Carotenoids are lipophilic isoprenoid pigments with essential roles in plants.While the cultivated allotetraploid cottons exhibit distinct mature anther coloration—yellow in Gossypium barbadense versus predominantly ...Carotenoids are lipophilic isoprenoid pigments with essential roles in plants.While the cultivated allotetraploid cottons exhibit distinct mature anther coloration—yellow in Gossypium barbadense versus predominantly white in G.hirsutum—the genetic basis of this divergence remains unclear.The purpose of this study was to identify the genetic basis of anther-color variation in cotton(Gossypium)species.We firstly identified carotenoids as the primary pigments underlying yellow-anthers coloration.Comparative transcriptomics of anthers revealed that the carotenoid biosynthesis gene GbPSY4 was expressed as a key regulator in G.barbadense.Functional validation via tissue-specific expression,subcellular localization,in vivo enzymatic assays,and virus-induced gene silencing confirmed its role in carotenoid biosynthesis and yellow pigmentation.Genome-wide association studies in a G.hirsutum population revealed GhPSY4_At,an ortholog of GbPSY4,as the causal gene of anther-color variation.We conclude that PSY4-regulated carotenoid biosynthesis governs yellow pigmentation.Furthermore,a finding that G.hirsutum accessions with yellow anthers showed greater pollen viability under high-temperature stress than those with white anthers suggests that the same pathway that governs yellow pigmentation influences heat tolerance.PSY4 is a promising target for breeding stress-tolerant cotton varieties.展开更多
Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor ...Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.展开更多
Ethylene(C_(2)H_(4))in vehicle exhaust is a highly reactive volatile organic compound(VOC).Its photooxidative reaction with NOx contributes to the formation of O3 and secondary organic aerosols(SOA),the latter being a...Ethylene(C_(2)H_(4))in vehicle exhaust is a highly reactive volatile organic compound(VOC).Its photooxidative reaction with NOx contributes to the formation of O3 and secondary organic aerosols(SOA),the latter being a key precursor of PM_(2.5).In this study,a novel MgO-supported Ag-Cu bimetallic catalyst was designed and investigated using density functional theory(DFT).The effects of Ag and Cu loading on the geometric structure,stability,and reactant adsorption characteristics of the catalyst were analyzed,and the catalytic oxidation pathways of C_(2)H_(4)over AgCu-MgO was elucidated.The results indicate that loading Ag significantly enhances the adsorption of C_(2)H_(4).The incorporation of Cu into Ag-MgO to form a AgCu-MgO bimetallic catalyst(dual atom catalyst,DACS)further improves the oxidative activity toward C_(2)H_(4).Based on the binding energies of the Ag and Cu bimetallic sites and the adsorption energies of C_(2)H_(4)and O_(2),three representative configurations were selected for detailed reaction pathway analysis.Among them,Configuration 6 of AgCu-MgO exhibited the highest catalytic oxidation performance.This study provides new atomic-scale insights for the rational design of efficient catalysts targeting olefinic pollutants in automotive emissions and offers valuable guidance for advancing exhaust after-treatment technologies.展开更多
Based on 4'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-2,4,6-tricarboxylic acid(H_(4)bta)ligand,zinc metal-organic framework(Zn-MOF):{[Zn_(2)(bta)(bpy)_(2)(H_(2)O)]·1.5H_(2)O}_(n)(bpy=2,2'-bipyridine)was desi...Based on 4'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-2,4,6-tricarboxylic acid(H_(4)bta)ligand,zinc metal-organic framework(Zn-MOF):{[Zn_(2)(bta)(bpy)_(2)(H_(2)O)]·1.5H_(2)O}_(n)(bpy=2,2'-bipyridine)was designed and synthesized by hydrothermal method.Its structure was characterized by elemental analysis,IR spectra,X-ray single crystal diffraction,etc.The asymmetric unit of Zn-MOF contains two crystallographically independent Zn^(2+)ions.Through the connection of Zn^(2+)ions via H_(4)bta,a 1D double-layer network structure is formed.Adjacent double-layer networks further form a 2D supramolecular network through hydrogen bonding.Notably,Zn-MOF exhibited excellent fluorescence properties and could efficiently and sensitively detect various water pollutants:4-nitrophenol(4-NP),Cu^(2+),and pyrimethanil(Pth).Additionally,the mechanism of fluorescence sensing was investigated.CCDC:2432230.展开更多
The utilization of solid wastes to prepare Li_(4)SiO_(4) based CO_(2) adsorbents and thermochemical energy storage(TES)materials has recently garnered significant interest.Considering practical application conditions,...The utilization of solid wastes to prepare Li_(4)SiO_(4) based CO_(2) adsorbents and thermochemical energy storage(TES)materials has recently garnered significant interest.Considering practical application conditions,the influence of CO_(2) concentration and temperature fluctuations on adsorbent performance remains a key research focus.Among various waste materials,waste clay bricks are particularly suitable for Li_(4)SiO_(4) synthesis due to their high SiO_(2) content(60% to 70%),while enabling waste valorization.Furthermore,it has been demonstrated that heteroatoms present in the waste materials positively in-fluence the CO_(2) adsorption performance of Li_(4)SiO_(4)-based adsorbents.In this study,Li_(4)SiO_(4) was syn thesized for the first time directly from waste clay bricks without pretreatment.Comprehensive characterization revealed that the resulting Li_(4)SiO_(4)-based adsorbent exhibits outstanding performance:a high CO_(2) capture capacity(27.9%(mass)),excellent cycling stability,and remarkable thermal energy storage capability(876.4 kJ·kg^(-1)).These superior properties position it as one of the most promising high-temperature adsorbents for simultaneous CO_(2) capture and thermal energy storage(TES)from fossil fuel flue gase.Moreover,the adsorbent maintained excellent stability under fluctuating temper-ature and CO_(2) concentration.Even at 20%(vol)CO_(2) and 500℃,it achieved a high capacity of 25.7%(mass),reaching equilibrium within 15 min.This CO_(2) capture performance is truly impressive.展开更多
Breast cancer remains the primary cause of cancer-related mortality for women globally;therefore,further breakthroughs in treatment approaches are crucial.Palbociclib,ribociclib,and abemaciclib are among the Cyclin-de...Breast cancer remains the primary cause of cancer-related mortality for women globally;therefore,further breakthroughs in treatment approaches are crucial.Palbociclib,ribociclib,and abemaciclib are among the Cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors that have become an innovative family of targeted therapy for hormone receptor-positive,Human Epidermal Growth factor receptor 2(HR+/HER2-)breast cancer.These inhibitors work by preventing the action of CDK4/6,which are crucial in the regulation of the cell cycle.Leading cancer cells to cell cycle arrest and undergo apoptosis.When these inhibitors are used with endocrine medicines like letrozole and fulvestrant,clinical trials lead positive impact in progression-free survival and,in a few cases,complete survival.However,despite their effectiveness,resistance mechanisms are primary and current acquired problems,requiring combined approaches with additional targeted medicines and continuous investigation into innovative therapeutic plans.To maintain patient compliance and quality of life,common side effects such as tiredness,gastrointestinal problems,and neutropenia need to be effectively managed.There is hopefulness for wider oncological applications as next-generation CDK inhibitor development and adaptive clinical trials continue to test their potential beyond breast cancer.CDK4/6 inhibitors continue to be a key part of breast cancer treatment as cancer biology advances,marking a major advancement towards more potent and customized cancer medicines.This review aims to provide current evidence on CDK4/6 inhibitors in HR+/HER2-breast cancer,highlighting their mechanisms,interaction with endocrine resistance,combination strategies,and emerging biomarkers guiding personalized therapy.展开更多
Softening of fleshy fruits during ripening and postharvest is a programmed physiological process that substantially impacts fruit quality and shelf life.However,the molecular mechanism underlying peach softening remai...Softening of fleshy fruits during ripening and postharvest is a programmed physiological process that substantially impacts fruit quality and shelf life.However,the molecular mechanism underlying peach softening remains largely unknown.Lateral organ boundary(LOB)domain(LBD)proteins are pivotal regulators of plant growth and development.To date,certain LOB/LBD transcription factors are seemingly implicated in fruit softening.In this study,we identified 42 LOB/LBD genes in the peach genome.Expression analysis showed a significant upregulation of PpLOB1 transcripts toward peach fruit ripening.PpLOB1 was classified into Class II subgroup,and showed high sequence similarity to several softening-related LOB/LBD transcription factors.Transient transformation assays showed that PpLOB1 positively modulates peach softening.Further experiments demonstrated that PpLOB1 directly targets and activates the promoters of pectate lyase 1(PpPL1)and PpPL15,thereby contributing to the regulation of fruit softening.Additionally,PpNAP4 up-regulates PpLOB1 expression by binding to its promoter.Meanwhile,our findings revealed that PpNAP4 and PpNAP6 cooperatively modulate the expression of Pp LOB1.Taken together,our findings revealed a novel regulatory module involving PpNAP4 and PpLOB1 that modulates peach fruit softening.展开更多
Locust plagues result in significant agricultural and ecological damage,and the current dependence on broadspectrum chemical pesticides raises serious concerns regarding environmental sustainability and public health....Locust plagues result in significant agricultural and ecological damage,and the current dependence on broadspectrum chemical pesticides raises serious concerns regarding environmental sustainability and public health.In this study,we elucidated the biosynthetic pathway of the locust aggregation pheromone 4-vinylanisole(4VA).Through analysis of the crystal structure of the 4VPMT2-4VA-SAM complex,it was determined that 4-nitrophenol acts as a substrate analogue,effectively inhibiting 4VPMT enzyme activity and thereby preventing the formation of 4VA.This study revealed key enzymatic targets and lead inhibitors for intervention,establishing a molecular foundation for pheromone-based,environmentally sustainable locust control strategies and offering a viable alternative to reduce reliance on conventional chemical pesticides.展开更多
High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symme...High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symmetric observation error model that differentiates between land and sea for FY-4A/AGRI all-sky assimilation,developed an all-sky assimilation scheme for FY-4A/AGRI based on hydrometeor control variables,and investigated the impacts of all-sky FY-4A/AGRI water vapor channels at different altitudes and rapid-update assimilation at different frequencies on the assimilation and forecasting of a severe convective weather event.Results show that simultaneous assimilation of two water vapor channels can enhance precipitation forecasts compared to single-channel assimilation,which is mainly attributable to a more accurate analysis of water vapor and hydrometeor information.Experiments with different assimilation frequencies demonstrate that the hourly assimilation frequency,compared to other frequencies,incorporates the high-frequency information from AGRI while reducing the impact of spurious oscillations caused by excessively high-frequency assimilation.This hourly assimilation frequency reduces the incoordination among thermal,dynamical,and water vapor conditions caused by excessively fast or slow assimilation frequencies,thus improving the forecast accuracy compared to other frequencies.展开更多
Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regula...Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.展开更多
Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a ...Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.展开更多
Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low...Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.展开更多
Ketosis,a common metabolic disease during early lactation,is associated with high circulating levels ofβ-hydroxybutyrate(BHB).A portion of BHB that reaches the mammary gland is utilized as precursor for synthesis of ...Ketosis,a common metabolic disease during early lactation,is associated with high circulating levels ofβ-hydroxybutyrate(BHB).A portion of BHB that reaches the mammary gland is utilized as precursor for synthesis of fatty acids.Recent findings from nonruminant studies revealed that long chain fatty acyl-CoA ligase 4(ACSL4)could play a role in the regulation of cellular fatty acid metabolism,but the mechanisms by which ACSL4 mediates cellular lipid metabolism in response to BHB remains unclear.To achieve the aims,we conducted in vivo or in vitro analyses using bovine mammary gland biopsies and the immortalized mammary epithelial cell line(MAC-T).The in vivo study(n=6 cows per group)involved healthy cows(plasma BHB<0.60 mmol L^(–1))or ketotic cows(plasma BHB>2.0 mmol L^(–1))from which mammary gland tissue was biopsied.In vitro,MAC-T cells were challenged with 0,0.3,0.6,1.2,or 2.4 mmol L^(–1)BHB for 24 h to determine an optimal dose.Subsequently,MAC-T were incubated with 1.2 mmol L^(–1)BHB for 0,3,6,12,24,or 48 h.Furthermore,MAC-T cells were treated with small interfering ACSL4(siACSL4)for 24 h or ACSL4 overexpression plasmid(pcACSL4)for 36 h followed by a challenge with 1.2 mmol L^(–1)BHB for 24 h.Results showed that increased mRNA and protein abundance of lipogenic genes were linked to both mammary gland and in vitro challenge with BHB.BHB increased fatty acid content by activating ACSL4 expression,whereas inhibition of ACSL4 reduced BHB-induced reactive oxygen species(ROS)overproduction,enhancement of mitochondrial membrane potential,increase in fatty acid content,and lipid droplet accumulation.Furthermore,we also elevated ACSL4 expression with an overexpression plasmid to clarify its molecular role in response to BHB challenge.ACSL4 overexpression enhances BHB-induced lipid droplet accumulation by increased fatty acid content.Overall,the information showed that ACSL4 is crucial for the process of producing fatty acids from exogenous BHB.Reduced ACSL4 decreased fatty acid content and lipid droplet accumulation,improved mitochondrial function,directed more fatty acids towards oxidation.Thus,ACSL4 plays an important role in determining the fate of intracellular fatty acids and BHB in BMECs.展开更多
Five samples of LiMgPO_(4):Gd were prepared via five different production processes using a solid-state reaction method.The effects of the preparation process on optically stimulated luminescence(OSL)and thermolumines...Five samples of LiMgPO_(4):Gd were prepared via five different production processes using a solid-state reaction method.The effects of the preparation process on optically stimulated luminescence(OSL)and thermoluminescence(TL)were investigated.Considering its high sensitivity,low fading,and minimum detectable dose(MDD),the LiMgPO_(4):Gd phosphor heated to 900℃for 15 h is concluded to be optimal.The effects of annealing on the OSL sensitivity,relative residual OSL signals measured after 24 h of irradiation,and MDD of LiMgPO_(4):Gd phosphors heated to 900℃for 15 h were also investigated.Considering its high sensitivity,low fading,and MDD,annealing at 350℃for 1 h is concluded to be optimal.The OSL signal of LiMgPO_(4):Gd was derived from the principal TL glow peak.For a maximum integration time of 5 s,the OSL signal was stable,with no fading 30 days after irradiation.LiMgPO_(4):Gd eliminated approximately 2.2%of the OSL signal at each readout for a readout time of 0.1 s,which is sufficient for fast and multiple OSL readout.The sensitivity of LiMgPO_(4):Gd phosphor,annealed for 1 h at 350℃with a reading time of 0.1 s,was found to be approximately 98%of that observed forα-Al_(2)O_(3):C(TLD-500k),which should be sufficient for low-dose measurements in personal,workplace,and environmental dosimetry.展开更多
The Northeast China Cold Vortex(NCCV)is a common cut-off low-pressure system in Northeast China,frequently causing localized heavy rainfall,strong winds,and thunderstorms during the early summer.In this study,the clea...The Northeast China Cold Vortex(NCCV)is a common cut-off low-pressure system in Northeast China,frequently causing localized heavy rainfall,strong winds,and thunderstorms during the early summer.In this study,the clear-sky radiance of 48 longwave channels from the FY-4B Geostationary Interferometric Infrared Sounder(GIIRS)is assimilated into the China Meteorological Administration mesoscale model(CMA-MESO)to evaluate its impact on NCCV development and its effects on rainfall forecasting.The results show that after assimilating the GIIRS radiance data,the warm center at 200 hPa and the cold center at 850 hPa of the NCCV are strengthened,and the dry intrusion at 850 hPa becomes more pronounced.This leads to a stronger NCCV intensity in the following 24 hours and brings the precipitation intensity and area closer to the observation,resulting in significant improvements compared to the experiments that do not assimilate GIIRS radiance data.Furthermore,it is found that the enhancement of the precipitation forecast is associated with the strengthening of cold air in the middle and lower troposphere,which intensifies the uplift of the warm,moist airflow.These results highlight the potential value of GIIRS data assimilation in enhancing early warnings and forecasts of extreme weather events influenced by the NCCV.展开更多
This study aimed to systematically regulate the performance of 4D printing composites by investigating the synergistic effects of dicumyl peroxide(DCP)and maleic anhydride-grafted polyethylene(MAH-g-PE)on a poly(lacti...This study aimed to systematically regulate the performance of 4D printing composites by investigating the synergistic effects of dicumyl peroxide(DCP)and maleic anhydride-grafted polyethylene(MAH-g-PE)on a poly(lactic acid)/thermoplastic polyurethane(PLA/TPU)matrix.Specifically,using a 70 wt%/30 wt%PLA/TPU matrix and an L_(9)(3^(2))orthogonal design,composites were evaluated via morphology,shape memory,mechanical tests,and multi-criteria analysis.Moderate DCP enhanced crosslinking,improving storage modulus and thermal stability,while excessive DCP caused brittleness.Furthermore,MAH-g-PE effectively improved interfacial compatibility,and its synergy with DCP was dosage-dependent.Consequently,Sample 5 achieved optimal performance,exhibiting uniform fracture morphology,a shape fixation rate of98.8%with the fastest recovery,and balanced strength-ductility.Multi-criteria analysis identified elongation at break and recovery time as the top contributing factors,with consistent rankings validated by Spearman analysis(ρ=0.833,p<0.01).In summary,adjusting DCP and MAH-g-PE contents effectively modulates the crosslinking structure and interfacial properties of PLA/TPU composites,providing a viable strategy for developing high-performance,tunable 4D printing materials.展开更多
Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal ...Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.展开更多
Background:This study investigated the role of polydatin in regulating macrophage-epithelial cell(EC)interactions during asthma.An asthma model was induced in BALB/c mice using ovalbumin(20μg).Methods:The therapeutic...Background:This study investigated the role of polydatin in regulating macrophage-epithelial cell(EC)interactions during asthma.An asthma model was induced in BALB/c mice using ovalbumin(20μg).Methods:The therapeutic effects of polydatin(20 and 40 mg/kg)were evaluated in this asthmatic mouse model.To assess the underlying mechanisms,Bronchial Epithelium Adenovirus 12-SV402B(BEAS-2B)cells were cocultured with Tohoku Hospital for Pediatrics-1(THP-1)macrophages,in which toll-like receptor 4(TLR4)was either overexpressed or knocked down,and subsequently stimulated with lipopoly-saccharide(LPS)and ATP.THP-1 cells underwent a 1-h pretreatment with polydatin(50 and 100μmol/L),Class Lipid Inhibitor-095(CLI-095,TLR4 inhibitor,1μg/mL),or A438079(P2X7R antagonist,10μmol/L)prior to LPS/ATP challenge.Results:Findings from Western blotting,enzyme-linked immunosorbent assay,flow cytometry,real-time polymerase chain reaction,and immunofluorescence assays demonstrated that modulating TLR4 expression significantly altered interleukin-1β(IL-1β)secretion from THP-1 macrophages and mitochondrial reactive oxygen species(mtROS)production in BEAS-2B ECs.In the mouse asthma model,polydatin significantly alleviated airway inflammation,oxidative stress,and apoptosis,likely by interfering with TLR4/P2X7R-mediated signaling and suppressing the activation of the NOD-like receptor protein inflammasome.Additionally,polydatin significantly reduced IL-1βand IL-18 levels and inhibited the infiltration of macrophages and eosinophils.Correspondingly,polydatin significantly attenuated TLR4/P2X7R signaling in THP-1 cells stimulated with ATP and LPS,thereby reducing IL-1βand IL-18 secretion,calcium influx,mtROS production,and apoptosis in BEAS-2B ECs.Conclusions:Polydatin is a promising therapeutic candidate for asthma,possibly by targeting macrophage-epithelium cross-talk via the TLR4/P2X7R axis.Future formulations as capsules or sprays may effectively alleviate airway inflammation and remodeling.展开更多
The rapid accumulation of spent LiFePO_(4)(LFP)cathodes from retired lithium-ion batteries necessitates the development of effective and environmental-friendly recycling strategies.In this context,direct regeneration ...The rapid accumulation of spent LiFePO_(4)(LFP)cathodes from retired lithium-ion batteries necessitates the development of effective and environmental-friendly recycling strategies.In this context,direct regeneration has emerged as a promising approach for reclaiming LFP cathode materials,offering a streamlined pathway to restore their electrochemical functionality.We report an integrated regeneration protocol that simultaneously repairs the degraded crystal structure and reconstructs the damaged carbon coating in spent LFP.The regenerated cathode material had superfast lithium-ion diffusion kinetics and a stable cathode-electrolyte interface,giving a remarkable rate capability with specific capacities of 122 m Ah g^(-1)at 5C and 106 m Ah g^(-1)at 10C(1C=170 m A g^(-1)).It also maintained capacities of 110.7 m Ah g^(-1)(5C)and 84.1 m Ah g^(-1)(10C)after 400 cycles.It could be used in harsh environments and could be stably cycled at subzero temperatures(-10 and-20°C)and in solid-state electrolyte batteries.Life cycle assessment combined with economic evaluation using the Ever Batt model reveals that this direct regeneration approach has high economic and environmental benefits.展开更多
Bi/Bi_(2)Fe_(4)O_(9)nanocomposites consisting of Bi_(2)Fe_(4)O_(9)nanosheets decorated with Bi nanodots were synthesized by a hydrothermal method.The formation of Bi nanodots on the Bi_(2)Fe_(4)O_(9)nanosheet surfaces...Bi/Bi_(2)Fe_(4)O_(9)nanocomposites consisting of Bi_(2)Fe_(4)O_(9)nanosheets decorated with Bi nanodots were synthesized by a hydrothermal method.The formation of Bi nanodots on the Bi_(2)Fe_(4)O_(9)nanosheet surfaces was attributed to the reducibility of 2-methoxyethanol in the precursor solution.Comparative photocatalytic evaluation reveals that the Bi/Bi_(2)Fe_(4)O_(9)nanocomposites significantly enhance the degradation efficiency(99.0%)of bisphenol A compared with Bi_(2)Fe_(4)O_(9)nanosheets(64.2%)under 120 min simulated solar irradiation.This remarkable enhancement can be attributed to the established Bi/Bi_(2)Fe_(4)O_(9)heterojunction structure,which effectively facilitates the separation of photogenerated electron-hole pairs and accelerates interfacial charge transfer between the metallic Bi nanodots and semiconductor Bi_(2)Fe_(4)O_(9)nanosheets.The synergistic effects arising from this unique architecture ultimately lead to superior photocatalytic performance.展开更多
基金the National Natural Science Foundation of China(32170271,32470277)the Project of Sanya Yazhou Bay Science and Technology City(SCKJ-JYRC-2023-52)the Natural Science Foundation of Henan Province(252300421076,222300420024).
文摘Carotenoids are lipophilic isoprenoid pigments with essential roles in plants.While the cultivated allotetraploid cottons exhibit distinct mature anther coloration—yellow in Gossypium barbadense versus predominantly white in G.hirsutum—the genetic basis of this divergence remains unclear.The purpose of this study was to identify the genetic basis of anther-color variation in cotton(Gossypium)species.We firstly identified carotenoids as the primary pigments underlying yellow-anthers coloration.Comparative transcriptomics of anthers revealed that the carotenoid biosynthesis gene GbPSY4 was expressed as a key regulator in G.barbadense.Functional validation via tissue-specific expression,subcellular localization,in vivo enzymatic assays,and virus-induced gene silencing confirmed its role in carotenoid biosynthesis and yellow pigmentation.Genome-wide association studies in a G.hirsutum population revealed GhPSY4_At,an ortholog of GbPSY4,as the causal gene of anther-color variation.We conclude that PSY4-regulated carotenoid biosynthesis governs yellow pigmentation.Furthermore,a finding that G.hirsutum accessions with yellow anthers showed greater pollen viability under high-temperature stress than those with white anthers suggests that the same pathway that governs yellow pigmentation influences heat tolerance.PSY4 is a promising target for breeding stress-tolerant cotton varieties.
基金supported by the Russian Science Foundation(Grant No.23-65-10017 to B.K.K.and M.K.)The Ministry of Science and Higher Education of the Russian Federation(Grant No.122020300042-4 to L.N.M.)supported the preparation of the minichapter titled"Opioids reduce inflammatory injury of the heart".
文摘Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.
基金Supported by the National Natural Science Foundation of China Project(22362018)the Yunnan Fundamental Research Projects(202401AS070102)。
文摘Ethylene(C_(2)H_(4))in vehicle exhaust is a highly reactive volatile organic compound(VOC).Its photooxidative reaction with NOx contributes to the formation of O3 and secondary organic aerosols(SOA),the latter being a key precursor of PM_(2.5).In this study,a novel MgO-supported Ag-Cu bimetallic catalyst was designed and investigated using density functional theory(DFT).The effects of Ag and Cu loading on the geometric structure,stability,and reactant adsorption characteristics of the catalyst were analyzed,and the catalytic oxidation pathways of C_(2)H_(4)over AgCu-MgO was elucidated.The results indicate that loading Ag significantly enhances the adsorption of C_(2)H_(4).The incorporation of Cu into Ag-MgO to form a AgCu-MgO bimetallic catalyst(dual atom catalyst,DACS)further improves the oxidative activity toward C_(2)H_(4).Based on the binding energies of the Ag and Cu bimetallic sites and the adsorption energies of C_(2)H_(4)and O_(2),three representative configurations were selected for detailed reaction pathway analysis.Among them,Configuration 6 of AgCu-MgO exhibited the highest catalytic oxidation performance.This study provides new atomic-scale insights for the rational design of efficient catalysts targeting olefinic pollutants in automotive emissions and offers valuable guidance for advancing exhaust after-treatment technologies.
文摘Based on 4'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-2,4,6-tricarboxylic acid(H_(4)bta)ligand,zinc metal-organic framework(Zn-MOF):{[Zn_(2)(bta)(bpy)_(2)(H_(2)O)]·1.5H_(2)O}_(n)(bpy=2,2'-bipyridine)was designed and synthesized by hydrothermal method.Its structure was characterized by elemental analysis,IR spectra,X-ray single crystal diffraction,etc.The asymmetric unit of Zn-MOF contains two crystallographically independent Zn^(2+)ions.Through the connection of Zn^(2+)ions via H_(4)bta,a 1D double-layer network structure is formed.Adjacent double-layer networks further form a 2D supramolecular network through hydrogen bonding.Notably,Zn-MOF exhibited excellent fluorescence properties and could efficiently and sensitively detect various water pollutants:4-nitrophenol(4-NP),Cu^(2+),and pyrimethanil(Pth).Additionally,the mechanism of fluorescence sensing was investigated.CCDC:2432230.
基金the National Natural Science Foundation of China(5240101142)Yunnan Province basic research project(202401CF070252)+1 种基金the Key R&D plan of Yunnan Province(202303AC100008)the Scientific Researching Fund Projects of Yunnan Provincial Department of Education(2025J0077),which funded this study。
文摘The utilization of solid wastes to prepare Li_(4)SiO_(4) based CO_(2) adsorbents and thermochemical energy storage(TES)materials has recently garnered significant interest.Considering practical application conditions,the influence of CO_(2) concentration and temperature fluctuations on adsorbent performance remains a key research focus.Among various waste materials,waste clay bricks are particularly suitable for Li_(4)SiO_(4) synthesis due to their high SiO_(2) content(60% to 70%),while enabling waste valorization.Furthermore,it has been demonstrated that heteroatoms present in the waste materials positively in-fluence the CO_(2) adsorption performance of Li_(4)SiO_(4)-based adsorbents.In this study,Li_(4)SiO_(4) was syn thesized for the first time directly from waste clay bricks without pretreatment.Comprehensive characterization revealed that the resulting Li_(4)SiO_(4)-based adsorbent exhibits outstanding performance:a high CO_(2) capture capacity(27.9%(mass)),excellent cycling stability,and remarkable thermal energy storage capability(876.4 kJ·kg^(-1)).These superior properties position it as one of the most promising high-temperature adsorbents for simultaneous CO_(2) capture and thermal energy storage(TES)from fossil fuel flue gase.Moreover,the adsorbent maintained excellent stability under fluctuating temper-ature and CO_(2) concentration.Even at 20%(vol)CO_(2) and 500℃,it achieved a high capacity of 25.7%(mass),reaching equilibrium within 15 min.This CO_(2) capture performance is truly impressive.
基金funded by School of Medical Sciences and Universiti Sains Malaysia。
文摘Breast cancer remains the primary cause of cancer-related mortality for women globally;therefore,further breakthroughs in treatment approaches are crucial.Palbociclib,ribociclib,and abemaciclib are among the Cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors that have become an innovative family of targeted therapy for hormone receptor-positive,Human Epidermal Growth factor receptor 2(HR+/HER2-)breast cancer.These inhibitors work by preventing the action of CDK4/6,which are crucial in the regulation of the cell cycle.Leading cancer cells to cell cycle arrest and undergo apoptosis.When these inhibitors are used with endocrine medicines like letrozole and fulvestrant,clinical trials lead positive impact in progression-free survival and,in a few cases,complete survival.However,despite their effectiveness,resistance mechanisms are primary and current acquired problems,requiring combined approaches with additional targeted medicines and continuous investigation into innovative therapeutic plans.To maintain patient compliance and quality of life,common side effects such as tiredness,gastrointestinal problems,and neutropenia need to be effectively managed.There is hopefulness for wider oncological applications as next-generation CDK inhibitor development and adaptive clinical trials continue to test their potential beyond breast cancer.CDK4/6 inhibitors continue to be a key part of breast cancer treatment as cancer biology advances,marking a major advancement towards more potent and customized cancer medicines.This review aims to provide current evidence on CDK4/6 inhibitors in HR+/HER2-breast cancer,highlighting their mechanisms,interaction with endocrine resistance,combination strategies,and emerging biomarkers guiding personalized therapy.
基金supported by grants from the China Postdoctoral Science Foundation(2023M742867)the High-level Innovation and Entrepreneurship Talents Program of QinChuangYuan,Shaanxi Province,China(QCYRCXM-2022-234)the National Key R&D Program of China(2019YFD1000203)。
文摘Softening of fleshy fruits during ripening and postharvest is a programmed physiological process that substantially impacts fruit quality and shelf life.However,the molecular mechanism underlying peach softening remains largely unknown.Lateral organ boundary(LOB)domain(LBD)proteins are pivotal regulators of plant growth and development.To date,certain LOB/LBD transcription factors are seemingly implicated in fruit softening.In this study,we identified 42 LOB/LBD genes in the peach genome.Expression analysis showed a significant upregulation of PpLOB1 transcripts toward peach fruit ripening.PpLOB1 was classified into Class II subgroup,and showed high sequence similarity to several softening-related LOB/LBD transcription factors.Transient transformation assays showed that PpLOB1 positively modulates peach softening.Further experiments demonstrated that PpLOB1 directly targets and activates the promoters of pectate lyase 1(PpPL1)and PpPL15,thereby contributing to the regulation of fruit softening.Additionally,PpNAP4 up-regulates PpLOB1 expression by binding to its promoter.Meanwhile,our findings revealed that PpNAP4 and PpNAP6 cooperatively modulate the expression of Pp LOB1.Taken together,our findings revealed a novel regulatory module involving PpNAP4 and PpLOB1 that modulates peach fruit softening.
基金support of the National Natural Science Foundation of China(32472594).
文摘Locust plagues result in significant agricultural and ecological damage,and the current dependence on broadspectrum chemical pesticides raises serious concerns regarding environmental sustainability and public health.In this study,we elucidated the biosynthetic pathway of the locust aggregation pheromone 4-vinylanisole(4VA).Through analysis of the crystal structure of the 4VPMT2-4VA-SAM complex,it was determined that 4-nitrophenol acts as a substrate analogue,effectively inhibiting 4VPMT enzyme activity and thereby preventing the formation of 4VA.This study revealed key enzymatic targets and lead inhibitors for intervention,establishing a molecular foundation for pheromone-based,environmentally sustainable locust control strategies and offering a viable alternative to reduce reliance on conventional chemical pesticides.
基金supported by the National Key R&D Program of China(Grant No.2022YFC3080500)the National Natural Science Foundation of China(Grant Nos.U2142208,42475158,and 42105149)the High-Performance Computing Center of Nanjing University of Information Science&Technology for supporting this work。
文摘High spatiotemporal resolution infrared radiances from FY-4A/AGRI(Advanced Geostationary Radiation Imager)can provide crucial information for rapidly developing severe convective weather.This study established a symmetric observation error model that differentiates between land and sea for FY-4A/AGRI all-sky assimilation,developed an all-sky assimilation scheme for FY-4A/AGRI based on hydrometeor control variables,and investigated the impacts of all-sky FY-4A/AGRI water vapor channels at different altitudes and rapid-update assimilation at different frequencies on the assimilation and forecasting of a severe convective weather event.Results show that simultaneous assimilation of two water vapor channels can enhance precipitation forecasts compared to single-channel assimilation,which is mainly attributable to a more accurate analysis of water vapor and hydrometeor information.Experiments with different assimilation frequencies demonstrate that the hourly assimilation frequency,compared to other frequencies,incorporates the high-frequency information from AGRI while reducing the impact of spurious oscillations caused by excessively high-frequency assimilation.This hourly assimilation frequency reduces the incoordination among thermal,dynamical,and water vapor conditions caused by excessively fast or slow assimilation frequencies,thus improving the forecast accuracy compared to other frequencies.
基金funded by the National Natural Science Foundation of China(Grant Nos.82204517 to T.Z.and 82404756 to J.Z.)the Science and Technology Program in Medicine and Health of Zhejiang Province(Grant No.2023KY726 to T.Z.).
文摘Background:Aberrant expression of transcription factors(TFs)is a key mechanism mediating tumor immune escape and therapeutic resistance.The involvement of E26 transformation-specific(ETS)family of TFs in immune regulation is not fully understood.The study aimed to elucidate the function of E-twenty-six variant 4(ETV4)in tumor immune evasion and its potential as a predictive biomarker for immunotherapy in melanoma.Methods:The expression patterns of ETS family TFs were analyzed in melanoma and hepatocellular carcinoma(HCC).Single-cell RNA sequencing(scRNA-seq)was used to dissect the cellular expression and function of ETV4 in the tumor microenvironment.Functional studies and murine models were employed to investigate the role of ETV4 in T cell-mediated tumor killing and tumor growth.The correlation between ETV4 expression level and patient responsiveness to programmed cell death protein 1(PD-1)blockade therapy was evaluated.Results:TFs in the ETS family were found to effectively stratify melanoma and HCC patients into prognostic subgroups.In melanoma,the polyoma enhancer activator 3(PEA3)subfamily,particularly ETV4 and ETV5,showed a negative correlation with immune infiltration.scRNA-seq analysis showed that ETV4 is preferentially expressed in melanoma cells and involves in mediating tumor-immunocyte interactions.Functional studies demonstrated that ETV4 impairs T cell-mediated tumor killing by transcriptionally upregulating programmed death-ligand 1(PD-L1).In immunocompetent murine models,ETV4 downregulation significantly suppressed tumor growth.Furthermore,high ETV4 expression correlated with poor responses to anti-PD-1 therapy.Conclusion:Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression.ETV4 may act as a predictive biomarker for immunotherapy outcomes.
基金supported by the Chinese Medicine"Dual Chain Integration"Young and Middle-aged Scientific Research and Innovation Teams(No.2022-SLRH-YQ-006)the Key R&D Programme Projects of Xianyang Municipality(No.L2023-ZDYF-SF-014)+1 种基金the Shaanxi University of Traditional Chinese Medicine Science,Education and Research Collaborative Educational Achievement Transformation Project(No.2024KC03)the open research topic from the Key Laboratory of Neurological Diseases in Traditional Chinese Medicine,Shaanxi Province(No.KF202315).
文摘Background:Baicalin(BC)and geniposide(GD)are effective components of natural remedies,and studies have shown that they protect against cerebral ischemic stroke(CIS).Transient receptor potential vanilloid 4(TRPV4)is a calcium-permeable channel that plays important roles in vascular function and vasodilation.However,no studies are available on the effect of BC/GD on the TRPV4 channel and rat cerebral basilar artery(CBA).This study examined the effect of the combination of BC/GD(7:3)on cerebral vascular function after CIS.Methods:We used western blotting to determine TRPV4 protein levels and live cell fluorescence Ca 2+imaging and patch clamp to determine how BC/GD activates TRPV4 channels.Isolated vessel experiments were used to observe the dilatory effects of BC/GD on CBA under different conditions.Laser Doppler imaging was used to measure cerebral blood flow in rats.Triphenyl tetrazolium chloride and Nissl stainings were used to determine the infarct area in the rat brain and neuronal damage,respectively.Results:BC/GD significantly boosted TRPV4 protein levels in vascular smooth muscle cells(VSMCs)during oxygen-glucose deprivation and increased[Ca 2+]i in TRPV4-HEK 293 cells and VSMCs.This effect was not observed in vector-HEK 293 cells.In patch clamp experiments,BC/GD increased Ca 2+currents in TRPV4-HEK 293 cells,whereas no significant changes were observed in vector-HEK 293 cells.BC/GD dilated CBA contractions induced by U46619 and KCl,with a concentration-dependent increase of the dilatory effect.In the middle cerebral artery occlusion model,cerebral blood flow in the ischemic side significantly decreased,whereas BC/GD intervention significantly increased cerebral blood perfusion in the ischemic side,reduced the infarct area,and improved neurological function scores and neuronal damage.Conclusion:BC/GD activates the TRPV4 channel,leading to Ca ^(2+) influx,which in turn activates the intermediate conductance calcium-activated potassium channels channel to regulate vasodilation in vascular smooth muscle.
基金supported by China International Medical Foundation(Z-2019-42-1908-4)Natural Science Basic Research Program of Shaanxi Province(2019JM-440).
文摘Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.
基金supported by the grants from the National Key Research and Development Program of China(2023YFD1800804 and 2023YFD1801100)the National Natural Science Foundation of China(32172926)the China Agriculture Research System(CARS-36)。
文摘Ketosis,a common metabolic disease during early lactation,is associated with high circulating levels ofβ-hydroxybutyrate(BHB).A portion of BHB that reaches the mammary gland is utilized as precursor for synthesis of fatty acids.Recent findings from nonruminant studies revealed that long chain fatty acyl-CoA ligase 4(ACSL4)could play a role in the regulation of cellular fatty acid metabolism,but the mechanisms by which ACSL4 mediates cellular lipid metabolism in response to BHB remains unclear.To achieve the aims,we conducted in vivo or in vitro analyses using bovine mammary gland biopsies and the immortalized mammary epithelial cell line(MAC-T).The in vivo study(n=6 cows per group)involved healthy cows(plasma BHB<0.60 mmol L^(–1))or ketotic cows(plasma BHB>2.0 mmol L^(–1))from which mammary gland tissue was biopsied.In vitro,MAC-T cells were challenged with 0,0.3,0.6,1.2,or 2.4 mmol L^(–1)BHB for 24 h to determine an optimal dose.Subsequently,MAC-T were incubated with 1.2 mmol L^(–1)BHB for 0,3,6,12,24,or 48 h.Furthermore,MAC-T cells were treated with small interfering ACSL4(siACSL4)for 24 h or ACSL4 overexpression plasmid(pcACSL4)for 36 h followed by a challenge with 1.2 mmol L^(–1)BHB for 24 h.Results showed that increased mRNA and protein abundance of lipogenic genes were linked to both mammary gland and in vitro challenge with BHB.BHB increased fatty acid content by activating ACSL4 expression,whereas inhibition of ACSL4 reduced BHB-induced reactive oxygen species(ROS)overproduction,enhancement of mitochondrial membrane potential,increase in fatty acid content,and lipid droplet accumulation.Furthermore,we also elevated ACSL4 expression with an overexpression plasmid to clarify its molecular role in response to BHB challenge.ACSL4 overexpression enhances BHB-induced lipid droplet accumulation by increased fatty acid content.Overall,the information showed that ACSL4 is crucial for the process of producing fatty acids from exogenous BHB.Reduced ACSL4 decreased fatty acid content and lipid droplet accumulation,improved mitochondrial function,directed more fatty acids towards oxidation.Thus,ACSL4 plays an important role in determining the fate of intracellular fatty acids and BHB in BMECs.
文摘Five samples of LiMgPO_(4):Gd were prepared via five different production processes using a solid-state reaction method.The effects of the preparation process on optically stimulated luminescence(OSL)and thermoluminescence(TL)were investigated.Considering its high sensitivity,low fading,and minimum detectable dose(MDD),the LiMgPO_(4):Gd phosphor heated to 900℃for 15 h is concluded to be optimal.The effects of annealing on the OSL sensitivity,relative residual OSL signals measured after 24 h of irradiation,and MDD of LiMgPO_(4):Gd phosphors heated to 900℃for 15 h were also investigated.Considering its high sensitivity,low fading,and MDD,annealing at 350℃for 1 h is concluded to be optimal.The OSL signal of LiMgPO_(4):Gd was derived from the principal TL glow peak.For a maximum integration time of 5 s,the OSL signal was stable,with no fading 30 days after irradiation.LiMgPO_(4):Gd eliminated approximately 2.2%of the OSL signal at each readout for a readout time of 0.1 s,which is sufficient for fast and multiple OSL readout.The sensitivity of LiMgPO_(4):Gd phosphor,annealed for 1 h at 350℃with a reading time of 0.1 s,was found to be approximately 98%of that observed forα-Al_(2)O_(3):C(TLD-500k),which should be sufficient for low-dose measurements in personal,workplace,and environmental dosimetry.
基金sponsored by the National Natural Science Foundation of China(Grant No.42275171)the Basic Research Operating Expenses of the Institute of Meteorological Sciences,CMA(Grant No.2023Z019)+3 种基金the National Key Research and Development Program of China(Grant No.2022YFF0801304)the China Meteorological Administration Youth Innovation Team Fund(Grant No.CMA2024QN05)a Liaoning Provincial Meteorological Bureau Project(Grant No.D202201)Shenyang Institute of Atmospheric Environment Projects(Grant Nos.2022SYIAEJY13 and 2018SYIAEZD5).
文摘The Northeast China Cold Vortex(NCCV)is a common cut-off low-pressure system in Northeast China,frequently causing localized heavy rainfall,strong winds,and thunderstorms during the early summer.In this study,the clear-sky radiance of 48 longwave channels from the FY-4B Geostationary Interferometric Infrared Sounder(GIIRS)is assimilated into the China Meteorological Administration mesoscale model(CMA-MESO)to evaluate its impact on NCCV development and its effects on rainfall forecasting.The results show that after assimilating the GIIRS radiance data,the warm center at 200 hPa and the cold center at 850 hPa of the NCCV are strengthened,and the dry intrusion at 850 hPa becomes more pronounced.This leads to a stronger NCCV intensity in the following 24 hours and brings the precipitation intensity and area closer to the observation,resulting in significant improvements compared to the experiments that do not assimilate GIIRS radiance data.Furthermore,it is found that the enhancement of the precipitation forecast is associated with the strengthening of cold air in the middle and lower troposphere,which intensifies the uplift of the warm,moist airflow.These results highlight the potential value of GIIRS data assimilation in enhancing early warnings and forecasts of extreme weather events influenced by the NCCV.
基金supported by the National Natural Science Foundation of China(No.51905543)。
文摘This study aimed to systematically regulate the performance of 4D printing composites by investigating the synergistic effects of dicumyl peroxide(DCP)and maleic anhydride-grafted polyethylene(MAH-g-PE)on a poly(lactic acid)/thermoplastic polyurethane(PLA/TPU)matrix.Specifically,using a 70 wt%/30 wt%PLA/TPU matrix and an L_(9)(3^(2))orthogonal design,composites were evaluated via morphology,shape memory,mechanical tests,and multi-criteria analysis.Moderate DCP enhanced crosslinking,improving storage modulus and thermal stability,while excessive DCP caused brittleness.Furthermore,MAH-g-PE effectively improved interfacial compatibility,and its synergy with DCP was dosage-dependent.Consequently,Sample 5 achieved optimal performance,exhibiting uniform fracture morphology,a shape fixation rate of98.8%with the fastest recovery,and balanced strength-ductility.Multi-criteria analysis identified elongation at break and recovery time as the top contributing factors,with consistent rankings validated by Spearman analysis(ρ=0.833,p<0.01).In summary,adjusting DCP and MAH-g-PE contents effectively modulates the crosslinking structure and interfacial properties of PLA/TPU composites,providing a viable strategy for developing high-performance,tunable 4D printing materials.
基金supported by grants from the National Natural Science Foundation of China(82372881 to Weiyang He)the Chongqing Biomedicine Key R&D Project(CSTB2021TIAD-KPX0041 to Weiyang He).
文摘Objective:While cisplatin-based chemotherapy is pivotal for advanced bladder cancer,acquired resistance remains a major obstacle.This study investigates key molecular drivers of this resistance and potential reversal strategies.Methods:We established GC(Gemcitabine and Cisplatin)-resistant T24-R and UC3-R cell lines from T24 and UM-UC-3(UC3)cells.Transcriptomic and proteomic analyses identified differentially expressed molecules.Apoptosis and cell viability were assessed by flow cytometry and CCK-8(Cell Counting Kit-8)assays,while RT-qPCR(Reverse Transcription Quantitative Polymerase Chain Reaction)and Western blot analyzed gene and protein expression.Immunofluorescence evaluated FAK(Focal Adhesion Kinase)phosphorylation,and a xenograft mouse model validated the findings in vivo.Results:Integrated transcriptomic and proteomic analysis identified FN1(fibronectin)as a consistently upregulated top candidate in resistant cells(T24-R transcript log_(2)FC=2.8,protein log_(2)FC=0.9;UC3-R transcript log_(2)FC=3.7;all p<0.001).Knockdown of FN1 reduced chemoresistance(Resistance Index:5.2 in T24-R and 2.0 in UC3-R cells,p<0.001)and enhanced apoptosis(approximately 4.5-fold in T24-R and 7.5-fold in UC3-R,p<0.001).ITGB4(Integrin Subunit Beta 4)was upregulated in resistant cells(transcript log_(2)FC:4.2 in T24-R and 3.03 in UC3-R;protein log_(2)FC:0.67 in T24-R;all p<0.01).Critically,ITGB4 knockdown abolished the chemoresistance promoted by exogenous FN1,which was associated with increased FAK(Y397)phosphorylation.Conclusion:Our results demonstrate that the FN1-ITGB4 axis drives chemoresistance in bladder cancer via FAK signaling.Targeting this axis represents a promising strategy to overcome chemoresistance.
基金National Natural Science Foundation of China,Grant/Award Number:82260007Jilin Province Health Commission,Grant/Award Number:2024A062+1 种基金Jilin Provincial Department of Education,Grant/Award Number:JJKH20240698KJJilin Province Science and Technology Department,Grant/Award Number:20240404025ZP and 20240602100RC。
文摘Background:This study investigated the role of polydatin in regulating macrophage-epithelial cell(EC)interactions during asthma.An asthma model was induced in BALB/c mice using ovalbumin(20μg).Methods:The therapeutic effects of polydatin(20 and 40 mg/kg)were evaluated in this asthmatic mouse model.To assess the underlying mechanisms,Bronchial Epithelium Adenovirus 12-SV402B(BEAS-2B)cells were cocultured with Tohoku Hospital for Pediatrics-1(THP-1)macrophages,in which toll-like receptor 4(TLR4)was either overexpressed or knocked down,and subsequently stimulated with lipopoly-saccharide(LPS)and ATP.THP-1 cells underwent a 1-h pretreatment with polydatin(50 and 100μmol/L),Class Lipid Inhibitor-095(CLI-095,TLR4 inhibitor,1μg/mL),or A438079(P2X7R antagonist,10μmol/L)prior to LPS/ATP challenge.Results:Findings from Western blotting,enzyme-linked immunosorbent assay,flow cytometry,real-time polymerase chain reaction,and immunofluorescence assays demonstrated that modulating TLR4 expression significantly altered interleukin-1β(IL-1β)secretion from THP-1 macrophages and mitochondrial reactive oxygen species(mtROS)production in BEAS-2B ECs.In the mouse asthma model,polydatin significantly alleviated airway inflammation,oxidative stress,and apoptosis,likely by interfering with TLR4/P2X7R-mediated signaling and suppressing the activation of the NOD-like receptor protein inflammasome.Additionally,polydatin significantly reduced IL-1βand IL-18 levels and inhibited the infiltration of macrophages and eosinophils.Correspondingly,polydatin significantly attenuated TLR4/P2X7R signaling in THP-1 cells stimulated with ATP and LPS,thereby reducing IL-1βand IL-18 secretion,calcium influx,mtROS production,and apoptosis in BEAS-2B ECs.Conclusions:Polydatin is a promising therapeutic candidate for asthma,possibly by targeting macrophage-epithelium cross-talk via the TLR4/P2X7R axis.Future formulations as capsules or sprays may effectively alleviate airway inflammation and remodeling.
基金financial support from the National Key R&D Program of China(2022YFB2402600)the National Natural Science Foundation of China(52372250,52125105,52173242)+1 种基金Shenzhen Science and Technology Planning Project(RCYX20221008092850072,JSGG20220831104004008,KJZD20230923113859006,JCYJ20220531100405012,KJZD20241122161900001)Science and Technology Planning Project of Guangdong Province(2024A1515030076)。
文摘The rapid accumulation of spent LiFePO_(4)(LFP)cathodes from retired lithium-ion batteries necessitates the development of effective and environmental-friendly recycling strategies.In this context,direct regeneration has emerged as a promising approach for reclaiming LFP cathode materials,offering a streamlined pathway to restore their electrochemical functionality.We report an integrated regeneration protocol that simultaneously repairs the degraded crystal structure and reconstructs the damaged carbon coating in spent LFP.The regenerated cathode material had superfast lithium-ion diffusion kinetics and a stable cathode-electrolyte interface,giving a remarkable rate capability with specific capacities of 122 m Ah g^(-1)at 5C and 106 m Ah g^(-1)at 10C(1C=170 m A g^(-1)).It also maintained capacities of 110.7 m Ah g^(-1)(5C)and 84.1 m Ah g^(-1)(10C)after 400 cycles.It could be used in harsh environments and could be stably cycled at subzero temperatures(-10 and-20°C)and in solid-state electrolyte batteries.Life cycle assessment combined with economic evaluation using the Ever Batt model reveals that this direct regeneration approach has high economic and environmental benefits.
基金Funded by the National Natural Science Foundation of China(No.50902108)。
文摘Bi/Bi_(2)Fe_(4)O_(9)nanocomposites consisting of Bi_(2)Fe_(4)O_(9)nanosheets decorated with Bi nanodots were synthesized by a hydrothermal method.The formation of Bi nanodots on the Bi_(2)Fe_(4)O_(9)nanosheet surfaces was attributed to the reducibility of 2-methoxyethanol in the precursor solution.Comparative photocatalytic evaluation reveals that the Bi/Bi_(2)Fe_(4)O_(9)nanocomposites significantly enhance the degradation efficiency(99.0%)of bisphenol A compared with Bi_(2)Fe_(4)O_(9)nanosheets(64.2%)under 120 min simulated solar irradiation.This remarkable enhancement can be attributed to the established Bi/Bi_(2)Fe_(4)O_(9)heterojunction structure,which effectively facilitates the separation of photogenerated electron-hole pairs and accelerates interfacial charge transfer between the metallic Bi nanodots and semiconductor Bi_(2)Fe_(4)O_(9)nanosheets.The synergistic effects arising from this unique architecture ultimately lead to superior photocatalytic performance.
