Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiolo...Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells,leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species(ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or,and even more likely,due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress,however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover,molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signalingpathways involved in the regulation of immunological,metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response,interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase(IDO) in monocyte-derived macrophages,fibroblasts,endothelial and epithelial cells. Neopterin,a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase(NOS) is induced in several cell types to generate nitric oxide(NO). NO,despite its low reactivity,is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin(BH4),which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic per展开更多
AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 m...AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 males; 85 females; mean age at diagnosis: 51.4 ± 17.6 years; mean age at time of US examination: 58.7 ± 18.2 years) were retrospectively reviewed with respect to the US morphology of hepatic AE lesions. The sonomorphological findings were grouped according to a five-part classification scheme.RESULTS: Application of the new classification resulted in the following distribution of sonomorphological patterns among the patients examined: hailstorm(54.1%); pseudocystic(13.5%); ossification(13.0%); hemangioma-like(8.1%); and metastasis-like(6.5%). Only 4.9% of lesions could not be assigned to a sonomorphological pattern.CONCLUSION: The sonomorphological classification proposed in the present study facilitates the diagnosis,interpretation and comparison of hepatic alveolar echinococcosis in routine practice and in the context of scientific studies.展开更多
Sedimentation based processes are widely used in industry to separate particles from a liquid phase. Since the advent of the ＂Nanoworld＂ the demand for effective separation technologies has rapidly risen, calling fo...Sedimentation based processes are widely used in industry to separate particles from a liquid phase. Since the advent of the ＂Nanoworld＂ the demand for effective separation technologies has rapidly risen, calling for the development of new separation concepts, one of which lies in hybrid separation using the superposition of a magnetic field for magnetic particles. Possible product portfolio of such separation consists of pigment production, nanomagnetics production for electronics and bio separation, A promising step in that direction is magnetic field enhanced cake filtration, which has by now progressed from batch to continuous ooeration. In sedimentation processes in a mass force field the settling behaviour of particles strongly depends on physico-chemical properties, concentration and size distribution of the particles. By adjusting the pH, the interparticle forces, in particular the electrostatic repulsion, can be manipulated. For remanent magnetic particles such as magnetite, pre-treatment in a magnetic field could lead to a change of interparticle interactions. By magnetizing the particles apart from van der Waals attraction and electrostatic repulsion, an additional potential is induced, the magnetic attraction, which could easily dominate the other potentials and result in agglomeration in the primary minimum. By sedimentation analysis, a wide spectrum of parameters like pH, magnetic field strength and concentration have been investigated. The results show a strong increase of sedimentation velocity by magnetic flocculation of the raw suspension. This leads to a rise in throughput due to the acceleration of sedimentation kinetics by imparting a non-chemical interaction to the physico-chemical properties in the feed stream of the separation apparatus.展开更多
The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent year...The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.展开更多
Organ transplantation is an effective therapeutic tool for treating many terminal diseases.However,one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogenei...Organ transplantation is an effective therapeutic tool for treating many terminal diseases.However,one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by,for example,preventing transplant rejection.In the current study,CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4(DPPIV)in allogeneic skin graft rejection by tail-skin transplantation.Compared with wild-type(CD26^(+/+))counterparts,CD26^(-/-)mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation.Concentrations of serum IgG,including its subclasses IgG1 and IgG2a,were significantly reduced in CD26^(-/-)mice during graft rejection.Moreover,after allogeneic skin transplantation,the secretion levels of the cytokines IFN-γ,IL-2,IL-6,IL-4,and IL-13 were significantly reduced,whereas the level of the cytokine IL-10 was increased in the serum of CD26^(-/-)mice compared with that in the serum of CD26^(+/+)mice.Additionally,the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes(MPBLs)were both significantly lower,while the percentage of regulatory T cells(Tregs)was significantly higher in MPBLs of CD26^(-/-)mice than in those of CD26^(+/+)mice.Furthermore,a lower percentage of CD8^(+)T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26^(-/-)mice were detected during graft rejection.These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.展开更多
BACKGROUND The clinical presentation of gastroesophageal reflux disease(GERD) shows a large symptom variation also in different intensities among patients. As several studies have shown, there is a large overlap in th...BACKGROUND The clinical presentation of gastroesophageal reflux disease(GERD) shows a large symptom variation also in different intensities among patients. As several studies have shown, there is a large overlap in the symptomatic spectrum between proven GERD and other disorders such as dyspepsia, functional heartburn and/or somatoform disorders.AIM To prospectively evaluate the GERD patients with and without somatoform disorders before and after laparoscopic antireflux surgery.METHODS In a tertiary referral center for foregut surgery over a period of 3 years patients with GERD, qualifying for the indication of laparoscopic antireflux surgery, were investigated prospectively regarding their symptomatic spectrum in order to identify GERD and associated somatoform disorders. Assessment of symptoms was performed by an instrument for the evaluation of somatoform disorders[Somatoform Symptom Index(SSI) > 17]. Quality of life was evaluated by Gastrointestinal Quality of Life Index(GIQLI).RESULTS In 123 patients an indication for laparoscopic antireflux surgery was established and in 43 patients further medical therapy was suggested. The portion of somatoform tendencies in the total patient population was 20.48%(34 patients).Patients with a positive SSI had a preoperative GIQLI of 77(32-111). Patients with a normal SSI had a GIQLI of 105(29-140)(P < 0.0001). In patients with GERD the quality of life could be normalized from preoperative reduced values of GIQLI102(47-140) to postoperative values of 117(44-144). In patients with GERD and somatoform disorders, the GIQLI was improved from preoperative GIQLI 75(47-111) to postoperative 95(44-122)(P < 0.0043).CONCLUSION Patients with GERD and associated somatoform disorders have significantly worse levels of quality of life. The latter patients can also benefit from laparoscopic fundoplication, however they will not reach a normal level.展开更多
Chemical looping combustion has the potential to be an efficient and low-cost technology capable of contributing to the reduction of the atmospheric concentration of CO_(2) in order to reach the 1.5/2°C goal and ...Chemical looping combustion has the potential to be an efficient and low-cost technology capable of contributing to the reduction of the atmospheric concentration of CO_(2) in order to reach the 1.5/2°C goal and mitigate climate change.In this process,a metal oxide is used as oxygen carrier in a dual fluidized bed to generate clean CO_(2) via combustion of biomass.Most commonly,natural ores or synthetic materials are used as oxygen carrier whereas both must meet special requirements for the conversion of solid fuels.Synthetic oxygen carriers are characterized by higher reactivity at the expense of higher costs versus the lower-cost natural ores.To determine the viability of both possibilities,a techno-economic comparison of a synthetic material based on manganese,iron,and copper to the natural ore ilmenite was conducted.The synthetic oxygen carrier was characterized and tested in a pilot plant,where high combustion efficiencies up to 98.4%and carbon capture rates up to 98.5%were reached.The techno-economic assessment resulted in CO_(2) capture costs of 75 and 40€/tCO_(2) for the synthetic and natural ore route respectively,whereas a sensitivity analysis showed the high impact of production costs and attrition rates of the synthetic material.The synthetic oxygen carrier could break even with the natural ore in case of lower production costs and attrition rates,which could be reached by adapting the production process and recycling material.By comparison to state-of-the-art technologies,it is demonstrated that both routes are viable and the capture cost of CO_(2) could be reduced by implementing the chemical looping combustion technology.展开更多
Realizing the full potential of ultrahigh-intensity lasers for particle and radiation generation will require multi-beam arrangements due to technology limitations.Here,we investigate how to optimize their coupling wi...Realizing the full potential of ultrahigh-intensity lasers for particle and radiation generation will require multi-beam arrangements due to technology limitations.Here,we investigate how to optimize their coupling with solid targets.Experimentally,we show that overlapping two intense lasers in a mirror-like configuration onto a solid with a large preplasma can greatly improve the generation of hot electrons at the target front and ion acceleration at the target backside.The underlying mechanisms are analyzed through multidimensional particle-in-cell simulations,revealing that the self-induced magnetic fields driven by the two laser beams at the target front are susceptible to reconnection,which is one possible mechanism to boost electron energization.In addition,the resistive magnetic field generated during the transport of the hot electrons in the target bulk tends to improve their collimation.Our simulations also indicate that such effects can be further enhanced by overlapping more than two laser beams.展开更多
文摘Multiple factors are involved in the etiology of cardiovascular disease(CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells,leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species(ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or,and even more likely,due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress,however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover,molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signalingpathways involved in the regulation of immunological,metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response,interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase(IDO) in monocyte-derived macrophages,fibroblasts,endothelial and epithelial cells. Neopterin,a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase Ⅰ in macrophages and dendritic cells. Nitric oxide synthase(NOS) is induced in several cell types to generate nitric oxide(NO). NO,despite its low reactivity,is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin(BH4),which is produced in humans primarily by fibroblasts and endothelial cells. Highly toxic per
文摘AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 males; 85 females; mean age at diagnosis: 51.4 ± 17.6 years; mean age at time of US examination: 58.7 ± 18.2 years) were retrospectively reviewed with respect to the US morphology of hepatic AE lesions. The sonomorphological findings were grouped according to a five-part classification scheme.RESULTS: Application of the new classification resulted in the following distribution of sonomorphological patterns among the patients examined: hailstorm(54.1%); pseudocystic(13.5%); ossification(13.0%); hemangioma-like(8.1%); and metastasis-like(6.5%). Only 4.9% of lesions could not be assigned to a sonomorphological pattern.CONCLUSION: The sonomorphological classification proposed in the present study facilitates the diagnosis,interpretation and comparison of hepatic alveolar echinococcosis in routine practice and in the context of scientific studies.
文摘Sedimentation based processes are widely used in industry to separate particles from a liquid phase. Since the advent of the ＂Nanoworld＂ the demand for effective separation technologies has rapidly risen, calling for the development of new separation concepts, one of which lies in hybrid separation using the superposition of a magnetic field for magnetic particles. Possible product portfolio of such separation consists of pigment production, nanomagnetics production for electronics and bio separation, A promising step in that direction is magnetic field enhanced cake filtration, which has by now progressed from batch to continuous ooeration. In sedimentation processes in a mass force field the settling behaviour of particles strongly depends on physico-chemical properties, concentration and size distribution of the particles. By adjusting the pH, the interparticle forces, in particular the electrostatic repulsion, can be manipulated. For remanent magnetic particles such as magnetite, pre-treatment in a magnetic field could lead to a change of interparticle interactions. By magnetizing the particles apart from van der Waals attraction and electrostatic repulsion, an additional potential is induced, the magnetic attraction, which could easily dominate the other potentials and result in agglomeration in the primary minimum. By sedimentation analysis, a wide spectrum of parameters like pH, magnetic field strength and concentration have been investigated. The results show a strong increase of sedimentation velocity by magnetic flocculation of the raw suspension. This leads to a rise in throughput due to the acceleration of sedimentation kinetics by imparting a non-chemical interaction to the physico-chemical properties in the feed stream of the separation apparatus.
基金supported by the STI2030-Major Projects(2021ZD0200900 to Y.G.Y.)"Light of West China" Program of the Chinese Academy of Sciences(xbzg-zdsys-202302 to Y.G.Y.)
文摘The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.
文摘Organ transplantation is an effective therapeutic tool for treating many terminal diseases.However,one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by,for example,preventing transplant rejection.In the current study,CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4(DPPIV)in allogeneic skin graft rejection by tail-skin transplantation.Compared with wild-type(CD26^(+/+))counterparts,CD26^(-/-)mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation.Concentrations of serum IgG,including its subclasses IgG1 and IgG2a,were significantly reduced in CD26^(-/-)mice during graft rejection.Moreover,after allogeneic skin transplantation,the secretion levels of the cytokines IFN-γ,IL-2,IL-6,IL-4,and IL-13 were significantly reduced,whereas the level of the cytokine IL-10 was increased in the serum of CD26^(-/-)mice compared with that in the serum of CD26^(+/+)mice.Additionally,the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes(MPBLs)were both significantly lower,while the percentage of regulatory T cells(Tregs)was significantly higher in MPBLs of CD26^(-/-)mice than in those of CD26^(+/+)mice.Furthermore,a lower percentage of CD8^(+)T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26^(-/-)mice were detected during graft rejection.These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.
文摘BACKGROUND The clinical presentation of gastroesophageal reflux disease(GERD) shows a large symptom variation also in different intensities among patients. As several studies have shown, there is a large overlap in the symptomatic spectrum between proven GERD and other disorders such as dyspepsia, functional heartburn and/or somatoform disorders.AIM To prospectively evaluate the GERD patients with and without somatoform disorders before and after laparoscopic antireflux surgery.METHODS In a tertiary referral center for foregut surgery over a period of 3 years patients with GERD, qualifying for the indication of laparoscopic antireflux surgery, were investigated prospectively regarding their symptomatic spectrum in order to identify GERD and associated somatoform disorders. Assessment of symptoms was performed by an instrument for the evaluation of somatoform disorders[Somatoform Symptom Index(SSI) > 17]. Quality of life was evaluated by Gastrointestinal Quality of Life Index(GIQLI).RESULTS In 123 patients an indication for laparoscopic antireflux surgery was established and in 43 patients further medical therapy was suggested. The portion of somatoform tendencies in the total patient population was 20.48%(34 patients).Patients with a positive SSI had a preoperative GIQLI of 77(32-111). Patients with a normal SSI had a GIQLI of 105(29-140)(P < 0.0001). In patients with GERD the quality of life could be normalized from preoperative reduced values of GIQLI102(47-140) to postoperative values of 117(44-144). In patients with GERD and somatoform disorders, the GIQLI was improved from preoperative GIQLI 75(47-111) to postoperative 95(44-122)(P < 0.0043).CONCLUSION Patients with GERD and associated somatoform disorders have significantly worse levels of quality of life. The latter patients can also benefit from laparoscopic fundoplication, however they will not reach a normal level.
文摘Chemical looping combustion has the potential to be an efficient and low-cost technology capable of contributing to the reduction of the atmospheric concentration of CO_(2) in order to reach the 1.5/2°C goal and mitigate climate change.In this process,a metal oxide is used as oxygen carrier in a dual fluidized bed to generate clean CO_(2) via combustion of biomass.Most commonly,natural ores or synthetic materials are used as oxygen carrier whereas both must meet special requirements for the conversion of solid fuels.Synthetic oxygen carriers are characterized by higher reactivity at the expense of higher costs versus the lower-cost natural ores.To determine the viability of both possibilities,a techno-economic comparison of a synthetic material based on manganese,iron,and copper to the natural ore ilmenite was conducted.The synthetic oxygen carrier was characterized and tested in a pilot plant,where high combustion efficiencies up to 98.4%and carbon capture rates up to 98.5%were reached.The techno-economic assessment resulted in CO_(2) capture costs of 75 and 40€/tCO_(2) for the synthetic and natural ore route respectively,whereas a sensitivity analysis showed the high impact of production costs and attrition rates of the synthetic material.The synthetic oxygen carrier could break even with the natural ore in case of lower production costs and attrition rates,which could be reached by adapting the production process and recycling material.By comparison to state-of-the-art technologies,it is demonstrated that both routes are viable and the capture cost of CO_(2) could be reduced by implementing the chemical looping combustion technology.
基金supported by the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation program(Grant Agreement No.787539)funding from EPRSC(Grant Nos.EP/E035728,EP/C003586,and EP/P010059/1)supported by the National Sciences and Engineering Research Council of Canada(NSERC)and Compute Canada(Job:pve-323-ac,PA).
文摘Realizing the full potential of ultrahigh-intensity lasers for particle and radiation generation will require multi-beam arrangements due to technology limitations.Here,we investigate how to optimize their coupling with solid targets.Experimentally,we show that overlapping two intense lasers in a mirror-like configuration onto a solid with a large preplasma can greatly improve the generation of hot electrons at the target front and ion acceleration at the target backside.The underlying mechanisms are analyzed through multidimensional particle-in-cell simulations,revealing that the self-induced magnetic fields driven by the two laser beams at the target front are susceptible to reconnection,which is one possible mechanism to boost electron energization.In addition,the resistive magnetic field generated during the transport of the hot electrons in the target bulk tends to improve their collimation.Our simulations also indicate that such effects can be further enhanced by overlapping more than two laser beams.
