Large-scale CO_(2)emissions have exacerbated the greenhouse effect,reinforcing the critical need for efficient CO_(2)mitigation methods.Plasma-catalytic technology enables CO_(2)conversion under mild conditions,especi...Large-scale CO_(2)emissions have exacerbated the greenhouse effect,reinforcing the critical need for efficient CO_(2)mitigation methods.Plasma-catalytic technology enables CO_(2)conversion under mild conditions,especially for CO_(2)methanation(the Sabatier reaction),which has attracted significant attention due to its economic benefits and the potential for safe energy transportation via existing natural gas pipelines.The development of high-performance CO_(2)methanation catalysts remains an ongoing and long-term objective,and there is a lack of adequate in-situ characterization techniques to investigate the mechanisms.This study focuses on the Ni/La_(2)O_(3)(LN)catalyst and introduces two CO_(2)activation strategies through F and Na modifications:the Ni-Ov-Ni site activation with electron transfer from Ni0 under low-power conditions and basic site activation under high-power conditions.The LN-NaF catalysts enhance CO_(2)methanation activity across the entire power range compared to LN,achieving a CO_(2)conversion of 86.3%and CH4 selectivity of 99.4%.Additionally,LN-F(h)reaches a CH4 yield 4.15 times higher than that of LN at low power.Furthermore,in-situ diffuse reflectance infrared Fourier transform(DRIFT)spectroscopy with a self-made reactor are performed under plasma-catalytic conditions to reveal the CO_(2)adsorption and conversion mechanisms,indicating that different dopants(F,Na,and NaF)exhibit promoting effects on different intermediates,resulting in variations in CO_(2)methanation activity.This study provides valuable insights for improving catalyst performance and a thorough comprehension of mechanisms in CO_(2)methanation.展开更多
Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To ad...Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.展开更多
Chitosan(CTS)was grafted onto the surface of amino‑functionalized silver chloride silicon dioxide(AgCl@SiO_(2)‑NH_(2))cores to obtain AgCl@SiO_(2)/CTS hybrid nanoparticles.The as‑obtained AgCl@SiO_(2)/CTS nanoparticle...Chitosan(CTS)was grafted onto the surface of amino‑functionalized silver chloride silicon dioxide(AgCl@SiO_(2)‑NH_(2))cores to obtain AgCl@SiO_(2)/CTS hybrid nanoparticles.The as‑obtained AgCl@SiO_(2)/CTS nanoparticles were chlorinated by NaClO solution to get AgCl@SiO_(2)/CTS‑based chloramine nano‑hybrid materials,denoted as AgCl@SiO_(2)/CTS‑Cl.A transmission electron microscope was used to observe the morphology of the as‑prepared samples AgCl@SiO_(2)/CTS and AgCl@SiO_(2)/CTS‑Cl.At the same time,an X‑ray diffractometer and an infrared spectroscope were utilized to characterize their crystal and chemical structures.Besides,ζpotentials were measured to elucidate the surface modification of AgCl nanoparticles by—NH_(2),the antibacterial mechanism of AgCl@SiO_(2)/CTS‑Cl was investigated by scanning electron microscopy,and Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)were used as the to‑be‑tested strains to evaluate the antimicrobial activity of samples AgCl@SiO_(2)/CTS and AgCl@SiO_(2)/CTS‑Cl.Findings demonstrate that sample AgCl@SiO_(2)/CTS exhibits a chain‑like structure ascribed to the interaction between—NH_(2),and each AgCl@SiO_(2)/CTS hybrid nanoparticle contains several AgCl cores.In the meantime,sample AgCl@SiO_(2)/CTS‑Cl exhibits excellent antibacterial activity against E.coli and S.aureus,which is attributed to the synergistic antibacterial effect of Ag^(+)and Cl^(-).Sample AgCl@SiO_(2)/CTS‑Cl with a dosage of 640.00μg·mL^(-1) could completely kill the two kinds of tested bacteria in 12 h of incubation;it retains a high antibacterial efficiency even after 10 cycles of antibacterial tests.展开更多
Background:Early detection of harmful brain activity in critically ill patients using electroencephalography(EEG)is vital for timely and effective clinical intervention.Automating EEG analysis with deep learning techn...Background:Early detection of harmful brain activity in critically ill patients using electroencephalography(EEG)is vital for timely and effective clinical intervention.Automating EEG analysis with deep learning techniques holds significant promise for enhancing diagnostic efficiency and accuracy.Methods:We implemented EfficientNetB2,which leverages convolutional neural networks with a novel Temporal Squeeze-and-Excitation module to capture temporal EEG features,and WaveNet,a sequential model designed to effectively model temporal dependencies in EEG data using dilated causal convolutions and temporal self-attention.Both models were trained and evaluated using a publicly available EEG dataset,with performance assessed via 4-fold cross-validation and a step-wise learning rate reduction strategy.Results:Our results demonstrate a significant reduction in training loss from 0.6459 to 0.3055 and validation loss from 0.9602 to 0.5719 over six epochs.Consistent improvements were observed across cross-validation folds,highlighting the robustness of the models.Additionally,ensemble learning of the two architectures further enhanced classification performance.Conclusion:This comparative analysis sheds light on the strengths and limitations of EfficientNetB2 and WaveNet for automated harmful brain activity detection in EEG signals.The findings contribute to the advancement of reliable and efficient deep learning models,paving the way for their clinical application in managing critically ill patients.展开更多
Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus...Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.展开更多
Two Gd_(2)complexes,namely[Gd_(2)(dbm)_(2)(HL_(1))_(2)(CH_(3)OH)_(2)]·4CH_(3)OH(1)and[Gd_(2)(dbm)_(2)(L_(2))_(2)(CH_(3)OH)_(2)]·2CH_(3)OH(2),where H_(3)L_(1)=(Z)-N'-[4-(diethylamino)-2-hydroxybenzylidene...Two Gd_(2)complexes,namely[Gd_(2)(dbm)_(2)(HL_(1))_(2)(CH_(3)OH)_(2)]·4CH_(3)OH(1)and[Gd_(2)(dbm)_(2)(L_(2))_(2)(CH_(3)OH)_(2)]·2CH_(3)OH(2),where H_(3)L_(1)=(Z)-N'-[4-(diethylamino)-2-hydroxybenzylidene]-2-hydroxyacetohydrazide,H_(2)L_(2)=(E)-N'-(5-bromo-2-hydroxy-3-methoxybenzylidene)nicotinohydrazide,Hdbm=dibenzoylmethane,have been constructed by adopting the solvothermal method.Structural characterization unveils that both complexes 1 and 2 are constituted by two Gd^(3+)ions,two dbm-ions,two CH_(3)OH molecules,and two polydentate Schiff-base ligands(HL_(1)^(2-)or L_(2)^(2-)).In addition,complex 1 contains four free methanol molecules,whereas complex 2 harbors two free methanol molecules.By investigating the interactions between complexes 1 and 2 and four types of bacteria(Bacillus subtilis,Escherichia coli,Staphylococcus aureus,Candida albicans),it was found that both complexes 1 and 2 exhibited potent antibacte-rial activities.The interaction mechanisms between the ligands H_(3)L_(1),H_(2)L_(2),complexes 1 and 2,and calf thymus DNA(CT-DNA)were studied using ultraviolet-visible spectroscopy,fluorescence titration,and cyclic voltammetry.The results demonstrated that both complexes 1 and 2 can intercalate into CT-DNA molecules,thereby inhibiting bacterial proliferation to achieve the antibacterial effects.CCDC:2401116,1;2401117,2.展开更多
BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA prog...BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.AIM To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.METHODS IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques,Western blot analysis,and quantitative reverse transcription PCR.The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation,migration,invasion,and apoptosis assays.The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects.ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.RESULTS IL-22R1 was overexpressed in CCA cell lines and tissues.IL-22 treatment increased the phosphorylation of ERK1/2,promoting tumor cell proliferation,migration,invasion,and resistance to apoptosis.ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.CONCLUSION The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling.Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.展开更多
Background Physical activity(PA)is considered beneficial for lowering cardiovascular risks following type 2 diabetes mellitus(T2DM)and prediabetes,but existing evidence relies mainly on self-reported measurements.We a...Background Physical activity(PA)is considered beneficial for lowering cardiovascular risks following type 2 diabetes mellitus(T2DM)and prediabetes,but existing evidence relies mainly on self-reported measurements.We aimed to describe the intensity-specific dose-response associations of PA and sedentary behavior(SB)with macrovascular and microvascular events among individuals with T2DM and prediabetes.Methods This study included 11,474 individuals with T2DM and prediabetes from the UK Biobank.PA,including total PA,moderate-to-vigorous intensity PA(MVPA),light-intensity PA(LPA),and SB,were measured by accelerometers over 7 days.MVPA was categorized according to the American Diabetes Association guideline-recommended level(at least 150 min/week),and total PA,LPA,and SB were grouped by tertiles.The outcomes were incidences of macrovascular events,microvascular events,heart failure(HF),and their combination(composite events).The events were ascertained using the International Classification of Diseases-10(ICD-10)codes on the hospital or death records.Results During a median follow-up of 6.8 years,1680 cases were documented,including 969 macrovascular events,839 microvascular events,and 284 incidents of HF.Accelerometer-measured PA,irrespective of intensity,was inversely associated with the risk of composite events and each outcome in the dose-response patterns.Regarding categorized PA,engagement in total PA(high vs.low)was associated with decreased risk of macrovascular events(hazard ratio(HR)=0.80;95%confidence interval(95%CI):0.67-0.95),microvascular events(HR=0.76;95%CI:0.63-0.93),and HF(HR=0.46;95%CI:0.32-0.66).Adherence to MVPA,but not LPA,above the guideline-recommended level(at least 150 min/week)was associated with reduced risk of macrovascular events(HR=0.80;95%CI:0.68-0.95),microvascular events(HR=0.76;95%CI:0.63-0.92),and HF(HR=0.65;95%CI:0.46-0.92).The minimum dose of MVPA for lowering the risk of composite events was approximately 59.0 min/week.More time spent in SB was associated with an increased risk of composite events(high vs.low,HR=1.17;95%CI:1.02-1.35)and HF(high vs.low,HR=1.54;95%CI:1.09-2.20).Replacement of 30 min of SB(HR=0.73;95%CI:0.65-0.81)and LPA(HR=0.74;95%CI:0.66-0.83)with MVPA dramatically reduced the risk of composite events.Conclusion Adherence to a higher amount of accelerometer-measured PA,especially MVPA at least 59 min/week,is associated with reduced risks of macrovascular and microvascular events among individuals with T2DM and prediabetes.Replacement of SB and LPA with MVPA helped lower the risk of diabetic vascular events.展开更多
Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxi...Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.展开更多
Objective:Suppression of tumorigenicity 2(ST2),the receptor for interleukin(IL)-33,has a critical role in tumor growth,angiogenesis,metastasis,and immune modulation.The IL-33/ST2 pathway is known to influence the pola...Objective:Suppression of tumorigenicity 2(ST2),the receptor for interleukin(IL)-33,has a critical role in tumor growth,angiogenesis,metastasis,and immune modulation.The IL-33/ST2 pathway is known to influence the polarization and function of macrophages,which is integral to modulating the tumor microenvironment.However,the precise role of IL-33/ST2 in tumors,particularly non-small cell lung cancer(NSCLC),has not been established.Methods:ST2 expression in NSCLC was analysed using a murine model and patient specimens.The effect of the IL-33/ST2 axis on macrophage polarization in NSCLC was determined.Results:Elevated ST2 expression was correlated with aggressive tumor growth.Specifically,ST2 expression on macrophages was associated with lung cancer progression and the absence of ST2 on macrophages was associated with diminished tumor growth.IL-33 promoted polarization of alternatively activated macrophages in an ST2-dependent manner that was mediated via the PI3K/Akt signalling pathway.Moreover,IL-33 inhibited T-cell function by inducing the secretion of transforming growth factorβfrom alternatively activated macrophages.Conclusions:Macrophages expressing ST2 can serve as promising therapeutic targets for NSCLC immunotherapy,highlighting the IL-33/ST2 axis as a potential target for future antitumor strategies.展开更多
BACKGROUND The relationship between low physical activity and cognitive impairment in type 2 diabetes mellitus(T2DM)patients remains unclear.AIM To explore this association and identify risk factors for cognitive impa...BACKGROUND The relationship between low physical activity and cognitive impairment in type 2 diabetes mellitus(T2DM)patients remains unclear.AIM To explore this association and identify risk factors for cognitive impairment in elderly T2DM patients.METHODS A retrospective analysis was conducted on 245 elderly T2DM patients treated at Xuanwu Hospital,Beijing,in 2023.Patients were categorized into low physical activity(n=126)and non-low physical activity(n=119)groups.After propensity score matching(PSM)of 100 pairs,univariate and binary logistic regression analyses identified risk factors for cognitive impairment.A predictive model was constructed and evaluated using receiver operating characteristic curve analysis.RESULTS Before PSM,the percentage of cognitive impairment was higher in the low physical activity group(P<0.05),but after PSM,this difference was not signi-ficant(P>0.05).Additionally,on regression analyses after PSM,age,occupation type,history of stroke,malnutrition,and frailty remained independent factors associated with cognitive impairment,while low physical activity did not.The constructed risk prediction model for cognitive impairment in elderly T2DM patients exhibited an area under the curve of 0.77.CONCLUSION Low physical activity was not associated with cognitive impairment in our study population.Some results differed before and after PSM analysis,indicating that PSM supports objective assessment of risk factors by controlling for selection bias and confounding factors related to population characteristics.The constructed cognitive risk model insight for the development of a clinical tool for early prevention of cognitive impairment in elderly patients.展开更多
There has been a continuous effort to improve the thermal stability of subnanometric platinum(Pt)cluster(<2 nm) catalyst because Pt cluster on CeO_(2) support can be mobile and aggregated into nanoparticle on heati...There has been a continuous effort to improve the thermal stability of subnanometric platinum(Pt)cluster(<2 nm) catalyst because Pt cluster on CeO_(2) support can be mobile and aggregated into nanoparticle on heating at elevated temperatures,yet this great challenge remains.In this study,a strategy is reported to improve the thermal stability of subnanometric Pt cluster by hydrothermal deposition method.Based on this method,zirconium(Zr) was precisely doped on surface of Ce_(0.95)Zr_(0.05)O_(2) by accurately controlling Pt subnanometric cluster size.The surface doping of Zr is favorable for forming the Zr-O-Ce site and activating surface lattice oxygen atoms,which results in strong electronic interactions to stabilize the Pt subnanometric cluster.After high-temperature aging treatment at 1000℃/4 h,the single atom Pt supported on CeO_(2) is aggregated into larger sized(>3 nm) nanoparticle.In contrast,the single atom Pt supported on Ce_(0.95)Zr_(0.0)5O_(2) displays less agglomeration into subnanometric cluster with size of(1.4±0.3) nm.Moreover,the CO oxide catalytic performance of Ce_(0.95)Zr_(0.0)5O_(2)-Pt is 26% and 31%higher than that of CeO_(2)-Pt and commercial Al_(2)O_(3)-Pt catalysts,respectively.The experimental and density functional theory(DFT) calculations indicate that the Zr-O-Ce site and Pt subnanometric cluster interface have more defect sites and active oxygen species than CeO_(2)-Pt interface,which activate the Mars van Krevelen(MvK) mechanism,facilitating the catalytic performance.展开更多
Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepati...Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepatitis B （HB）, together with 33 healthy adults as controls. At same time the NK activity was detected when PBMCs were pretreated with recombinant IL-2 （rIL-2） in 19 patients with various types of HB and 14 normal controls. We also determined the IL-2 activity produced by PBMCs in 26 HB patients and 14 normal controls. The following results were obtained: （1） The NK activity was markedly elevated in early acute hepatitis B （AH） （P【0.01）; significantly decreased in chronic active hepatitis （CAH）, chronic persistent hepatitis （CPH） and fulminant hepatitis （FH） （P【0.01）, while that of convalescents with AH was within normal range 35.85±12.52%. （2） The early rise of NK activity in acute infection and the decline in convalescence and also the parallel change in SGPT level in 3 AH cases were observed. （3） The amount of IL-2 produced by PBMCs in HB patients was lower than that of normal controls （P【0.01 ）. （4）There was no correlation between the change of IL-2 activity and NK activity in HB patients （r=0.15; P】O.05）. （5） The NK activity of most normal subjects were enhanced when the PBMCs were pretreated with rIL-2 but the latter was still within the normal ranges. These results suggest that the mechanism of the effect of IL-2 in modulating the NK activity of HB patients is very complicated. IL-2 not only directly enhances the low NK activity of HB patients, but also depresses the high NK activity. This immunomodulating effect may be influenced by serum inhibitory facts as well as the amount and the combining ability of IL-2 receptor or on NK cell surface.展开更多
基金supported by the National Natural Science Foundation of China(No.51878292).
文摘Large-scale CO_(2)emissions have exacerbated the greenhouse effect,reinforcing the critical need for efficient CO_(2)mitigation methods.Plasma-catalytic technology enables CO_(2)conversion under mild conditions,especially for CO_(2)methanation(the Sabatier reaction),which has attracted significant attention due to its economic benefits and the potential for safe energy transportation via existing natural gas pipelines.The development of high-performance CO_(2)methanation catalysts remains an ongoing and long-term objective,and there is a lack of adequate in-situ characterization techniques to investigate the mechanisms.This study focuses on the Ni/La_(2)O_(3)(LN)catalyst and introduces two CO_(2)activation strategies through F and Na modifications:the Ni-Ov-Ni site activation with electron transfer from Ni0 under low-power conditions and basic site activation under high-power conditions.The LN-NaF catalysts enhance CO_(2)methanation activity across the entire power range compared to LN,achieving a CO_(2)conversion of 86.3%and CH4 selectivity of 99.4%.Additionally,LN-F(h)reaches a CH4 yield 4.15 times higher than that of LN at low power.Furthermore,in-situ diffuse reflectance infrared Fourier transform(DRIFT)spectroscopy with a self-made reactor are performed under plasma-catalytic conditions to reveal the CO_(2)adsorption and conversion mechanisms,indicating that different dopants(F,Na,and NaF)exhibit promoting effects on different intermediates,resulting in variations in CO_(2)methanation activity.This study provides valuable insights for improving catalyst performance and a thorough comprehension of mechanisms in CO_(2)methanation.
基金supported by the Macao Science and Technology Development Fund (FDCT 0148/2022/A3 and 0019/2024/RIA1)the National Natural Science Foundation of China (No. 81572979)
文摘Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.
文摘Chitosan(CTS)was grafted onto the surface of amino‑functionalized silver chloride silicon dioxide(AgCl@SiO_(2)‑NH_(2))cores to obtain AgCl@SiO_(2)/CTS hybrid nanoparticles.The as‑obtained AgCl@SiO_(2)/CTS nanoparticles were chlorinated by NaClO solution to get AgCl@SiO_(2)/CTS‑based chloramine nano‑hybrid materials,denoted as AgCl@SiO_(2)/CTS‑Cl.A transmission electron microscope was used to observe the morphology of the as‑prepared samples AgCl@SiO_(2)/CTS and AgCl@SiO_(2)/CTS‑Cl.At the same time,an X‑ray diffractometer and an infrared spectroscope were utilized to characterize their crystal and chemical structures.Besides,ζpotentials were measured to elucidate the surface modification of AgCl nanoparticles by—NH_(2),the antibacterial mechanism of AgCl@SiO_(2)/CTS‑Cl was investigated by scanning electron microscopy,and Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)were used as the to‑be‑tested strains to evaluate the antimicrobial activity of samples AgCl@SiO_(2)/CTS and AgCl@SiO_(2)/CTS‑Cl.Findings demonstrate that sample AgCl@SiO_(2)/CTS exhibits a chain‑like structure ascribed to the interaction between—NH_(2),and each AgCl@SiO_(2)/CTS hybrid nanoparticle contains several AgCl cores.In the meantime,sample AgCl@SiO_(2)/CTS‑Cl exhibits excellent antibacterial activity against E.coli and S.aureus,which is attributed to the synergistic antibacterial effect of Ag^(+)and Cl^(-).Sample AgCl@SiO_(2)/CTS‑Cl with a dosage of 640.00μg·mL^(-1) could completely kill the two kinds of tested bacteria in 12 h of incubation;it retains a high antibacterial efficiency even after 10 cycles of antibacterial tests.
文摘Background:Early detection of harmful brain activity in critically ill patients using electroencephalography(EEG)is vital for timely and effective clinical intervention.Automating EEG analysis with deep learning techniques holds significant promise for enhancing diagnostic efficiency and accuracy.Methods:We implemented EfficientNetB2,which leverages convolutional neural networks with a novel Temporal Squeeze-and-Excitation module to capture temporal EEG features,and WaveNet,a sequential model designed to effectively model temporal dependencies in EEG data using dilated causal convolutions and temporal self-attention.Both models were trained and evaluated using a publicly available EEG dataset,with performance assessed via 4-fold cross-validation and a step-wise learning rate reduction strategy.Results:Our results demonstrate a significant reduction in training loss from 0.6459 to 0.3055 and validation loss from 0.9602 to 0.5719 over six epochs.Consistent improvements were observed across cross-validation folds,highlighting the robustness of the models.Additionally,ensemble learning of the two architectures further enhanced classification performance.Conclusion:This comparative analysis sheds light on the strengths and limitations of EfficientNetB2 and WaveNet for automated harmful brain activity detection in EEG signals.The findings contribute to the advancement of reliable and efficient deep learning models,paving the way for their clinical application in managing critically ill patients.
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2023AFB671)the National Natural Science Foundation of China(Grant Nos.82360177 and 82560182)+1 种基金the Key Project of Jiangxi Provincial Natural Science Foundation(Grant No.20224ACB206011)“Xuncheng Talents”Project in Jiujiang City,Jiangxi Province(Grant No.JJXC2023071).
文摘Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.
文摘Two Gd_(2)complexes,namely[Gd_(2)(dbm)_(2)(HL_(1))_(2)(CH_(3)OH)_(2)]·4CH_(3)OH(1)and[Gd_(2)(dbm)_(2)(L_(2))_(2)(CH_(3)OH)_(2)]·2CH_(3)OH(2),where H_(3)L_(1)=(Z)-N'-[4-(diethylamino)-2-hydroxybenzylidene]-2-hydroxyacetohydrazide,H_(2)L_(2)=(E)-N'-(5-bromo-2-hydroxy-3-methoxybenzylidene)nicotinohydrazide,Hdbm=dibenzoylmethane,have been constructed by adopting the solvothermal method.Structural characterization unveils that both complexes 1 and 2 are constituted by two Gd^(3+)ions,two dbm-ions,two CH_(3)OH molecules,and two polydentate Schiff-base ligands(HL_(1)^(2-)or L_(2)^(2-)).In addition,complex 1 contains four free methanol molecules,whereas complex 2 harbors two free methanol molecules.By investigating the interactions between complexes 1 and 2 and four types of bacteria(Bacillus subtilis,Escherichia coli,Staphylococcus aureus,Candida albicans),it was found that both complexes 1 and 2 exhibited potent antibacte-rial activities.The interaction mechanisms between the ligands H_(3)L_(1),H_(2)L_(2),complexes 1 and 2,and calf thymus DNA(CT-DNA)were studied using ultraviolet-visible spectroscopy,fluorescence titration,and cyclic voltammetry.The results demonstrated that both complexes 1 and 2 can intercalate into CT-DNA molecules,thereby inhibiting bacterial proliferation to achieve the antibacterial effects.CCDC:2401116,1;2401117,2.
基金National Natural Science Foundation of China,No.82372194.
文摘BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.AIM To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.METHODS IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques,Western blot analysis,and quantitative reverse transcription PCR.The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation,migration,invasion,and apoptosis assays.The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects.ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.RESULTS IL-22R1 was overexpressed in CCA cell lines and tissues.IL-22 treatment increased the phosphorylation of ERK1/2,promoting tumor cell proliferation,migration,invasion,and resistance to apoptosis.ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.CONCLUSION The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling.Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.
基金supported by the National Natural Science Foundation of China(Grant No.32100880)Guangzhou Research-oriented Hospital。
文摘Background Physical activity(PA)is considered beneficial for lowering cardiovascular risks following type 2 diabetes mellitus(T2DM)and prediabetes,but existing evidence relies mainly on self-reported measurements.We aimed to describe the intensity-specific dose-response associations of PA and sedentary behavior(SB)with macrovascular and microvascular events among individuals with T2DM and prediabetes.Methods This study included 11,474 individuals with T2DM and prediabetes from the UK Biobank.PA,including total PA,moderate-to-vigorous intensity PA(MVPA),light-intensity PA(LPA),and SB,were measured by accelerometers over 7 days.MVPA was categorized according to the American Diabetes Association guideline-recommended level(at least 150 min/week),and total PA,LPA,and SB were grouped by tertiles.The outcomes were incidences of macrovascular events,microvascular events,heart failure(HF),and their combination(composite events).The events were ascertained using the International Classification of Diseases-10(ICD-10)codes on the hospital or death records.Results During a median follow-up of 6.8 years,1680 cases were documented,including 969 macrovascular events,839 microvascular events,and 284 incidents of HF.Accelerometer-measured PA,irrespective of intensity,was inversely associated with the risk of composite events and each outcome in the dose-response patterns.Regarding categorized PA,engagement in total PA(high vs.low)was associated with decreased risk of macrovascular events(hazard ratio(HR)=0.80;95%confidence interval(95%CI):0.67-0.95),microvascular events(HR=0.76;95%CI:0.63-0.93),and HF(HR=0.46;95%CI:0.32-0.66).Adherence to MVPA,but not LPA,above the guideline-recommended level(at least 150 min/week)was associated with reduced risk of macrovascular events(HR=0.80;95%CI:0.68-0.95),microvascular events(HR=0.76;95%CI:0.63-0.92),and HF(HR=0.65;95%CI:0.46-0.92).The minimum dose of MVPA for lowering the risk of composite events was approximately 59.0 min/week.More time spent in SB was associated with an increased risk of composite events(high vs.low,HR=1.17;95%CI:1.02-1.35)and HF(high vs.low,HR=1.54;95%CI:1.09-2.20).Replacement of 30 min of SB(HR=0.73;95%CI:0.65-0.81)and LPA(HR=0.74;95%CI:0.66-0.83)with MVPA dramatically reduced the risk of composite events.Conclusion Adherence to a higher amount of accelerometer-measured PA,especially MVPA at least 59 min/week,is associated with reduced risks of macrovascular and microvascular events among individuals with T2DM and prediabetes.Replacement of SB and LPA with MVPA helped lower the risk of diabetic vascular events.
基金supported by the National Natural Science Foundation of China(82003451 and 82003455)Yunnan Fundamental Research Projects(202101AT070033)the Start-Up Fund for Introduction of High-level Talents to Dali University(YBS2021015).
文摘Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.
基金supported by the National Key R&D Program of China(2023YFC2413100)the National Natural Science Foundation of China(No.81501423)the Fundamental Research Funds for the Central Universities。
文摘Objective:Suppression of tumorigenicity 2(ST2),the receptor for interleukin(IL)-33,has a critical role in tumor growth,angiogenesis,metastasis,and immune modulation.The IL-33/ST2 pathway is known to influence the polarization and function of macrophages,which is integral to modulating the tumor microenvironment.However,the precise role of IL-33/ST2 in tumors,particularly non-small cell lung cancer(NSCLC),has not been established.Methods:ST2 expression in NSCLC was analysed using a murine model and patient specimens.The effect of the IL-33/ST2 axis on macrophage polarization in NSCLC was determined.Results:Elevated ST2 expression was correlated with aggressive tumor growth.Specifically,ST2 expression on macrophages was associated with lung cancer progression and the absence of ST2 on macrophages was associated with diminished tumor growth.IL-33 promoted polarization of alternatively activated macrophages in an ST2-dependent manner that was mediated via the PI3K/Akt signalling pathway.Moreover,IL-33 inhibited T-cell function by inducing the secretion of transforming growth factorβfrom alternatively activated macrophages.Conclusions:Macrophages expressing ST2 can serve as promising therapeutic targets for NSCLC immunotherapy,highlighting the IL-33/ST2 axis as a potential target for future antitumor strategies.
基金Supported by The Capital Funds for Health Improvement and Research,No.2024-2-1033The Beijing Municipal Administration of Hospitals Incubating Program,No.PX2022032+1 种基金Post-subsidy Fund from the National Clinical Research Center,the Ministry of Science and Technology of China,No.303-01-001-0272-08The Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes,No.JYY2023-13.
文摘BACKGROUND The relationship between low physical activity and cognitive impairment in type 2 diabetes mellitus(T2DM)patients remains unclear.AIM To explore this association and identify risk factors for cognitive impairment in elderly T2DM patients.METHODS A retrospective analysis was conducted on 245 elderly T2DM patients treated at Xuanwu Hospital,Beijing,in 2023.Patients were categorized into low physical activity(n=126)and non-low physical activity(n=119)groups.After propensity score matching(PSM)of 100 pairs,univariate and binary logistic regression analyses identified risk factors for cognitive impairment.A predictive model was constructed and evaluated using receiver operating characteristic curve analysis.RESULTS Before PSM,the percentage of cognitive impairment was higher in the low physical activity group(P<0.05),but after PSM,this difference was not signi-ficant(P>0.05).Additionally,on regression analyses after PSM,age,occupation type,history of stroke,malnutrition,and frailty remained independent factors associated with cognitive impairment,while low physical activity did not.The constructed risk prediction model for cognitive impairment in elderly T2DM patients exhibited an area under the curve of 0.77.CONCLUSION Low physical activity was not associated with cognitive impairment in our study population.Some results differed before and after PSM analysis,indicating that PSM supports objective assessment of risk factors by controlling for selection bias and confounding factors related to population characteristics.The constructed cognitive risk model insight for the development of a clinical tool for early prevention of cognitive impairment in elderly patients.
基金supported by National Natural Science Foundation of China (52204376)Youth Foundation of Hebei Province (E2022103007)+1 种基金Open Project of Yunnan Precious Metals Laboratory Co.(YPML-20240502059)Young Elite Scientists Sponsorship Program by CAST (2021QNRC001)。
文摘There has been a continuous effort to improve the thermal stability of subnanometric platinum(Pt)cluster(<2 nm) catalyst because Pt cluster on CeO_(2) support can be mobile and aggregated into nanoparticle on heating at elevated temperatures,yet this great challenge remains.In this study,a strategy is reported to improve the thermal stability of subnanometric Pt cluster by hydrothermal deposition method.Based on this method,zirconium(Zr) was precisely doped on surface of Ce_(0.95)Zr_(0.05)O_(2) by accurately controlling Pt subnanometric cluster size.The surface doping of Zr is favorable for forming the Zr-O-Ce site and activating surface lattice oxygen atoms,which results in strong electronic interactions to stabilize the Pt subnanometric cluster.After high-temperature aging treatment at 1000℃/4 h,the single atom Pt supported on CeO_(2) is aggregated into larger sized(>3 nm) nanoparticle.In contrast,the single atom Pt supported on Ce_(0.95)Zr_(0.0)5O_(2) displays less agglomeration into subnanometric cluster with size of(1.4±0.3) nm.Moreover,the CO oxide catalytic performance of Ce_(0.95)Zr_(0.0)5O_(2)-Pt is 26% and 31%higher than that of CeO_(2)-Pt and commercial Al_(2)O_(3)-Pt catalysts,respectively.The experimental and density functional theory(DFT) calculations indicate that the Zr-O-Ce site and Pt subnanometric cluster interface have more defect sites and active oxygen species than CeO_(2)-Pt interface,which activate the Mars van Krevelen(MvK) mechanism,facilitating the catalytic performance.
文摘Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepatitis B （HB）, together with 33 healthy adults as controls. At same time the NK activity was detected when PBMCs were pretreated with recombinant IL-2 （rIL-2） in 19 patients with various types of HB and 14 normal controls. We also determined the IL-2 activity produced by PBMCs in 26 HB patients and 14 normal controls. The following results were obtained: （1） The NK activity was markedly elevated in early acute hepatitis B （AH） （P【0.01）; significantly decreased in chronic active hepatitis （CAH）, chronic persistent hepatitis （CPH） and fulminant hepatitis （FH） （P【0.01）, while that of convalescents with AH was within normal range 35.85±12.52%. （2） The early rise of NK activity in acute infection and the decline in convalescence and also the parallel change in SGPT level in 3 AH cases were observed. （3） The amount of IL-2 produced by PBMCs in HB patients was lower than that of normal controls （P【0.01 ）. （4）There was no correlation between the change of IL-2 activity and NK activity in HB patients （r=0.15; P】O.05）. （5） The NK activity of most normal subjects were enhanced when the PBMCs were pretreated with rIL-2 but the latter was still within the normal ranges. These results suggest that the mechanism of the effect of IL-2 in modulating the NK activity of HB patients is very complicated. IL-2 not only directly enhances the low NK activity of HB patients, but also depresses the high NK activity. This immunomodulating effect may be influenced by serum inhibitory facts as well as the amount and the combining ability of IL-2 receptor or on NK cell surface.
