proliferation and lym-phokine production in lal-/- mice, which lead to severe pathogeneses in multiple organs. The gene transcrip-tional profle analysis in MDSCs from the bone marrow has identified multiple defects responsible for MDSCs malformation and malfunction in lal-/- mice, including G protein signaling, cell cycles, glycolysis metabolism, mitochondrial bioenergetics, mTOR pathway etc. In a sep-arate gene transcriptional profle analysis in the lung of lal-/- mice, matrix metalloproteinase 12 （MMP12） and apoptosis inhibitor 6 （Api6） are highly overexpressed due to lack of ligand synthesis for PPARγ. PPARγ nega-tively regulates MMP12 and Api6. Blocking the PPAR signaling by overexpression of a dominant negative PPARγ （dnPPARγ） form, or overexpressing MMP12 or Api6 in myeloid or lung epithelial cells in inducible transgenic mouse models results in elevated MDSCs and infammation-induced tumorigenesis. These stud-ies demonstrate that LAL and its downstream effectors are critical for MDSCs development, differentiation and malfunction.
文摘We give two results about Harnack type inequalities.First,on Riemannian surfaces,we have an estimate of type sup+inf.The second result concern the solutions of prescribed scalar curvature equation on the unit ball of Rn with Dirichlet condition.Next,we give an inequality of type(supK^u)^2s-1×infπu≤c for positive solutions of△u=V u^5 onΩbelong toR^3,where K is a compact set ofΩand V is s-Holderian,s∈]-1/2,1].For the case s=1/2 andΩ=S3,we prove that,if minΩu〉m〉0(for some particular constant m〉0),and the H¨olderian constant A of V tends to 0(in certain meaning),we have the uniform boundedness of the supremum of the solutions of the previous equation on any compact set ofΩ.
文摘Mild cognitive impairment (MCI) can be regarded as a non-demented transitional stage during the development of Alzheimer’s disease. Early recognition of this stage might increase the chance of prevention by early treatment. Within a pilot study, two plant-derived preparations and mixtures thereof were tested successfully in subjects suffering from MCI. A combination of Sideritis scardica and Bacopa monnieri extract (memoLoges<sup>®</sup>) was chosen now for a repetitive dosing during 4 weeks. Thirty-two subjects aged 50 to 80 years and suffering from MCI (having a DemTect questionnaire score between 8 and 13) were recruited for intake of 2 capsules of the preparation per day. Quantitative EEG recording during relaxation and concomitant performance of three 5 minutes lasting psychometric tests (d2-concentration test, arithmetic calculation test and memory test) was achieved at the first day and one day after the last repetitive intake. Seventeen channels of EEG and one channel EOG (for artefact rejection) were recorded. After frequency analysis (FFT) current source density was calculated as reported earlier. One, two and three hours after intake of the herbal extract or placebo the whole procedure was repeated. Brain imaging was achieved by conversion of numerical values of spectral EEG power into spectral colors and additive color mixture according to RGB as used in TV settings. Intake of memoLoges<sup>®</sup> induced a trend of improvement of performance in psychometric testing (all three tests). During relaxation quantitative assessment of EEG data revealed attenuation of delta and theta spectral power in frontal brain as likewise reported in the presence of the Alzheimer drug rivastigmine, bringing the spectrum back to “normality”. During mental work memoLoges<sup>®</sup> induced statistically significant increases of beta power. Since MCI subjects produce less beta power in comparison to healthy subjects, this increase must likewise be seen as a positive effect pointing to a healthier spectrum.
文摘In the tumor immune microenvironment, CD8<sup>+</sup> T cells differentiate towards functional failure. The exhaustion of CD8<sup>+</sup> T cells (Tex) showed varying degrees of effect dysfunction, loss of proliferation ability, and sustained high expression of a variety of inhibitory receptors, with metabolic and epigenetic changes. Tex cells are heterogeneous, including several subsets with different characteristics at different stages of differentiation. Immune checkpoint inhibitors (ICIs) can restore the effect or function of Tex cells, indicating that this T cell subset plays a key role in tumor immunotherapy. The understanding of the mechanism of CD8<sup>+</sup> T cell exhaustion will be helpful to the implementation of tumor immunotherapy. This article reviews the production, differentiation and functional characteristics of Tex cells and their relationship with tumor immunotherapy.
文摘The endemic South African succulent plant Sceletium tortuosum (L.) N.E. Br., family Mesembryathemaceae, is known as kanna in Nama, kougoed in Afrikaans, and sceletium in English. The plant has been used as a tea and as a masticatory for millennia by indigenous San hunter-gatherers and Nama pastoralists for endurance and well-being. It has been reported that the plant “gives strength to their limbs, and takes away pain, and makes their memory strong”. The current investigation aimed at the psychophysiological characterization of 25.0 and 50.0 mg of a special extract marketed as Zembrin<sup>®</sup> in comparison to placebo using a new methodology called “EnkephaloVision”. This combination of EEG Neurocode-Tracking and Eye-Tracking allows for concomitant analysis of time epochs of only 364 ms duration. Spectral EEG analysis during cognitive and emotional challenges revealed statistically significant increases of delta (p < 0.01 during arithmetic calculation and watching a boring animal video) and theta spectral power (p < 0.10 during these same challenges) in the presence of Zembrin<sup>®</sup> within the frontal brain. It is these same increases of slow waves in the frontal brain that are described in the literature during performance of mental tests. This indicates a positive effect of Zembrin<sup>®</sup> on the electrical activity of the brain during cognitive processing. In addition, alpha1 and alpha2 spectral power in the frontal brain was increased during several challenges including brain teasing, arithmetic calculations and performance of a memory test. From the literature, increases of spectral alpha1 power indicate a greater degree of calmness and may represent decreased depressive symptoms, while increases in alpha2 waves have been related to memory. Beta2 waves increased during mental performance in the presence of the higher dosage of Zembrin<sup>®</sup> in parietal, occipital and temporal brain regions. In comparison to placebo, Zembrin<sup>®</sup> induced frequency changes in the brain, which have been related to enhanced attention and memory. These results may represent a positive action of Zembrin<sup>®</sup> on cognitive and emotional processes in the brain.
