Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum st...Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum stress and reactive oxygen species.Our previous research demonstrated that cerebral dopamine neurotrophic factor has anti-inflammatory effects and promotes the repair of the damaged spinal cord after injury.However,the molecular mechanism remains unclear.In this study,we found that cerebral dopamine neurotrophic factor binds JNK1 and regulates JNK1/2-c-Jun-p53 signaling in lipopolysaccharide-induced microglia.Cerebral dopamine neurotrophic factor also alleviated neuroinflammation by reducing the secretion of pro-inflammatory cytokines.Overexpression of cerebral dopamine neurotrophic factor in a mouse model of spinal cord injury promoted nerve regeneration and motor function recovery.These findings indicate the possibility for cerebral dopamine neurotrophic factor treating spinal cord injury by targeting the JNK1/2-c-Jun-p53 pathway.展开更多
To adapt to gravitational forces during the transition to terrestrial life,animals evolved specialized paw skin to withstand their body weight and allow for locomotion.In a recent Cell article,Di et al.demonstrate SLU...To adapt to gravitational forces during the transition to terrestrial life,animals evolved specialized paw skin to withstand their body weight and allow for locomotion.In a recent Cell article,Di et al.demonstrate SLURP1 as an endoplasmic reticulum(ER)membrane protein that protects palmoplantar keratinocytes from mechanical stress by preserving SERCA2b activity and inhibiting the pPERK-NRF2 signaling under mechanical pressure.展开更多
Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors ...Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.展开更多
Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ...Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ionizing radiation exposure was used to establish the HCC rat model.All rats were divided into 4 groups:the control group,the chitinase group,the HCC group,and the HCC+chitinase group.The antiproliferative effect of chitinase was evaluated in human HCC cells.The effect of chitinase in vivo on oxidative stress,endoplasmic reticulum stress chaperones,autophagy markers,PI3K/AKT/mTOR,AMPK pathway expression,and apoptotic indicators was determined and confirmed by histological examination.Results:Chitinase significantly inhibited the viabilities of HepG2 cells.Moreover,in the Wistar male rat model of HCC,chitinase decreased ATP levels,modulated endoplasmic reticulum stress,mediated autophagy factors,and promoted apoptosis.Conclusions:Chitinase might play a role in the apoptosis as well as autophagy pathways and may act as a potential tumor suppressor.展开更多
Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neu...Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neurodegenerative fallback.The global prevalence of this disease is estimated at 1 in 770,000(Lee et al.,2023).It is most commonly caused by biallelic(point)mutations in the Wolframin endoplasmic reticulum(ER)transmembrane glycoprotein(WFS1)gene(in case of WS type 1),but mutations in the CDGSH Iron Sulfur Domain 2(CISD2)are also linked to WS(type 2).The latter,however,often present with less severe pathological manifestations(Lee et al.,2023).WFS1 is located on chromosome 4p16.1 and spans over 33 kilobases.Many mutation variants have been identified in WFS1,encompassing missense,nonsense,and frameshift mutations.These mutations are spread across the coding region of WFS1,but certain regions,such as exon 8,the largest exon,appear particularly mutation-prone and associated with the classical WS type 1 phenotype(Lee et al.,2023).展开更多
In this paper, we have demonstrated an Er-doped ultrafast laser with a single mode fiber-gradient index multimode fiber-single mode fiber(SMF-GIMF-SMF, SMS) structure as saturable absorber(SA), which can generate not ...In this paper, we have demonstrated an Er-doped ultrafast laser with a single mode fiber-gradient index multimode fiber-single mode fiber(SMF-GIMF-SMF, SMS) structure as saturable absorber(SA), which can generate not only stable single-pulse state, but also special mode-locked pulses with the characteristics of high energy and noisy behaviors at proper pump power and cavity polarization state. In addition, we have deeply investigated the real-time spectral evolutions of the mode-locked pulses through the dispersive Fourier transformation(DFT) technique. It can be found that the pulse regime can actually consist of a lot of small noise pulses with randomly varying intensities. We believe that these results will further enrich the nonlinear dynamical processes in the ultrafast lasers.展开更多
This paper reports the preparation of yttrium oxide(Y_(2)O_(3))doped with various concentrations of Er^(3+)using high temperature synthesis method.Photoluminescence(PL)emission spectra of the samples were recorded at ...This paper reports the preparation of yttrium oxide(Y_(2)O_(3))doped with various concentrations of Er^(3+)using high temperature synthesis method.Photoluminescence(PL)emission spectra of the samples were recorded at an excitation of 980 nm laser source.Two prominent peaks centered at 484 nm and 574 nm were found and attributed to the^(2)P3/2→^(4)I_(11/2)and^(4)S_(3/2)→^(4)I_(15/2),respectively.The sample with 2.5 mol%of Er^(3+)provided the optimum intensity in emission spectra.The sample with optimum PL emission was investigated for its thermoluminescence(TL)glow curve exhibited the second order kinetics.The peak TL intensity was found around 236°C,i.e.,towards high temperature which supports the fact of formation of deeper traps.Therefore,the material taken may be regarded as a good candidate for light emitting diode(LED)applications.展开更多
基金National Natural Science Foundation of China,No.81601067(to HZ)Shandong Natural Science Foundation of Shandong Province,Nos.ZR2021MH134(to HZ)and ZR2020MH080(to PD).
文摘Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis,necrosis,and pro-inflammatory microenvironment after spinal cord injury.The JNK pathway is activated by endoplasmic reticulum stress and reactive oxygen species.Our previous research demonstrated that cerebral dopamine neurotrophic factor has anti-inflammatory effects and promotes the repair of the damaged spinal cord after injury.However,the molecular mechanism remains unclear.In this study,we found that cerebral dopamine neurotrophic factor binds JNK1 and regulates JNK1/2-c-Jun-p53 signaling in lipopolysaccharide-induced microglia.Cerebral dopamine neurotrophic factor also alleviated neuroinflammation by reducing the secretion of pro-inflammatory cytokines.Overexpression of cerebral dopamine neurotrophic factor in a mouse model of spinal cord injury promoted nerve regeneration and motor function recovery.These findings indicate the possibility for cerebral dopamine neurotrophic factor treating spinal cord injury by targeting the JNK1/2-c-Jun-p53 pathway.
基金supported by Applied Basic Research Foundation of Yunnan Province,No.202501AT070205(W.N.).
文摘To adapt to gravitational forces during the transition to terrestrial life,animals evolved specialized paw skin to withstand their body weight and allow for locomotion.In a recent Cell article,Di et al.demonstrate SLURP1 as an endoplasmic reticulum(ER)membrane protein that protects palmoplantar keratinocytes from mechanical stress by preserving SERCA2b activity and inhibiting the pPERK-NRF2 signaling under mechanical pressure.
基金supported by the National Natural Science Foundation of China to L.H.(32470754 and 32070750)to X.M.(32170824 and 32322027)HRHl program of Westlake Laboratory of Life Sciences and Biomedicine to X.M.(1011103360222B1).
文摘Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.
文摘Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ionizing radiation exposure was used to establish the HCC rat model.All rats were divided into 4 groups:the control group,the chitinase group,the HCC group,and the HCC+chitinase group.The antiproliferative effect of chitinase was evaluated in human HCC cells.The effect of chitinase in vivo on oxidative stress,endoplasmic reticulum stress chaperones,autophagy markers,PI3K/AKT/mTOR,AMPK pathway expression,and apoptotic indicators was determined and confirmed by histological examination.Results:Chitinase significantly inhibited the viabilities of HepG2 cells.Moreover,in the Wistar male rat model of HCC,chitinase decreased ATP levels,modulated endoplasmic reticulum stress,mediated autophagy factors,and promoted apoptosis.Conclusions:Chitinase might play a role in the apoptosis as well as autophagy pathways and may act as a potential tumor suppressor.
基金Research into Wolfram syndrome in the De Groef team has been supported by the Eye Hope Foundation(Belgium),Wolfram UK(UK)and The Snow Foundation(USA).
文摘Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neurodegenerative fallback.The global prevalence of this disease is estimated at 1 in 770,000(Lee et al.,2023).It is most commonly caused by biallelic(point)mutations in the Wolframin endoplasmic reticulum(ER)transmembrane glycoprotein(WFS1)gene(in case of WS type 1),but mutations in the CDGSH Iron Sulfur Domain 2(CISD2)are also linked to WS(type 2).The latter,however,often present with less severe pathological manifestations(Lee et al.,2023).WFS1 is located on chromosome 4p16.1 and spans over 33 kilobases.Many mutation variants have been identified in WFS1,encompassing missense,nonsense,and frameshift mutations.These mutations are spread across the coding region of WFS1,but certain regions,such as exon 8,the largest exon,appear particularly mutation-prone and associated with the classical WS type 1 phenotype(Lee et al.,2023).
基金supported by the Guangdong Basic and Applied Basic Research Foundation (No.2023A1515010093)the Shenzhen Fundamental Research Program (Stable Support Plan Program)(Nos.JCYJ20220809170611004, 20231121110828001 and 20231121113641002)the National Taipei University of Technology-Shenzhen University Joint Research Program (No.2024001)。
文摘In this paper, we have demonstrated an Er-doped ultrafast laser with a single mode fiber-gradient index multimode fiber-single mode fiber(SMF-GIMF-SMF, SMS) structure as saturable absorber(SA), which can generate not only stable single-pulse state, but also special mode-locked pulses with the characteristics of high energy and noisy behaviors at proper pump power and cavity polarization state. In addition, we have deeply investigated the real-time spectral evolutions of the mode-locked pulses through the dispersive Fourier transformation(DFT) technique. It can be found that the pulse regime can actually consist of a lot of small noise pulses with randomly varying intensities. We believe that these results will further enrich the nonlinear dynamical processes in the ultrafast lasers.
文摘This paper reports the preparation of yttrium oxide(Y_(2)O_(3))doped with various concentrations of Er^(3+)using high temperature synthesis method.Photoluminescence(PL)emission spectra of the samples were recorded at an excitation of 980 nm laser source.Two prominent peaks centered at 484 nm and 574 nm were found and attributed to the^(2)P3/2→^(4)I_(11/2)and^(4)S_(3/2)→^(4)I_(15/2),respectively.The sample with 2.5 mol%of Er^(3+)provided the optimum intensity in emission spectra.The sample with optimum PL emission was investigated for its thermoluminescence(TL)glow curve exhibited the second order kinetics.The peak TL intensity was found around 236°C,i.e.,towards high temperature which supports the fact of formation of deeper traps.Therefore,the material taken may be regarded as a good candidate for light emitting diode(LED)applications.
