For eliminating the negative effects of lock-in region and optical elements in cavity,the non-planar structure is strongly needed in laser gyro. In this paper,the theoretical formula of rotatory effect in non-planar c...For eliminating the negative effects of lock-in region and optical elements in cavity,the non-planar structure is strongly needed in laser gyro. In this paper,the theoretical formula of rotatory effect in non-planar cavity is presented deducing from basic light propagating law. Based on the 8-like plane cavity,a novel non-planar structure is designed and numerically calculated. The results show that for obtaining the required rotatory angle,it just needs to adjust the structural parameters of the original 8-like plane cavity. The four-frequency-differential laser gyro which adopts the non-planar 8-like structure has the same advantages as those with the planar 8-like structure,such as the gain region locates at one leg,the position of Faraday rotator has better spatial symmetry and the coating films of the output mirror is easily designed.展开更多
Atherosclerosis is the major complication of diabetes and has become a major issue in the provision of medical care.In particular the economic burden is growing at an alarming rate in parallel with the increasing worl...Atherosclerosis is the major complication of diabetes and has become a major issue in the provision of medical care.In particular the economic burden is growing at an alarming rate in parallel with the increasing worldwide prevalence of diabetes.The major disturbance of lipid metabolism in diabetes relates to the effect of insulin on fat metabolism.Raised triglycerides being the hallmark of uncontrolled diabetes,i.e.,in the presence of hyperglycaemia.The explosion of type 2 diabetes has generated increasing interest on the aetiology ofatherosclerosis in diabetic patients.The importance of the atherogenic properties of triglyceride rich lipoproteins has only recently been recognised by the majority of diabetologists and cardiologists even though experimental evidence has been strong for many years.In the post-prandial phase 50% of triglyceride rich lipoproteins come from chylomicrons produced in the intestine.Recent evidence has secured the chylomicron as a major player in the atherogenic process.In diabetes chylomicron production is increased through disturbance in cholesterol absorption,in particular Neimann Pick C1-like1 activity is increased as is intestinal synthesis of cholesterol through 3-hydroxy-3-methyl glutaryl co enzyme A reductase.ATP binding cassette proteins G5 and G8 which regulate cholesterol in the intestine is reduced leading to chylomicronaemia.The chylomicron particle itself is atherogenic but the increase in the triglyceride-rich lipoproteins lead to an atherogenic low density lipoprotein and low high density lipoprotein.The various steps in the absorption process and the disturbance in chylomicron synthesis are discussed.展开更多
Autophagy plays an important role in tissue remodeling during insect development.The interplay between autophagy-related(ATG)proteins and caspases regulates the autophagic activity of ATGs,thereby modulating the proce...Autophagy plays an important role in tissue remodeling during insect development.The interplay between autophagy-related(ATG)proteins and caspases regulates the autophagic activity of ATGs,thereby modulating the process of autophagy.Our previous study characterized BmCaspase-8-like(BmCasp8L)as a caspase suppressor that inhibits apoptosis and immune signaling by suppressing the activation of death-related ced-3/Nedd2-like caspase(DREDD),a caspase-8 homolog in silkworm.In this study,we explored the regulatory role of BmCasp8L in autophagy.We found that the expression of Bmcasp8l increased from the late spinning stage to the pupa stage in the posterior silk gland(PSG),correlating with the expression patterns of Bmatg8 and Bmatg6.RNA interference-mediated downregulation of BmCasp8L expression significantly decreased starvation-induced autophagic influx as determined by the levels of BmATG8–phosphatidylethanolamine and the percentage of cells displaying punctate enhanced green fluorescent protein-BmATG8.Conversely,the overexpression of BmCasp8L significantly increased autophagic influx.We also found that BmCasp8L underwent autophagic degradation induced by starvation and that it was colocalized with BmATG8.Lastly,we demonstrated that BmDREDD attenuated autophagy and BmCasp8L suppressed BmDREDD-mediated cleavage of BmATG6.Taken together,our results demonstrated that BmCasp8L is a novel proautophagic molecule which suppresses BmDREDD-mediated cleavage of BmATG6 and is a target for autophagy.展开更多
Background:Interleukin-1 receptor-associated kinase 1(IRAK1),an active serine/threonine kinase,is an indispensable mediator of inflammatory responses and innate immunity.Emerging evidence has highlighted the oncogenic...Background:Interleukin-1 receptor-associated kinase 1(IRAK1),an active serine/threonine kinase,is an indispensable mediator of inflammatory responses and innate immunity.Emerging evidence has highlighted the oncogenic role of IRAK1 in tumors.However,the role of IRAK1 in gastric cancer(GC)progression remains unclear.Methods:IRAK1 expression levels in patients with GC at Peking Union Medical College Hospital were assessed by Western blotting,quantitative real-time polymerase chain reaction,and immunohistochemistry.To elucidate the role of IRAK1 in GC pathogenesis,we established GC cells with clustered regularly interspaced short palindromic repeats(CRISPR)and CRISPR-associated protein 9 (Cas9)mediated IRAK1 knockout and lentiviral vector-mediated IRAK1 overexpression and subsequently conducted in vitro and in vivo experiments.Additionally,we assessed the effect of IRAK1 expression levels in GC cells on the M2 polarization of tumor-associated macrophages(TAMs)via a Transwell coculture system.Functional assays were subsequently carried out to determine whether IRAK1 regulates the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of GC cells through the induction of TAM M2 polarization and to clarify the associated regulatory mechanisms.Results:IRAK1 expression was progressively increased during GC progression.Clinicopathological feature analysis revealed that high IRAK1 expression predicted poor survival outcomes.In vitro and in vivo experiments revealed that IRAK1 was highly expressed in GC cells and facilitated the proliferation,migration,invasion,and EMT of GC cells via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway.More interestingly,IRAK1 affected the malignant biological behavior of GC cells by inducing M2-like polarization of macrophages.Mechanistically,coculturing M0 macrophages with IRAK1-knockout GC cells suppressed interleukin(IL)-8 secretion,thereby inhibiting Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway activation in TAMs.Inactivation of the JAK2/STAT3 pathway suppressed the M2 polarization of TAMs,ultimately inhibiting GC progression.Conclusions:IRAK1 influences the malignant biological behavior of GC cells by activating the PI3K/AKT/mTOR pathway and inducing the M2-like polarization of macrophages via the IL-8/JAK2/STAT3 pathway in TAMs.Our findings provide a novel diagnostic biomarker and a promising therapeutic strategy for GC.展开更多
文摘For eliminating the negative effects of lock-in region and optical elements in cavity,the non-planar structure is strongly needed in laser gyro. In this paper,the theoretical formula of rotatory effect in non-planar cavity is presented deducing from basic light propagating law. Based on the 8-like plane cavity,a novel non-planar structure is designed and numerically calculated. The results show that for obtaining the required rotatory angle,it just needs to adjust the structural parameters of the original 8-like plane cavity. The four-frequency-differential laser gyro which adopts the non-planar 8-like structure has the same advantages as those with the planar 8-like structure,such as the gain region locates at one leg,the position of Faraday rotator has better spatial symmetry and the coating films of the output mirror is easily designed.
文摘Atherosclerosis is the major complication of diabetes and has become a major issue in the provision of medical care.In particular the economic burden is growing at an alarming rate in parallel with the increasing worldwide prevalence of diabetes.The major disturbance of lipid metabolism in diabetes relates to the effect of insulin on fat metabolism.Raised triglycerides being the hallmark of uncontrolled diabetes,i.e.,in the presence of hyperglycaemia.The explosion of type 2 diabetes has generated increasing interest on the aetiology ofatherosclerosis in diabetic patients.The importance of the atherogenic properties of triglyceride rich lipoproteins has only recently been recognised by the majority of diabetologists and cardiologists even though experimental evidence has been strong for many years.In the post-prandial phase 50% of triglyceride rich lipoproteins come from chylomicrons produced in the intestine.Recent evidence has secured the chylomicron as a major player in the atherogenic process.In diabetes chylomicron production is increased through disturbance in cholesterol absorption,in particular Neimann Pick C1-like1 activity is increased as is intestinal synthesis of cholesterol through 3-hydroxy-3-methyl glutaryl co enzyme A reductase.ATP binding cassette proteins G5 and G8 which regulate cholesterol in the intestine is reduced leading to chylomicronaemia.The chylomicron particle itself is atherogenic but the increase in the triglyceride-rich lipoproteins lead to an atherogenic low density lipoprotein and low high density lipoprotein.The various steps in the absorption process and the disturbance in chylomicron synthesis are discussed.
基金supported by grants from the National Natural Science Foundation of China(No.31672495)Natural Science Foundation of Chongqing,China(cstc2020jcyj-msxmX0193).
文摘Autophagy plays an important role in tissue remodeling during insect development.The interplay between autophagy-related(ATG)proteins and caspases regulates the autophagic activity of ATGs,thereby modulating the process of autophagy.Our previous study characterized BmCaspase-8-like(BmCasp8L)as a caspase suppressor that inhibits apoptosis and immune signaling by suppressing the activation of death-related ced-3/Nedd2-like caspase(DREDD),a caspase-8 homolog in silkworm.In this study,we explored the regulatory role of BmCasp8L in autophagy.We found that the expression of Bmcasp8l increased from the late spinning stage to the pupa stage in the posterior silk gland(PSG),correlating with the expression patterns of Bmatg8 and Bmatg6.RNA interference-mediated downregulation of BmCasp8L expression significantly decreased starvation-induced autophagic influx as determined by the levels of BmATG8–phosphatidylethanolamine and the percentage of cells displaying punctate enhanced green fluorescent protein-BmATG8.Conversely,the overexpression of BmCasp8L significantly increased autophagic influx.We also found that BmCasp8L underwent autophagic degradation induced by starvation and that it was colocalized with BmATG8.Lastly,we demonstrated that BmDREDD attenuated autophagy and BmCasp8L suppressed BmDREDD-mediated cleavage of BmATG6.Taken together,our results demonstrated that BmCasp8L is a novel proautophagic molecule which suppresses BmDREDD-mediated cleavage of BmATG6 and is a target for autophagy.
文摘Background:Interleukin-1 receptor-associated kinase 1(IRAK1),an active serine/threonine kinase,is an indispensable mediator of inflammatory responses and innate immunity.Emerging evidence has highlighted the oncogenic role of IRAK1 in tumors.However,the role of IRAK1 in gastric cancer(GC)progression remains unclear.Methods:IRAK1 expression levels in patients with GC at Peking Union Medical College Hospital were assessed by Western blotting,quantitative real-time polymerase chain reaction,and immunohistochemistry.To elucidate the role of IRAK1 in GC pathogenesis,we established GC cells with clustered regularly interspaced short palindromic repeats(CRISPR)and CRISPR-associated protein 9 (Cas9)mediated IRAK1 knockout and lentiviral vector-mediated IRAK1 overexpression and subsequently conducted in vitro and in vivo experiments.Additionally,we assessed the effect of IRAK1 expression levels in GC cells on the M2 polarization of tumor-associated macrophages(TAMs)via a Transwell coculture system.Functional assays were subsequently carried out to determine whether IRAK1 regulates the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of GC cells through the induction of TAM M2 polarization and to clarify the associated regulatory mechanisms.Results:IRAK1 expression was progressively increased during GC progression.Clinicopathological feature analysis revealed that high IRAK1 expression predicted poor survival outcomes.In vitro and in vivo experiments revealed that IRAK1 was highly expressed in GC cells and facilitated the proliferation,migration,invasion,and EMT of GC cells via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)pathway.More interestingly,IRAK1 affected the malignant biological behavior of GC cells by inducing M2-like polarization of macrophages.Mechanistically,coculturing M0 macrophages with IRAK1-knockout GC cells suppressed interleukin(IL)-8 secretion,thereby inhibiting Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway activation in TAMs.Inactivation of the JAK2/STAT3 pathway suppressed the M2 polarization of TAMs,ultimately inhibiting GC progression.Conclusions:IRAK1 influences the malignant biological behavior of GC cells by activating the PI3K/AKT/mTOR pathway and inducing the M2-like polarization of macrophages via the IL-8/JAK2/STAT3 pathway in TAMs.Our findings provide a novel diagnostic biomarker and a promising therapeutic strategy for GC.
