Surface polaritons,as surface electromagnetic waves propagating along the surface of a medium,have played a crucial role in enhancing photonic spin Hall effect(PSHE)and developing highly sensitive refractive index(RI)...Surface polaritons,as surface electromagnetic waves propagating along the surface of a medium,have played a crucial role in enhancing photonic spin Hall effect(PSHE)and developing highly sensitive refractive index(RI)sensors.Among them,the traditional surface plasmon polariton(SPP)based on noble metals limits its application beyond the near-infrared(IR)regime due to the large negative permittivity and optical losses.In this contribution,we theoretically proposed a highly sensitive PSHE sensor with the structure of Ge prism-SiC-Si:InAs-sensing medium,by taking advantage of the hybrid surface plasmon phonon polariton(SPPhP)in mid-IR regime.Here,heavily Si-doped InAs(Si:InAs)and SiC excite the SPP and surface phonon polariton(SPhP),and the hybrid SPPhP is realized in this system.More importantly,the designed PSHE sensor based on this SPPhP mechanism achieves the multi-stage RI measurements from 1.00025-1.00225 to 1.70025-1.70225,and the maximal intensity sensitivity and angle sensitivity can be up to 9.4×10^(4)μm/RIU and245°/RIU,respectively.These findings provide a new pathway for the enhancement of PSHE in mid-IR regime,and offer new opportunities to develop highly sensitive RI sensors in multi-scenario applications,such as harmful gas monitoring and biosensing.展开更多
Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and ...Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.展开更多
Urban forests are highly multifunctional and provide numerous ecological functions.Plant functional traits individually or jointly influence the ecological multifunctionality of tree species(TS-EMF)and can also modify...Urban forests are highly multifunctional and provide numerous ecological functions.Plant functional traits individually or jointly influence the ecological multifunctionality of tree species(TS-EMF)and can also modify TSEMF in response to environmental changes.However,there has been limited exploration of multitrait combinations for predicting TS-EMF across seasons and of trait thresholds that enhance TS-EMF.Here,for 10 dominant tree species in urban forests of Northeast China,14 traits were measured and four aboveground and three belowground ecological functions assessed in three seasons.Ecological functions and TS-EMF differed significantly throughout the seasons(P<0.05).Synergistic relationships were found between carbon sequestration and oxygen release,between cooling and humidification,and between organic carbon accumulation and nutrient cycling.Notably,aboveground multifunctionality played a leading role in TS-EMF.With seasonal changes,resource allocation shifted toward traits related to resource acquisition rather than conservation to maintain TS-EMF.The combination of traits that predicted TS-EMF varied by type,accounting for up to 66.45%of the variation.TS-EMF was primarily driven by leaf structure in spring and by nutrient accumulation in autumn.Leaf carbon content(LCC)consistently served as a stabilizing factor for predicting TS-EMF across seasons.At 36.5-36.8 mg g^(-1),LCC had its optimal effect on TS-EMF.Other traits in combination that positively influence total TS-EMF include leaf nitrogen content(3.43-3.45 mg g^(-1)),leaf phosphorus content(0.80-0.83 mg g^(-1)),and leaf area(65.86-68.43 cm^(2)).Within these specified trait thresholds,Morus alba and Quercus mongolica were identified as key species.These findings suggest that the trade-off between various ecological functions can be managed by altering plant traits across seasons.This approach could provide a theoretical foundation for enhancing the TS-EMF of urban forests through trait-based management,offering practical guidance for selecting tree species.展开更多
Unstable operating conditions such as surge could cause damage to both aerodynamic performance and structural integrity of a compression system.This paper addresses the critical issue of aerodynamic instability in com...Unstable operating conditions such as surge could cause damage to both aerodynamic performance and structural integrity of a compression system.This paper addresses the critical issue of aerodynamic instability in compressor design,particularly focusing on an axial-centrifugal combined compressor,a widely used yet underexplored configuration.An experimental investigation was conducted on a three-stage axial and one-stage centrifugal compressor(3A1C),using two pipe systems and employing fast-responding transducers to capture the dynamic instability process from choke condition to deep surge.Results reveal that at the design speed,3A1C enters deep surge directly,whereas at off-design speeds,it experiences rotating stall and mild surge across a wide mass flow range.Some special instability features in the combined compressor can be found in the steady state map and dynamic process.The characteristic curve of the first axial stage keeps a positive slope during the whole mass flow range at an off-design speed.The first stage could work stably on the stall characteristic curve because the centrifugal stage has stronger pressurization and plays a dominant role in global aerodynamic instability.Besides,rotating instability occurs at the first rotor tip and disappears as the back pressure increases,which is also rarely seen in a single-axial compressor.This is also related to the strong pressurization of the centrifugal stage.The findings of this paper will contribute to the understanding of aerodynamic instabilities in combined compressors.展开更多
The application of machine learning for pyrite discrimination establishes a robust foundation for constructing the ore-forming history of multi-stage deposits;however,published models face challenges related to limite...The application of machine learning for pyrite discrimination establishes a robust foundation for constructing the ore-forming history of multi-stage deposits;however,published models face challenges related to limited,imbalanced datasets and oversampling.In this study,the dataset was expanded to approximately 500 samples for each type,including 508 sedimentary,573 orogenic gold,548 sedimentary exhalative(SEDEX)deposits,and 364 volcanogenic massive sulfides(VMS)pyrites,utilizing random forest(RF)and support vector machine(SVM)methodologies to enhance the reliability of the classifier models.The RF classifier achieved an overall accuracy of 99.8%,and the SVM classifier attained an overall accuracy of 100%.The model was evaluated by a five-fold cross-validation approach with 93.8%accuracy for the RF and 94.9%for the SVM classifier.These results demonstrate the strong feasibility of pyrite classification,supported by a relatively large,balanced dataset and high accuracy rates.The classifier was employed to reveal the genesis of the controversial Keketale Pb-Zn deposit in NW China,which has been inconclusive among SEDEX,VMS,or a SEDEX-VMS transition.Petrographic investigations indicated that the deposit comprises early fine-grained layered pyrite(Py1)and late recrystallized pyrite(Py2).The majority voting classified Py1 as the VMS type,with an accuracy of RF and SVM being 72.2%and 75%,respectively,and confirmed Py2 as an orogenic type with 74.3% and 77.1%accuracy,respectively.The new findings indicated that the Keketale deposit originated from a submarine VMS mineralization system,followed by late orogenic-type overprinting of metamorphism and deformation,which is consistent with the geological and geochemical observations.This study further emphasizes the advantages of Machine learning(ML)methods in accurately and directly discriminating the deposit types and reconstructing the formation history of multi-stage deposits.展开更多
The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with...The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.展开更多
A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that r...A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that regulates heading date,plant height and grain number.Here,we investigated the relationship between Ghd7 and florigen genes Hd3a and RFT1,to determine their roles in regulating heading date and grain number under different photoperiods.Our results revealed that under long-day(LD)conditions,Hd3a acts prior to RFT1 to promote heading while negatively regulating plant height and grain number.In contrast,Ghd7 positively regulates heading date,plant height,and grain number by inhibiting both Hd3a and RFT1.Under short-day(SD)conditions,the functions of Hd3a and RFT1 remain consistent with those under LD conditions,but Ghd7 does not inhibit their expression,resulting in a weaker phenotypic effect compared to Hd3a.Additionally,under both LD and SD conditions,increased Ghd7 expression enhances its inhibitory effect on Hd3a and RFT1,leading to later heading and increased grain number;however,once the heading date exceeds 94 d,grain number no longer increases.Moreover,the gn1a allele increased grain number by 16.5%to 42.5%,while combinations of the elite alleles from Ghd7,Hd3a,RFT1,and Gn1a significantly increased grain number by up to 240.9%.Therefore,we propose a new breeding strategy to optimize the heading date and grain number using the Ghd7Hd3aRFT1gn1a combination of Ghd7,Hd3a,RFT1,and Gn1a under LD conditions,and the Ghd7hd3aRFT1gn1a combination under SD conditions.This strategy improved the yield of the high-quality Northeast variety Kongyu 131(KY131)by 69.1%in Beijing and 93.7%in Hainan.This strategy will greatly improve the efficiency of north-to-south adaptation in rice,providing theoretical guidance for expanding the geographical adaptability of rice varieties.展开更多
Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergist...Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergistic drug combination discovery,their applications remain constrained by experimental data fragmentation,high costs,and extensive combinatorial space.Recent developments in artificial intelligence(AI),encompassing traditional machine learning and deep learning algorithms,have been extensively applied in NPDC identification.Through the integration of multi-source heterogeneous data and autonomous feature extraction,prediction accuracy has markedly improved,offering a robust technical approach for novel NPDC discovery.This review comprehensively examines recent advances in AI-driven NPDC prediction,presents relevant data resources and algorithmic frameworks,and evaluates current limitations and future prospects.AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.展开更多
The high proportion of uncertain distributed power sources and the access to large-scale random electric vehicle(EV)charging resources further aggravate the voltage fluctuation of the distribution network,and the exis...The high proportion of uncertain distributed power sources and the access to large-scale random electric vehicle(EV)charging resources further aggravate the voltage fluctuation of the distribution network,and the existing research has not deeply explored the EV active-reactive synergistic regulating characteristics,and failed to realize themulti-timescale synergistic control with other regulatingmeans,For this reason,this paper proposes amultilevel linkage coordinated optimization strategy to reduce the voltage deviation of the distribution network.Firstly,a capacitor bank reactive power compensation voltage control model and a distributed photovoltaic(PV)activereactive power regulationmodel are established.Additionally,an external characteristicmodel of EVactive-reactive power regulation is developed considering the four-quadrant operational characteristics of the EVcharger.Amultiobjective optimization model of the distribution network is then constructed considering the time-series coupling constraints of multiple types of voltage regulators.A multi-timescale control strategy is proposed by considering the impact of voltage regulators on active-reactive EV energy consumption and PV energy consumption.Then,a four-stage voltage control optimization strategy is proposed for various types of voltage regulators with multiple time scales.Themulti-objective optimization is solved with the improvedDrosophila algorithmto realize the power fluctuation control of the distribution network and themulti-stage voltage control optimization.Simulation results validate that the proposed voltage control optimization strategy achieves the coordinated control of decentralized voltage control resources in the distribution network.It effectively reduces the voltage deviation of the distribution network while ensuring the energy demand of EV users and enhancing the stability and economic efficiency of the distribution network.展开更多
The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated t...The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated to reveal the main controlling factors of shale oil occurrence under different lamina combinations.The differential enrichment mechanisms and patterns of shale oil were discussed using the shale oil micro-migration characterization and evaluation methods from the perspectives of relay hydrocarbon supply,stepwise migration,and multi-stage differentiation.The results are obtained in five aspects.First,Chang 73 shale mainly develops five types of lamina combination,i.e.non-laminated shale,sandy laminated shale,tuffaceous laminated shale,mixed laminated shale,and organic-rich laminated shale.Second,shales with different lamina combinations are obviously different in the reservoir space.Specifically,shales with sandy laminae and tuffaceous laminae have a large number of intergranular pores,dissolution pores and hydrocarbon generation-induced fractures.The multi-scale pore and fracture system constitutes the main place for liquid hydrocarbon occurrence.Third,the occurrence and distribution of shale oil in shale with different lamina combinations are jointly controlled by organic matter abundance,reservoir property,thermal evolution degree,mineral composition and laminae scale.The micro-nano-scale pore-fracture networks within shales containing rigid laminae,particularly sandy and tuffaceous laminations,primarily contain free-state light hydrocarbon components.In contrast,adsorption-phase heavy hydrocarbon components predominantly occupy surfaces of organic matter assemblages,clay mineral matrices,and framework mineral particulates.Fourth,there is obvious shale oil micro-migration between shales with different lamina combinations in Chang 73.Generally,such micro-migration is stepwise in a sequence of organic-rich laminated shale→tuffaceous laminated shale→mixed laminated shale→sandy lamiated shale→non-laminated shale.Fifth,the relay hydrocarbon supply of organic matter under the control of the spatial superposition of shales with various laminae,the stepwise migration via multi-scale pore and fracture network,and the multi-differentiation in shales with different lamina combinations under the control of organic-inorganic interactions fundamentally decide the differences of shale oil components between shales with different lamina combinations.展开更多
Although previous researchers have attempted to decipher ore genesis and mineralization in the Erdaokan Ag-Pb-Zn deposit,some uncertainties regarding the mineralization process and evolution of both ore-forming fluids...Although previous researchers have attempted to decipher ore genesis and mineralization in the Erdaokan Ag-Pb-Zn deposit,some uncertainties regarding the mineralization process and evolution of both ore-forming fluids and magnetite types still need to be addressed.In this study,we obtained new EPMA,LA-ICP-MS,and in situ Fe isotope data from magnetite from the Erdaokan deposit,in order to better understand the mineralization mechanism and evolution of both magnetite and the ore-forming fluids.Our results identified seven types of magnetite at Erdaokan:disseminated magnetite(Mag1),coarse-grained magnetite(Mag2a),radial magnetite(Mag2b),fragmented fine-grained magnetite(Mag2c),vermicular gel magnetite(Mag3a1 and Mag3a2),colloidal magnetite(Mag3b)and dark gray magnetite(Mag4).All of the magnetite types were hydrothermal in origin and generally low in Ti(<400 ppm)and Ni(<800 ppm),while being enriched in light Fe isotopes(δ^(56)Fe ranging from−1.54‰to−0.06‰).However,they exhibit different geochemical signatures and are thus classified into high-manganese magnetite(Mag1,MnO>5 wt%),low-silicon magnetite(Mag2a-c,SiO_(2)<1 wt%),high-silicon magnetite(Mag3a-b,SiO_(2)from 1 to 7 wt%)and high-silicon-manganese magnetite(Mag4,SiO_(2)>1 wt%,MnO>0.2 wt%),each being formed within distinct hydrothermal environments.Based on mineralogy,elemental geochemistry,Fe isotopes,temperature trends,TMg-mag and(Ti+V)vs.(Al+Mn)diagrams,we propose that the Erdaokan Ag-Pb-Zn deposit underwent multi-stage mineralization,which can be broken down into four stages and nine sub-stages.Mag1,Mag2a-c,Mag3a-b and Mag4 were formed during the first sub-stage of each of the four stages,respectively.Additionally,fluid mixing,cooling and depressurization boiling were identified as the main mechanisms for mineral precipitation.The enrichment of Ag was significantly enhanced by the superposition of multi-stage ore-forming hydrothermal fluids in the Erdaokan Ag-Pb-Zn deposit.展开更多
This paper presents a new criterion for determining the unloading points quantitatively and consistently in a multi-stage triaxial test.The radial strain gradient(RSG)is first introduced as an arc tangent function of ...This paper presents a new criterion for determining the unloading points quantitatively and consistently in a multi-stage triaxial test.The radial strain gradient(RSG)is first introduced as an arc tangent function of the rate of change of radial strain to time.RSG is observed to correlate closely with the stress state of a compressed sample,and reaches a horizontal asymptote as approaching failure.For a given rock type,RSG value at peak stress is almost the same,irrespective of the porosity and permeability.These findings lead to the development of RSG criterion:Unloading points can be precisely determined at the time when RSG reaches a pre-determined value that is a little smaller than or equal to the RSG at peak stress.The RSG criterion is validated against other criteria and the single-stage triaxial test on various types of rocks.Failure envelopes from the RSG criterion match well with those from single-stage tests.A practical procedure is recommended to use the RSG criterion:an unconfined compression or single-stage test is first conducted to determine the RSG at peak stress for one sample,the unloading point is then selected to be a value close to the RSG at peak stress,and the multi-stage test is finally performed on another sample using the pre-selected RSG unloading criterion.Generally,the RSG criterion is applicable for any type of rocks,especially brittle rocks,where other criteria are not suitable.Further,it can be practically implemented on the most available rock mechanical testing instruments.展开更多
A new hang-off system has been proposed to improve the security of risers in hang-off modes during typhoons.However,efficient anti-typhoon evacuation strategies have not been investigated.Optimiza-tion model and metho...A new hang-off system has been proposed to improve the security of risers in hang-off modes during typhoons.However,efficient anti-typhoon evacuation strategies have not been investigated.Optimiza-tion model and method for the anti-typhoon evacuation strategies should be researched.Therefore,multi-objective functions are proposed based on operation time,evacuation speed stability,and steering stability.An evacuation path model and a dynamic model of risers with the new hang-off system are developed for design variables and constraints.A multi-objective optimization model with high-dimensional variables and complex constraints is established.Finally,a three-stage optimization method based on genetic algorithm,least square method,and the penalty function method is proposed to solve the multi-objective optimization model.Optimization results show that the operation time can be reduced through operation parameter optimization,especially evacuation heading optimization.The optimal anti-typhoon strategy is evacuation with all risers suspended along a variable path when the direction angle is large,while evacuation with all risers suspended along a straight path at another di-rection angle.Besides,the influencing factors on anti-typhoon evacuation strategies indicate that the proposed optimization model and method have strong applicability to working conditions and remarkable optimization effects.展开更多
Nano zero-valent iron(nZVI)is a promising phosphate adsorbent for advanced phosphate removal.However,the rapid passivation of nZVI and the low activity of adsorption sites seriously limit its phosphate removal perform...Nano zero-valent iron(nZVI)is a promising phosphate adsorbent for advanced phosphate removal.However,the rapid passivation of nZVI and the low activity of adsorption sites seriously limit its phosphate removal performance,accounting for its inapplicability to meet the emission criteria of 0.1 mg P/L phosphate.In this study,we report that the oxalate modification can inhibit the passivation of nZVI and alter the multi-stage phosphate adsorption mechanism by changing the adsorption sites.As expected,the stronger antipassivation ability of oxalate modified nZVI(OX-nZVI)strongly favored its phosphate adsorption.Interestingly,the oxalate modification endowed the surface Fe(III)sites with the lowest chemisorption energy and the fastest phosphate adsorption ability than the other adsorption sites,by in situ forming a Fe(III)-phosphate-oxalate ternary complex,therefore enabling an advanced phosphate removal process.At an initial phosphate concentration of 1.00 mg P/L,pH of 6.0 and a dosage of 0.3 g/L of adsorbents,OX-nZVI exhibited faster phosphate removal rate(0.11 g/mg/min)and lower residual phosphate level(0.02 mg P/L)than nZVI(0.055 g/mg/min and 0.19 mg P/L).This study sheds light on the importance of site manipulation in the development of high-performance adsorbents,and offers a facile surface modification strategy to prepare superior iron-basedmaterials for advanced phosphate removal.展开更多
Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effec...Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.展开更多
Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease in...Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.展开更多
To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-dec...To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-decomposition associated with kernel-based-extreme-learningmachine optimized by the whale optimization algorithm(VMD-WOA-KELM)is proposed in this paper.Firstly,the displacement is decomposed by VMD to three IMF components and a residual component of different fluctuation characteristics.The key impact factors of each IMF component are selected according to Copula model,and the corresponding WOA-KELM is established to conduct point prediction.Subsequently,the parametric method(PM)and non-parametric method(NPM)are used to estimate the prediction error probability density distribution(PDF)of each component,whose prediction interval(PI)under the 95%confidence level is also obtained.By means of the differential evolution algorithm(DE),a weighted combination model based on the PIs is built to construct the combination-interval(CI).Finally,the CIs of each component are added to generate the total PI.A comparative case study shows that the CIPM performs better in constructing landslide displacement PI with high performance.展开更多
BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of a...BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of albumin-bound paclitaxel(nab-ptx)combined with the small molecule vascular endothelial growth factor inhibitor anlotinib in secondline and beyond treatment of AGC.METHODS We collected data from AGC patients at our hospital who experienced disease progression after first-line chemotherapy and received anlotinib combined with nab-ptx.The primary endpoints included overall survival(OS)and progressionfree survival(PFS),while the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and adverse events(AEs).RESULTS Preliminary results indicated that anlotinib combined with nab-ptx can provide significant efficacy in second-line or above treatment for AGC(median PFS=6.0 months,median OS=12.0 months),with an ORR of 42%and a DCR of 78%.Further analysis revealed that patients who experienced hypertension,proteinuria,and hand-foot syndrome during treatment had better efficacy compared to those who did not experience these AEs.Mechanistic studies suggest that this regimen likely exerts synergistic anti-tumor effects by activating the immune response through the reduction of regulatory T-cell proportions.Common adverse reactions included bone marrow suppression,peripheral neuropathy,hypertension,proteinuria,and hand-foot syndrome,which were manageable and resolved with appropriate interventions,indicating the promising application of this regimen in second-line or above treatment for AGC.CONCLUSION The combination of anlotinib and nab-ptx shows promising efficacy with fewer toxicities in AGC treatment.The regimen holds promise as a second-line treatment of AGC;however,its specific clinical value requires further research.展开更多
Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances m...Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances made in recent years with regard to immunotherapy in both basic research and clinical practice,there remains scope for further improvement,particularly with respect to its efficacy against solid tumors.With advancements in nanotechnology,tumor nanovaccines hold immense potential for preventing tumor recurrence and treating metastatic tumors.Nevertheless,the considerable heterogeneity of tumor immunogenicity presents a number of significant challenges in the development of nanometrescale vaccines targeting solid tumors.Recent findings indicate that immune checkpoint inhibitor(ICI)therapy can improve the immunosuppressive microenvironment within tumors,while nanovaccines can also augment tumor sensitivity toward ICIs.Consequently,combining tumor nanovaccine with ICI therapy holds promise for effectively eradicating tumors or controlling their recurrence and metastasis during cancer treatment.This review delves into the mechanism behind combining tumor nanovaccine with ICI while focusing on factors influencing this combined therapy approach.Moreover,it offers an overview of the current research status regarding the combination of tumor nanovaccines with chemotherapy,radiotherapy,photothermal therapy,and sonodynamic therapy,as well as prospects for future developments in this field.展开更多
Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.Howe...Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.However,emerging evidence indicates that unintended pro-metastatic effects may offset the therapeutic benefits of HDACis.Chen et al elucidate this paradox,demonstrating that TSA-induced hyperacetylation activates the BRD4/c-Myc/ER-stress axis,thereby promoting epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma(ESCC).Furthermore,they clarify the clinical significance of histone acetylation in the prognostic evaluation of ESCC.Their findings underscore the complexity of epigenetic therapies and highlight the necessity of reevaluating the associated risks and combinatorial therapeutic strategies with HDACi-based treatments.Here,we summarize the potential risks of HDACis therapy and discuss feasible combination therapeutic strategies.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant No.12175107)the Qing Lan Project of Jiangsu Province+2 种基金the Hua Li Talents Program of Nanjing University of PostsTelecommunications,Natural Science Foundation of Nanjing Vocational University of Industry Technology(Grant No.YK22-02-08)the Fund from the Research Center of Industrial Perception and Intelligent Manufacturing Equipment Engineering of Jiangsu Province,China(Grant No.ZK21-05-09)。
文摘Surface polaritons,as surface electromagnetic waves propagating along the surface of a medium,have played a crucial role in enhancing photonic spin Hall effect(PSHE)and developing highly sensitive refractive index(RI)sensors.Among them,the traditional surface plasmon polariton(SPP)based on noble metals limits its application beyond the near-infrared(IR)regime due to the large negative permittivity and optical losses.In this contribution,we theoretically proposed a highly sensitive PSHE sensor with the structure of Ge prism-SiC-Si:InAs-sensing medium,by taking advantage of the hybrid surface plasmon phonon polariton(SPPhP)in mid-IR regime.Here,heavily Si-doped InAs(Si:InAs)and SiC excite the SPP and surface phonon polariton(SPhP),and the hybrid SPPhP is realized in this system.More importantly,the designed PSHE sensor based on this SPPhP mechanism achieves the multi-stage RI measurements from 1.00025-1.00225 to 1.70025-1.70225,and the maximal intensity sensitivity and angle sensitivity can be up to 9.4×10^(4)μm/RIU and245°/RIU,respectively.These findings provide a new pathway for the enhancement of PSHE in mid-IR regime,and offer new opportunities to develop highly sensitive RI sensors in multi-scenario applications,such as harmful gas monitoring and biosensing.
基金supported by the Shaanxi Qinchuang Yuan“scientist+engineer”team construction(No.2023KXJ-080)Shaanxi Chiral Drug Engineering Technology Research Center(Department of Science and Technology of Shaanxi Province.No.[2011]-251).
文摘Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.
基金supported by the National Natural Science Foundation(32130068,32271634,and 32071597)CAS Key Laboratory of Forest Ecology and Silviculture,Institute of Applied Ecology,Chinese Academy of Sciences(KLFES-2025)。
文摘Urban forests are highly multifunctional and provide numerous ecological functions.Plant functional traits individually or jointly influence the ecological multifunctionality of tree species(TS-EMF)and can also modify TSEMF in response to environmental changes.However,there has been limited exploration of multitrait combinations for predicting TS-EMF across seasons and of trait thresholds that enhance TS-EMF.Here,for 10 dominant tree species in urban forests of Northeast China,14 traits were measured and four aboveground and three belowground ecological functions assessed in three seasons.Ecological functions and TS-EMF differed significantly throughout the seasons(P<0.05).Synergistic relationships were found between carbon sequestration and oxygen release,between cooling and humidification,and between organic carbon accumulation and nutrient cycling.Notably,aboveground multifunctionality played a leading role in TS-EMF.With seasonal changes,resource allocation shifted toward traits related to resource acquisition rather than conservation to maintain TS-EMF.The combination of traits that predicted TS-EMF varied by type,accounting for up to 66.45%of the variation.TS-EMF was primarily driven by leaf structure in spring and by nutrient accumulation in autumn.Leaf carbon content(LCC)consistently served as a stabilizing factor for predicting TS-EMF across seasons.At 36.5-36.8 mg g^(-1),LCC had its optimal effect on TS-EMF.Other traits in combination that positively influence total TS-EMF include leaf nitrogen content(3.43-3.45 mg g^(-1)),leaf phosphorus content(0.80-0.83 mg g^(-1)),and leaf area(65.86-68.43 cm^(2)).Within these specified trait thresholds,Morus alba and Quercus mongolica were identified as key species.These findings suggest that the trade-off between various ecological functions can be managed by altering plant traits across seasons.This approach could provide a theoretical foundation for enhancing the TS-EMF of urban forests through trait-based management,offering practical guidance for selecting tree species.
基金supported by the National Science and Technology Major Project of China(Nos.2017-II-0004-0016 and J2019-I-0011-0011).
文摘Unstable operating conditions such as surge could cause damage to both aerodynamic performance and structural integrity of a compression system.This paper addresses the critical issue of aerodynamic instability in compressor design,particularly focusing on an axial-centrifugal combined compressor,a widely used yet underexplored configuration.An experimental investigation was conducted on a three-stage axial and one-stage centrifugal compressor(3A1C),using two pipe systems and employing fast-responding transducers to capture the dynamic instability process from choke condition to deep surge.Results reveal that at the design speed,3A1C enters deep surge directly,whereas at off-design speeds,it experiences rotating stall and mild surge across a wide mass flow range.Some special instability features in the combined compressor can be found in the steady state map and dynamic process.The characteristic curve of the first axial stage keeps a positive slope during the whole mass flow range at an off-design speed.The first stage could work stably on the stall characteristic curve because the centrifugal stage has stronger pressurization and plays a dominant role in global aerodynamic instability.Besides,rotating instability occurs at the first rotor tip and disappears as the back pressure increases,which is also rarely seen in a single-axial compressor.This is also related to the strong pressurization of the centrifugal stage.The findings of this paper will contribute to the understanding of aerodynamic instabilities in combined compressors.
基金the National Key Research and Development Program of China(2021YFC2900300)the Natural Science Foundation of Guangdong Province(2024A1515030216)+2 种基金MOST Special Fund from State Key Laboratory of Geological Processes and Mineral Resources,China University of Geosciences(GPMR202437)the Guangdong Province Introduced of Innovative R&D Team(2021ZT09H399)the Third Xinjiang Scientific Expedition Program(2022xjkk1301).
文摘The application of machine learning for pyrite discrimination establishes a robust foundation for constructing the ore-forming history of multi-stage deposits;however,published models face challenges related to limited,imbalanced datasets and oversampling.In this study,the dataset was expanded to approximately 500 samples for each type,including 508 sedimentary,573 orogenic gold,548 sedimentary exhalative(SEDEX)deposits,and 364 volcanogenic massive sulfides(VMS)pyrites,utilizing random forest(RF)and support vector machine(SVM)methodologies to enhance the reliability of the classifier models.The RF classifier achieved an overall accuracy of 99.8%,and the SVM classifier attained an overall accuracy of 100%.The model was evaluated by a five-fold cross-validation approach with 93.8%accuracy for the RF and 94.9%for the SVM classifier.These results demonstrate the strong feasibility of pyrite classification,supported by a relatively large,balanced dataset and high accuracy rates.The classifier was employed to reveal the genesis of the controversial Keketale Pb-Zn deposit in NW China,which has been inconclusive among SEDEX,VMS,or a SEDEX-VMS transition.Petrographic investigations indicated that the deposit comprises early fine-grained layered pyrite(Py1)and late recrystallized pyrite(Py2).The majority voting classified Py1 as the VMS type,with an accuracy of RF and SVM being 72.2%and 75%,respectively,and confirmed Py2 as an orogenic type with 74.3% and 77.1%accuracy,respectively.The new findings indicated that the Keketale deposit originated from a submarine VMS mineralization system,followed by late orogenic-type overprinting of metamorphism and deformation,which is consistent with the geological and geochemical observations.This study further emphasizes the advantages of Machine learning(ML)methods in accurately and directly discriminating the deposit types and reconstructing the formation history of multi-stage deposits.
基金National Natural Science Foundation of China under Grant No.51578463。
文摘The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.
基金supported by grants from the Chinese Academy of Sciences(XDA24010101)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Key Research and Development Program of China(2023YFF1001200)Natural Science Foundation of Zhejiang Province(LD24C130001)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS。
文摘A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that regulates heading date,plant height and grain number.Here,we investigated the relationship between Ghd7 and florigen genes Hd3a and RFT1,to determine their roles in regulating heading date and grain number under different photoperiods.Our results revealed that under long-day(LD)conditions,Hd3a acts prior to RFT1 to promote heading while negatively regulating plant height and grain number.In contrast,Ghd7 positively regulates heading date,plant height,and grain number by inhibiting both Hd3a and RFT1.Under short-day(SD)conditions,the functions of Hd3a and RFT1 remain consistent with those under LD conditions,but Ghd7 does not inhibit their expression,resulting in a weaker phenotypic effect compared to Hd3a.Additionally,under both LD and SD conditions,increased Ghd7 expression enhances its inhibitory effect on Hd3a and RFT1,leading to later heading and increased grain number;however,once the heading date exceeds 94 d,grain number no longer increases.Moreover,the gn1a allele increased grain number by 16.5%to 42.5%,while combinations of the elite alleles from Ghd7,Hd3a,RFT1,and Gn1a significantly increased grain number by up to 240.9%.Therefore,we propose a new breeding strategy to optimize the heading date and grain number using the Ghd7Hd3aRFT1gn1a combination of Ghd7,Hd3a,RFT1,and Gn1a under LD conditions,and the Ghd7hd3aRFT1gn1a combination under SD conditions.This strategy improved the yield of the high-quality Northeast variety Kongyu 131(KY131)by 69.1%in Beijing and 93.7%in Hainan.This strategy will greatly improve the efficiency of north-to-south adaptation in rice,providing theoretical guidance for expanding the geographical adaptability of rice varieties.
基金supported by National Natural Science Foundation of China(Nos.82404511,82373790)Central Guidance on Local Science and Technology Development Fund of Hebei Province(No.226Z2605G)Program for Young Scientists in the Field of Natural Science of Hebei Medical University(No.CYCZ2023011).
文摘Natural product-based drug combinations(NPDCs)present distinctive advantages in treating complex diseases.While high-throughput screening(HTS)and conventional computational methods have partially accelerated synergistic drug combination discovery,their applications remain constrained by experimental data fragmentation,high costs,and extensive combinatorial space.Recent developments in artificial intelligence(AI),encompassing traditional machine learning and deep learning algorithms,have been extensively applied in NPDC identification.Through the integration of multi-source heterogeneous data and autonomous feature extraction,prediction accuracy has markedly improved,offering a robust technical approach for novel NPDC discovery.This review comprehensively examines recent advances in AI-driven NPDC prediction,presents relevant data resources and algorithmic frameworks,and evaluates current limitations and future prospects.AI methodologies are anticipated to substantially expedite NPDC discovery and inform experimental validation.
基金funded by the State Grid Corporation Science and Technology Project(5108-202218280A-2-391-XG).
文摘The high proportion of uncertain distributed power sources and the access to large-scale random electric vehicle(EV)charging resources further aggravate the voltage fluctuation of the distribution network,and the existing research has not deeply explored the EV active-reactive synergistic regulating characteristics,and failed to realize themulti-timescale synergistic control with other regulatingmeans,For this reason,this paper proposes amultilevel linkage coordinated optimization strategy to reduce the voltage deviation of the distribution network.Firstly,a capacitor bank reactive power compensation voltage control model and a distributed photovoltaic(PV)activereactive power regulationmodel are established.Additionally,an external characteristicmodel of EVactive-reactive power regulation is developed considering the four-quadrant operational characteristics of the EVcharger.Amultiobjective optimization model of the distribution network is then constructed considering the time-series coupling constraints of multiple types of voltage regulators.A multi-timescale control strategy is proposed by considering the impact of voltage regulators on active-reactive EV energy consumption and PV energy consumption.Then,a four-stage voltage control optimization strategy is proposed for various types of voltage regulators with multiple time scales.Themulti-objective optimization is solved with the improvedDrosophila algorithmto realize the power fluctuation control of the distribution network and themulti-stage voltage control optimization.Simulation results validate that the proposed voltage control optimization strategy achieves the coordinated control of decentralized voltage control resources in the distribution network.It effectively reduces the voltage deviation of the distribution network while ensuring the energy demand of EV users and enhancing the stability and economic efficiency of the distribution network.
基金Supported by the National Natural Science Foundation of China(42302184)Innovation Group Project of Basic Research in Gansu Province,China(22JR5RA045)。
文摘The lamina(combination)types,reservoir characteristics and shale oil occurrence states of organic-rich shale in the Triassic Yanchang Formation Chang 73 sub-member in the Ordos Basin were systematically investigated to reveal the main controlling factors of shale oil occurrence under different lamina combinations.The differential enrichment mechanisms and patterns of shale oil were discussed using the shale oil micro-migration characterization and evaluation methods from the perspectives of relay hydrocarbon supply,stepwise migration,and multi-stage differentiation.The results are obtained in five aspects.First,Chang 73 shale mainly develops five types of lamina combination,i.e.non-laminated shale,sandy laminated shale,tuffaceous laminated shale,mixed laminated shale,and organic-rich laminated shale.Second,shales with different lamina combinations are obviously different in the reservoir space.Specifically,shales with sandy laminae and tuffaceous laminae have a large number of intergranular pores,dissolution pores and hydrocarbon generation-induced fractures.The multi-scale pore and fracture system constitutes the main place for liquid hydrocarbon occurrence.Third,the occurrence and distribution of shale oil in shale with different lamina combinations are jointly controlled by organic matter abundance,reservoir property,thermal evolution degree,mineral composition and laminae scale.The micro-nano-scale pore-fracture networks within shales containing rigid laminae,particularly sandy and tuffaceous laminations,primarily contain free-state light hydrocarbon components.In contrast,adsorption-phase heavy hydrocarbon components predominantly occupy surfaces of organic matter assemblages,clay mineral matrices,and framework mineral particulates.Fourth,there is obvious shale oil micro-migration between shales with different lamina combinations in Chang 73.Generally,such micro-migration is stepwise in a sequence of organic-rich laminated shale→tuffaceous laminated shale→mixed laminated shale→sandy lamiated shale→non-laminated shale.Fifth,the relay hydrocarbon supply of organic matter under the control of the spatial superposition of shales with various laminae,the stepwise migration via multi-scale pore and fracture network,and the multi-differentiation in shales with different lamina combinations under the control of organic-inorganic interactions fundamentally decide the differences of shale oil components between shales with different lamina combinations.
基金financially supported by the Heilongjiang Provincial Key R&D Program Project(No.GA21A204)Heilongjiang Provincial Natural Science Foundation of China(No.LH2022D031)the Research Project of Heilongjiang Province Bureau of Geology and Mineral Resources(No.HKY202302).
文摘Although previous researchers have attempted to decipher ore genesis and mineralization in the Erdaokan Ag-Pb-Zn deposit,some uncertainties regarding the mineralization process and evolution of both ore-forming fluids and magnetite types still need to be addressed.In this study,we obtained new EPMA,LA-ICP-MS,and in situ Fe isotope data from magnetite from the Erdaokan deposit,in order to better understand the mineralization mechanism and evolution of both magnetite and the ore-forming fluids.Our results identified seven types of magnetite at Erdaokan:disseminated magnetite(Mag1),coarse-grained magnetite(Mag2a),radial magnetite(Mag2b),fragmented fine-grained magnetite(Mag2c),vermicular gel magnetite(Mag3a1 and Mag3a2),colloidal magnetite(Mag3b)and dark gray magnetite(Mag4).All of the magnetite types were hydrothermal in origin and generally low in Ti(<400 ppm)and Ni(<800 ppm),while being enriched in light Fe isotopes(δ^(56)Fe ranging from−1.54‰to−0.06‰).However,they exhibit different geochemical signatures and are thus classified into high-manganese magnetite(Mag1,MnO>5 wt%),low-silicon magnetite(Mag2a-c,SiO_(2)<1 wt%),high-silicon magnetite(Mag3a-b,SiO_(2)from 1 to 7 wt%)and high-silicon-manganese magnetite(Mag4,SiO_(2)>1 wt%,MnO>0.2 wt%),each being formed within distinct hydrothermal environments.Based on mineralogy,elemental geochemistry,Fe isotopes,temperature trends,TMg-mag and(Ti+V)vs.(Al+Mn)diagrams,we propose that the Erdaokan Ag-Pb-Zn deposit underwent multi-stage mineralization,which can be broken down into four stages and nine sub-stages.Mag1,Mag2a-c,Mag3a-b and Mag4 were formed during the first sub-stage of each of the four stages,respectively.Additionally,fluid mixing,cooling and depressurization boiling were identified as the main mechanisms for mineral precipitation.The enrichment of Ag was significantly enhanced by the superposition of multi-stage ore-forming hydrothermal fluids in the Erdaokan Ag-Pb-Zn deposit.
文摘This paper presents a new criterion for determining the unloading points quantitatively and consistently in a multi-stage triaxial test.The radial strain gradient(RSG)is first introduced as an arc tangent function of the rate of change of radial strain to time.RSG is observed to correlate closely with the stress state of a compressed sample,and reaches a horizontal asymptote as approaching failure.For a given rock type,RSG value at peak stress is almost the same,irrespective of the porosity and permeability.These findings lead to the development of RSG criterion:Unloading points can be precisely determined at the time when RSG reaches a pre-determined value that is a little smaller than or equal to the RSG at peak stress.The RSG criterion is validated against other criteria and the single-stage triaxial test on various types of rocks.Failure envelopes from the RSG criterion match well with those from single-stage tests.A practical procedure is recommended to use the RSG criterion:an unconfined compression or single-stage test is first conducted to determine the RSG at peak stress for one sample,the unloading point is then selected to be a value close to the RSG at peak stress,and the multi-stage test is finally performed on another sample using the pre-selected RSG unloading criterion.Generally,the RSG criterion is applicable for any type of rocks,especially brittle rocks,where other criteria are not suitable.Further,it can be practically implemented on the most available rock mechanical testing instruments.
基金supported by the National Natural Science Foundation of China(Grant No:52271300,52071337)National Key Research and Development Program of China(2022YFC2806501)+1 种基金High-tech Ship Research Projects Sponsored by MIIT(CBG2N21-4-25)Program for Changjiang Scholars and Innovative Research Team in University(Grant No.IRT14R58).
文摘A new hang-off system has been proposed to improve the security of risers in hang-off modes during typhoons.However,efficient anti-typhoon evacuation strategies have not been investigated.Optimiza-tion model and method for the anti-typhoon evacuation strategies should be researched.Therefore,multi-objective functions are proposed based on operation time,evacuation speed stability,and steering stability.An evacuation path model and a dynamic model of risers with the new hang-off system are developed for design variables and constraints.A multi-objective optimization model with high-dimensional variables and complex constraints is established.Finally,a three-stage optimization method based on genetic algorithm,least square method,and the penalty function method is proposed to solve the multi-objective optimization model.Optimization results show that the operation time can be reduced through operation parameter optimization,especially evacuation heading optimization.The optimal anti-typhoon strategy is evacuation with all risers suspended along a variable path when the direction angle is large,while evacuation with all risers suspended along a straight path at another di-rection angle.Besides,the influencing factors on anti-typhoon evacuation strategies indicate that the proposed optimization model and method have strong applicability to working conditions and remarkable optimization effects.
基金supported by the National Key Research and Development Program of China(Nos.2022YFA1205602,and 2023YFC3707801)the National Natural Science Foundation of China(Nos.U22A20402,22376073,21936003 and 22306119)China Postdoctoral Science Foundation(No.2023T160419).
文摘Nano zero-valent iron(nZVI)is a promising phosphate adsorbent for advanced phosphate removal.However,the rapid passivation of nZVI and the low activity of adsorption sites seriously limit its phosphate removal performance,accounting for its inapplicability to meet the emission criteria of 0.1 mg P/L phosphate.In this study,we report that the oxalate modification can inhibit the passivation of nZVI and alter the multi-stage phosphate adsorption mechanism by changing the adsorption sites.As expected,the stronger antipassivation ability of oxalate modified nZVI(OX-nZVI)strongly favored its phosphate adsorption.Interestingly,the oxalate modification endowed the surface Fe(III)sites with the lowest chemisorption energy and the fastest phosphate adsorption ability than the other adsorption sites,by in situ forming a Fe(III)-phosphate-oxalate ternary complex,therefore enabling an advanced phosphate removal process.At an initial phosphate concentration of 1.00 mg P/L,pH of 6.0 and a dosage of 0.3 g/L of adsorbents,OX-nZVI exhibited faster phosphate removal rate(0.11 g/mg/min)and lower residual phosphate level(0.02 mg P/L)than nZVI(0.055 g/mg/min and 0.19 mg P/L).This study sheds light on the importance of site manipulation in the development of high-performance adsorbents,and offers a facile surface modification strategy to prepare superior iron-basedmaterials for advanced phosphate removal.
基金supported by the National Natural Science Foundation of China(No.82173947).
文摘Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
基金supported by grants from the National Natural Science Foundation of China(U21A20400,81973789,82004327).
文摘Objective:To explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.Method:We used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin(55 mg/kg),geniposide(5 mg/kg),or their 11:1 combination.Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining,Evans blue assay,enzyme-linked immunosorbent assay,and Western blot.Results:The results revealed that the nuclear factor-kappa B(NF-κB)signaling pathway is inhibited in combination treatment of cerebral ischemia.Ten targets were identified as key nodes in the protein-protein interaction network:interleukin 6(IL-6),interleukin-1β,interleukin 18,C-C motif ligand 2,C-C motif ligand 4,interleukin 10,interferon-γ-inducible protein 10,C-C motif ligand 3,tumor necrosis factor-α(TNF-α),interleukin-1α.The baicalin-geniposide combination significantly reduced infarct volume,improved neurological deficits,and alleviated brain edema/blood-brain barrier leakage compared with monotherapy.Additionally,it significantly inhibited toll-like receptor 4(TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-αand IL-6 levels.Conclusion:The baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.
基金financially supported by the National Natural Science Foundation of China(Nos.42277149,41502299,41372306)the Research Planning of Sichuan Education Department,China(No.16ZB0105)+3 种基金the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection Independent Research Project(Nos.SKLGP2016Z007,SKLGP2018Z017,SKLGP2020Z009)Chengdu University of Technology Young and Middle Aged Backbone Program(No.KYGG201720)Sichuan Provincial Science and Technology Department Program(No.19YYJC2087)China Scholarship Council。
文摘To tackle the difficulties of the point prediction in quantifying the reliability of landslide displacement prediction,a data-driven combination-interval prediction method(CIPM)based on copula and variational-mode-decomposition associated with kernel-based-extreme-learningmachine optimized by the whale optimization algorithm(VMD-WOA-KELM)is proposed in this paper.Firstly,the displacement is decomposed by VMD to three IMF components and a residual component of different fluctuation characteristics.The key impact factors of each IMF component are selected according to Copula model,and the corresponding WOA-KELM is established to conduct point prediction.Subsequently,the parametric method(PM)and non-parametric method(NPM)are used to estimate the prediction error probability density distribution(PDF)of each component,whose prediction interval(PI)under the 95%confidence level is also obtained.By means of the differential evolution algorithm(DE),a weighted combination model based on the PIs is built to construct the combination-interval(CI).Finally,the CIs of each component are added to generate the total PI.A comparative case study shows that the CIPM performs better in constructing landslide displacement PI with high performance.
基金Supported by Natural Science Foundation of Hubei Province,No.2019CFC929.
文摘BACKGROUND Chemotherapy combined with anti-angiogenic therapy has become an important strategy for the treatment of advanced gastric cancer(AGC);however,the regimen needs optimization.AIM To evaluate the efficacy of albumin-bound paclitaxel(nab-ptx)combined with the small molecule vascular endothelial growth factor inhibitor anlotinib in secondline and beyond treatment of AGC.METHODS We collected data from AGC patients at our hospital who experienced disease progression after first-line chemotherapy and received anlotinib combined with nab-ptx.The primary endpoints included overall survival(OS)and progressionfree survival(PFS),while the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and adverse events(AEs).RESULTS Preliminary results indicated that anlotinib combined with nab-ptx can provide significant efficacy in second-line or above treatment for AGC(median PFS=6.0 months,median OS=12.0 months),with an ORR of 42%and a DCR of 78%.Further analysis revealed that patients who experienced hypertension,proteinuria,and hand-foot syndrome during treatment had better efficacy compared to those who did not experience these AEs.Mechanistic studies suggest that this regimen likely exerts synergistic anti-tumor effects by activating the immune response through the reduction of regulatory T-cell proportions.Common adverse reactions included bone marrow suppression,peripheral neuropathy,hypertension,proteinuria,and hand-foot syndrome,which were manageable and resolved with appropriate interventions,indicating the promising application of this regimen in second-line or above treatment for AGC.CONCLUSION The combination of anlotinib and nab-ptx shows promising efficacy with fewer toxicities in AGC treatment.The regimen holds promise as a second-line treatment of AGC;however,its specific clinical value requires further research.
基金financially supported by the Key Scientific Research Project of Henan Provincial Universities in 2024(No.24A350013)the Project of Basic Research Fund of Henan Institute of Medical and Pharmaceutical Sciences(No.2024BP0202)+1 种基金the Key Scientific and Technological Project of Henan Province(No.242102311213)the Henan Province Postdoctoral Program(No.343915)。
文摘Cancer remains one of the major threats to public health.Traditional chemotherapy,radiotherapy,and other anti-tumor therapies have numerous limitations in clinical treatment.Notwithstanding the considerable advances made in recent years with regard to immunotherapy in both basic research and clinical practice,there remains scope for further improvement,particularly with respect to its efficacy against solid tumors.With advancements in nanotechnology,tumor nanovaccines hold immense potential for preventing tumor recurrence and treating metastatic tumors.Nevertheless,the considerable heterogeneity of tumor immunogenicity presents a number of significant challenges in the development of nanometrescale vaccines targeting solid tumors.Recent findings indicate that immune checkpoint inhibitor(ICI)therapy can improve the immunosuppressive microenvironment within tumors,while nanovaccines can also augment tumor sensitivity toward ICIs.Consequently,combining tumor nanovaccine with ICI therapy holds promise for effectively eradicating tumors or controlling their recurrence and metastasis during cancer treatment.This review delves into the mechanism behind combining tumor nanovaccine with ICI while focusing on factors influencing this combined therapy approach.Moreover,it offers an overview of the current research status regarding the combination of tumor nanovaccines with chemotherapy,radiotherapy,photothermal therapy,and sonodynamic therapy,as well as prospects for future developments in this field.
基金Supported by National Natural Science Foundation of China,No.32270768,No.82273970,No.32070726 and No.82370715Hubei Natural Science Foundation of China,No.2024AFB218+1 种基金National Key R&D Program of China,No.2023YFC2507904Doctoral Startup Foundation of Hubei University of Technology,No.XJ2022003901.
文摘Histone deacetylase inhibitors(HDACis),such as trichostatin A(TSA),have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes.However,emerging evidence indicates that unintended pro-metastatic effects may offset the therapeutic benefits of HDACis.Chen et al elucidate this paradox,demonstrating that TSA-induced hyperacetylation activates the BRD4/c-Myc/ER-stress axis,thereby promoting epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma(ESCC).Furthermore,they clarify the clinical significance of histone acetylation in the prognostic evaluation of ESCC.Their findings underscore the complexity of epigenetic therapies and highlight the necessity of reevaluating the associated risks and combinatorial therapeutic strategies with HDACi-based treatments.Here,we summarize the potential risks of HDACis therapy and discuss feasible combination therapeutic strategies.
