Some active metal oxides(Al_(2)O_(3),TiO_(2),and Cr_(2)O_(3))were selected as dopants to the Al_(2)O_(3)-based ceramic shells for investment casting of K417G superalloy.The effects of dopant types and contents(0,2,5,a...Some active metal oxides(Al_(2)O_(3),TiO_(2),and Cr_(2)O_(3))were selected as dopants to the Al_(2)O_(3)-based ceramic shells for investment casting of K417G superalloy.The effects of dopant types and contents(0,2,5,and 8 wt.%)on the wettability and interfacial reaction between the alloy and shell were investigated by a sessile-drop experiment.The results show that increasing the Al_(2)O_(3) doping contents(0−8 wt.%)reduces the porosity(21.74%−10.08%)and roughness(3.22−1.34μm)of the shell surface.The increase in Cr_(2)O_(3) dopant content(2−8 wt.%)further exacerbates the interfacial reaction,leading to an increase in the thickness of the reaction layer(2.6−3.1μm)and a decrease in the wetting angle(93.9°−91.0°).The addition of Al_(2)O_(3) and TiO_(2) dopants leads to the formation of Al_(2)TiO_(5) composite oxides in the reaction products,which effectively inhibits the interfacial reaction.The increase in TiO_(2) dopant contents(0−8 wt.%)further promotes the formation of Al_(2)TiO_(5),which decreases the thickness of the interfacial reaction layer(3.9−1.2μm)and increases the wetting angle(95.0°−103.8°).The introduced dopants enhance the packing density of the shell surface,while simultaneously suppress the diffusion of active metal elements from the alloy matrix to the interface.展开更多
Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)indu...Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.展开更多
Background:Depression,a prevalent mental health disorder,benefits from traditional Chinese medicine(TCM).Echinacoside(ECH),a natural phenolic compound extracted from Cistanche tubulosa and Echinacea angustifolia,exhib...Background:Depression,a prevalent mental health disorder,benefits from traditional Chinese medicine(TCM).Echinacoside(ECH),a natural phenolic compound extracted from Cistanche tubulosa and Echinacea angustifolia,exhibits neuroprotective and antioxidant properties.However,research on the potential mechanism of ECH’s antidepressant activity is limited.This study explored the antidepressant potential of ECH in mice subjected to chronic unpredictable mild stress(CUMS)and its underlying molecular mechanisms.Methods:Mice received ECH(10,20,40 mg/kg/d,i.p.)during the last 14 days of a 28-day CUMS protocol.The therapeutic effect was assessed via the sucrose preference test(SPT),tail suspension test(TST)and forced swim test(FST).Hematoxylin-eosin(H&E)and Nissl staining were employed to evaluate the changes of neuronal injury in hippocampus.Network pharmacology was used to explore the potential targets and pathway enrichment in ECH-mediated antidepression.The expression changes of PI3K/AKT/Nrf2/HO-1 were evaluated by Western blotting.Furthermore,the neuroprotection effects of ECH were assessed on cultured primary neurons injured by corticosterone(CORT)using CCK-8 assay.Results:The results indicated that ECH significantly alleviated depression-like behaviors in CUMS mice characterized as the improved sucrose intake in SPT,reduced immobility duration in TST and FST,reversed weight loss and hippocampal neuronal injury induced after CUMS.PI3K/AKT was selected as core targets by network pharmacology and supported by molecular docking and dynamics simulations.WB results indicated that ECH administration offered neuroprotection by recovering the expression levels of p-PI3K,p-AKT,Nrf2,and HO-1 in CUMS mice hippocampus.Moreover,ECH rescued CORT-induced neuron death in vitro by activating PI3K/AKT/Nrf2/HO-1 pathway,which was abolished by PI3K inhibitor LY294002.Conclusion:These findings demonstrated that ECH alleviated depressive-like behaviors via PI3K/AKT/Nrf2/HO-1 activation,highlighting its potential as a novel antidepressant.展开更多
Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effec...Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.展开更多
OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic tar...OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 2(PI3K/Akt/m TORC2)signaling pathway.METHODS:CAG was induced in rats and treated with high-,medium-,or low-dose Jiawei Huangqi Guizhi decoction.Gastric histopathology was observed by hematoxylin and eosin staining.Serum levels of gastrin,PI3K,Akt,and m TORC2 were detected by enzyme-linked immunosorbent assay.Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.RESULTS:The decoction alleviated gastric mucosal injury,reduced inflammation,and restored epithelial structure.It regulated PI3K,Akt,and m TORC2 expression at both m RNA and protein levels.CONCLUSION:Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/m TORC2 signaling pathway.展开更多
BACKGROUND Gastric cancer(GC)is a widespread malignancy and associated with high rates of morbidity and mortality worldwide.AIM To examine the functional role of long non-coding RNAs small nucleolar RNA host gene 5(SN...BACKGROUND Gastric cancer(GC)is a widespread malignancy and associated with high rates of morbidity and mortality worldwide.AIM To examine the functional role of long non-coding RNAs small nucleolar RNA host gene 5(SNHG5)and its regulation of miR-92a-3p and B-cell translocation gene 2(BTG2)in GC progression.METHODS Quantitative reverse transcription PCR and western blot analysis determined the expression of SNHG5,miR-92a-3p,and BTG2 in GC and adjacent non-neoplastic mucosa.Dual-luciferase assays demonstrated interactions of SNHG5 with miR-92a-3p and BTG2.AGS cells were transfected with SNHG5 overexpression and miR-92a-3p knockdown models.Various assays,including CCK-8,colony formation,scratch wound healing,and Transwell assays,were used to determine cell proliferation and migration.An experimental model of a xenograft mouse was used to determine in vivo tumor growth.At the same time histological changes were evaluated by hematoxylin and eosin staining,with western blot analysis used to evaluate signaling pathway protein expression.RESULTS BTG2 and SNHG5 were downregulated in GC tissues,and miR-92a-3p was upregulated.Overexpression of SNHG5 or knockdown of miR-92a-3p reduced GC cell proliferation and migration,and increased BTG2 expression while decreasing PI3K/AKT signaling activity.The dual-luciferase assays demonstrated direct binding of miR-92a-3p to SNHG5 and BTG2.Tumor volume and weight were significantly reduced in mice transplanted with AGS cells treated with miR-92a-3p inhibitor or SNHG5 overexpression compared with control AGS cells.Hematoxylin and eosin staining revealed that treated tumors exhibited degenerative characteristics,including irregular morphology and nucleolysis.CONCLUSION LncRNA SNHG5 inhibited GC cell growth and migration by modulating the PI3K/AKT pathway via the miR-92a-3p/BTG2 axis.展开更多
基金supported by the National Natural Science Foundation of China (No. 52374292)China Baowu Low Carbon Metallurgy Innovation Foundation, China (No. BWLCF202309)the Natural Science Foundation of Changsha City, China (No. KQ2208271)。
文摘Some active metal oxides(Al_(2)O_(3),TiO_(2),and Cr_(2)O_(3))were selected as dopants to the Al_(2)O_(3)-based ceramic shells for investment casting of K417G superalloy.The effects of dopant types and contents(0,2,5,and 8 wt.%)on the wettability and interfacial reaction between the alloy and shell were investigated by a sessile-drop experiment.The results show that increasing the Al_(2)O_(3) doping contents(0−8 wt.%)reduces the porosity(21.74%−10.08%)and roughness(3.22−1.34μm)of the shell surface.The increase in Cr_(2)O_(3) dopant content(2−8 wt.%)further exacerbates the interfacial reaction,leading to an increase in the thickness of the reaction layer(2.6−3.1μm)and a decrease in the wetting angle(93.9°−91.0°).The addition of Al_(2)O_(3) and TiO_(2) dopants leads to the formation of Al_(2)TiO_(5) composite oxides in the reaction products,which effectively inhibits the interfacial reaction.The increase in TiO_(2) dopant contents(0−8 wt.%)further promotes the formation of Al_(2)TiO_(5),which decreases the thickness of the interfacial reaction layer(3.9−1.2μm)and increases the wetting angle(95.0°−103.8°).The introduced dopants enhance the packing density of the shell surface,while simultaneously suppress the diffusion of active metal elements from the alloy matrix to the interface.
基金funded by Yunnan Youth Top-notch Talent Support Program(YNWR-QNBJ2018-173)Agricultural Joint project of Yunnan Provincial S&T Programs(202301BD070001-195)+2 种基金S&T project of Yunnan provincial finance(K212020001-01)supported by Yunnan Province Education Department’s Engineering Research Center of Eco-friendly Products from Yunnan Characteristic Edible FungiYunnan Province Yongsheng County Farmer Academician Technology service station.
文摘Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.
基金funded by the Clinical Research Project(No.2024LC2432)the National Natural Science Foundation of China(No.82071515)the Key Research and Development Program of Shaanxi Province(No.2024SF-YBXM-061).
文摘Background:Depression,a prevalent mental health disorder,benefits from traditional Chinese medicine(TCM).Echinacoside(ECH),a natural phenolic compound extracted from Cistanche tubulosa and Echinacea angustifolia,exhibits neuroprotective and antioxidant properties.However,research on the potential mechanism of ECH’s antidepressant activity is limited.This study explored the antidepressant potential of ECH in mice subjected to chronic unpredictable mild stress(CUMS)and its underlying molecular mechanisms.Methods:Mice received ECH(10,20,40 mg/kg/d,i.p.)during the last 14 days of a 28-day CUMS protocol.The therapeutic effect was assessed via the sucrose preference test(SPT),tail suspension test(TST)and forced swim test(FST).Hematoxylin-eosin(H&E)and Nissl staining were employed to evaluate the changes of neuronal injury in hippocampus.Network pharmacology was used to explore the potential targets and pathway enrichment in ECH-mediated antidepression.The expression changes of PI3K/AKT/Nrf2/HO-1 were evaluated by Western blotting.Furthermore,the neuroprotection effects of ECH were assessed on cultured primary neurons injured by corticosterone(CORT)using CCK-8 assay.Results:The results indicated that ECH significantly alleviated depression-like behaviors in CUMS mice characterized as the improved sucrose intake in SPT,reduced immobility duration in TST and FST,reversed weight loss and hippocampal neuronal injury induced after CUMS.PI3K/AKT was selected as core targets by network pharmacology and supported by molecular docking and dynamics simulations.WB results indicated that ECH administration offered neuroprotection by recovering the expression levels of p-PI3K,p-AKT,Nrf2,and HO-1 in CUMS mice hippocampus.Moreover,ECH rescued CORT-induced neuron death in vitro by activating PI3K/AKT/Nrf2/HO-1 pathway,which was abolished by PI3K inhibitor LY294002.Conclusion:These findings demonstrated that ECH alleviated depressive-like behaviors via PI3K/AKT/Nrf2/HO-1 activation,highlighting its potential as a novel antidepressant.
基金supported by the China Agriculture Research System(CARS-35-PIG)the National Natural Science Foundation of China(32272847,U22A20516)+1 种基金the National Key Research and Development Program of China(No.2021YFF1000602)the Key Research and Development Program of Shaanxi Province(No.2022ZDLNY01–04)。
文摘Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.
基金Supported by Guangzhou Science and Technology Bureau Research Fund:the Mechanism of Action of Huangqi Guizhi Decoction on Precancerous Lesions in Cag Rats was Studied based on the Phosphatidylinositol 3-Kinase-Protein Kinase B-Mechanistic Target of Rapamycin Complex 2 Pathway(No.202102080643)Guangzhou Traditional Chinese Medicine and Integrative Medicine Research Project:Observation on the Therapeutic Effect of Wenyang Jianpi Ointment on Chronic Atrophic Gastritis of Spleen and Stomach Weakness Type and Study on its Regulatory Effect on Transforming Growth Factor Beta 3(No.20222A010079)Panyu District Science and Technology Project:the Mechanism by which the Modified Huangqi Guizhi Decoction Regulates the Transforming Growth Factor-β3 Signaling Pathway to Improve Precancerous Lesions in Rats with Chronic Atrophic Gastritis(No.2020-Z04-025)。
文摘OBJECTIVE:To investigate the effects of Jiawei Huangqi Guizhi decoction(加味黄芪桂枝汤)on chronic atrophic gastritis(CAG)in rats and its modulation of the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin complex 2(PI3K/Akt/m TORC2)signaling pathway.METHODS:CAG was induced in rats and treated with high-,medium-,or low-dose Jiawei Huangqi Guizhi decoction.Gastric histopathology was observed by hematoxylin and eosin staining.Serum levels of gastrin,PI3K,Akt,and m TORC2 were detected by enzyme-linked immunosorbent assay.Gene and protein expression levels were analyzed by reverse transcription polymerase chain reaction and western blot.RESULTS:The decoction alleviated gastric mucosal injury,reduced inflammation,and restored epithelial structure.It regulated PI3K,Akt,and m TORC2 expression at both m RNA and protein levels.CONCLUSION:Jiawei Huangqi Guizhi decoction may prevent CAG progression by improving gastric tissue and modulating the PI3K/Akt/m TORC2 signaling pathway.
文摘BACKGROUND Gastric cancer(GC)is a widespread malignancy and associated with high rates of morbidity and mortality worldwide.AIM To examine the functional role of long non-coding RNAs small nucleolar RNA host gene 5(SNHG5)and its regulation of miR-92a-3p and B-cell translocation gene 2(BTG2)in GC progression.METHODS Quantitative reverse transcription PCR and western blot analysis determined the expression of SNHG5,miR-92a-3p,and BTG2 in GC and adjacent non-neoplastic mucosa.Dual-luciferase assays demonstrated interactions of SNHG5 with miR-92a-3p and BTG2.AGS cells were transfected with SNHG5 overexpression and miR-92a-3p knockdown models.Various assays,including CCK-8,colony formation,scratch wound healing,and Transwell assays,were used to determine cell proliferation and migration.An experimental model of a xenograft mouse was used to determine in vivo tumor growth.At the same time histological changes were evaluated by hematoxylin and eosin staining,with western blot analysis used to evaluate signaling pathway protein expression.RESULTS BTG2 and SNHG5 were downregulated in GC tissues,and miR-92a-3p was upregulated.Overexpression of SNHG5 or knockdown of miR-92a-3p reduced GC cell proliferation and migration,and increased BTG2 expression while decreasing PI3K/AKT signaling activity.The dual-luciferase assays demonstrated direct binding of miR-92a-3p to SNHG5 and BTG2.Tumor volume and weight were significantly reduced in mice transplanted with AGS cells treated with miR-92a-3p inhibitor or SNHG5 overexpression compared with control AGS cells.Hematoxylin and eosin staining revealed that treated tumors exhibited degenerative characteristics,including irregular morphology and nucleolysis.CONCLUSION LncRNA SNHG5 inhibited GC cell growth and migration by modulating the PI3K/AKT pathway via the miR-92a-3p/BTG2 axis.
