Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,memb...Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway.Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.展开更多
Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries,including glaucoma,diabetic retinopathy,traumatic optic neuropathy and optic neuritis,etc.The current clinical...Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries,including glaucoma,diabetic retinopathy,traumatic optic neuropathy and optic neuritis,etc.The current clinical treatment is not very effective.We investigated indirubin,one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill,in the present study for its role in retinal neurodegeneration.Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro.Moreover,indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo.Furthermore,indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro.In addition,indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress.Mechanically,indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling.In conclusion,indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury.The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.展开更多
Symmetric six oxygen-coordinated Mn structural units(MnO6)in MnO2 with small Mn–O orbital overlap hamper electron transfer rates during energy storage.Herein,we report a novel bond angle modulation strategy to manipu...Symmetric six oxygen-coordinated Mn structural units(MnO6)in MnO2 with small Mn–O orbital overlap hamper electron transfer rates during energy storage.Herein,we report a novel bond angle modulation strategy to manipulate Mn–O orbital overlap in MnO2 through the construction of Mn vacancies(MnO2-VMn),aiming at expediting electron transfer,and thus enhancing energy storage performance.Both experimental and theoretical results disclose that the amplification of Mn–O–Mn bond angles exclusively augments the Mn(dx2-y2)-O(py)orbital overlap and triggers the electron redistribution in MnO2-VMn,inducing an augmented Mn dx2-y2 electron occupation.This heightened presence of active electrons in the Mn dx2-y2 orbital paves the way for accelerating electron transfer and ion transfer in MnO2-VMn.Notably,MnO2-VMn delivers an improved specific capacitance of 425 F g−1 at 1 A g−1 and a superior rate capacity of 265 F g−1 at 20 A g−1.Furthermore,an asymmetric supercapacitor(MnO2-VMn//AC ASC)was fabricated,exhibiting a high energy density of 64.3 Wh kg−1 at a power density of 1000 W kg−1.Furthermore,theoretical insights uncover the profound implications of metal–oxygen–metal bond angle regulation on interatomic orbital overlap modulation.These revelations illuminate pathways for the design of advanced energy storage materials.展开更多
BACKGROUND： The effects of N-methyl-D-aspartic acid （NMDA） receptor antagonist on neurodegeneration in the immature brain following traumatic brain injury （TBI） are still widely unknown. OBJECTIVE： To study the ...BACKGROUND： The effects of N-methyl-D-aspartic acid （NMDA） receptor antagonist on neurodegeneration in the immature brain following traumatic brain injury （TBI） are still widely unknown. OBJECTIVE： To study the effects of dizocipine maleate （MK-801）, a non-competitive NMDA receptor antagonist, on mitochondrial ultramicrostructure of neurons in the ipsilateral cingulate cortex and hippocampus after TBI in neonatal rats, and to analyze the optimal time interval of MK-801 administration （1 mg/kg）. DESIGN： Completely randomized controlled study. SETTING： Shanghai Jiao Tong University. MATERIALS： Eight 7-day-old neonatal SD rats, irrespective of gender, were provided by Experimental Animal Center, Medical College of Fudan University. The experiment was approved by a local ethics committee. MK-801 was provided by Sigma. A CM-120 transmission electron microscope （Philips, Holland） was used for tissue analysis. METHODS： This study was performed at the Departments of Anatomy, Neuromorphology, and Biophysics, Medical College of Shanghai, Jiaotong University, between October 2006 and January 2007. Focal models of contusion and laceration of brain were established by the free-falling impact method. Eight rats were randomly divided into a normal control group （n = 2 ） and a MK-801 group （n = 6）. Rats in the normal control group did not receive model establishment and administration, and they were only analyzed by an electron microscope. In the MK-801 group, the cingulate cortex was damaged using a contusion device. MK-801 （1 mg/kg） was intraperitoneally injected 30 minutes before lesion, immediately after lesion, and 30 minutes after lesion （n = 2 for each time point）.MAIN OUTCOME MEASURES： The cingulate cortex and hippocampal tissues from the injured side were removed 24 hours after lesion and routinely processed for analysis of neuronal ultramicrostructure using transmission electron microscopy. RESULTS： Differential therapeutic effects of MK-801 （1 mg/kg） at distinct administration time points： thirty minutes before lesion, the shape of cortical and hippocampal neurons was similar to that observed during excitotoxicity-induced cell death. Organelles were enlarged, the nuclear membrane of cortical neurons was complete with gear wheel-like changes, and the nuclear chromatin was irregularly aggregated around the edge. When MK-801 was applied 30 minutes after lesion, the cingulate cortex contained apoptotic neurons in early and late stages. The nuclear membrane of hippocampal neurons displayed incisures. The chromatin shape was not similar to necrosis in an early stage. Immediate administration of MK-801 after lesion slightly altered the neuronal architecture, such that mitochondria were enlarged. The neuronal shape in the control group was normal. Effects of immediate administration of MK-801 on mitochondrial injury following TBI were that the mitochondria in cortical and hippocampal neurons were damaged to a certain degree in the MK-801 group. Mitochondrial injury was reversible, when MK-801 was applied 30 minutes before lesion and immediately after lesion. Application 30 minutes after lesion produced irreversible changes. In addition, mitochondrial injury occurred earlier than other organelle and nuclear changes. CONCLUSION： Mitochondrial injury occurs earlier than other organelle and nuclear changes. Early administration of MK-801 （1 mg/kg） can prevent or reduce necrosis following TBI, decrease the degree of neuronal injury, and protect nerve cells.展开更多
The nitrogen(N)and phosphorus(P)addition promotes the abundance of soybean soil nematodes.The addition of nitrogen can alleviate the suppression of phosphorus on nematodes.Phosphorus addition affects nematode abundanc...The nitrogen(N)and phosphorus(P)addition promotes the abundance of soybean soil nematodes.The addition of nitrogen can alleviate the suppression of phosphorus on nematodes.Phosphorus addition affects nematode abundance by ammonium nitrogen.展开更多
Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus(H1N1), a single-stranded, negative-se...Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus(H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial(A549) cells. In detail, the expression of hexokinase 2(HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells,and the expression of pyruvate kinase M2(PKM2) and pyruvate dehydrogenase kinase 3(PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1(HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future.展开更多
Age estimation plays an important role in human-computer interaction system.The lack of large number of facial images with definite age label makes age estimation al-gorithms inefficient.Deep label distribution learni...Age estimation plays an important role in human-computer interaction system.The lack of large number of facial images with definite age label makes age estimation al-gorithms inefficient.Deep label distribution learning(DLDL)which employs convolutional neural networks(CNN)and label distribution learning to learn ambiguity from ground-truth age and adjacent ages,has been proven to outperform current state-of-the-art framework.However,DLDL assumes a rough label distribution which covers all ages for any given age label.In this paper,a more practical label distribution paradigm is proposed:we limit age label distribution that only covers a reasonable number of neighboring ages.In addition,we explore different label distributions to improve the performance of the proposed learning model.We employ CNN and the improved label distribution learning to estimate age.Experimental results show that compared to the DLDL,our method is more effective for facial age recognition.展开更多
基金supported by the Natural Science Research Project of colleges and Universities in Anhui Province[2022AH052336]High Level Talent Research Initiation Fund Of Anhui Medical College[2023RC004]。
文摘Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway.Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81970823 and 82271107)the Natural Science Foundation of Jiangsu Province(Grant No.BK20221186).
文摘Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries,including glaucoma,diabetic retinopathy,traumatic optic neuropathy and optic neuritis,etc.The current clinical treatment is not very effective.We investigated indirubin,one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill,in the present study for its role in retinal neurodegeneration.Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro.Moreover,indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo.Furthermore,indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro.In addition,indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress.Mechanically,indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling.In conclusion,indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury.The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.
基金Financial support from the National Natural Science Foundation of China(21575016U20A20154+1 种基金22279005)the National Program for Support of Top-notch Young Professionals。
文摘Symmetric six oxygen-coordinated Mn structural units(MnO6)in MnO2 with small Mn–O orbital overlap hamper electron transfer rates during energy storage.Herein,we report a novel bond angle modulation strategy to manipulate Mn–O orbital overlap in MnO2 through the construction of Mn vacancies(MnO2-VMn),aiming at expediting electron transfer,and thus enhancing energy storage performance.Both experimental and theoretical results disclose that the amplification of Mn–O–Mn bond angles exclusively augments the Mn(dx2-y2)-O(py)orbital overlap and triggers the electron redistribution in MnO2-VMn,inducing an augmented Mn dx2-y2 electron occupation.This heightened presence of active electrons in the Mn dx2-y2 orbital paves the way for accelerating electron transfer and ion transfer in MnO2-VMn.Notably,MnO2-VMn delivers an improved specific capacitance of 425 F g−1 at 1 A g−1 and a superior rate capacity of 265 F g−1 at 20 A g−1.Furthermore,an asymmetric supercapacitor(MnO2-VMn//AC ASC)was fabricated,exhibiting a high energy density of 64.3 Wh kg−1 at a power density of 1000 W kg−1.Furthermore,theoretical insights uncover the profound implications of metal–oxygen–metal bond angle regulation on interatomic orbital overlap modulation.These revelations illuminate pathways for the design of advanced energy storage materials.
基金the Fourth Key Disciplines Foundation of Shanghai Education Commission, No.2004JY04
文摘BACKGROUND： The effects of N-methyl-D-aspartic acid （NMDA） receptor antagonist on neurodegeneration in the immature brain following traumatic brain injury （TBI） are still widely unknown. OBJECTIVE： To study the effects of dizocipine maleate （MK-801）, a non-competitive NMDA receptor antagonist, on mitochondrial ultramicrostructure of neurons in the ipsilateral cingulate cortex and hippocampus after TBI in neonatal rats, and to analyze the optimal time interval of MK-801 administration （1 mg/kg）. DESIGN： Completely randomized controlled study. SETTING： Shanghai Jiao Tong University. MATERIALS： Eight 7-day-old neonatal SD rats, irrespective of gender, were provided by Experimental Animal Center, Medical College of Fudan University. The experiment was approved by a local ethics committee. MK-801 was provided by Sigma. A CM-120 transmission electron microscope （Philips, Holland） was used for tissue analysis. METHODS： This study was performed at the Departments of Anatomy, Neuromorphology, and Biophysics, Medical College of Shanghai, Jiaotong University, between October 2006 and January 2007. Focal models of contusion and laceration of brain were established by the free-falling impact method. Eight rats were randomly divided into a normal control group （n = 2 ） and a MK-801 group （n = 6）. Rats in the normal control group did not receive model establishment and administration, and they were only analyzed by an electron microscope. In the MK-801 group, the cingulate cortex was damaged using a contusion device. MK-801 （1 mg/kg） was intraperitoneally injected 30 minutes before lesion, immediately after lesion, and 30 minutes after lesion （n = 2 for each time point）.MAIN OUTCOME MEASURES： The cingulate cortex and hippocampal tissues from the injured side were removed 24 hours after lesion and routinely processed for analysis of neuronal ultramicrostructure using transmission electron microscopy. RESULTS： Differential therapeutic effects of MK-801 （1 mg/kg） at distinct administration time points： thirty minutes before lesion, the shape of cortical and hippocampal neurons was similar to that observed during excitotoxicity-induced cell death. Organelles were enlarged, the nuclear membrane of cortical neurons was complete with gear wheel-like changes, and the nuclear chromatin was irregularly aggregated around the edge. When MK-801 was applied 30 minutes after lesion, the cingulate cortex contained apoptotic neurons in early and late stages. The nuclear membrane of hippocampal neurons displayed incisures. The chromatin shape was not similar to necrosis in an early stage. Immediate administration of MK-801 after lesion slightly altered the neuronal architecture, such that mitochondria were enlarged. The neuronal shape in the control group was normal. Effects of immediate administration of MK-801 on mitochondrial injury following TBI were that the mitochondria in cortical and hippocampal neurons were damaged to a certain degree in the MK-801 group. Mitochondrial injury was reversible, when MK-801 was applied 30 minutes before lesion and immediately after lesion. Application 30 minutes after lesion produced irreversible changes. In addition, mitochondrial injury occurred earlier than other organelle and nuclear changes. CONCLUSION： Mitochondrial injury occurs earlier than other organelle and nuclear changes. Early administration of MK-801 （1 mg/kg） can prevent or reduce necrosis following TBI, decrease the degree of neuronal injury, and protect nerve cells.
基金financially supported by the National Natural Science Foundation of China(42107225 and 31770522)Xinyang Academy of Ecological Research Open Foundation(2023XYQN15)Natural Science Foundation of Henan(222300420108).
文摘The nitrogen(N)and phosphorus(P)addition promotes the abundance of soybean soil nematodes.The addition of nitrogen can alleviate the suppression of phosphorus on nematodes.Phosphorus addition affects nematode abundance by ammonium nitrogen.
基金This work was supported by the National Natural Science Funds of China under Grant 81471891 and 82000022Key and Weak Subject Construction Project of Shanghai Health and Family Planning System under Grant 2016ZB0205Natural Science Foundation of Shanghai under Grant 18ZR1431900。
文摘Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus(H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial(A549) cells. In detail, the expression of hexokinase 2(HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells,and the expression of pyruvate kinase M2(PKM2) and pyruvate dehydrogenase kinase 3(PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1(HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future.
基金the financial support of the China National Natural Science Foundation(61702095)Natural Science Founda-tion(njpj2018209)of Nanjing Tech University Pujiang Institute,Anhui Polytechnic University Scientific Research Foundation(S031702004)+1 种基金Natural Science Foundation of Fujian Province(2018J01806)Scientific Research Pro-gram of Outstanding Talents in Universities of Fujian。
文摘Age estimation plays an important role in human-computer interaction system.The lack of large number of facial images with definite age label makes age estimation al-gorithms inefficient.Deep label distribution learning(DLDL)which employs convolutional neural networks(CNN)and label distribution learning to learn ambiguity from ground-truth age and adjacent ages,has been proven to outperform current state-of-the-art framework.However,DLDL assumes a rough label distribution which covers all ages for any given age label.In this paper,a more practical label distribution paradigm is proposed:we limit age label distribution that only covers a reasonable number of neighboring ages.In addition,we explore different label distributions to improve the performance of the proposed learning model.We employ CNN and the improved label distribution learning to estimate age.Experimental results show that compared to the DLDL,our method is more effective for facial age recognition.
