Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute...Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome （ALI/ARDS） remains unclear.Methods：C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide （LPS） ＋ vehicle,LPS ＋ acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone （Ac-YVAD-CMK） and LPS ＋ Z-Asp-Glu-Val-Asp-fluoromethylketone groups.Mice were given intraperitoneal （IP） injections of LPS.Drugs were IP injected 1 h before LPS administration.Mice were sacrificed 16 h after LPS administration,and AMs were isolated.Western blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were performed.AMs were treated with LPS and adenosine triphosphate （ATP）;caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） pyroptosomes were examined by immunofluorescence.Results：The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group.In the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation.The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death.Ac-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid （BALF）.In addition,Ac-YVAD-CMK significantly inhibited interleukin-β （IL-lβ） release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α （TNF-α）,High Mobility Group Box 1 （HMGB1） in BALF during LPS-induced ALI/ARDS.Conclusions：This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.These 展开更多
AIM: To identify the effect of Houttuynia cordata Thunb(HCT) on lipopolysaccharide(LPS)-induced microglial activation and investigate its possible molecular mechanisms. METHODS: The primary retinal microglial cells we...AIM: To identify the effect of Houttuynia cordata Thunb(HCT) on lipopolysaccharide(LPS)-induced microglial activation and investigate its possible molecular mechanisms. METHODS: The primary retinal microglial cells were cultured from the retinas of newborn Sprague-Dawley rats and exposed to LPS, and/or HCT with different concentrations. The survival ability of retinal microglia cells was tested by standard MTT method. BrdU cell proliferation assay was used to evaluate the proliferation of retinal microglia. Inflammatory factors in the culture supernatants, including TNF-α, iNOS and IL-1β, were measured using ELISA. Microglia cells’ migration was determined with Transwell migration assay. The total p38-MAPK and phosphorylation of p38-MAPK(p-p38-MAPK) were detected with Western blot.RESULTS: Primary retinal microglia in culture exposed to LPS to induce microglia activation. Pretreatment with HCT significantly inhibited the LPS-induced cell proliferation, but not the cell viability. LPS induced inflammatory reaction in microglia and cell migration. HCT significantly reduced LPS-stimulated release of pro-inflammatory factors and decreased the number of migrating cells substantially in a concentration-dependent manner. Moreover, the protein levels of p-p38 MAPK were identified as the up regulation and co-treatment with HCT obviously inhibited the upregulation of p-p38 MAPK, but had no effect on the levels of total p38-MAPK.CONCLUSION: The data suggest that HCT inhibits LPSinduced retinal microglial activation via suppression of the p-p38-MAPK. HCT may be used for the treatment of ocular diseases characterized by over-activated microglia.展开更多
In view of the high complexity of the objective world, an economic dependence between subsystems(paired and unpaired) is proposed, and then the maintenance cost and time under different economic dependences are formul...In view of the high complexity of the objective world, an economic dependence between subsystems(paired and unpaired) is proposed, and then the maintenance cost and time under different economic dependences are formulated in a simple and consistent manner. Selective maintenance problem under economic dependence(EDSMP) is presented based on a series–parallel system in this paper. A case study shows that the system reliability is promoted to a certain extent, which can validate the validity of the EDSMP model. The influence of the ratio of set-up cost on system performance is mainly discussed under different economic dependences. Several existing improvements of classical exhaust algorithm are further modified to solve a large sized EDSMP rapidly. Experimental results illustrate that these improvements can reduce CPU time significantly.Furthermore the contribution of each improvement is defined here, and then their contributions are compared thoroughly.展开更多
BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However...BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patien展开更多
AIM: To investigate the anti-scarring effect of sodium hyaluronate(HA) at filtration pathway after filtering surgery in a rabbit model.METHODS: Fifteen healthy adult New Zealand white rabbits were selected for trabecu...AIM: To investigate the anti-scarring effect of sodium hyaluronate(HA) at filtration pathway after filtering surgery in a rabbit model.METHODS: Fifteen healthy adult New Zealand white rabbits were selected for trabeculectomy in both eyes. The right eyes were used as HA group with 0.1 m L HA injected into the anterior chamber at the end of the operation;the left eyes were used with 0.1 m L sodium lactate Ringer’s solution(RS) injected into the anterior chamber as RS group. Intraocular pressure(IOP), filtering blebs morphology, inflammatory reaction and complications were observed at the 7, 60, and 90 d after surgery.RESULTS: One day after surgery, the IOP of HA and RS groups were 12.75±1.92 and 10.50±1.59 mm Hg(P=0.005). At the 7;day postoperative, the filtering blebs of each group were functional type and TGF-β expression was significantly difference in both groups(0.10±0.01 vs 0.14±0.02, P=0.024). After 60 d of the operation, all filtering blebs were scarring and alpha-smooth muscle actin(α-SMA) expression was significantly difference in both groups(0.40±0.04 vs 0.35±0.02, P=0.032). α-SMA positive cells were mainly distributed in the junction of conjunctiva and sclera and around the blood vessels. The collagen volume fraction(CVF) of HA and RS group was(75.49±7.01)% and(79.93±5.35)%(P=0.044). On the 90;day after the operation, CVF was(82.57±5.19)% and(88.08±1.75)% in HA and RS groups(P=0.036). There was no α-SMA positive cell in HA group, while a few positive cells were observed in RS group(P=0.000).CONCLUSION: HA has effect of anti-scar and antiinflammation on filtration pathway after filtering surgery within 3 mo by inhibiting fibroblast proliferation and collagen deposition.展开更多
AIM:To determine whether Houttuynia cordata Thunb(HCT)can increase the survival of the retinal ganglion cells(RGCs)and inhibit microglia activation following retinal ischemia-reperfusion(RIR)injury.METHODS:Rat model o...AIM:To determine whether Houttuynia cordata Thunb(HCT)can increase the survival of the retinal ganglion cells(RGCs)and inhibit microglia activation following retinal ischemia-reperfusion(RIR)injury.METHODS:Rat model of RIR was induced by transient elevation of the intraocular pressure(IOP).HCT was orally administered for 2 d before the performance of retinal RIR model and once a day for the next 14 d.After 14 d of RIR injury,the rats were sacrificed for further analysis.Survival RGCs were stained with haematoxylin and eosin(H&E).Apoptosis of RGCs was detected by TUNEL staining.Retinal function was examined by flash-electroretinography(F-ERG).Retinal microglia were labeled using Iba-1,one specific marker for microglia.The m RNA expression levels of inducible nitric oxide synthase(i NOS),tumor necrosis factor alpha(TNF-α),and interleukin 1 beta(IL-1β)were assessed by quantitative real time reverse transcription polymerase chain reaction(q RT-PCR).RESULTS:Systemic HCT treatment significantly reduced RGCs death by H&E staining and exhibited an anti-apoptotic effect as assessed by TUNEL staining at day 14 after RIR injury.HCT greatly improved the retinal function as examined by F-ERG.The number of activated microglia significantly increased after RIR injury,which was significantly attenuated by HCT treatment.Besides,RIR injury induced a strong upregulation of pro-inflammatory genes TNF-α,i NOS and IL-1βm RNAs at day 14 post injury,which was suppressed by HCT.CONCLUSION:Neuroprotective effects of HCT encourage the survival of RGCs through inhibiting microglia activation due to RIR injury.Together these results support the use of HCT as promising therapy for the ischemic events of the retina diseases.展开更多
Distinction of predator＇s diet and prey choice preference is a hot topic of current investigations. Spider being generalist predator and cosmopoliter in nature acts as biological control agent in many agro-ecosystems...Distinction of predator＇s diet and prey choice preference is a hot topic of current investigations. Spider being generalist predator and cosmopoliter in nature acts as biological control agent in many agro-ecosystems. In the current study, predatory efficacy of five spiders （Pardosa birmanica, Cyclosa insulana, Thomisus projectus, Plexippus paykulli and Lycosa terrestris） inhabiting the cotton fieldevaluated in the laboratory conditions maintained at （27＋2）℃ temperature, 65%-5% relative humidity and 12 ： 12 h of light and dark photoperiod. Four key cotton pests＇ viz. Bemisiatabaci, Amrascaderastans Thripstabaci and Helicoverpa armigera were utilized in the choice and no-choice predatory studies. The findings of current investigation revealed that each predatory spider utilized at least one pest species. Predation rate was found higher in the no-choice predation because of unavailability of substitutes feeding source. The investigation also indicated each predatory spider killed more pests than consumed. The findings of this study support the predatory role of spiders in controlling the cotton major pests.展开更多
基金The author thanks the National Natural Science Foundation of China （No. 81470266）.
文摘Background：Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage （AM） pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome （ALI/ARDS） remains unclear.Methods：C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide （LPS） ＋ vehicle,LPS ＋ acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone （Ac-YVAD-CMK） and LPS ＋ Z-Asp-Glu-Val-Asp-fluoromethylketone groups.Mice were given intraperitoneal （IP） injections of LPS.Drugs were IP injected 1 h before LPS administration.Mice were sacrificed 16 h after LPS administration,and AMs were isolated.Western blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were performed.AMs were treated with LPS and adenosine triphosphate （ATP）;caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） pyroptosomes were examined by immunofluorescence.Results：The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group.In the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation.The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death.Ac-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid （BALF）.In addition,Ac-YVAD-CMK significantly inhibited interleukin-β （IL-lβ） release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α （TNF-α）,High Mobility Group Box 1 （HMGB1） in BALF during LPS-induced ALI/ARDS.Conclusions：This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.These
文摘AIM: To identify the effect of Houttuynia cordata Thunb(HCT) on lipopolysaccharide(LPS)-induced microglial activation and investigate its possible molecular mechanisms. METHODS: The primary retinal microglial cells were cultured from the retinas of newborn Sprague-Dawley rats and exposed to LPS, and/or HCT with different concentrations. The survival ability of retinal microglia cells was tested by standard MTT method. BrdU cell proliferation assay was used to evaluate the proliferation of retinal microglia. Inflammatory factors in the culture supernatants, including TNF-α, iNOS and IL-1β, were measured using ELISA. Microglia cells’ migration was determined with Transwell migration assay. The total p38-MAPK and phosphorylation of p38-MAPK(p-p38-MAPK) were detected with Western blot.RESULTS: Primary retinal microglia in culture exposed to LPS to induce microglia activation. Pretreatment with HCT significantly inhibited the LPS-induced cell proliferation, but not the cell viability. LPS induced inflammatory reaction in microglia and cell migration. HCT significantly reduced LPS-stimulated release of pro-inflammatory factors and decreased the number of migrating cells substantially in a concentration-dependent manner. Moreover, the protein levels of p-p38 MAPK were identified as the up regulation and co-treatment with HCT obviously inhibited the upregulation of p-p38 MAPK, but had no effect on the levels of total p38-MAPK.CONCLUSION: The data suggest that HCT inhibits LPSinduced retinal microglial activation via suppression of the p-p38-MAPK. HCT may be used for the treatment of ocular diseases characterized by over-activated microglia.
基金supported by the National Science Foundation of China (Grant No. 61305083)
文摘In view of the high complexity of the objective world, an economic dependence between subsystems(paired and unpaired) is proposed, and then the maintenance cost and time under different economic dependences are formulated in a simple and consistent manner. Selective maintenance problem under economic dependence(EDSMP) is presented based on a series–parallel system in this paper. A case study shows that the system reliability is promoted to a certain extent, which can validate the validity of the EDSMP model. The influence of the ratio of set-up cost on system performance is mainly discussed under different economic dependences. Several existing improvements of classical exhaust algorithm are further modified to solve a large sized EDSMP rapidly. Experimental results illustrate that these improvements can reduce CPU time significantly.Furthermore the contribution of each improvement is defined here, and then their contributions are compared thoroughly.
基金the National Natural Science Foundation of Hunan Province,No.2023JJ60039Natural Science Foundation of Hunan Province National Health Commission,No.B202303027655+3 种基金Natural Science Foundation of Changsha Science and Technology Bureau,No.Kq2208150Wu Jieping Foundation of China,No.320.6750.2022-22-59,320.6750.2022-17-41Guangdong Association of Clinical Trials(GACT)/Chinese Thoracic Oncology Group(CTONG)and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer,No.2017B030314120.
文摘BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patien
基金Supported by National Natural Science Fundation of China(No.81974132No.81770927)+1 种基金National Key R&D Program of China(No.2021YFA1101202)Hunan Provincial Health Commission(No.202207022839)。
文摘AIM: To investigate the anti-scarring effect of sodium hyaluronate(HA) at filtration pathway after filtering surgery in a rabbit model.METHODS: Fifteen healthy adult New Zealand white rabbits were selected for trabeculectomy in both eyes. The right eyes were used as HA group with 0.1 m L HA injected into the anterior chamber at the end of the operation;the left eyes were used with 0.1 m L sodium lactate Ringer’s solution(RS) injected into the anterior chamber as RS group. Intraocular pressure(IOP), filtering blebs morphology, inflammatory reaction and complications were observed at the 7, 60, and 90 d after surgery.RESULTS: One day after surgery, the IOP of HA and RS groups were 12.75±1.92 and 10.50±1.59 mm Hg(P=0.005). At the 7;day postoperative, the filtering blebs of each group were functional type and TGF-β expression was significantly difference in both groups(0.10±0.01 vs 0.14±0.02, P=0.024). After 60 d of the operation, all filtering blebs were scarring and alpha-smooth muscle actin(α-SMA) expression was significantly difference in both groups(0.40±0.04 vs 0.35±0.02, P=0.032). α-SMA positive cells were mainly distributed in the junction of conjunctiva and sclera and around the blood vessels. The collagen volume fraction(CVF) of HA and RS group was(75.49±7.01)% and(79.93±5.35)%(P=0.044). On the 90;day after the operation, CVF was(82.57±5.19)% and(88.08±1.75)% in HA and RS groups(P=0.036). There was no α-SMA positive cell in HA group, while a few positive cells were observed in RS group(P=0.000).CONCLUSION: HA has effect of anti-scar and antiinflammation on filtration pathway after filtering surgery within 3 mo by inhibiting fibroblast proliferation and collagen deposition.
文摘AIM:To determine whether Houttuynia cordata Thunb(HCT)can increase the survival of the retinal ganglion cells(RGCs)and inhibit microglia activation following retinal ischemia-reperfusion(RIR)injury.METHODS:Rat model of RIR was induced by transient elevation of the intraocular pressure(IOP).HCT was orally administered for 2 d before the performance of retinal RIR model and once a day for the next 14 d.After 14 d of RIR injury,the rats were sacrificed for further analysis.Survival RGCs were stained with haematoxylin and eosin(H&E).Apoptosis of RGCs was detected by TUNEL staining.Retinal function was examined by flash-electroretinography(F-ERG).Retinal microglia were labeled using Iba-1,one specific marker for microglia.The m RNA expression levels of inducible nitric oxide synthase(i NOS),tumor necrosis factor alpha(TNF-α),and interleukin 1 beta(IL-1β)were assessed by quantitative real time reverse transcription polymerase chain reaction(q RT-PCR).RESULTS:Systemic HCT treatment significantly reduced RGCs death by H&E staining and exhibited an anti-apoptotic effect as assessed by TUNEL staining at day 14 after RIR injury.HCT greatly improved the retinal function as examined by F-ERG.The number of activated microglia significantly increased after RIR injury,which was significantly attenuated by HCT treatment.Besides,RIR injury induced a strong upregulation of pro-inflammatory genes TNF-α,i NOS and IL-1βm RNAs at day 14 post injury,which was suppressed by HCT.CONCLUSION:Neuroprotective effects of HCT encourage the survival of RGCs through inhibiting microglia activation due to RIR injury.Together these results support the use of HCT as promising therapy for the ischemic events of the retina diseases.
文摘Distinction of predator＇s diet and prey choice preference is a hot topic of current investigations. Spider being generalist predator and cosmopoliter in nature acts as biological control agent in many agro-ecosystems. In the current study, predatory efficacy of five spiders （Pardosa birmanica, Cyclosa insulana, Thomisus projectus, Plexippus paykulli and Lycosa terrestris） inhabiting the cotton fieldevaluated in the laboratory conditions maintained at （27＋2）℃ temperature, 65%-5% relative humidity and 12 ： 12 h of light and dark photoperiod. Four key cotton pests＇ viz. Bemisiatabaci, Amrascaderastans Thripstabaci and Helicoverpa armigera were utilized in the choice and no-choice predatory studies. The findings of current investigation revealed that each predatory spider utilized at least one pest species. Predation rate was found higher in the no-choice predation because of unavailability of substitutes feeding source. The investigation also indicated each predatory spider killed more pests than consumed. The findings of this study support the predatory role of spiders in controlling the cotton major pests.
