Soil desiccation cracking is ubiquitous in nature and has significantpotential impacts on the engineering geological properties of soils.Previous studies have extensively examined various factors affecting soil cracki...Soil desiccation cracking is ubiquitous in nature and has significantpotential impacts on the engineering geological properties of soils.Previous studies have extensively examined various factors affecting soil cracking behavior through a numerous small-sample experiments.However,experimental studies alone cannot accurately describe soil cracking behavior.In this study,we firstly propose a modeling framework for predicting the surface crack ratio of soil desiccation cracking based on machine learning and interpretable analysis.The framework utilizes 1040 sets of soil cracking experimental data and employs random forest(RF),extreme gradient boosting(XGBoost),and artificialneural network(ANN)models to predict the surface crack ratio of soil desiccation cracking.To clarify the influenceof input features on soil cracking behavior,feature importance and Shapley additive explanations(SHAP)are applied for interpretability analysis.The results reveal that ensemble methods(RF and XGBoost)provide better predictive performance than the deep learning model(ANN).The feature importance analysis shows that soil desiccation cracking is primarily influencedby initial water content,plasticity index,finalwater content,liquid limit,sand content,clay content and thickness.Moreover,SHAP-based interpretability analysis further explores how soil cracking responds to various input variables.This study provides new insight into the evolution of soil cracking behavior,enhancing the understanding of its physical mechanisms and facilitating the assessment of potential regional development of soil desiccation cracking.展开更多
The micro-area characterization experiments like scanning Kelvin probe force microscope(SKPFM)and Kernel average misorientation have the defects of complex sample preparation and occasional errors in test results,whic...The micro-area characterization experiments like scanning Kelvin probe force microscope(SKPFM)and Kernel average misorientation have the defects of complex sample preparation and occasional errors in test results,which makes it impossible to accurately and quickly analyze the pitting behavior induced by inclusions in some cases,prompting attempts to turn to simulation calculation research.The method of calculating band structure and work function can be used to replace current-sensing atomic force microscopy and SKPFM to detect the potential and conductivity of the sample.The band structure results show that Al_(2)O_(3) inclusion is an insulator and non-conductive,and it will not form galvanic corrosion with the matrix.Al_(2)O_(3) inclusion does not dissolve because its work function is higher than that of the matrix.Moreover,the stress concentration of the matrix around the inclusion can be characterized by first-principles calculation coupled with finite element simulation.The results show that the stress concentration degree of the matrix around Al_(2)O_(3) inclusion is serious,and the galvanic corrosion is formed between the high and the low stress concentration areas,which can be used to explain the reason of the pitting induced by Al_(2)O_(3) inclusions.展开更多
Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace.It has a complex pathogenesis and currently lacks effective treatments.Homoharringtonine(HHT)is a natural compound...Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace.It has a complex pathogenesis and currently lacks effective treatments.Homoharringtonine(HHT)is a natural compound approved for the treatment of acute myeloid leukemia,but its effects on silicosis remain unclear.In the present study,we constructed a mouse model of silica(SiO_(2))-induced pulmonary fibrosis and evaluated the preventive and therapeutic effects of HHT.The results showed that HHT significantly attenuated the progression of SiO_(2)-induced pulmonary fibrosis in mice.We then used MRC-5,a human lung fibroblast cell line,to explore the mechanisms underlying HHT's inhibitory effects in vitro and found that HHT significantly inhibited the activation and migratory capacity of MRC-5 cells.Mechanistically,these effects were mediated by enhanced ubiquitination and degradation of the CCR1 protein.Furthermore,HHT exhibited favorable biocompatibility in vivo,and its preventive and therapeutic effects were validated in SiO_(2)-treated mice.Collectively,the current study demonstrates that HHT shows significant potential as a therapeutic agent for silicosis by targeting CCR1 and the PI3K/AKT/m TOR signaling pathway,highlighting it as a promising candidate for clinical translation for silicosis treatment.展开更多
As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant chal...As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant challenges primarily stemming from the difficulty in efficiently delivering large-sized genome editing system(including Cas9 protein and sgRNA)into targeted cells and spatiotemporally controlling their activity in vitro and in vivo.Therefore,the development of CRISPR/Cas9 nanovectors that integrate high loading capacity,efficient encapsulation and spatiotemporally-controlled release is highly desirable.Herein,we have engineered a near-infrared(NIR)light-activated upconversion-DNA nanocapsule for the remote control of CRISPR-Cas9 genome editing.The light-responsive upconversion-DNA nanocapsules consist of macroporous silica(mSiO_(2))coated upconversion nanoparticles(UCNPs)and photocleavable onitrobenzyl-phosphate-modified DNA shells.The UCNPs act as a“nanotransducers”to convert NIR light(980 nm)into local ultraviolet light,thereby facilitating the cleavage of photosensitive DNA nanocapsules and enabling on-demand release of CRISPR-Cas9 encapsuled in the macroporous silica.Furthermore,by formulating a sgRNA targeted to a tumor gene(polo-like kinase-1,PLK-1),the CRISPR-Cas9 loaded UCNPDNA nanocapsules(crUCNP-DNA nanocapsules)have effectively suppressed the proliferation of tumor cells through NIR light-activated gene editing both in vitro and in vivo.Overall,this UCNP-DNA nanocapsule holds tremendous potential for CRISPR-Cas9 delivery and remote-controlled gene editing in deep tissues,as well as the treatment of diverse diseases.展开更多
Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-me...Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-ments in karst hydrology,significant gaps remain in long-term trends,underlying processes,and quantitative effects of environmental changes.This is especially true in areas like the Wujiang River(WJ)in China,where human activities such as reservoir construction and land use/cover changes have accelerated hydrochemical changes.We combined recent and historical monitoring data to provide a detailed analysis of the spatial and temporal characteristics,evolution,and controlling factors of major ions in WJ.These findings are important for local water management and contribute to global efforts to manage similar karst systems facing human-induced pressures.Our research shows clear seasonal differences in solute concentrations,with higher levels during the dry season.WJ’s water is rich in calcium,with Ca-HCO_(3) ion pairs being the most common.Reservoir monitor-ing stations show much higher levels of NO_(3)^(−)and SO_(4)^(2−)compared to river-type stations,likely due to longer hydraulic retention time and increased acid deposition.The study confirms the significant role of pH and water temperature in rock weathering processes.Land use/cover changes were identified as the primary drivers of solute variations(46.37%),followed by lithology(13.92%)and temperature(8.35%).Over the past two decades,in-tense carbonate weathering has been observed,especially during wet seasons.Among karstic provinces,Guizhou Province stands out with the highest ion concentrations,indicative of its extensive karst coverage and heightened weathering processes.展开更多
Ammonia(NH3)has been widely recognized as a key precursor of atmospheric secondary aerosol formation.Vehicle emission is a major source of urban atmospheric NH3.With the tightening of emission standards and the growin...Ammonia(NH3)has been widely recognized as a key precursor of atmospheric secondary aerosol formation.Vehicle emission is a major source of urban atmospheric NH3.With the tightening of emission standards and the growing trend of vehicle fleet electrification,it is imperative to update the emission factors for NH3 from real-world on-road fleets.In this study,a tunnel measurement was conducted in the urban area of Tianjin,China.The fleet-average NH3 emission factor(EF)was 11.2 mg/(km·veh),significantly lower than those in previous studies,showing the benefit of emission standard updating.Through a multiple linear regression analysis,the EFs of light-duty gasoline vehicles,light-duty diesel vehicles,and heavy-duty diesel vehicles(HDDVs)were estimated to be 5.7±0.6 mg/(km·veh),40.8±5.1 mg/(km·veh),and 160.2±16.6 mg/(km·veh),respectively.Based on the results from this study,we found that HDDVs,which comprise<3%of the total vehicles may contribute approximately 22%of total NH3 emissions in Tianjin.Our results highlight NH3 emissions from HDDVs,a previously potentially overlooked source of NH3 emissions in urban areas.The actual on-road NH3 emissions from HDDVs may exceed current expectations,posing a growing concern for the future.展开更多
Three-dimensional(3D)ordered porous carbon is generally believed to be a promising electromagnetic wave(EMW)absorbing material.However,most research works targeted performance improvement of 3D ordered porous carbon,a...Three-dimensional(3D)ordered porous carbon is generally believed to be a promising electromagnetic wave(EMW)absorbing material.However,most research works targeted performance improvement of 3D ordered porous carbon,and the specific attenuation mechanism is still ambiguous.Therefore,in this work,a novel ultra-light egg-derived porous carbon foam(EDCF)structure has been successfully constructed by a simple carbonization combined with the silica microsphere template-etching process.Based on an equivalent substitute strategy,the influence of pore volume and specific surface area on the electromagnetic parameters and EMW absorption properties of the EDCF products was confirmed respectively by adjusting the addition content and diameter of silica microspheres.As a primary attenuation mode,the dielectric loss originates from the comprehensive effect of conduction loss and polarization loss in S-band and C band,and the value is dominated by polarization loss in X band and Ku band,which is obviously greater than that of conduction loss.Furthermore,in all samples,the largest effective absorption bandwidth of EDCF-3 is 7.12 GHz under the thickness of 2.13 mm with the filling content of approximately 5 wt%,covering the whole Ku band.Meanwhile,the EDCF-7 sample with optimized pore volume and specific surface area achieves minimum reflection loss(RL_(min))of−58.08 dB at 16.86 GHz while the thickness is 1.27 mm.The outstanding research results not only provide a novel insight into enhancement of EMW absorption properties but also clarify the dominant dissipation mechanism for the porous carbon-based absorber from the perspective of objective experiments.展开更多
A novel melting-assisted solvent-free route using solid oxalic acid was proposed for the post-treatment of SAPO-11 zeolite,followed by loading with 0.5 wt%Pt by the incipient wetness impregnation method.Subsequently,t...A novel melting-assisted solvent-free route using solid oxalic acid was proposed for the post-treatment of SAPO-11 zeolite,followed by loading with 0.5 wt%Pt by the incipient wetness impregnation method.Subsequently,the performance of the obtained bifunctional catalysts toward the hydroisomerization of n-dodecane was examined.The prepared samples were characterized by XRD,SEM,BET,XRF,Py-IR,and solid-state NMR.From the results,it was found that the high crystallinity and uniform morphology were retained after the post-treatment and that more(002)crystal faces were exposed,which was beneficial since more acid sites were provided.More importantly,the total Bronsted acid sites and the ratio(Ra)of the micropore area to the total surface area were optimized by this method.Thus,the catalytic performance was enhanced significantly,and the prepared Pt-SAPO-11-10%catalyst had the highest i-dodecane yield of 80.1%compared to 55.3%of Pt-SAPO-11.Expectedly,this facile and cost-effective method is promising for the hydroisomerization of normal paraffin in the production of lubricant base oils.展开更多
The regulation of apple(Malus domestica)fruit texture during ripening is complex and a fundamental determinant of its commercial quality.In climacteric fruit,ripening-related processes are regulated by ethylene(ET),an...The regulation of apple(Malus domestica)fruit texture during ripening is complex and a fundamental determinant of its commercial quality.In climacteric fruit,ripening-related processes are regulated by ethylene(ET),and jasmonate(JA)is also involved in the ethylene biosynthesis pathway,mainly through the transcription factor MYC2.However,the molecular genetic mechanism for fruit ripening processes between the JA and ET signaling pathways still needs to be elucidated.In order to explore how JA regulates apple fruit ripening through ERF4,we used’Gala’and’Ralls Janet’fruit at different developmental stages as experimental materials to determine the fruit firmness and related gene expression analysis.Meanwhile,we carried out different hormone treatments on’Gala’fruit at ripening stage.Here,we show that ERF4 is a core JA signaling hub protein JASMONATE ZIM-DOMAIN(JAZ)interactor that affects ethylene signaling pathways.During fruit development,ERF4 represses the expression of ACS1 and ACO1 by interacting with JAZ,as well as with the JA-activated transcription factor MYC2.Ripening is promoted in JAZ-suppressed apples.Thus,ERF4 acts as a molecular link between ethylene and JA hormone signals,and the natural variation of the ERF4Ethylene-responsive binding factor-associated amphiphilic repression(EAR)motif decreases repression of ethylene biosynthesis genes.展开更多
BACKGROUND Diabetic cardiomyopathy(DCM)increases the risk of hospitalization for heart failure(HF)and mortality in patients with diabetes mellitus.However,no specific therapy to delay the progression of DCM has been i...BACKGROUND Diabetic cardiomyopathy(DCM)increases the risk of hospitalization for heart failure(HF)and mortality in patients with diabetes mellitus.However,no specific therapy to delay the progression of DCM has been identified.Mitochondrial dysfunction,oxidative stress,inflammation,and calcium handling imbalance play a crucial role in the pathological processes of DCM,ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions.Empagliflozin,a novel glucoselowering agent,has been confirmed to reduce the risk of hospitalization for HF in diabetic patients.Nevertheless,the molecular mechanisms by which this agent provides cardioprotection remain unclear.AIM To investigate the effects of empagliflozin on high glucose(HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism.METHODS Twelve-week-old db/db mice and primary cardiomyocytes from neonatal rats stimulated with HG(30 mmol/L)were separately employed as in vivo and in vitro models.Echocardiography was used to evaluate cardiac function.Flow cytometry and TdT-mediated dUTP-biotin nick end labeling staining were used to assess apoptosis in myocardial cells.Mitochondrial function was assessed by cellular ATP levels and changes in mitochondrial membrane potential.Furthermore,intracellular reactive oxygen species production and superoxide dismutase activity were analyzed.Real-time quantitative PCR was used to analyze Bax and Bcl-2 mRNA expression.Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase(AMPK)and myosin phosphatase target subunit 1(MYPT1),as well as the peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)and active caspase-3 protein levels.RESULTSIn the in vivo experiment, db/db mice developed DCM. However, the treatment of db/db mice with empagliflozin(10 mg/kg/d) for 8 wk substantially enhanced cardiac function and significantly reduced myocardial apoptosis,accompanied by an increase in the phosphorylation of AMPK and PGC-1α protein levels, as well as a decrease inthe phosphorylation of MYPT1 in the heart. In the in vitro experiment, the findings indicate that treatment ofcardiomyocytes with empagliflozin (10 μM) or fasudil (FA) (a ROCK inhibitor, 100 μM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis.However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG,empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylatedMYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressingPGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucosecotransporter (SGLT)2 protein expression was detected in cardiomyocytes.CONCLUSION Empagliflozin partially achieves anti-oxidative stress and anti-apoptotic effects on cardiomyocytes under HGconditions by activating AMPK/PGC-1α and suppressing of the RhoA/ROCK pathway independent of SGLT2.展开更多
AIM: To investigate whether Tg737 is regulated by micro RNA-548a-5p(mi R-548a-5p), and correlates with hepatocellular carcinoma(HCC) cell proliferation and apoptosis.METHODS: Assays of loss of function of Tg737 were p...AIM: To investigate whether Tg737 is regulated by micro RNA-548a-5p(mi R-548a-5p), and correlates with hepatocellular carcinoma(HCC) cell proliferation and apoptosis.METHODS: Assays of loss of function of Tg737 were performed by the colony formation assay, CCK assay and cell cycle assay in HCC cell lines. The interaction between mi R-548a-5p and its downstream target, Tg737, was evaluated by a dual-luciferase reporter assay and quantitative real-time polymerase chain reaction. Tg737 was then up-regulated in HCC cells to evaluate its effect on mi R-548a-5p regulation. Hep G2 cells stably overexpressing mi R-548a-5p or mi R-control were also subcutaneously inoculated into nude mice to evaluate the effect of mi R-548a-5p up-regulation on in vivo tumor growth. As the final step, the effect of mi R-548a-5p on the apoptosis induced by cisplatin was evaluated by flow cytometry.RESULTS: Down-regulation of Tg737, which is a target gene of mi R-548a-5p, accelerated HCC cell proliferation, and mi R-548a-5p promoted HCC cell proliferation in vitro and in vivo. Like the downregulation of Tg737, overexpression of mi R-548a-5p in HCC cell lines promoted cell proliferation, increased colony forming ability and hampered cell apoptosis. In addition, mi R-548a-5p overexpression increased HCC cell growth in vivo. Mi R-548a-5p downregulated Tg737 expression through direct contact with its 3' untranslated region(UTR), and mi R-548a-5p expression was negatively correlated with Tg737 levels in HCC specimens. Restoring Tg737(without the 3'UTR) significantly hampered mi R-548a-5p induced cell proliferation, and rescued the mi R-548a-5p induced cell proliferation inhibition and apoptosis induced by cisplatin.CONCLUSION: Mi R-548a-5p negatively regulates the tumor inhibitor gene Tg737 and promotes tumorigenesis in vitro and in vivo, indicating its potential as a novel therapeutic target for HCC.展开更多
Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,...Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.展开更多
Red emitting phosphors play a significant role in accelerating the improvement of illumination quality for white light emitting diodes(WLEDs).In this work,by using solid-state reaction method,an efficient novel Ba_(2)...Red emitting phosphors play a significant role in accelerating the improvement of illumination quality for white light emitting diodes(WLEDs).In this work,by using solid-state reaction method,an efficient novel Ba_(2)LuNbO_(6):Eu^(3+)phosphor with double-perovskite structure was successfully prepared.Here,a series of Ba_(2)LuNbO_(6):Eu^(3+)red phosphors can be efficiently pumped by the near-ultraviolet(UV)light and then present high-brightness at orange emission(598 nm,~5D_(0)→~7 F_(1))and red emission(610 nm,~5D_(0)→~7 F_(2)).The ratio values of 610 to 598 nm in Ba_(2)LuNbO_(6):Eu^(3+)phosphors exceed 1 when the content of Eu^(3+)is larger than 0.4 mol,because the occupation of Eu^(3+)ions is changed from Lu^(3+)ions with symmetric sites to Ba^(2+)ions with asymmetric sites.Besides,the optimized concentration of Eu^(3+)at the~5D_(0)→~7 F_(2)transitions is obtained when x=1,indicating that there is non-concentration quenching in Ba_(2)LuNbO_(6):Eu^(3+)phosphors.Moreover,the CIE chromaticity coordinates of Ba_(2)LuNbO_(6):Eu^(3+)was calculated to be(0.587,0.361),the color purity was calculated to be 72.26%and internal quenching efficiency(IQE)was measured to be 67%.Finally,the thermal stability of Ba_(2)LuNbO_(6):Eu^(3+)phosphors was also studied.Our work demonstrates that the novel double-perovskite red-emitting Ba_(2)LuNbO_(6):Eu^(3+)phosphors are prospective red emitting elements for WLEDs applications.展开更多
To develop an efficient way to overcome the contradiction among flame retardancy,smoke suppression,and thermal insulation in expanded polystyrene(EPS)foams,which are widely used insulation materials in buildings,a nov...To develop an efficient way to overcome the contradiction among flame retardancy,smoke suppression,and thermal insulation in expanded polystyrene(EPS)foams,which are widely used insulation materials in buildings,a novel"green"porous bio-based flame-retard ant starch(FRS)coating was designed from starch modified with phytic acid(PA)that simultaneously acts as both a flame retardant and an adhesive.This porous FRS coating has open pores,which,in combination with the closed cells formed by EPS beads,create a hierarchically porous structure in FRS-EPS that results in superior thermal insulation with a lower thermal conductivity of 27.0 mW·(m·K)^(-1).The resultant FRS-EPS foam showed extremely low heat-release rates and smoke-production release,indicating excellent fire retardancy and smoke suppression.The specific optical density was as low as 121,which was 80.6%lower than that of neat EPS,at 624.The FRS-EPS also exhibited self-extinguishing behavior in vertical burning tests and had a high limiting oxygen index(LOI)value of 35.5%.More interestingly,after being burnt with an alcohol lamp for 30 min,the top side temperature of the FRS-EPS remained at only 140℃with ignition,thereby exhibiting excellent fire resistance.Mechanism analysis confirmed the intumescent action of FRS,which forms a compact phosphorus-rich hybrid barrier,and the phosphorus-containing compounds that formed in the gas phase contributed to the excellent flame retardancy and smoke suppression of FRS-EPS.This novel porous biomass-based FRS system provides a promising strategy for fabricating polymer foams with excellent flame retardancy,smoke suppression,and thermal insulation.展开更多
Septic encephalopathy is a frequent complication of sepsis,but there are few studies examining the role of micro RNAs（mi Rs） in its pathogenesis.In this study,a mi R-219 mimic was transfected into rat hippocampal ne...Septic encephalopathy is a frequent complication of sepsis,but there are few studies examining the role of micro RNAs（mi Rs） in its pathogenesis.In this study,a mi R-219 mimic was transfected into rat hippocampal neurons to model mi R-219 overexpression.A protective effect of mi R-219 was observed for glutamate-induced neurotoxicity of rat hippocampal neurons,and an underlying mechanism involving calmodulin-dependent protein kinase II γ（Ca MKIIγ） was demonstrated.mi R-219 and Ca MKIIγ m RNA expression induced by glutamate in hippocampal neurons was determined by quantitative real-time reverse transcription-polymerase chain reaction（q RT-PCR）.After neurons were transfected with mi R-219 mimic,effects on cell viability and apoptosis were measured by 3-（4,5-dimethylthiazolyl-2）-2,5-diphenyltetrazolium bromide（MTT） assay and flow cytometry.In addition,a luciferase reporter gene system was used to confirm Ca MKIIγ as a target gene of mi R-219.Western blot assay and rescue experiments were also utilized to detect Ca MKIIγ expression and further verify that mi R-219 in hippocampal neurons exerted its effect through regulation of Ca MKIIγ.MTT assay and q RT-PCR results revealed obvious decreases in cell viability and mi R-219 expression after glutamate stimulation,while Ca MKIIγ m RNA expression was increased.MTT,flow cytometry,and caspase-3 activity assays showed that mi R-219 overexpression could elevate glutamate-induced cell viability,and reduce cell apoptosis and caspase-3 activity.Moreover,luciferase Ca MKIIγ-reporter activity was remarkably decreased by co-transfection with mi R-219 mimic,and the results of a rescue experiment showed that Ca MKIIγ overexpression could reverse the biological effects of mi R-219.Collectively,these findings verify that mi R-219 expression was decreased in glutamate-induced neurons,Ca MKIIγ was a target gene of mi R-219,and mi R-219 alleviated glutamate-induced neuronal excitotoxicity by negatively controlling Ca MKIIγ expression.展开更多
Corneal diseases are currently the second main cause of blindness in China.Although most of the corneal blindness could be treated by corneal transplantation,only about 10 000 operations were carried out each year owi...Corneal diseases are currently the second main cause of blindness in China.Although most of the corneal blindness could be treated by corneal transplantation,only about 10 000 operations were carried out each year owing to the severe shortage of corneal donors and limited eye bank programs.A feasible cornea donation program was established through the organization of the Red Cross,and in situ corneal removal techniques were developed to avoid conflicts with Chinese traditions of keeping the deceased intact.The number of donated corneas,which had a safe and secure quality,increased significantly year by year.展开更多
BACKGROUND People with diabetes mellitus(DM)suffer from multiple chronic complications due to sustained hyperglycemia,especially diabetic cardiomyopathy(DCM).Oxidative stress and inflammatory cells play crucial roles ...BACKGROUND People with diabetes mellitus(DM)suffer from multiple chronic complications due to sustained hyperglycemia,especially diabetic cardiomyopathy(DCM).Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling.Macrophages polarize to two distinct phenotypes:M1 and M2,and such plasticity in phenotypes provide macrophages various biological functions.AIM To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms.METHODS DCM mouse models were established and randomly divided into DM,atorvastatin,and metformin groups.C57BL/6 mice were used as the control.Cardiac function was evaluated by echocardiography.Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues.The expression of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),M1 macrophages(iNOS^(+)),and M2 macrophages(CD206^(+))were demonstrated by immunohistochemistry and immunofluorescence staining.The levels of TGF-β1,IL-1β,and TNF-αwere detected by ELISA and real-time quantitative polymerase chain reaction.Malondialdehyde(MDA)concentrations and superoxide dismutase(SOD)activities were also measured.RESULTS Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardialfibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment.Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin;lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium;decreased the concentration of MDAand increased SOD activity in myocardium of db/db mice;inhibited M1 macrophages;and promoted M2macrophages.CONCLUSION Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with theantioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulatingmacrophage polarization.展开更多
AIM: To explore the effect of lysine acetylation in related proteins on regulation of the proliferation of gastric cancer cells, and determine the lysine-acetylated proteins and the acetylated modified sites in AGS ga...AIM: To explore the effect of lysine acetylation in related proteins on regulation of the proliferation of gastric cancer cells, and determine the lysine-acetylated proteins and the acetylated modified sites in AGS gastric cancer cells. METHODS: The CCK-8 experiment and flow cytometry were used to observe the changes in proliferation and cycle of AGS cells treated with trichostatin A (TSA). Real time polymerase chain reaction and Western blotting were used to observe expression changes in p21, p53, Bax, Bcl-2, CDK2, and CyclinD1 in gastric cancer cells exposed to TSA. Cytoplasmic proteins in gastric cancer cells before and after TSA treatment were immunoprecipitated with anti-acetylated lysine antibodies, separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis gel and silver-stained to detect the proteins by mass spectrometry after removal of the gel. The acetylated proteins in AGS cells were enriched with lysine-acetylated antibodies, and a high-resolution mass spectrometer was used to detect the acetylated proteins and modified sites. RESULTS: TSA significantly inhibited AGS cell proliferation, and promoted cell apoptosis, leading to AGS cell cycle arrest in G0/G1 and G2/M phases, especially G0/G1 phase. p21, p53 and Bax gene expression levels in AGS cells were increased with TSA treatment duration; Bcl-2, CDK2, and CyclinD1 gene expression levels were decreased with TSA treatment duration. Two unknown protein bands, 72 kDa (before exposure to TSA) and 28 kDa (after exposure to TSA), were identified by silver-staining after immunoprecipitation of AGS cells with the lysine-acetylated monoclonal antibodies. Mass spectrometry showed that the 72 kDa protein band may be PKM2 and the 28 kDa protein band may be ATP5O. The acetylated proteins and modified sites in AGS cells were determined. CONCLUSION: TSA can inhibit gastric cancer cell proliferation, which possibly activated signaling pathways in a variety of tumor-associated factors. ATP5O was obviously acetylated in AGS cells following TSA treatment.展开更多
The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the princ...The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.展开更多
Mechano-luminescence(ML) has been found diverse applications such as stress sensing,3-D signature,energy harvesting,and anti-counterfeiting,due to the unique properties of the corresponding ML phosphors performing in-...Mechano-luminescence(ML) has been found diverse applications such as stress sensing,3-D signature,energy harvesting,and anti-counterfeiting,due to the unique properties of the corresponding ML phosphors performing in-situ and real-time response to mechanical stimulus.Trap-controlled ML materials realize reproducible,quantitative mechano-optical conversion resulting from the released carriers for the trap-mediated charge storage and release.Herein,modulating traps matters the controllable ML behavior for their promising applications.In this work,a deep trap distributed ranging from 0.9 to 1,3 eV is realized consecutively for the introduction of Sm^(3+)ions into LaGaO_(3) matrix,which contributes to the red emission at 600 nm under mechanical stimuli.Moreover,tunable ML emission modulated from 600to 545 nm is successfully achieved for the codopant of Tb^(3+)ions.It is unambiguously indicated that the released carriers from the trap sharing rather than an additional constructed trap contribute to the modulated ML color.Accordingly,multi-mode anti-counterfeiting and encryption are achieved with the as-explored Sm^(3+),Tb^(3+)co-activated ML phosphor.展开更多
基金supported by the National Key Research and Development Program of China(Grant Nos.2023YFC3707900 and 2024YFC3012700)the National Natural Science Foundation of China(Grant No.42230710).
文摘Soil desiccation cracking is ubiquitous in nature and has significantpotential impacts on the engineering geological properties of soils.Previous studies have extensively examined various factors affecting soil cracking behavior through a numerous small-sample experiments.However,experimental studies alone cannot accurately describe soil cracking behavior.In this study,we firstly propose a modeling framework for predicting the surface crack ratio of soil desiccation cracking based on machine learning and interpretable analysis.The framework utilizes 1040 sets of soil cracking experimental data and employs random forest(RF),extreme gradient boosting(XGBoost),and artificialneural network(ANN)models to predict the surface crack ratio of soil desiccation cracking.To clarify the influenceof input features on soil cracking behavior,feature importance and Shapley additive explanations(SHAP)are applied for interpretability analysis.The results reveal that ensemble methods(RF and XGBoost)provide better predictive performance than the deep learning model(ANN).The feature importance analysis shows that soil desiccation cracking is primarily influencedby initial water content,plasticity index,finalwater content,liquid limit,sand content,clay content and thickness.Moreover,SHAP-based interpretability analysis further explores how soil cracking responds to various input variables.This study provides new insight into the evolution of soil cracking behavior,enhancing the understanding of its physical mechanisms and facilitating the assessment of potential regional development of soil desiccation cracking.
基金supported by the National Natural Science Foundation of China(Nos.52364044 and 52204364)Central Guidance on Local Science and Technology Development Fund Projects of Inner Mongolia Autonomous Region(No.2022ZY0090)Basic Scientific Research Business Expenses of Colleges and Universities in Inner Mongolia Autonomous Region(Nos.2023QNJS011 and 0406082226).
文摘The micro-area characterization experiments like scanning Kelvin probe force microscope(SKPFM)and Kernel average misorientation have the defects of complex sample preparation and occasional errors in test results,which makes it impossible to accurately and quickly analyze the pitting behavior induced by inclusions in some cases,prompting attempts to turn to simulation calculation research.The method of calculating band structure and work function can be used to replace current-sensing atomic force microscopy and SKPFM to detect the potential and conductivity of the sample.The band structure results show that Al_(2)O_(3) inclusion is an insulator and non-conductive,and it will not form galvanic corrosion with the matrix.Al_(2)O_(3) inclusion does not dissolve because its work function is higher than that of the matrix.Moreover,the stress concentration of the matrix around the inclusion can be characterized by first-principles calculation coupled with finite element simulation.The results show that the stress concentration degree of the matrix around Al_(2)O_(3) inclusion is serious,and the galvanic corrosion is formed between the high and the low stress concentration areas,which can be used to explain the reason of the pitting induced by Al_(2)O_(3) inclusions.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82473601 to Y.L.,82404234 to W.S.,and 82073518 to C.N.)the Foundation of Chongqing Key Laboratory of Prevention and Treatment for Occupational Diseases and Poisoning(Grant No.2022-2023ZYBKF04 to C.N.)。
文摘Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace.It has a complex pathogenesis and currently lacks effective treatments.Homoharringtonine(HHT)is a natural compound approved for the treatment of acute myeloid leukemia,but its effects on silicosis remain unclear.In the present study,we constructed a mouse model of silica(SiO_(2))-induced pulmonary fibrosis and evaluated the preventive and therapeutic effects of HHT.The results showed that HHT significantly attenuated the progression of SiO_(2)-induced pulmonary fibrosis in mice.We then used MRC-5,a human lung fibroblast cell line,to explore the mechanisms underlying HHT's inhibitory effects in vitro and found that HHT significantly inhibited the activation and migratory capacity of MRC-5 cells.Mechanistically,these effects were mediated by enhanced ubiquitination and degradation of the CCR1 protein.Furthermore,HHT exhibited favorable biocompatibility in vivo,and its preventive and therapeutic effects were validated in SiO_(2)-treated mice.Collectively,the current study demonstrates that HHT shows significant potential as a therapeutic agent for silicosis by targeting CCR1 and the PI3K/AKT/m TOR signaling pathway,highlighting it as a promising candidate for clinical translation for silicosis treatment.
基金supported by the National Natural Science Foundation of China(Nos.21804059 and 21701059)the Natural Science Foundation of Jiangsu Province(No.BK20180974)+1 种基金the China Postdoctoral Science Foundation(No.2020M681544)the Postdoctoral Science Foundation of Jiangsu Province(No.2020Z351)。
文摘As a renovator in the field of gene editing,CRISPR-Cas9 has demonstrated immense potential for advancing next-generation gene therapy owing to its simplicity and precision.However,this potential faces significant challenges primarily stemming from the difficulty in efficiently delivering large-sized genome editing system(including Cas9 protein and sgRNA)into targeted cells and spatiotemporally controlling their activity in vitro and in vivo.Therefore,the development of CRISPR/Cas9 nanovectors that integrate high loading capacity,efficient encapsulation and spatiotemporally-controlled release is highly desirable.Herein,we have engineered a near-infrared(NIR)light-activated upconversion-DNA nanocapsule for the remote control of CRISPR-Cas9 genome editing.The light-responsive upconversion-DNA nanocapsules consist of macroporous silica(mSiO_(2))coated upconversion nanoparticles(UCNPs)and photocleavable onitrobenzyl-phosphate-modified DNA shells.The UCNPs act as a“nanotransducers”to convert NIR light(980 nm)into local ultraviolet light,thereby facilitating the cleavage of photosensitive DNA nanocapsules and enabling on-demand release of CRISPR-Cas9 encapsuled in the macroporous silica.Furthermore,by formulating a sgRNA targeted to a tumor gene(polo-like kinase-1,PLK-1),the CRISPR-Cas9 loaded UCNPDNA nanocapsules(crUCNP-DNA nanocapsules)have effectively suppressed the proliferation of tumor cells through NIR light-activated gene editing both in vitro and in vivo.Overall,this UCNP-DNA nanocapsule holds tremendous potential for CRISPR-Cas9 delivery and remote-controlled gene editing in deep tissues,as well as the treatment of diverse diseases.
基金supported by Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515110824 and 2025A1515011839)Shenzhen Science and Technology Program(No.RCBS20231211090638066).
文摘Understanding water chemistry in karst regions is crucial for improving global water resource management and deepening our knowledge of the biogeochemical cycles shaping these sensitive environments.Despite advance-ments in karst hydrology,significant gaps remain in long-term trends,underlying processes,and quantitative effects of environmental changes.This is especially true in areas like the Wujiang River(WJ)in China,where human activities such as reservoir construction and land use/cover changes have accelerated hydrochemical changes.We combined recent and historical monitoring data to provide a detailed analysis of the spatial and temporal characteristics,evolution,and controlling factors of major ions in WJ.These findings are important for local water management and contribute to global efforts to manage similar karst systems facing human-induced pressures.Our research shows clear seasonal differences in solute concentrations,with higher levels during the dry season.WJ’s water is rich in calcium,with Ca-HCO_(3) ion pairs being the most common.Reservoir monitor-ing stations show much higher levels of NO_(3)^(−)and SO_(4)^(2−)compared to river-type stations,likely due to longer hydraulic retention time and increased acid deposition.The study confirms the significant role of pH and water temperature in rock weathering processes.Land use/cover changes were identified as the primary drivers of solute variations(46.37%),followed by lithology(13.92%)and temperature(8.35%).Over the past two decades,in-tense carbonate weathering has been observed,especially during wet seasons.Among karstic provinces,Guizhou Province stands out with the highest ion concentrations,indicative of its extensive karst coverage and heightened weathering processes.
基金supported by the National key research and development program of China(No.2022YFE0135000)the National Natural Science Foundation of China(No.42175123)the Natural Science Foundation of Tianjin(No.23JCJQJC00170).
文摘Ammonia(NH3)has been widely recognized as a key precursor of atmospheric secondary aerosol formation.Vehicle emission is a major source of urban atmospheric NH3.With the tightening of emission standards and the growing trend of vehicle fleet electrification,it is imperative to update the emission factors for NH3 from real-world on-road fleets.In this study,a tunnel measurement was conducted in the urban area of Tianjin,China.The fleet-average NH3 emission factor(EF)was 11.2 mg/(km·veh),significantly lower than those in previous studies,showing the benefit of emission standard updating.Through a multiple linear regression analysis,the EFs of light-duty gasoline vehicles,light-duty diesel vehicles,and heavy-duty diesel vehicles(HDDVs)were estimated to be 5.7±0.6 mg/(km·veh),40.8±5.1 mg/(km·veh),and 160.2±16.6 mg/(km·veh),respectively.Based on the results from this study,we found that HDDVs,which comprise<3%of the total vehicles may contribute approximately 22%of total NH3 emissions in Tianjin.Our results highlight NH3 emissions from HDDVs,a previously potentially overlooked source of NH3 emissions in urban areas.The actual on-road NH3 emissions from HDDVs may exceed current expectations,posing a growing concern for the future.
基金supported by the National Natural Science Foundation of China under Grant No.52072196,52002199,52002200,52102106Major Basic Research Program of Natural Science Foundation of Shandong Province under Grant No.ZR2020ZD09+2 种基金the Natural Science Foundation of Shandong Province under Grant No.ZR2019BEM042,ZR2020QE063the Innovation and Technology Program of Shandong Province under Grant No.2020KJA004the Taishan Scholars Program of Shandong Province under No.ts201511034
文摘Three-dimensional(3D)ordered porous carbon is generally believed to be a promising electromagnetic wave(EMW)absorbing material.However,most research works targeted performance improvement of 3D ordered porous carbon,and the specific attenuation mechanism is still ambiguous.Therefore,in this work,a novel ultra-light egg-derived porous carbon foam(EDCF)structure has been successfully constructed by a simple carbonization combined with the silica microsphere template-etching process.Based on an equivalent substitute strategy,the influence of pore volume and specific surface area on the electromagnetic parameters and EMW absorption properties of the EDCF products was confirmed respectively by adjusting the addition content and diameter of silica microspheres.As a primary attenuation mode,the dielectric loss originates from the comprehensive effect of conduction loss and polarization loss in S-band and C band,and the value is dominated by polarization loss in X band and Ku band,which is obviously greater than that of conduction loss.Furthermore,in all samples,the largest effective absorption bandwidth of EDCF-3 is 7.12 GHz under the thickness of 2.13 mm with the filling content of approximately 5 wt%,covering the whole Ku band.Meanwhile,the EDCF-7 sample with optimized pore volume and specific surface area achieves minimum reflection loss(RL_(min))of−58.08 dB at 16.86 GHz while the thickness is 1.27 mm.The outstanding research results not only provide a novel insight into enhancement of EMW absorption properties but also clarify the dominant dissipation mechanism for the porous carbon-based absorber from the perspective of objective experiments.
基金supported by the National Natural Science Foundation of China(21776295)the Youth Innovation Promotion Association,CAS(2017355)~~
文摘A novel melting-assisted solvent-free route using solid oxalic acid was proposed for the post-treatment of SAPO-11 zeolite,followed by loading with 0.5 wt%Pt by the incipient wetness impregnation method.Subsequently,the performance of the obtained bifunctional catalysts toward the hydroisomerization of n-dodecane was examined.The prepared samples were characterized by XRD,SEM,BET,XRF,Py-IR,and solid-state NMR.From the results,it was found that the high crystallinity and uniform morphology were retained after the post-treatment and that more(002)crystal faces were exposed,which was beneficial since more acid sites were provided.More importantly,the total Bronsted acid sites and the ratio(Ra)of the micropore area to the total surface area were optimized by this method.Thus,the catalytic performance was enhanced significantly,and the prepared Pt-SAPO-11-10%catalyst had the highest i-dodecane yield of 80.1%compared to 55.3%of Pt-SAPO-11.Expectedly,this facile and cost-effective method is promising for the hydroisomerization of normal paraffin in the production of lubricant base oils.
基金supported by the National Key Research and Development Program [Grant No.2018YFD1000200]the National Natural Science Foundation of China [Grant Nos.31872941,32072543]+2 种基金the Construction of Beijing Science and Technology Innovation and Service Capacity in Top Subjects [Grant No.CEFFPXM2019_014207_000032]the 111 Project [Grant No.B17043]the Engineering Research Center of Breeding and Propagation of Horticultural Crops,Ministry of Education。
文摘The regulation of apple(Malus domestica)fruit texture during ripening is complex and a fundamental determinant of its commercial quality.In climacteric fruit,ripening-related processes are regulated by ethylene(ET),and jasmonate(JA)is also involved in the ethylene biosynthesis pathway,mainly through the transcription factor MYC2.However,the molecular genetic mechanism for fruit ripening processes between the JA and ET signaling pathways still needs to be elucidated.In order to explore how JA regulates apple fruit ripening through ERF4,we used’Gala’and’Ralls Janet’fruit at different developmental stages as experimental materials to determine the fruit firmness and related gene expression analysis.Meanwhile,we carried out different hormone treatments on’Gala’fruit at ripening stage.Here,we show that ERF4 is a core JA signaling hub protein JASMONATE ZIM-DOMAIN(JAZ)interactor that affects ethylene signaling pathways.During fruit development,ERF4 represses the expression of ACS1 and ACO1 by interacting with JAZ,as well as with the JA-activated transcription factor MYC2.Ripening is promoted in JAZ-suppressed apples.Thus,ERF4 acts as a molecular link between ethylene and JA hormone signals,and the natural variation of the ERF4Ethylene-responsive binding factor-associated amphiphilic repression(EAR)motif decreases repression of ethylene biosynthesis genes.
基金Health Commission of Hebei Province,No.20210196S&T Program of Hebei,No.22377726D。
文摘BACKGROUND Diabetic cardiomyopathy(DCM)increases the risk of hospitalization for heart failure(HF)and mortality in patients with diabetes mellitus.However,no specific therapy to delay the progression of DCM has been identified.Mitochondrial dysfunction,oxidative stress,inflammation,and calcium handling imbalance play a crucial role in the pathological processes of DCM,ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions.Empagliflozin,a novel glucoselowering agent,has been confirmed to reduce the risk of hospitalization for HF in diabetic patients.Nevertheless,the molecular mechanisms by which this agent provides cardioprotection remain unclear.AIM To investigate the effects of empagliflozin on high glucose(HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism.METHODS Twelve-week-old db/db mice and primary cardiomyocytes from neonatal rats stimulated with HG(30 mmol/L)were separately employed as in vivo and in vitro models.Echocardiography was used to evaluate cardiac function.Flow cytometry and TdT-mediated dUTP-biotin nick end labeling staining were used to assess apoptosis in myocardial cells.Mitochondrial function was assessed by cellular ATP levels and changes in mitochondrial membrane potential.Furthermore,intracellular reactive oxygen species production and superoxide dismutase activity were analyzed.Real-time quantitative PCR was used to analyze Bax and Bcl-2 mRNA expression.Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase(AMPK)and myosin phosphatase target subunit 1(MYPT1),as well as the peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)and active caspase-3 protein levels.RESULTSIn the in vivo experiment, db/db mice developed DCM. However, the treatment of db/db mice with empagliflozin(10 mg/kg/d) for 8 wk substantially enhanced cardiac function and significantly reduced myocardial apoptosis,accompanied by an increase in the phosphorylation of AMPK and PGC-1α protein levels, as well as a decrease inthe phosphorylation of MYPT1 in the heart. In the in vitro experiment, the findings indicate that treatment ofcardiomyocytes with empagliflozin (10 μM) or fasudil (FA) (a ROCK inhibitor, 100 μM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis.However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG,empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylatedMYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressingPGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucosecotransporter (SGLT)2 protein expression was detected in cardiomyocytes.CONCLUSION Empagliflozin partially achieves anti-oxidative stress and anti-apoptotic effects on cardiomyocytes under HGconditions by activating AMPK/PGC-1α and suppressing of the RhoA/ROCK pathway independent of SGLT2.
基金Supported by National Natural Science Foundation of ChinaNo.81272648
文摘AIM: To investigate whether Tg737 is regulated by micro RNA-548a-5p(mi R-548a-5p), and correlates with hepatocellular carcinoma(HCC) cell proliferation and apoptosis.METHODS: Assays of loss of function of Tg737 were performed by the colony formation assay, CCK assay and cell cycle assay in HCC cell lines. The interaction between mi R-548a-5p and its downstream target, Tg737, was evaluated by a dual-luciferase reporter assay and quantitative real-time polymerase chain reaction. Tg737 was then up-regulated in HCC cells to evaluate its effect on mi R-548a-5p regulation. Hep G2 cells stably overexpressing mi R-548a-5p or mi R-control were also subcutaneously inoculated into nude mice to evaluate the effect of mi R-548a-5p up-regulation on in vivo tumor growth. As the final step, the effect of mi R-548a-5p on the apoptosis induced by cisplatin was evaluated by flow cytometry.RESULTS: Down-regulation of Tg737, which is a target gene of mi R-548a-5p, accelerated HCC cell proliferation, and mi R-548a-5p promoted HCC cell proliferation in vitro and in vivo. Like the downregulation of Tg737, overexpression of mi R-548a-5p in HCC cell lines promoted cell proliferation, increased colony forming ability and hampered cell apoptosis. In addition, mi R-548a-5p overexpression increased HCC cell growth in vivo. Mi R-548a-5p downregulated Tg737 expression through direct contact with its 3' untranslated region(UTR), and mi R-548a-5p expression was negatively correlated with Tg737 levels in HCC specimens. Restoring Tg737(without the 3'UTR) significantly hampered mi R-548a-5p induced cell proliferation, and rescued the mi R-548a-5p induced cell proliferation inhibition and apoptosis induced by cisplatin.CONCLUSION: Mi R-548a-5p negatively regulates the tumor inhibitor gene Tg737 and promotes tumorigenesis in vitro and in vivo, indicating its potential as a novel therapeutic target for HCC.
基金supported by the National Natural Science Foundation of China (U21A20361 and 82130039 to Y.W.Z.)Fundamental Research Funds for the Central Universities (20720220133 to Y.W.Z.)+2 种基金Natural Science Foundation of Fujian Province (2021J02057 to Q.L.M.)Science and Technology Plan Projects of Fujian Province (2020Y2015 to Z.X.W.)2020 Joint Support of Key Projects on Health Care (3502Z20209005 to Z.X.W.)。
文摘Synaptic dysfunction is an important pathological hallmark and cause of Alzheimer's disease(AD).High-frequency stimulation(HFS)-induced long-term potentiation(LTP)has been widely used to study synaptic plasticity,with impaired LTP found to be associated with AD.However,the exact molecular mechanism underlying synaptic plasticity has yet to be completely elucidated.Whether genes regulating synaptic plasticity are altered in AD and contribute to disease onset also remains unclear.Herein,we induced LTP in the hippocampal CA1 region of wildtype(WT)and AD model mice by administering HFS to the CA3 region and then studied transcriptome changes in the CA1 region.We identified 89 genes that may participate in normal synaptic plasticity by screening HFS-induced differentially expressed genes(DEGs)in mice with normal LTP,and 43 genes that may contribute to synaptic dysfunction in AD by comparing HFS-induced DEGs in mice with normal LTP and AD mice with impaired LTP.We further refined the 43 genes down to 14 by screening for genes with altered expression in pathological-stage AD mice without HFS induction.Among them,we found that the expression of Pygm,which catabolizes glycogen,was also decreased in AD patients.We further demonstrated that down-regulation of PYGM in neurons impaired synaptic plasticity and cognition in WT mice,while its overexpression attenuated synaptic dysfunction and cognitive deficits in AD mice.Moreover,we showed that PYGM directly regulated energy generation in neurons.Our study not only indicates that PYGM-mediated energy production in neurons plays an important role in synaptic function,but also provides a novel LTP-based strategy to systematically identify genes regulating synaptic plasticity under physiological and pathological conditions.
基金Project supported by the Excellent Youth Project of Yunnan Province Applied Basic Research Project(2019FI001)the National Natural Science Foundation of China(61775187,61965012,12064022)the Key Project of Yunnan Provincial Natural Science Foundation(202101AT070126)。
文摘Red emitting phosphors play a significant role in accelerating the improvement of illumination quality for white light emitting diodes(WLEDs).In this work,by using solid-state reaction method,an efficient novel Ba_(2)LuNbO_(6):Eu^(3+)phosphor with double-perovskite structure was successfully prepared.Here,a series of Ba_(2)LuNbO_(6):Eu^(3+)red phosphors can be efficiently pumped by the near-ultraviolet(UV)light and then present high-brightness at orange emission(598 nm,~5D_(0)→~7 F_(1))and red emission(610 nm,~5D_(0)→~7 F_(2)).The ratio values of 610 to 598 nm in Ba_(2)LuNbO_(6):Eu^(3+)phosphors exceed 1 when the content of Eu^(3+)is larger than 0.4 mol,because the occupation of Eu^(3+)ions is changed from Lu^(3+)ions with symmetric sites to Ba^(2+)ions with asymmetric sites.Besides,the optimized concentration of Eu^(3+)at the~5D_(0)→~7 F_(2)transitions is obtained when x=1,indicating that there is non-concentration quenching in Ba_(2)LuNbO_(6):Eu^(3+)phosphors.Moreover,the CIE chromaticity coordinates of Ba_(2)LuNbO_(6):Eu^(3+)was calculated to be(0.587,0.361),the color purity was calculated to be 72.26%and internal quenching efficiency(IQE)was measured to be 67%.Finally,the thermal stability of Ba_(2)LuNbO_(6):Eu^(3+)phosphors was also studied.Our work demonstrates that the novel double-perovskite red-emitting Ba_(2)LuNbO_(6):Eu^(3+)phosphors are prospective red emitting elements for WLEDs applications.
基金financially supported by the National Natural Science Foundation of China(51827803,51320105011,51790504,and 51721091)the Young Elite Scientists Sponsorship Program by CASTFundamental Research Funds for the Central Universities。
文摘To develop an efficient way to overcome the contradiction among flame retardancy,smoke suppression,and thermal insulation in expanded polystyrene(EPS)foams,which are widely used insulation materials in buildings,a novel"green"porous bio-based flame-retard ant starch(FRS)coating was designed from starch modified with phytic acid(PA)that simultaneously acts as both a flame retardant and an adhesive.This porous FRS coating has open pores,which,in combination with the closed cells formed by EPS beads,create a hierarchically porous structure in FRS-EPS that results in superior thermal insulation with a lower thermal conductivity of 27.0 mW·(m·K)^(-1).The resultant FRS-EPS foam showed extremely low heat-release rates and smoke-production release,indicating excellent fire retardancy and smoke suppression.The specific optical density was as low as 121,which was 80.6%lower than that of neat EPS,at 624.The FRS-EPS also exhibited self-extinguishing behavior in vertical burning tests and had a high limiting oxygen index(LOI)value of 35.5%.More interestingly,after being burnt with an alcohol lamp for 30 min,the top side temperature of the FRS-EPS remained at only 140℃with ignition,thereby exhibiting excellent fire resistance.Mechanism analysis confirmed the intumescent action of FRS,which forms a compact phosphorus-rich hybrid barrier,and the phosphorus-containing compounds that formed in the gas phase contributed to the excellent flame retardancy and smoke suppression of FRS-EPS.This novel porous biomass-based FRS system provides a promising strategy for fabricating polymer foams with excellent flame retardancy,smoke suppression,and thermal insulation.
基金supported by the National Natural Science Foundation of China,No.81101159the Natural Science Foundation of Jiangsu Province of China,No.BK20151268
文摘Septic encephalopathy is a frequent complication of sepsis,but there are few studies examining the role of micro RNAs（mi Rs） in its pathogenesis.In this study,a mi R-219 mimic was transfected into rat hippocampal neurons to model mi R-219 overexpression.A protective effect of mi R-219 was observed for glutamate-induced neurotoxicity of rat hippocampal neurons,and an underlying mechanism involving calmodulin-dependent protein kinase II γ（Ca MKIIγ） was demonstrated.mi R-219 and Ca MKIIγ m RNA expression induced by glutamate in hippocampal neurons was determined by quantitative real-time reverse transcription-polymerase chain reaction（q RT-PCR）.After neurons were transfected with mi R-219 mimic,effects on cell viability and apoptosis were measured by 3-（4,5-dimethylthiazolyl-2）-2,5-diphenyltetrazolium bromide（MTT） assay and flow cytometry.In addition,a luciferase reporter gene system was used to confirm Ca MKIIγ as a target gene of mi R-219.Western blot assay and rescue experiments were also utilized to detect Ca MKIIγ expression and further verify that mi R-219 in hippocampal neurons exerted its effect through regulation of Ca MKIIγ.MTT assay and q RT-PCR results revealed obvious decreases in cell viability and mi R-219 expression after glutamate stimulation,while Ca MKIIγ m RNA expression was increased.MTT,flow cytometry,and caspase-3 activity assays showed that mi R-219 overexpression could elevate glutamate-induced cell viability,and reduce cell apoptosis and caspase-3 activity.Moreover,luciferase Ca MKIIγ-reporter activity was remarkably decreased by co-transfection with mi R-219 mimic,and the results of a rescue experiment showed that Ca MKIIγ overexpression could reverse the biological effects of mi R-219.Collectively,these findings verify that mi R-219 expression was decreased in glutamate-induced neurons,Ca MKIIγ was a target gene of mi R-219,and mi R-219 alleviated glutamate-induced neuronal excitotoxicity by negatively controlling Ca MKIIγ expression.
基金Supported by the National Natural Science Foundation of China(No.81500702,No.81530027)the Shandong Provincial Natural Science Foundation(No.2016GSF201216)+1 种基金the Taishan Scholar Program(No.spd20150215,No.20161059)the Innovation Project of Shandong Academy of Medical Sciences
文摘Corneal diseases are currently the second main cause of blindness in China.Although most of the corneal blindness could be treated by corneal transplantation,only about 10 000 operations were carried out each year owing to the severe shortage of corneal donors and limited eye bank programs.A feasible cornea donation program was established through the organization of the Red Cross,and in situ corneal removal techniques were developed to avoid conflicts with Chinese traditions of keeping the deceased intact.The number of donated corneas,which had a safe and secure quality,increased significantly year by year.
基金the Health Commission of Hebei Province,No.20220998.
文摘BACKGROUND People with diabetes mellitus(DM)suffer from multiple chronic complications due to sustained hyperglycemia,especially diabetic cardiomyopathy(DCM).Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling.Macrophages polarize to two distinct phenotypes:M1 and M2,and such plasticity in phenotypes provide macrophages various biological functions.AIM To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms.METHODS DCM mouse models were established and randomly divided into DM,atorvastatin,and metformin groups.C57BL/6 mice were used as the control.Cardiac function was evaluated by echocardiography.Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues.The expression of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),M1 macrophages(iNOS^(+)),and M2 macrophages(CD206^(+))were demonstrated by immunohistochemistry and immunofluorescence staining.The levels of TGF-β1,IL-1β,and TNF-αwere detected by ELISA and real-time quantitative polymerase chain reaction.Malondialdehyde(MDA)concentrations and superoxide dismutase(SOD)activities were also measured.RESULTS Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardialfibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment.Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin;lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium;decreased the concentration of MDAand increased SOD activity in myocardium of db/db mice;inhibited M1 macrophages;and promoted M2macrophages.CONCLUSION Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with theantioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulatingmacrophage polarization.
基金Supported by Shanghai Municipal Health Bureau Key Disciplines Grant, No. ZK2012A05National Natural Science Foundation, No. 81070344
文摘AIM: To explore the effect of lysine acetylation in related proteins on regulation of the proliferation of gastric cancer cells, and determine the lysine-acetylated proteins and the acetylated modified sites in AGS gastric cancer cells. METHODS: The CCK-8 experiment and flow cytometry were used to observe the changes in proliferation and cycle of AGS cells treated with trichostatin A (TSA). Real time polymerase chain reaction and Western blotting were used to observe expression changes in p21, p53, Bax, Bcl-2, CDK2, and CyclinD1 in gastric cancer cells exposed to TSA. Cytoplasmic proteins in gastric cancer cells before and after TSA treatment were immunoprecipitated with anti-acetylated lysine antibodies, separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis gel and silver-stained to detect the proteins by mass spectrometry after removal of the gel. The acetylated proteins in AGS cells were enriched with lysine-acetylated antibodies, and a high-resolution mass spectrometer was used to detect the acetylated proteins and modified sites. RESULTS: TSA significantly inhibited AGS cell proliferation, and promoted cell apoptosis, leading to AGS cell cycle arrest in G0/G1 and G2/M phases, especially G0/G1 phase. p21, p53 and Bax gene expression levels in AGS cells were increased with TSA treatment duration; Bcl-2, CDK2, and CyclinD1 gene expression levels were decreased with TSA treatment duration. Two unknown protein bands, 72 kDa (before exposure to TSA) and 28 kDa (after exposure to TSA), were identified by silver-staining after immunoprecipitation of AGS cells with the lysine-acetylated monoclonal antibodies. Mass spectrometry showed that the 72 kDa protein band may be PKM2 and the 28 kDa protein band may be ATP5O. The acetylated proteins and modified sites in AGS cells were determined. CONCLUSION: TSA can inhibit gastric cancer cell proliferation, which possibly activated signaling pathways in a variety of tumor-associated factors. ATP5O was obviously acetylated in AGS cells following TSA treatment.
基金supported by“Jiaotong University Star”Program,China(Grant No.:YG2022QN082)the National Natural Science Foundation of China(Grant No.:82204887)+1 种基金the Science Foundation for Shanghai Committee of Science Project,China(Grant Nos.:21S21901400,23S21901200)the Natural Science Research Foundation of Jiading District,China(Grant No.:JDKW-2021-0023).
文摘The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.
基金Project supported by the Yunnan Provincial Natural Science Foundation (202101AT070126)the Research Start-up Fund of Chengdu University of Technology (10912-KYQD2020-08476)+1 种基金Fund of Hubei Key Laboratory of Plasma Chemistry,Advanced Materials (KF202103)Sichuan Natural Science Foundation (2022YFH0108,2022JDJQ0030)。
文摘Mechano-luminescence(ML) has been found diverse applications such as stress sensing,3-D signature,energy harvesting,and anti-counterfeiting,due to the unique properties of the corresponding ML phosphors performing in-situ and real-time response to mechanical stimulus.Trap-controlled ML materials realize reproducible,quantitative mechano-optical conversion resulting from the released carriers for the trap-mediated charge storage and release.Herein,modulating traps matters the controllable ML behavior for their promising applications.In this work,a deep trap distributed ranging from 0.9 to 1,3 eV is realized consecutively for the introduction of Sm^(3+)ions into LaGaO_(3) matrix,which contributes to the red emission at 600 nm under mechanical stimuli.Moreover,tunable ML emission modulated from 600to 545 nm is successfully achieved for the codopant of Tb^(3+)ions.It is unambiguously indicated that the released carriers from the trap sharing rather than an additional constructed trap contribute to the modulated ML color.Accordingly,multi-mode anti-counterfeiting and encryption are achieved with the as-explored Sm^(3+),Tb^(3+)co-activated ML phosphor.
