Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context...Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context still unclear.Methods:The colorectal carcinoma cell lines HCT116 and SW620 were exposed to TNF-αfor a period of 24 h to instigate an inflammatory response.Subsequent assessments were conducted to measure the expression of inflammatory cytokines,the activity within the p38 mitogen-activated protein kinase(p38 MAPK)and Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway(PI3K/AKT)signaling cascades.Transcriptome sequencing and subsequent integrative analysis with the Cancer Genome Atlas(TCGA)program database revealed a significant downregulation of the key factor MAD2L2.Enhancement of MAD2L2 expression was facilitated via lentiviral vector-mediated transfection.The influence of this overexpression on TNF-α-prompted inflammation,intracellular signaling pathways,and the migratory and invasive behaviors of the colorectal cancer cells was then scrutinized.Results:TNF-αtreatment significantly increased the expression of Interleukin-1 beta(IL-1β)and Interleukin-6(IL-6),activated the MAPK p38 and PI3K/AKT signaling pathways,and enhanced cell migration and invasion.A decrease in MAD2L2 expression was observed following TNF-αtreatment.However,overexpression of MAD2L2 reversed the effects of TNF-α,reducing IL-1βand IL-6 levels,attenuating PI3K/AKT pathway activation,and inhibiting cell migration and invasion.Conclusions:Overexpression of MAD2L2 attenuates the pro-inflammatory effects of TNF-α,suggesting that MAD2L2 plays a protective role against TNF-α-induced migration and invasion of colorectal carcinoma cells.Therefore,MAD2L2 holds potential as a therapeutic target in the treatment of colorectal cancer.展开更多
Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifical...Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifically up-regulated in Schwann cells.Furthermore,using Schwann cell-specific Runx2 knocko ut mice,we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent.Changes observed in Runx2 knoc kout mice include increased prolife ration of Schwann cells,impaired Schwann cell migration and axonal regrowth,reduced re-myelination of axo ns,and a block in macrophage clearance in the late stage of regeneration.Taken together,our findings indicate that Runx2 is a key regulator of Schwann cell plasticity,and therefore peripheral nerve repair.Thus,our study shows that Runx2 plays a major role in Schwann cell migration,re-myelination,and peripheral nerve functional recovery following injury.展开更多
BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations ...BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.展开更多
Exploring carbon emission effects based on the evolution of residents’ dietary structure to achieve the carbon neutrality goal and mitigate climate change is an important task.This study took China as the research ob...Exploring carbon emission effects based on the evolution of residents’ dietary structure to achieve the carbon neutrality goal and mitigate climate change is an important task.This study took China as the research object(data excluding Hong Kong,Macao and Taiwan) and used the carbon emission coefficient method to quantitatively measure the food carbon emissions from 1987–2020,then analyzed the carbon emission effects under the evolution of dietary structure.The results showed that during the study period,the Chinese dietary structure gradually changed to a high-carbon consumption pattern.The dietary structure of urban residents developed to a balanced one,while that of rural residents developed to a high-quality one.During the study period,the per capita food carbon emissions and total food consumption of Chinese showed an increasing trend.The per capita food carbon emissions of residents in urban and rural showed an overall upward trend.The total food carbon emissions in urban increased significantly,while that in rural increased first and then decreased.The influence of beef and mutton on carbon emissions is the highest in dietary structure.Compared with the balanced dietary pattern,the food carbon emissions of Chinese residents had not yet reached the peak,but were evolving to a high-carbon consumption pattern.展开更多
Objective:To study the effect of plumbagin(PL)on the migration and invasion of human hepatocellular carcinoma(HCC)cells and its possible mechanism.Methods:The cell counting kit(CCK-8)was used to detect the effects of ...Objective:To study the effect of plumbagin(PL)on the migration and invasion of human hepatocellular carcinoma(HCC)cells and its possible mechanism.Methods:The cell counting kit(CCK-8)was used to detect the effects of different concentrations of plumbagin on the proliferation of human hepatocellular carcinoma Huh-7 and LM3 cells.The effect of plumbagin on the migration ability of Huh-7 and LM3 cells was detected by scratch test and Transwell migration test,and the effect of on the invasion ability of Huh-7 and LM3 cells was detected by Transwell invasion test.Western Blot was used to detect the expression of E-cadherin,N-cadherin,matrix metalloproteinase-2 and related proteins in JAK2/STAT3 signaling pathway in Huh-7 and LM3 cells.Results:Plumbagin could inhibit the proliferation of Huh-7 and LM3 cells in a time-and concentration-dependent manner.Plumbagin inhibited the migration and invasion of Huh-7 and LM3 cells in a concentration dependent manner,and it can down-regulate the expression of N-cadherin and MMP-2 protein,up-regulate the expression of E-cadherin protein,and inhibit the activation of JAK2/STAT3 signaling pathway.Conclusion:Plumbagin can inhibit the migration and invasion of human hepatocellular carcinoma Huh-7 and LM3 cells,and the molecular mechanism of this process may be related to the inhibition of JAK2/STAT3 signaling pathway activation.展开更多
The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).Whil...The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).While such DRFEs have been explored at low to middle latitudes,the aerosol impacts on pan-Arctic ecosystems and the contributions by anthropogenic and natural emission sources remain less quantified.Here,we perform regional simulations at 0.2o×0.2ousing a well-validated vegetation model(Yale Interactive terrestrial Biosphere,YIBs)in combination with multi-source of observations to quantify the impacts of aerosol DRFEs on the net primary productivity(NPP)in the pan-Arctic during 2001-19.Results show that aerosol DRFEs increase pan-Arctic NPP by 2.19 Pg C(12.8%)yr^(-1)under clear-sky conditions,in which natural and anthropogenic sources contribute to 8.9% and 3.9%,respectively.Under all-sky conditions,such DRFEs are largely dampened by cloud to only 0.26 Pg C(1.24%)yr^(-1),with contributions of 0.65% by natural and 0.59% by anthropogenic species.Natural aerosols cause a positive NPP trend of 0.022% yr^(-1)following the increased fire activities in the pan-Arctic.In contrast,anthropogenic aerosols induce a negative trend of-0.01% yr^(-1)due to reduced emissions from the middle latitudes.Such trends in aerosol DRFEs show a turning point in the year of 2007 with more positive NPP trends by natural aerosols but negative NPP trends by anthropogenic aerosols thereafter.Though affected by modeling uncertainties,this study suggests a likely increasing impact of aerosols on terrestrial ecosystems in the pan-Arctic under global warming.展开更多
[Objectives]To study the effects of JAG-1 on silencing TRAIP(tumor necrosis factor receptor associated factor interaction protein)after regulating Notch signaling pathway on the proliferation and migration of gastric ...[Objectives]To study the effects of JAG-1 on silencing TRAIP(tumor necrosis factor receptor associated factor interaction protein)after regulating Notch signaling pathway on the proliferation and migration of gastric adenocarcinoma cells.[Methods]Gastric adenocarcinoma cells were categorized into si-NC+DMSO(control+DMSO),si-TRAIP#1+DMSO(transfected with TRAIP+DMSO),si-NC+JAG-1(control+JAG-1),and si-TRAIP#1+JAG-1(transfected with TRAIP+JAG-1),and the proliferation of the cells was detected by CCK-8 assay and plate colony formation assay.Transwell assay was used to detect cell migration,and Western blot was adopted to detect the expression of proliferation-associated protein CyclinD1,migration-associated protein MMP2,and key proteins of Notch signaling pathway Notch1,Hes1 and Jagged1.[Results]Compared with siTRAIP#1+DMSO,the gastric adenocarcinoma cells in si-TRAIP#1+JAG-1 group showed increased proliferation and migration(P<0.05),and there was a significant increase in the expression of CyclinD1,MMP2,Notch1,Hes1,and Jagged1(P<0.05).[Conclusions]After TRAIP knockdown,JAG-1 increased not only the proliferation and migration ability of gastric adenocarcinoma cells,but also the expression of key proteins of Notch signaling pathway Notch1,Hes1,and Jagged1.展开更多
In unconsolidated sandstone reservoirs,presence of numerous movable grains and a complex grain size composition necessitates a clear understanding of the physical clogging process for effective groundwater recharge in...In unconsolidated sandstone reservoirs,presence of numerous movable grains and a complex grain size composition necessitates a clear understanding of the physical clogging process for effective groundwater recharge in groundwater-source heat pump systems.To investigate this,a series of seepage experiments was conducted under in situ stress conditions using unconsolidated sandstone samples with varying grain compositions.The clogging phenomenon arises from the combined effects of grain migration and compaction,wherein the migration of both original and secondary crushed fine-grain particles blocks the seepage channels.Notably,grain composition influences the migration and transport properties of the grains.For samples composed of smaller grains,the apparent permeability demonstrates a transition from stability to decrease.In contrast,samples with larger grains experience a skip at the stability stage and directly enter the decrease stage,with a minor exception of a slight increase observed.Furthermore,a unique failure mode characterized by diameter shrinkage in the upper part of the sample is observed due to the combined effects of grain migration and in situ stress-induced compaction.These testing results contribute to a better understanding of the clogging mechanism caused by the coupled effects of grain migration and compaction during groundwater recharge in unconsolidated sandstone reservoirs used in groundwater-source heat pump systems.展开更多
Birds exhibit a high degree of migratory diversity,which is influenced by various ecological factors and life history strategies.Conducting studies on tropical bird migration,of which research is scarce,and comparing ...Birds exhibit a high degree of migratory diversity,which is influenced by various ecological factors and life history strategies.Conducting studies on tropical bird migration,of which research is scarce,and comparing it with temperate birds can enhance our understanding of bird migration behaviour and its underlying mecha-nisms.In this study,we explored the migration behaviour of a breeding population of the Barn Swallow(Hirundo rustica)in Zhanjiang,southern China,a region located in the northern tropics,using light-level geolocators.From 2021 to 2023,we deployed geolocators on 92 breeding swallows and retrieved geolocators successfully from 23 individuals.These swallows all exhibited migratory behaviour,and wintering on various islands in Southeast Asia.They displayed sex differences in their wintering locations.All males concentrated in Borneo,while females primarily chose Borneo but also dispersed to the Philippines,South China Sea,and Vietnam for wintering.The studied swallow population adopted a seasonal migration pattern of“indirect in autumn,direct in spring”,bypassing the ecological barrier of the South China Sea in autumn and tending to directly cross it in spring migration.Moreover,the distance and duration of autumn migration was significantly longer than those of the spring migration.Compared to temperate Barn Swallows,the Barn Swallow population breeding in Zhanjiang adopts a pattern of“intra-tropical migration”and initiates autumn migration earlier.The formation of their migration pattern may be limited by ecological and physiological factors.展开更多
The detection of hypersonic targets usually confronts range migration(RM)issue before coherent integration(CI).The traditional methods aiming at correcting RM to obtain CI mainly considers the narrow-band radar condit...The detection of hypersonic targets usually confronts range migration(RM)issue before coherent integration(CI).The traditional methods aiming at correcting RM to obtain CI mainly considers the narrow-band radar condition.However,with the increasing requirement of far-range detection,the time bandwidth product,which is corresponding to radar’s mean power,should be promoted in actual application.Thus,the echo signal generates the scale effect(SE)at large time bandwidth product situation,influencing the intra and inter pulse integration performance.To eliminate SE and correct RM,this paper proposes an effective algorithm,i.e.,scaled location rotation transform(ScLRT).The ScLRT can remove SE to obtain the matching pulse compression(PC)as well as correct RM to complete CI via the location rotation transform,being implemented by seeking the actual rotation angle.Compared to the traditional coherent detection algorithms,Sc LRT can address the SE problem to achieve better detection/estimation capabilities.At last,this paper gives several simulations to assess the viability of ScLRT.展开更多
Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF i...Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.展开更多
The Chepaizi Exploration Area,Junggar Basin(NW China)holds substantial importance for seismic exploration endeavors,yet it poses notable challenges due to the intricate nature of its subsurface and near-surface condit...The Chepaizi Exploration Area,Junggar Basin(NW China)holds substantial importance for seismic exploration endeavors,yet it poses notable challenges due to the intricate nature of its subsurface and near-surface conditions.To address these challenges,we introduce a novel and comprehensive workflow tailored to evaluate and optimize seismic acquisition geometries while considering the impacts of near-surface viscosity.By integrating geological knowledge,historical seismic data,and subsurface modeling,we conduct simulations employing the visco-acoustic wave equation and reverse-time migration to produce detailed subsurface images.The quality of these images is quantitatively evaluated using a local similarity metric,a pivotal tool for evaluating the accuracy of seismic imaging.The culmination of this workflow results in an automated optimization strategy for acquisition geometries that enhances subsurface exploration.Our proposed methodology underscores the importance of incorporating near-surface viscosity effects in seismic imaging,offering a robust framework for improving the accuracy of subsurface imaging.Herein,we aim to contribute to the advancement of seismic imaging methodologies by providing valuable insights for achieving high-quality seismic exploration outcomes in regions characterized by complex subsurface and near-surface conditions.展开更多
During the 1950s the Hula wetlands and old lake were drained and the land converted utilization to agriculture and ecotourism. As a result of the drainage, the Peat Soil was exposed to atmospheric oxygen. The geochemi...During the 1950s the Hula wetlands and old lake were drained and the land converted utilization to agriculture and ecotourism. As a result of the drainage, the Peat Soil was exposed to atmospheric oxygen. The geochemical environment was modified from reductive to oxidative and the Nitrogen in it was converted from Ammonium to Nitrate. Intensive migration of Nitrate from the Hula Valley induced a national concern of water quality deterioration in the lake which was dissipated when Nitrogen deficiency was developed in Lake Kinneret. Forty years after drainage the ecosystem structure was renovated (Hula Project, HP) aimed at agricultural management and nutrient migration reduction. The paper examines through evaluation of the ecological data record (1993-2018) the impact of hydrological changes, attributed to the HP implementation on nutrient dynamics within surface waters in the Hula Valley. It is suggested that soil moisture elevation by irrigation in summer reduced Phosphorus and enhanced Nitrate concentrations.展开更多
It was a 36-year-old patient, 5th Pregnancy, 5th Delivery, 4 live children, and I deceased, had a consultation in the department for the removal of implants. Questioning revealed that she had had the implant three yea...It was a 36-year-old patient, 5th Pregnancy, 5th Delivery, 4 live children, and I deceased, had a consultation in the department for the removal of implants. Questioning revealed that she had had the implant three years ago without medical follow-up. It was in view of the difficulties in extracting the capsule that the chest X-ray and CT scan carried out concluded that the implant had migrated into a branch of the left pulmonary artery. Therapeutic abstention has been the attitude of cardiovascular surgeons.展开更多
The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1...The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.展开更多
Differences in forest attributes and carbon sequestration of each organ and layer between broadleaved and conifer forests of central and outer urban areas are not well-defined,hindering the precise management of urban...Differences in forest attributes and carbon sequestration of each organ and layer between broadleaved and conifer forests of central and outer urban areas are not well-defined,hindering the precise management of urban forests and improvement of function.To clarify the effect of two forest types with different urbanization intensities,we determined differences in vegetation composition and diversity,structural traits,and carbon stocks of 152 plots(20 m×20 m)in urban park forests in Changchun,which had the largest green quantity and carbon density effectiveness.We found that 1.1-fold thicker and healthier trees,and 1.6-to 2.0-fold higher,healthier,denser,and more various shrubs but with sparser trees and herbs occurred in the central urban forests(p<0.05)than in the outer forests.The conifer forests exhibited 30–70%obviously higher tree aboveground carbon sequestration(including stem and leaf)and 20%bigger trees,especially in the outer forests(p<0.05).In contrast,1.1-to 1.5-fold higher branch stocks,healthier and more diverse trees were found in broadleaved forests of both the inner and outer forests(p<0.05).Plant size and dominant species had similarly important roles in carbon stock improvement,especially big-sized woody plants and Pinus tabuliformis.In addition,a higher number of deciduous or needle species positively affected the broadleaved forest of the central urban area and conifer forest of the outer urban area,respectively.These findings can be used to guide precise management and accelerate the improvement of urban carbon function in Northeast China in the future.展开更多
Wide-bandgap(>1.7 eV)perovskites suffer from severe light-induced phase segregation due to high bromine content,causing irreversible damage to devices stability.However,the strategies of suppressing photoinduced ph...Wide-bandgap(>1.7 eV)perovskites suffer from severe light-induced phase segregation due to high bromine content,causing irreversible damage to devices stability.However,the strategies of suppressing photoinduced phase segregation and related mechanisms have not been fully disclosed.Here,we report a new passivation agent 4-aminotetrahydrothiopyran hydrochloride(4-ATpHCl)with multifunctional groups for the interface treatment of a 1.77-eV wide-bandgap perovskite film.4-ATpH^(+)impeded halogen ion migration by anchoring on the perovskite surface,leading to the inhibition of phase segregation and thus the passivation of defects,which is ascribed to the interaction of 4-ATpH^(+)with perovskite and the formation of low-dimensional perovskites.Finally,the champion device achieved an efficiency of 19.32%with an open-circuit voltage(V_(OC))of 1.314 V and a fill factor of 83.32%.Moreover,4-ATpHCl modified device exhibited significant improved stability as compared with control one.The target device maintained 80%of its initial efficiency after 519 h of maximum power output(MPP)tracking under 1 sun illumination,however,the control device showed a rapid decrease in efficiency after 267 h.Finally,an efficiency of 27.38%of the champion 4-terminal all-perovskite tandem solar cell was achieved by mechanically stacking this wide-bandgap top subcell with a 1.25-eV low-bandgap perovskite bottom subcell.展开更多
Objectives:Sciadopitysin(SP)is aflavonoid in Ginkgo biloba that exhibits various pharmacological activities.This study aimed to investigate its antitumor effects and the underlying molecular mechanism of SP in hepatoce...Objectives:Sciadopitysin(SP)is aflavonoid in Ginkgo biloba that exhibits various pharmacological activities.This study aimed to investigate its antitumor effects and the underlying molecular mechanism of SP in hepatocellular carcinoma(HCC)cells.Methods:Network pharmacology was used for target prediction analysis.Cell Counting Kit-8(CCK-8)assay was used to test the cell viability.Flow cytometry was used to test the cell cycle distribution,apoptosis status,and reactive oxygen species(ROS)levels.Transwell and wound-healing assay was used to test the migration effect of SP on HepG2 cells.Western Blot assay was used to test the expression levels of proteins.Results:Network pharmacology analysis results showed that the mitogen-activated protein kinase(MAPK)and other signaling pathways are involved in the SP anti-HCC biological process.CCK-8 assay results demonstrated that SP showed an obvious killing effect on three types of HCC cells and low cytotoxic effect on normal cells.Western Blot andflow cytometry results showed that SP regulated MAPK/signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa-B(NF-κB)signaling pathway to induce mitochondrion-dependent apoptosis in HepG2 cells.Additionally,SP can arrest the G0/G1 phase cell cycle via the protein kinase B(AKT)/p21/p27/cyclin-dependent kinase(CDK)/Cyclin signaling pathway.Wound healing and transwell assays showed that SP inhibited cell motility and invasion through the AKT/glycogen synthase kinase3β(GSK-3β)/vimentin/β-catenin signaling pathway.Conclusion:Thesefindings demonstrated that SP induced mitochondrion-dependent apoptosis,arrested cell cycle in the G0/G1 phase,and inhibited cell migration by regulating the ROS-mediated signaling pathway in HepG2 cells.Thus,SP could serve as a therapeutic agent for the treatment of human HCC.展开更多
Background:The role of Claudin-1 in tongue squamous cell carcinoma(TSCC)metastasis needs further clarification,particularly its impact on cell migration.Herein,our study aims to investigate the role of Claudin-1 in TS...Background:The role of Claudin-1 in tongue squamous cell carcinoma(TSCC)metastasis needs further clarification,particularly its impact on cell migration.Herein,our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms.Methods:36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1.Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells.Claudin-1 knockdown cell lines were established using short hairpin RNA transfection.Migration effects were assessed through wound healing assays.Furthermore,the expression of EMTassociated molecules was measured via western blotting.Results:Claudin-1 expression decreased as TSCC malignancy increased.Adenosine monophosphate–activated protein kinase(AMPK)activation led to increased Claudin-1 expression and membrane translocation,inhibiting TSCC cell migration and epithelial–mesenchymal transition(EMT).Conversely,Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation.Conclusions:Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.展开更多
Climate change is the most significant threat to public health and exerts myriad influences on health,including the occurrence of extreme temperature events.Studies have demonstrated that populations will experience s...Climate change is the most significant threat to public health and exerts myriad influences on health,including the occurrence of extreme temperature events.Studies have demonstrated that populations will experience significantly severe cold waves in the future^([1]),increasing the risk of respiratory diseases.展开更多
基金supported by the Ningxia Hui Autonomous Region key research and development programs(Grant No.2021BEG03084)the National Natural Science Foundation of China(Grant No.31660336).
文摘Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context still unclear.Methods:The colorectal carcinoma cell lines HCT116 and SW620 were exposed to TNF-αfor a period of 24 h to instigate an inflammatory response.Subsequent assessments were conducted to measure the expression of inflammatory cytokines,the activity within the p38 mitogen-activated protein kinase(p38 MAPK)and Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway(PI3K/AKT)signaling cascades.Transcriptome sequencing and subsequent integrative analysis with the Cancer Genome Atlas(TCGA)program database revealed a significant downregulation of the key factor MAD2L2.Enhancement of MAD2L2 expression was facilitated via lentiviral vector-mediated transfection.The influence of this overexpression on TNF-α-prompted inflammation,intracellular signaling pathways,and the migratory and invasive behaviors of the colorectal cancer cells was then scrutinized.Results:TNF-αtreatment significantly increased the expression of Interleukin-1 beta(IL-1β)and Interleukin-6(IL-6),activated the MAPK p38 and PI3K/AKT signaling pathways,and enhanced cell migration and invasion.A decrease in MAD2L2 expression was observed following TNF-αtreatment.However,overexpression of MAD2L2 reversed the effects of TNF-α,reducing IL-1βand IL-6 levels,attenuating PI3K/AKT pathway activation,and inhibiting cell migration and invasion.Conclusions:Overexpression of MAD2L2 attenuates the pro-inflammatory effects of TNF-α,suggesting that MAD2L2 plays a protective role against TNF-α-induced migration and invasion of colorectal carcinoma cells.Therefore,MAD2L2 holds potential as a therapeutic target in the treatment of colorectal cancer.
基金supported by the National Natural Science Foundation of China,No.82104795 (to RH)。
文摘Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifically up-regulated in Schwann cells.Furthermore,using Schwann cell-specific Runx2 knocko ut mice,we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent.Changes observed in Runx2 knoc kout mice include increased prolife ration of Schwann cells,impaired Schwann cell migration and axonal regrowth,reduced re-myelination of axo ns,and a block in macrophage clearance in the late stage of regeneration.Taken together,our findings indicate that Runx2 is a key regulator of Schwann cell plasticity,and therefore peripheral nerve repair.Thus,our study shows that Runx2 plays a major role in Schwann cell migration,re-myelination,and peripheral nerve functional recovery following injury.
基金National Natural Science Foundation of China,No.72101236China Postdoctoral Science Foundation,No.2022M722900+1 种基金Collaborative Innovation Project of Zhengzhou City,No.XTCX2023006Nursing Team Project of the First Affiliated Hospital of Zhengzhou University,No.HLKY2023005.
文摘BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.
基金Under the auspices of National Natural Science Foundation of China(No.42171230)。
文摘Exploring carbon emission effects based on the evolution of residents’ dietary structure to achieve the carbon neutrality goal and mitigate climate change is an important task.This study took China as the research object(data excluding Hong Kong,Macao and Taiwan) and used the carbon emission coefficient method to quantitatively measure the food carbon emissions from 1987–2020,then analyzed the carbon emission effects under the evolution of dietary structure.The results showed that during the study period,the Chinese dietary structure gradually changed to a high-carbon consumption pattern.The dietary structure of urban residents developed to a balanced one,while that of rural residents developed to a high-quality one.During the study period,the per capita food carbon emissions and total food consumption of Chinese showed an increasing trend.The per capita food carbon emissions of residents in urban and rural showed an overall upward trend.The total food carbon emissions in urban increased significantly,while that in rural increased first and then decreased.The influence of beef and mutton on carbon emissions is the highest in dietary structure.Compared with the balanced dietary pattern,the food carbon emissions of Chinese residents had not yet reached the peak,but were evolving to a high-carbon consumption pattern.
基金Program of Guangxi Natural Science Foundation(No.2019GXNSDA 245003)The second batch of"Qihuang Project"high-level talent team cultivation project of Guangxi University of Traditional Chinese Medicine(No.2021001)+1 种基金Doctoral Research Initiation Fund of Guangxi University of Traditional Chinese Medicine(2020BS027)2021 Guangxi Postgraduate Innovation Project(No.YCXJ2021007)。
文摘Objective:To study the effect of plumbagin(PL)on the migration and invasion of human hepatocellular carcinoma(HCC)cells and its possible mechanism.Methods:The cell counting kit(CCK-8)was used to detect the effects of different concentrations of plumbagin on the proliferation of human hepatocellular carcinoma Huh-7 and LM3 cells.The effect of plumbagin on the migration ability of Huh-7 and LM3 cells was detected by scratch test and Transwell migration test,and the effect of on the invasion ability of Huh-7 and LM3 cells was detected by Transwell invasion test.Western Blot was used to detect the expression of E-cadherin,N-cadherin,matrix metalloproteinase-2 and related proteins in JAK2/STAT3 signaling pathway in Huh-7 and LM3 cells.Results:Plumbagin could inhibit the proliferation of Huh-7 and LM3 cells in a time-and concentration-dependent manner.Plumbagin inhibited the migration and invasion of Huh-7 and LM3 cells in a concentration dependent manner,and it can down-regulate the expression of N-cadherin and MMP-2 protein,up-regulate the expression of E-cadherin protein,and inhibit the activation of JAK2/STAT3 signaling pathway.Conclusion:Plumbagin can inhibit the migration and invasion of human hepatocellular carcinoma Huh-7 and LM3 cells,and the molecular mechanism of this process may be related to the inhibition of JAK2/STAT3 signaling pathway activation.
基金jointly supported by the National Key Research and Development Program of China(Grant No.2022YFE0106500)Jiangsu Science Fund for Distinguished Young Scholars(Grant No.BK20200040)。
文摘The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).While such DRFEs have been explored at low to middle latitudes,the aerosol impacts on pan-Arctic ecosystems and the contributions by anthropogenic and natural emission sources remain less quantified.Here,we perform regional simulations at 0.2o×0.2ousing a well-validated vegetation model(Yale Interactive terrestrial Biosphere,YIBs)in combination with multi-source of observations to quantify the impacts of aerosol DRFEs on the net primary productivity(NPP)in the pan-Arctic during 2001-19.Results show that aerosol DRFEs increase pan-Arctic NPP by 2.19 Pg C(12.8%)yr^(-1)under clear-sky conditions,in which natural and anthropogenic sources contribute to 8.9% and 3.9%,respectively.Under all-sky conditions,such DRFEs are largely dampened by cloud to only 0.26 Pg C(1.24%)yr^(-1),with contributions of 0.65% by natural and 0.59% by anthropogenic species.Natural aerosols cause a positive NPP trend of 0.022% yr^(-1)following the increased fire activities in the pan-Arctic.In contrast,anthropogenic aerosols induce a negative trend of-0.01% yr^(-1)due to reduced emissions from the middle latitudes.Such trends in aerosol DRFEs show a turning point in the year of 2007 with more positive NPP trends by natural aerosols but negative NPP trends by anthropogenic aerosols thereafter.Though affected by modeling uncertainties,this study suggests a likely increasing impact of aerosols on terrestrial ecosystems in the pan-Arctic under global warming.
基金Supported by the Chengde Medical University-National Natural Science Foundation Project Cultivation Fund(202114)Discipline Construction Fund of Chengde Medical College[(2023)No.2]Chengde Medical University-School-level Key Project Fund(201711).
文摘[Objectives]To study the effects of JAG-1 on silencing TRAIP(tumor necrosis factor receptor associated factor interaction protein)after regulating Notch signaling pathway on the proliferation and migration of gastric adenocarcinoma cells.[Methods]Gastric adenocarcinoma cells were categorized into si-NC+DMSO(control+DMSO),si-TRAIP#1+DMSO(transfected with TRAIP+DMSO),si-NC+JAG-1(control+JAG-1),and si-TRAIP#1+JAG-1(transfected with TRAIP+JAG-1),and the proliferation of the cells was detected by CCK-8 assay and plate colony formation assay.Transwell assay was used to detect cell migration,and Western blot was adopted to detect the expression of proliferation-associated protein CyclinD1,migration-associated protein MMP2,and key proteins of Notch signaling pathway Notch1,Hes1 and Jagged1.[Results]Compared with siTRAIP#1+DMSO,the gastric adenocarcinoma cells in si-TRAIP#1+JAG-1 group showed increased proliferation and migration(P<0.05),and there was a significant increase in the expression of CyclinD1,MMP2,Notch1,Hes1,and Jagged1(P<0.05).[Conclusions]After TRAIP knockdown,JAG-1 increased not only the proliferation and migration ability of gastric adenocarcinoma cells,but also the expression of key proteins of Notch signaling pathway Notch1,Hes1,and Jagged1.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFE0137200)National Natural Science Foundation of China(Grant Nos.52309147 and 52179114).
文摘In unconsolidated sandstone reservoirs,presence of numerous movable grains and a complex grain size composition necessitates a clear understanding of the physical clogging process for effective groundwater recharge in groundwater-source heat pump systems.To investigate this,a series of seepage experiments was conducted under in situ stress conditions using unconsolidated sandstone samples with varying grain compositions.The clogging phenomenon arises from the combined effects of grain migration and compaction,wherein the migration of both original and secondary crushed fine-grain particles blocks the seepage channels.Notably,grain composition influences the migration and transport properties of the grains.For samples composed of smaller grains,the apparent permeability demonstrates a transition from stability to decrease.In contrast,samples with larger grains experience a skip at the stability stage and directly enter the decrease stage,with a minor exception of a slight increase observed.Furthermore,a unique failure mode characterized by diameter shrinkage in the upper part of the sample is observed due to the combined effects of grain migration and in situ stress-induced compaction.These testing results contribute to a better understanding of the clogging mechanism caused by the coupled effects of grain migration and compaction during groundwater recharge in unconsolidated sandstone reservoirs used in groundwater-source heat pump systems.
基金supported by the National Natural Science Foundation of China(32101236,32270518)National Key R&D Program of China(2022YFF0802400).
文摘Birds exhibit a high degree of migratory diversity,which is influenced by various ecological factors and life history strategies.Conducting studies on tropical bird migration,of which research is scarce,and comparing it with temperate birds can enhance our understanding of bird migration behaviour and its underlying mecha-nisms.In this study,we explored the migration behaviour of a breeding population of the Barn Swallow(Hirundo rustica)in Zhanjiang,southern China,a region located in the northern tropics,using light-level geolocators.From 2021 to 2023,we deployed geolocators on 92 breeding swallows and retrieved geolocators successfully from 23 individuals.These swallows all exhibited migratory behaviour,and wintering on various islands in Southeast Asia.They displayed sex differences in their wintering locations.All males concentrated in Borneo,while females primarily chose Borneo but also dispersed to the Philippines,South China Sea,and Vietnam for wintering.The studied swallow population adopted a seasonal migration pattern of“indirect in autumn,direct in spring”,bypassing the ecological barrier of the South China Sea in autumn and tending to directly cross it in spring migration.Moreover,the distance and duration of autumn migration was significantly longer than those of the spring migration.Compared to temperate Barn Swallows,the Barn Swallow population breeding in Zhanjiang adopts a pattern of“intra-tropical migration”and initiates autumn migration earlier.The formation of their migration pattern may be limited by ecological and physiological factors.
基金supported by the National Natural Science Foundation of China(62101099)the Chinese Postdoctoral Science Foundation(2021M690558,2022T150100,2018M633352,2019T120825)+3 种基金the Young Elite Scientist Sponsorship Program(YESS20200082)the Aeronautical Science Foundation of China(2022Z017080001)the Open Foundation of Science and Technology on Electronic Information Control Laboratorythe Natural Science Foundation of Sichuan Province(2023NSFSC1386)。
文摘The detection of hypersonic targets usually confronts range migration(RM)issue before coherent integration(CI).The traditional methods aiming at correcting RM to obtain CI mainly considers the narrow-band radar condition.However,with the increasing requirement of far-range detection,the time bandwidth product,which is corresponding to radar’s mean power,should be promoted in actual application.Thus,the echo signal generates the scale effect(SE)at large time bandwidth product situation,influencing the intra and inter pulse integration performance.To eliminate SE and correct RM,this paper proposes an effective algorithm,i.e.,scaled location rotation transform(ScLRT).The ScLRT can remove SE to obtain the matching pulse compression(PC)as well as correct RM to complete CI via the location rotation transform,being implemented by seeking the actual rotation angle.Compared to the traditional coherent detection algorithms,Sc LRT can address the SE problem to achieve better detection/estimation capabilities.At last,this paper gives several simulations to assess the viability of ScLRT.
基金supported by the Key Program of Natural Science Foundation of Shaanxi Province,No.2021JZ-60(to HZ)。
文摘Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.
基金supported by the Research on Vibroseis Ultra-wideband Excitation Technology in Re-exploration Area of Quasi Western Margin(Project No.:SG22-44K)。
文摘The Chepaizi Exploration Area,Junggar Basin(NW China)holds substantial importance for seismic exploration endeavors,yet it poses notable challenges due to the intricate nature of its subsurface and near-surface conditions.To address these challenges,we introduce a novel and comprehensive workflow tailored to evaluate and optimize seismic acquisition geometries while considering the impacts of near-surface viscosity.By integrating geological knowledge,historical seismic data,and subsurface modeling,we conduct simulations employing the visco-acoustic wave equation and reverse-time migration to produce detailed subsurface images.The quality of these images is quantitatively evaluated using a local similarity metric,a pivotal tool for evaluating the accuracy of seismic imaging.The culmination of this workflow results in an automated optimization strategy for acquisition geometries that enhances subsurface exploration.Our proposed methodology underscores the importance of incorporating near-surface viscosity effects in seismic imaging,offering a robust framework for improving the accuracy of subsurface imaging.Herein,we aim to contribute to the advancement of seismic imaging methodologies by providing valuable insights for achieving high-quality seismic exploration outcomes in regions characterized by complex subsurface and near-surface conditions.
文摘During the 1950s the Hula wetlands and old lake were drained and the land converted utilization to agriculture and ecotourism. As a result of the drainage, the Peat Soil was exposed to atmospheric oxygen. The geochemical environment was modified from reductive to oxidative and the Nitrogen in it was converted from Ammonium to Nitrate. Intensive migration of Nitrate from the Hula Valley induced a national concern of water quality deterioration in the lake which was dissipated when Nitrogen deficiency was developed in Lake Kinneret. Forty years after drainage the ecosystem structure was renovated (Hula Project, HP) aimed at agricultural management and nutrient migration reduction. The paper examines through evaluation of the ecological data record (1993-2018) the impact of hydrological changes, attributed to the HP implementation on nutrient dynamics within surface waters in the Hula Valley. It is suggested that soil moisture elevation by irrigation in summer reduced Phosphorus and enhanced Nitrate concentrations.
文摘It was a 36-year-old patient, 5th Pregnancy, 5th Delivery, 4 live children, and I deceased, had a consultation in the department for the removal of implants. Questioning revealed that she had had the implant three years ago without medical follow-up. It was in view of the difficulties in extracting the capsule that the chest X-ray and CT scan carried out concluded that the implant had migrated into a branch of the left pulmonary artery. Therapeutic abstention has been the attitude of cardiovascular surgeons.
基金supported by the Natural Science Foundation of Xiamen City(3502Z20227307)the National Natural Science Foundation of China(81472458,82372809)the Special Fund for Public Welfare Research Institutes of Fujian Province(2023R1001001,2023R1001003,2023R1035).
文摘The high mortality rate associated with gastric cancer(GC)has resulted in an urgent need to identify novel therapeutic targets for GC.This study aimed to investigate whether GAIP interacting protein,C terminus 1(GIPC1)represents a therapeutic target and its regulating mechanism in GC.GIPC1 expression was elevated in GC tissues,liver metastasis tissues,and lymph node metastases.GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor(PDGFR)/PI3K/AKT signaling pathway,and inhibited the proliferation and migration of GC cells.Conversely,GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway,and promoted GC cell proliferation and migration.Furthermore,platelet-derived growth factor subunit BB(PDGF-BB)cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression.Moreover,GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice,while GIPC1 overexpression had contrasting effects.Taken together,our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.
基金the Youth Growth Technology Project,Science and Technology Department of Jilin Province(20230508130RC)Bureau of Forestry and Landscaping of Changchun.
文摘Differences in forest attributes and carbon sequestration of each organ and layer between broadleaved and conifer forests of central and outer urban areas are not well-defined,hindering the precise management of urban forests and improvement of function.To clarify the effect of two forest types with different urbanization intensities,we determined differences in vegetation composition and diversity,structural traits,and carbon stocks of 152 plots(20 m×20 m)in urban park forests in Changchun,which had the largest green quantity and carbon density effectiveness.We found that 1.1-fold thicker and healthier trees,and 1.6-to 2.0-fold higher,healthier,denser,and more various shrubs but with sparser trees and herbs occurred in the central urban forests(p<0.05)than in the outer forests.The conifer forests exhibited 30–70%obviously higher tree aboveground carbon sequestration(including stem and leaf)and 20%bigger trees,especially in the outer forests(p<0.05).In contrast,1.1-to 1.5-fold higher branch stocks,healthier and more diverse trees were found in broadleaved forests of both the inner and outer forests(p<0.05).Plant size and dominant species had similarly important roles in carbon stock improvement,especially big-sized woody plants and Pinus tabuliformis.In addition,a higher number of deciduous or needle species positively affected the broadleaved forest of the central urban area and conifer forest of the outer urban area,respectively.These findings can be used to guide precise management and accelerate the improvement of urban carbon function in Northeast China in the future.
基金financially supported by the National Key R&D Program of China (2022YFB4200304)the National Natural Science Foundation of China (52303347)+3 种基金the Fundamental Research Funds for the Central Universities (YJ2021157)the Engineering Featured Team Fund of Sichuan University (2020SCUNG102)open foundation of Guangxi Key Laboratory of Processing for Non-Ferrous Metals and Featured Materials, Guangxi University (2022GXYSOF05)the support from the National Natural Science Foundation of China (E30853YM19)
文摘Wide-bandgap(>1.7 eV)perovskites suffer from severe light-induced phase segregation due to high bromine content,causing irreversible damage to devices stability.However,the strategies of suppressing photoinduced phase segregation and related mechanisms have not been fully disclosed.Here,we report a new passivation agent 4-aminotetrahydrothiopyran hydrochloride(4-ATpHCl)with multifunctional groups for the interface treatment of a 1.77-eV wide-bandgap perovskite film.4-ATpH^(+)impeded halogen ion migration by anchoring on the perovskite surface,leading to the inhibition of phase segregation and thus the passivation of defects,which is ascribed to the interaction of 4-ATpH^(+)with perovskite and the formation of low-dimensional perovskites.Finally,the champion device achieved an efficiency of 19.32%with an open-circuit voltage(V_(OC))of 1.314 V and a fill factor of 83.32%.Moreover,4-ATpHCl modified device exhibited significant improved stability as compared with control one.The target device maintained 80%of its initial efficiency after 519 h of maximum power output(MPP)tracking under 1 sun illumination,however,the control device showed a rapid decrease in efficiency after 267 h.Finally,an efficiency of 27.38%of the champion 4-terminal all-perovskite tandem solar cell was achieved by mechanically stacking this wide-bandgap top subcell with a 1.25-eV low-bandgap perovskite bottom subcell.
基金This research was funded by the Heilongjiang Province Key Research and Development Plan Guidance Project(Grant No.GZ20220039)the National Natural Science Foundation of China(Grant No.82060118)+2 种基金the Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region(Grant No.NJYT24032)the Central Government Supports Local College Reform and Development Fund Talent Training Project(Grant No.2020GSP16)Heilongjiang Touyan Innovation Team Program(Grant No.2019HTY078).
文摘Objectives:Sciadopitysin(SP)is aflavonoid in Ginkgo biloba that exhibits various pharmacological activities.This study aimed to investigate its antitumor effects and the underlying molecular mechanism of SP in hepatocellular carcinoma(HCC)cells.Methods:Network pharmacology was used for target prediction analysis.Cell Counting Kit-8(CCK-8)assay was used to test the cell viability.Flow cytometry was used to test the cell cycle distribution,apoptosis status,and reactive oxygen species(ROS)levels.Transwell and wound-healing assay was used to test the migration effect of SP on HepG2 cells.Western Blot assay was used to test the expression levels of proteins.Results:Network pharmacology analysis results showed that the mitogen-activated protein kinase(MAPK)and other signaling pathways are involved in the SP anti-HCC biological process.CCK-8 assay results demonstrated that SP showed an obvious killing effect on three types of HCC cells and low cytotoxic effect on normal cells.Western Blot andflow cytometry results showed that SP regulated MAPK/signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa-B(NF-κB)signaling pathway to induce mitochondrion-dependent apoptosis in HepG2 cells.Additionally,SP can arrest the G0/G1 phase cell cycle via the protein kinase B(AKT)/p21/p27/cyclin-dependent kinase(CDK)/Cyclin signaling pathway.Wound healing and transwell assays showed that SP inhibited cell motility and invasion through the AKT/glycogen synthase kinase3β(GSK-3β)/vimentin/β-catenin signaling pathway.Conclusion:Thesefindings demonstrated that SP induced mitochondrion-dependent apoptosis,arrested cell cycle in the G0/G1 phase,and inhibited cell migration by regulating the ROS-mediated signaling pathway in HepG2 cells.Thus,SP could serve as a therapeutic agent for the treatment of human HCC.
基金supported by grants from National Natural Science Foundation of China(no.:82174020 and no.:31301137)Shanxi Basic Research Program of China(202103021224378)Shanxi Bethune Hospital Talent Introduction Research Start-up Fund of China(2022RC13)。
文摘Background:The role of Claudin-1 in tongue squamous cell carcinoma(TSCC)metastasis needs further clarification,particularly its impact on cell migration.Herein,our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms.Methods:36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1.Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells.Claudin-1 knockdown cell lines were established using short hairpin RNA transfection.Migration effects were assessed through wound healing assays.Furthermore,the expression of EMTassociated molecules was measured via western blotting.Results:Claudin-1 expression decreased as TSCC malignancy increased.Adenosine monophosphate–activated protein kinase(AMPK)activation led to increased Claudin-1 expression and membrane translocation,inhibiting TSCC cell migration and epithelial–mesenchymal transition(EMT).Conversely,Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation.Conclusions:Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.
基金supported by the National Natural Science Foundation of China[Grant Nos.42375177,41975141]Natural Science Foundation of Gansu[Grant No.23JRRA1079]Fundamental Research Funds for the Central Universities[number:lzujbky-2023-it29].
文摘Climate change is the most significant threat to public health and exerts myriad influences on health,including the occurrence of extreme temperature events.Studies have demonstrated that populations will experience significantly severe cold waves in the future^([1]),increasing the risk of respiratory diseases.