Introduction of the photothermal effect into transition-metal oxide photoanodes has been proven to be an effective method to improve the photoelectrochemical(PEC)water-splitting performance.However,the precise role of...Introduction of the photothermal effect into transition-metal oxide photoanodes has been proven to be an effective method to improve the photoelectrochemical(PEC)water-splitting performance.However,the precise role of the photothermal effect on the PEC performance of photoanodes is still not well understood.Herein,spinel-structured ZnFe_(2)O_(4)nanoparticles are deposited on the surface of hematite(Fe_(2)O_(3)),and the ZnFe_(2)O_(4)/Fe_(2)O_(3)photoanode achieves a high photocurrent density of 3.17 mA cm^(-2)at 1.23 V versus a reversible hydrogen electrode(VRHE)due to the photothermal effect of ZnFe_(2)O_(4).Considering that the hopping of electron small polarons induced by oxygen vacancies is thermally activated,we clarify that the main reason for the enhanced PEC performance via the photothermal effect is the promoted mobility of electron small polarons that are bound to positively charged oxygen vacancies.Under the synergistic effect of oxygen vacancies and the photothermal effect,the electron conductivity and PEC performance are significantly improved,which provide fundamental insights into the impact of the photothermal effect on the PEC performance of small polaron-type semiconductor photoanodes.展开更多
Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and...Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.展开更多
Dear Editor, As a complex disease, the development and progression of hepatocellular carcinoma (HCC) involves the interactions of multiple proteins, genes and miRNAs in various biological pathways, and it has been ...Dear Editor, As a complex disease, the development and progression of hepatocellular carcinoma (HCC) involves the interactions of multiple proteins, genes and miRNAs in various biological pathways, and it has been extensively studied with different high-throughput techniques. However, efforts to integrate multiple data sources at different levels, especially with regard to biological pathways and interaction networks, are still negligible in the HCC research field.展开更多
AIM: To observe the curative effect of galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticles in liver caner mice and its side effects. METHODS: The GC/5-FU nanoparticle is a nanomate- rial made by cou...AIM: To observe the curative effect of galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticles in liver caner mice and its side effects. METHODS: The GC/5-FU nanoparticle is a nanomate- rial made by coupling GC and 5-FU. The release experiment was performed in vitro. The orthotropic liver cancer mouse models were established and divided into control, GC, 5-FU and GC/5-FU groups. Mice in the control and GC group received an intravenous injection of 200 μL saline and GC, respectively. Mice in the 5-FU and GC/5-FU groups received 200 μL (containing 0.371 mg 5-FU) 5-FU and GC/5-FU, respectively. The tumor weight and survival time were observed. The cell cycle and apoptosis in tumor tissues were monitored by flow cytometry. The expression of p53, Bax, Bcl-2, caspase-3 and poly adenosine 50-diphosphate-ribose polymerase 1 (PARP-1) was detected by immunohistochemistry, reverse transcription-polymerase chain reaction and Western blot. The serum blood biochemical parameters and cytotoxic activity of natural killer (NK) cell and cy- totoxicity T lymphocyte (CTL) were measured. RESULTS: The GC/5-FU nanoparticle is a sustained release system. The drug loading was 6.12% ± 1.36%, the encapsulation efficiency was 81.82% ± 5.32%, and the Zeta potential was 10.34 ± 1.43 mV. The tu- mor weight in the GC/5-FU group (0.4361±0.1153 g vs 1.5801 ± 0.2821 g, P 〈 0.001) and the 5-FU (0.7932±0.1283 g vs 1.5801 ±0.2821 g, P 〈 0.001) was sig- nificantly lower than that in the control group; GC/5- FU treatment can significantly lower the tumor weight (0.4361± 0.1153 g vs 0.7932±0.1283 g, P 〈 0.001), and the longest median survival time was seen in the GC/5-FU group, compared with the control (12 d vs 30 d, P 〈 0.001), GC (13 d vs 30 d, P 〈 0.001) and 5-FU groups (17 d vs 30 d, P 〈 0.001). Flow cytom- etry revealed that compared with the control, GC/5- FU caused a higher rate of G0-G1 arrest (52.79% ± 13.42% vs 23.92%±9.09%, P = 0.014 ) and apopto- sis (2.55% ±1.10% vs 11.13% ±11.73%, P 〈 0.001) in hepatic cancer cells. Analysis of the apoptosis path- ways showed that GC/5-FU upregulated the expression of p53 at both the protein and the mRNA levels, which in turn lowered the ratio of Bcl-2lBax expression; this led to the release of cytochrome C into the cytosol from the mitochondria and the subsequent activation of caspase-3. Upregulation of caspase-3 expression de- creased the PARP-1 at both the mRNA and the protein levels, which contributed to apoptosis. 5-FU increased the levels of aspartate aminotransferase and alanine aminotransferase, and decreased the numbers of platelet, white blood cell and lymphocyte and cytotoxic activities of CTL and NK cells, however, there were no such side effects in the GC/5-FU group. CONCLUSION: GC/5-FU nanoparticles can significant- ly inhibit the growth of liver cancer in mice via the p53 apoptosis pathway, and relieve the side effects and im- munosuppression of 5-FU.展开更多
Aurum nanomaterials(ANM), combining the features of nanotechnology and metal elements, have demonstrated enormous potential and aroused great attention on biomedical applications over the past few decades. Particularl...Aurum nanomaterials(ANM), combining the features of nanotechnology and metal elements, have demonstrated enormous potential and aroused great attention on biomedical applications over the past few decades. Particularly, their advantages, such as controllable particle size, flexible surface modification, higher drug loading, good stability and biocompatibility, especially unique optical properties, promote the development of ANM in biomedical field. In this review, we will discuss the advanced preparation process of ANM and summarize their recent applications as well as their prospects in diagnosis and therapy. Besides, multi-functional ANM-based theranostic nanosystems will be introduced in details, including radiotherapy(RT), photothermal therapy(PTT), photodynamic therapy(PDT), immunotherapy(IT), and so on.展开更多
The combination regimen of trastuzumab(Tras)plus Nab-paclitaxel(Nab)is recommended to treat HER2-positive(HER2+)cancers.However,they exert effects in different mechanisms:Tras need to stay on cell membranes,while Nab ...The combination regimen of trastuzumab(Tras)plus Nab-paclitaxel(Nab)is recommended to treat HER2-positive(HER2+)cancers.However,they exert effects in different mechanisms:Tras need to stay on cell membranes,while Nab need to be endocytosed,therefore the concurrent combination regimen may not be the best one in HER2+tumors treatment.Caveolin-1(Cav-1)is a key player in mediating their endocytosis and is associated with their efficacy,but few researches noticed the opposite effect of Cav-1 expression on the combination efficacy.Herein,we systematically studied the Cav-1 expression level on the combination efficacy and proposed an optimized and clinically feasible combination regimen for HER2+Cav-1 High tumor treatment.In the regimen,lovastatin(Lova)was introduced to modulate the Cav-1 expression and the results indicated that Lova could downregulate Cav-1 expression,increase Tras retention on cell membrane and enhance the in vitro cytotoxicity of Tras in HER2+Cav-1 High cells but not in HER2+Cav-1 Low cells.Therefore,by exchanging the dosing sequence of Nab and Tras,and by adding Lova at appropriate time points,the precise three-drug-sequential regimen(PTDS,Nab(D1)-Lova(D2)-Lova&Tras(D2+12 h))was established.Compared with the concurrent regimen,the PTDS regimen exhibited a higher in vitro cytotoxicity and a stronger tumor growth inhibition in HER2+Cav-1 High tumors,which might be a promising combination regimen for these patients in clinics.展开更多
Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparati...Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns(SWCNH), zinc phthalocyanine(ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 ℃ due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise(to 65 ℃) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.展开更多
[Objectives]This study was conducted to investigate the effects of artificially cultured Eisenia foetida and wild earthworms ( Pheretima sp.) on the changes of microbial populations in forest soil in different seasons...[Objectives]This study was conducted to investigate the effects of artificially cultured Eisenia foetida and wild earthworms ( Pheretima sp.) on the changes of microbial populations in forest soil in different seasons.[Methods]Artificially cultured E.foetida and wild earthworms were introduced to forest soil,and changes in the number of microbial populations under earthworm-microbe interaction were investigated in different seasons by tracking observation.The effects of earthworm activities on the number of different microbial populations were discussed also.[Results]Different microbial populations all increased in the soil to different degrees after the introduction of earthworms.The effects of the wild earthworms on the changes in bacteria,actinomycetes and fungi in the soil were different from those of artificially cultivated earthworms to certain degrees.[Conclusions]This study provides a theoretical basis for organic agriculture that relies on the decomposition of organic matter to release nutrients.展开更多
A calculation method for heats of formation (HOF, referred to as △Hf) based on the density functional theory (DFT) is presented in this work. Similar to Gaussian-3 theory, the atomic scheme is applied to calculate th...A calculation method for heats of formation (HOF, referred to as △Hf) based on the density functional theory (DFT) is presented in this work. Similar to Gaussian-3 theory, the atomic scheme is applied to calculate the heats of formation of the molecules. In this method, we have modified the formula for calculation of Gaussian-3 theory in several ways, including the correction for diffuse functions and the correction for higher polarization functions. These corrections are found to be significant. The average absolute deviation from experiment for the 164 calculated heats of formation is about 1.9 kcal·mol?1, while average absolute deviation from G3MP2 for the 149 (among the 164 molecules, 15 large-sized molecules can not be calculated at the G3MP2 level) calculated heats of formation is only about 1.9 kcal·mol?1. It indicates that the present method can be applied to predict the heats of formation of medium-sized and large-sized molecules, while the heats of formation of these molecules using Gaussian-3 theory are much difficult, even impossible, to calculate. That is, this method provides a choice in the calculation of △Hf for medium-sized and large-sized molecules.展开更多
Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel ...Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel the value of this classical therapeutic strategy.Here,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic drugs.Alendronate in BC-LNPs@PTX,a bisphosphonate to block mevalonate metabolism,works as both the structure and drug constituent in nanogranules,where alendronate coordinated with calcium ions to form the particle core.The synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic mechanism.Differing from the paclitaxel-induced apoptosis,the involvement of alendronate inhibits the mevalonate metabolism,changes the mitochondrial morphology,disturbs the redox homeostasis,and causes theaccumulation of mitochondrial ROS and lethal lipid peroxides(LPO).These factors finally trigger the ferroptosis of tumor cells,an immunogenic cell death mode,which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy.Therefore,by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis,BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.展开更多
Contact angle is an essential parameter to characterize substrate wettability.The measurement of contact angle in experiment and simulation is a complex and time-consuming task.In this paper,an improved method of meas...Contact angle is an essential parameter to characterize substrate wettability.The measurement of contact angle in experiment and simulation is a complex and time-consuming task.In this paper,an improved method of measuring contact angle in multiphase lattice Boltzmann simulations is proposed,which can accurately obtain the real-time contact angle at a low temperature and larger density ratio.The three-phase contact point is determined by an extrapolation,and its position is not affected by the local deformation of flow field in the three-phase contact region.A series of simulations confirms that the present method has high accuracy and gird-independence.The contact angle keeps an excellent linear relationship with the chemical potential of the surface,so that it is very convenient to specify the wettability of a surface.The real-time contact angle measurement enables us to obtain the dynamic contact angle hysteresis on chemically heterogeneous surface,while the mechanical analyses can be effectively implemented at the moving contact line.展开更多
Backgrounds This work emphasizes the current research status of the urban Digital Twins to establish an intelligent spatiotemporal framework.A Geospatial Artificial Intelligent(GeoAI)system is developed based on the G...Backgrounds This work emphasizes the current research status of the urban Digital Twins to establish an intelligent spatiotemporal framework.A Geospatial Artificial Intelligent(GeoAI)system is developed based on the Geographic Information System and Artificial Intelligence.It integrates multi-video technology and Virtual City in urban Digital Twins.Methods Besides,an improved small object detection model is proposed:YOLOv5-Pyramid,and Siamese network video tracking models,namely MPSiam and FSSiamese,are established.Finally,an experimental platform is built to verify the georeferencing correction scheme of video images.Result The MultiplyAccumulate value of MPSiam is 0.5B,and that of ResNet50-Siam is 4.5B.Besides,the model is compressed by 4.8times.The inference speed has increased by 3.3 times,reaching 83 Frames Per Second.3%of the Average Expectation Overlap is lost.Therefore,the urban Digital Twins-oriented GeoAI framework established here has excellent performance for video georeferencing and target detection problems.展开更多
Background This work aims to build a comprehensive and effective fire emergency management system based on the Internet of Things(IoT)and achieve an actual intelligent fire rescue.A smart fire protection information s...Background This work aims to build a comprehensive and effective fire emergency management system based on the Internet of Things(IoT)and achieve an actual intelligent fire rescue.A smart fire protection information system was designed based on the IoT.A detailed analysis was conducted on the problem of rescue vehicle scheduling and the evacuation of trapped persons in the process of fire rescue.Methods The intelligent fire visualization platform based on the three-dimensional(3D)Geographic Information Science(GIS)covers project overview,equipment status,equipment classification,equipment alarm information,alarm classification,alarm statistics,equipment account information,and other modules.The live video accessed through the visual interface can clearly identify the stage of the fire,which facilitates the arrangement of rescue equipment and personnel.The vehicle scheduling model in the system primarily used two objective functions to solve the Pareto Non-Dominated Solution Set Optimization:emergency rescue time and the number of vehicles.In addition,an evacuation path optimization method based on the Improved Ant Colony(IAC)algorithm was designed to realize the dynamic optimization of building fire evacuation paths.Results The experimental results indicate that all the values of detection signals were significantly larger in the smoldering fire scene at t=17s than the initial value.In addition,the probability of smoldering fire and the probability of open fire were relatively large according to the probability function of the corresponding fire situation,demonstrating that this model could detect fire.Conclusions The IAC algorithm reported here avoided the passages near the fire and spreading areas as much as possible and took the safety of the trapped persons as the premise when planning the evacuation route.Therefore,the IoT-based fire information system has important value for ensuring fire safety and carrying out emergency rescue and is worthy of popularization and application.展开更多
Methane dominated gas is one of the cleanest energy resources;however, there is no direct method to determine its source rock. Natural gases produced from the eastern Sichuan Basin together with seismic data were stud...Methane dominated gas is one of the cleanest energy resources;however, there is no direct method to determine its source rock. Natural gases produced from the eastern Sichuan Basin together with seismic data were studied for their sources and secondary alteration by thermochemical sulfate reduction(TSR). Our results demonstrate that Upper Permian to Lower Triassic(P_(3)ch-T_(1)f) gases in the surrounding of the Kaijiang-Liangping area show volatile organic sulfur compounds(VOSCs) δ^(34)S values close to those of the associated H_(2)S, and may have been altered by methane-dominated TSR, resulting in positive shift in methane δ^(13)C_(1)values with increasing TSR extents. Other(or group 2) gases produced from the P_(3)ch-T_(1)f reservoirs from the southern area and the Upper Carboniferous to Middle Permian(C_(2)h-P_(2)q) from the eastern Sichuan Basin are not significantly changed by TSR, show similar δ^(34)S values between the kerogens and some VOSCs, and may have been derived from the Lower Silurian and Middle Permian source rocks. This study demonstrates a case for the first time showing the δ^(34)S values of VOSCs can be used as a tool for direct correlation between non-TSR altered gas and source rocks. Methane-dominated gas pools can be found using gas and source rock geochemistry combined with seismic data.展开更多
Prussian blue analogs(PBAs)are potential contestants for aqueous Mg-ion batteries(AMIBs)on account of their high discharge voltage and threedimensional open frameworks.However,the low capacity arising from single reac...Prussian blue analogs(PBAs)are potential contestants for aqueous Mg-ion batteries(AMIBs)on account of their high discharge voltage and threedimensional open frameworks.However,the low capacity arising from single reaction site severely restricts PBAs'practical applications in highenergy-density AMIBs.Here,an organic acid co-coordination combined with etching method is reported to fabricate defect-rich potassium-free copper hexacyanoferrate with structural water on carbon nanotube fiber(DCuHCF@CNTF).Benefiting from the high-valence-state reactive sites,arrayed structure and defect effect,the well-designed D-CuHCF@CNTF exhibits an extraordinary reversible capacity of 146.6 mAh g1 with two-electron reaction,nearly close to its theoretical capacity.It is interesting to unlock the reaction mechanism of the Fe2+/Fe3+and Cu+/Cu2+redox couples via x-ray photoelectron spectroscopy.Furthermore,density functional theory calculations reveal that Fe and Cu in potassium-free D-CuHCF participate in charge transfer during the Mg2+insertion/extraction process.As a proof-of-concept demonstration,a rocking-chair fiber-shaped AMIBs was constructed via coupling with the NaTi2(PO4)3/CNTF anode,achieving high energy density and impressive mechanical flexibility.This work provides new possibilities to develop potassium-free PBAs with dual-active sites as high-capacity cathodes for wearable AMIBs.展开更多
In general,different extrusion conditions will affect the microstructure of magnesium alloys and further determine the mechanical properties.The effects of extrusion parameters and heat treatment processes such as ext...In general,different extrusion conditions will affect the microstructure of magnesium alloys and further determine the mechanical properties.The effects of extrusion parameters and heat treatment processes such as extrusion speed,pre-forging,annealing time,extrusion ratio and cooling rate on the microstructure,texture evolution and tensile properties of Mg-2Gd-0.3Zr alloys were investigated in this study.Compared with the as-cast alloy,the extrusion process significantly refines the grains and exhibit the rare earth texture.With the increase of extrusion speed and annealing time,the growth of recrystallized grains is accelerated,leading to the increase of elongation.Large pre-forging deformation achieves to refine the grains by promoting recrystallization nucleation,resulting in increased strength of Mg-2Gd-0.3Zr alloy.Decreasing the extrusion ratio or increasing the cooling rate will introduce coarse un-DRXed grains,which transformed the texture into the basal texture.In particular,the effect of rapid cooling on refining the recrystallized grains is also obvious.Different extrusion conditions influence the mechanical properties of the Mg-2Gd-0.3Zr alloy through the grain size,proportion of non-recrystallization region and texture type.展开更多
Currently,the cancer immunotherapy has made great progress while antitumor vaccine attracts substantial attention.Still,the selection of adjuvants as well as antigens are always the most crucial issues for better vacc...Currently,the cancer immunotherapy has made great progress while antitumor vaccine attracts substantial attention.Still,the selection of adjuvants as well as antigens are always the most crucial issues for better vaccination.In this study,we proposed a biomimetic antitumor nanovaccine based on biocompatible nanocarriers and tumor cell membrane antigens.Briefly,endogenous calcium pyrophosphate nanogranules with possible immune potentiating effect are designed and engineered,both as delivery vehicles and adjuvants.Then,these nanocarriers are coated with lipids and B16-OVA tumor cell membranes,so the biomembrane proteins can serve as tumor-specific antigens.It was found that calcium pyrophosphate nanogranules themselves were compatible and possessed adjuvant effect,while membrane proteins including tumor associated antigen were transferred onto the nanocarriers.It was demonstrated that such a biomimetic nanovaccine could be well endocytosed by dendritic cells,promote their maturation and antigen-presentation,facilitate lymph retention,and trigger obvious immune response.It was confirmed that the biomimetic vaccine could induce strong T-cell response,exhibit excellent tumor therapy and prophylactic effects,and simultaneously possess nice biocompatibility.In general,the present investigation might provide insights for the further design and application of antitumor vaccines.展开更多
Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells.It plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significan...Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells.It plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significant events in cells,such as the interaction with foreign particles.Therefore,it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay,since more and more nanomedicine are supposed to be used in biomedical field.However,there is no review in this aspect.This review summarizes the small GTPases in terms of the structure,biological function and its interaction with nanoparticles.We briefly introduced the various nanoparticles such as gold/silver nanoparticles,SWCNT,polymeric micelles and other nano delivery systems that interacted with different GTPases.These current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases study.This will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research direction.It is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines.展开更多
基金This work was supported by the National Natural Science Foundation of China(51902297,52002361,52003300,and 22109120)the Zhejiang Provincial Natural Science Foundation of China(LQ21B030002)the fund of the Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education,and Hubei Key Laboratory of Catalysis and Materials Science.
文摘Introduction of the photothermal effect into transition-metal oxide photoanodes has been proven to be an effective method to improve the photoelectrochemical(PEC)water-splitting performance.However,the precise role of the photothermal effect on the PEC performance of photoanodes is still not well understood.Herein,spinel-structured ZnFe_(2)O_(4)nanoparticles are deposited on the surface of hematite(Fe_(2)O_(3)),and the ZnFe_(2)O_(4)/Fe_(2)O_(3)photoanode achieves a high photocurrent density of 3.17 mA cm^(-2)at 1.23 V versus a reversible hydrogen electrode(VRHE)due to the photothermal effect of ZnFe_(2)O_(4).Considering that the hopping of electron small polarons induced by oxygen vacancies is thermally activated,we clarify that the main reason for the enhanced PEC performance via the photothermal effect is the promoted mobility of electron small polarons that are bound to positively charged oxygen vacancies.Under the synergistic effect of oxygen vacancies and the photothermal effect,the electron conductivity and PEC performance are significantly improved,which provide fundamental insights into the impact of the photothermal effect on the PEC performance of small polaron-type semiconductor photoanodes.
基金supported by Natural Science Foundation of Beijing Municipality(L212013)National Key Research and Development Program of China(No.2022YFA1206104)+2 种基金AI+Health Collaborative Innovation Cultivation Project(Z211100003521002)National Natural Science Foundation of China(81971718,82073786,81872809,U20A20412,81821004)Beijing Natural Science Foundation(7222020).
文摘Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.
基金Supplementary information is linked to the online version of the paper on the Cell Research website. Acknowledgments We are very thankful to Dr Dusan M Jeftinija (Department of Neurosience & Anatomy, University of Louisville, Kentucky, USA) for his help during the manuscript preparation. This work was supported by grants from the State Key Program of Basic Research of China (2007CB108800, 2009CB918400, 2010CB912102), the Hi-Tech Research and Development Program of China (2006AA02Z313), National Natural Science Foundation of China (30870575) and Science and Technology Commission of Shanghai Municipality (06DZ22923).
文摘Dear Editor, As a complex disease, the development and progression of hepatocellular carcinoma (HCC) involves the interactions of multiple proteins, genes and miRNAs in various biological pathways, and it has been extensively studied with different high-throughput techniques. However, efforts to integrate multiple data sources at different levels, especially with regard to biological pathways and interaction networks, are still negligible in the HCC research field.
基金Supported by Natural Science Foundation of Shanghai,No.09ZR1424700 and 114119a4700Minhang District Natural Science Foundation of Shanghai,No. 2009MHZ085grants from Minhang District Public Health Bureau of Shanghai,No.2009MW28
文摘AIM: To observe the curative effect of galactosylated chitosan (GC)/5-fluorouracil (5-FU) nanoparticles in liver caner mice and its side effects. METHODS: The GC/5-FU nanoparticle is a nanomate- rial made by coupling GC and 5-FU. The release experiment was performed in vitro. The orthotropic liver cancer mouse models were established and divided into control, GC, 5-FU and GC/5-FU groups. Mice in the control and GC group received an intravenous injection of 200 μL saline and GC, respectively. Mice in the 5-FU and GC/5-FU groups received 200 μL (containing 0.371 mg 5-FU) 5-FU and GC/5-FU, respectively. The tumor weight and survival time were observed. The cell cycle and apoptosis in tumor tissues were monitored by flow cytometry. The expression of p53, Bax, Bcl-2, caspase-3 and poly adenosine 50-diphosphate-ribose polymerase 1 (PARP-1) was detected by immunohistochemistry, reverse transcription-polymerase chain reaction and Western blot. The serum blood biochemical parameters and cytotoxic activity of natural killer (NK) cell and cy- totoxicity T lymphocyte (CTL) were measured. RESULTS: The GC/5-FU nanoparticle is a sustained release system. The drug loading was 6.12% ± 1.36%, the encapsulation efficiency was 81.82% ± 5.32%, and the Zeta potential was 10.34 ± 1.43 mV. The tu- mor weight in the GC/5-FU group (0.4361±0.1153 g vs 1.5801 ± 0.2821 g, P 〈 0.001) and the 5-FU (0.7932±0.1283 g vs 1.5801 ±0.2821 g, P 〈 0.001) was sig- nificantly lower than that in the control group; GC/5- FU treatment can significantly lower the tumor weight (0.4361± 0.1153 g vs 0.7932±0.1283 g, P 〈 0.001), and the longest median survival time was seen in the GC/5-FU group, compared with the control (12 d vs 30 d, P 〈 0.001), GC (13 d vs 30 d, P 〈 0.001) and 5-FU groups (17 d vs 30 d, P 〈 0.001). Flow cytom- etry revealed that compared with the control, GC/5- FU caused a higher rate of G0-G1 arrest (52.79% ± 13.42% vs 23.92%±9.09%, P = 0.014 ) and apopto- sis (2.55% ±1.10% vs 11.13% ±11.73%, P 〈 0.001) in hepatic cancer cells. Analysis of the apoptosis path- ways showed that GC/5-FU upregulated the expression of p53 at both the protein and the mRNA levels, which in turn lowered the ratio of Bcl-2lBax expression; this led to the release of cytochrome C into the cytosol from the mitochondria and the subsequent activation of caspase-3. Upregulation of caspase-3 expression de- creased the PARP-1 at both the mRNA and the protein levels, which contributed to apoptosis. 5-FU increased the levels of aspartate aminotransferase and alanine aminotransferase, and decreased the numbers of platelet, white blood cell and lymphocyte and cytotoxic activities of CTL and NK cells, however, there were no such side effects in the GC/5-FU group. CONCLUSION: GC/5-FU nanoparticles can significant- ly inhibit the growth of liver cancer in mice via the p53 apoptosis pathway, and relieve the side effects and im- munosuppression of 5-FU.
基金Supported by the National Basic Research Program of China(2015CB932100)
文摘Aurum nanomaterials(ANM), combining the features of nanotechnology and metal elements, have demonstrated enormous potential and aroused great attention on biomedical applications over the past few decades. Particularly, their advantages, such as controllable particle size, flexible surface modification, higher drug loading, good stability and biocompatibility, especially unique optical properties, promote the development of ANM in biomedical field. In this review, we will discuss the advanced preparation process of ANM and summarize their recent applications as well as their prospects in diagnosis and therapy. Besides, multi-functional ANM-based theranostic nanosystems will be introduced in details, including radiotherapy(RT), photothermal therapy(PTT), photodynamic therapy(PDT), immunotherapy(IT), and so on.
基金by the National Natural Science Foundation of China(Nos.81872809,82073786)the Beijing Natural Science Foundation(L212013).
文摘The combination regimen of trastuzumab(Tras)plus Nab-paclitaxel(Nab)is recommended to treat HER2-positive(HER2+)cancers.However,they exert effects in different mechanisms:Tras need to stay on cell membranes,while Nab need to be endocytosed,therefore the concurrent combination regimen may not be the best one in HER2+tumors treatment.Caveolin-1(Cav-1)is a key player in mediating their endocytosis and is associated with their efficacy,but few researches noticed the opposite effect of Cav-1 expression on the combination efficacy.Herein,we systematically studied the Cav-1 expression level on the combination efficacy and proposed an optimized and clinically feasible combination regimen for HER2+Cav-1 High tumor treatment.In the regimen,lovastatin(Lova)was introduced to modulate the Cav-1 expression and the results indicated that Lova could downregulate Cav-1 expression,increase Tras retention on cell membrane and enhance the in vitro cytotoxicity of Tras in HER2+Cav-1 High cells but not in HER2+Cav-1 Low cells.Therefore,by exchanging the dosing sequence of Nab and Tras,and by adding Lova at appropriate time points,the precise three-drug-sequential regimen(PTDS,Nab(D1)-Lova(D2)-Lova&Tras(D2+12 h))was established.Compared with the concurrent regimen,the PTDS regimen exhibited a higher in vitro cytotoxicity and a stronger tumor growth inhibition in HER2+Cav-1 High tumors,which might be a promising combination regimen for these patients in clinics.
基金supported by the National Natural Science Foundation of China (81690264)the National Basic Research Program of China (2015CB932100)the Innovation Team of the Ministry of Education (BMU20110263)。
文摘Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns(SWCNH), zinc phthalocyanine(ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 ℃ due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise(to 65 ℃) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.
基金Supported by Scientific Reserch Fund of Sichuan Provincial Education Department in 2015(15ZA0335)
文摘[Objectives]This study was conducted to investigate the effects of artificially cultured Eisenia foetida and wild earthworms ( Pheretima sp.) on the changes of microbial populations in forest soil in different seasons.[Methods]Artificially cultured E.foetida and wild earthworms were introduced to forest soil,and changes in the number of microbial populations under earthworm-microbe interaction were investigated in different seasons by tracking observation.The effects of earthworm activities on the number of different microbial populations were discussed also.[Results]Different microbial populations all increased in the soil to different degrees after the introduction of earthworms.The effects of the wild earthworms on the changes in bacteria,actinomycetes and fungi in the soil were different from those of artificially cultivated earthworms to certain degrees.[Conclusions]This study provides a theoretical basis for organic agriculture that relies on the decomposition of organic matter to release nutrients.
文摘A calculation method for heats of formation (HOF, referred to as △Hf) based on the density functional theory (DFT) is presented in this work. Similar to Gaussian-3 theory, the atomic scheme is applied to calculate the heats of formation of the molecules. In this method, we have modified the formula for calculation of Gaussian-3 theory in several ways, including the correction for diffuse functions and the correction for higher polarization functions. These corrections are found to be significant. The average absolute deviation from experiment for the 164 calculated heats of formation is about 1.9 kcal·mol?1, while average absolute deviation from G3MP2 for the 149 (among the 164 molecules, 15 large-sized molecules can not be calculated at the G3MP2 level) calculated heats of formation is only about 1.9 kcal·mol?1. It indicates that the present method can be applied to predict the heats of formation of medium-sized and large-sized molecules, while the heats of formation of these molecules using Gaussian-3 theory are much difficult, even impossible, to calculate. That is, this method provides a choice in the calculation of △Hf for medium-sized and large-sized molecules.
基金supported by National Key Research and Development Program (2022YFA1206100, China)Natural Science Foundation of Beijing Municipality (L212013, China)+1 种基金AI+Health Collaborative Innovation Cultivation Project (Z211100003521002,China)National Natural Science Foundation of China(82073786, 81872809, U20A20412, 81821004)
文摘Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel the value of this classical therapeutic strategy.Here,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic drugs.Alendronate in BC-LNPs@PTX,a bisphosphonate to block mevalonate metabolism,works as both the structure and drug constituent in nanogranules,where alendronate coordinated with calcium ions to form the particle core.The synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic mechanism.Differing from the paclitaxel-induced apoptosis,the involvement of alendronate inhibits the mevalonate metabolism,changes the mitochondrial morphology,disturbs the redox homeostasis,and causes theaccumulation of mitochondrial ROS and lethal lipid peroxides(LPO).These factors finally trigger the ferroptosis of tumor cells,an immunogenic cell death mode,which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy.Therefore,by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis,BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.
基金the Guangxi Bagui Scholar Teams for Innovation and Research Projectthe National Natural Science Foundation of China(Grant Nos.12272100,81860635,and 12062005)。
文摘Contact angle is an essential parameter to characterize substrate wettability.The measurement of contact angle in experiment and simulation is a complex and time-consuming task.In this paper,an improved method of measuring contact angle in multiphase lattice Boltzmann simulations is proposed,which can accurately obtain the real-time contact angle at a low temperature and larger density ratio.The three-phase contact point is determined by an extrapolation,and its position is not affected by the local deformation of flow field in the three-phase contact region.A series of simulations confirms that the present method has high accuracy and gird-independence.The contact angle keeps an excellent linear relationship with the chemical potential of the surface,so that it is very convenient to specify the wettability of a surface.The real-time contact angle measurement enables us to obtain the dynamic contact angle hysteresis on chemically heterogeneous surface,while the mechanical analyses can be effectively implemented at the moving contact line.
基金Supported by Key R&D Program of the Ministry of Science and Technology (2019YFC0810704)Key R&D Program of Guangdong Province (2019B111102002)Shenzhen Science and Technology Program (KCXFZ202002011007040)。
文摘Backgrounds This work emphasizes the current research status of the urban Digital Twins to establish an intelligent spatiotemporal framework.A Geospatial Artificial Intelligent(GeoAI)system is developed based on the Geographic Information System and Artificial Intelligence.It integrates multi-video technology and Virtual City in urban Digital Twins.Methods Besides,an improved small object detection model is proposed:YOLOv5-Pyramid,and Siamese network video tracking models,namely MPSiam and FSSiamese,are established.Finally,an experimental platform is built to verify the georeferencing correction scheme of video images.Result The MultiplyAccumulate value of MPSiam is 0.5B,and that of ResNet50-Siam is 4.5B.Besides,the model is compressed by 4.8times.The inference speed has increased by 3.3 times,reaching 83 Frames Per Second.3%of the Average Expectation Overlap is lost.Therefore,the urban Digital Twins-oriented GeoAI framework established here has excellent performance for video georeferencing and target detection problems.
基金Supported by the Key Area Research and Development Program of Guangdong Province(2019B111102002)Shenzhen Science and Technology Program(KCXFZ202002011007040)National Key Research and Development Program of China(2019YFC0810704)。
文摘Background This work aims to build a comprehensive and effective fire emergency management system based on the Internet of Things(IoT)and achieve an actual intelligent fire rescue.A smart fire protection information system was designed based on the IoT.A detailed analysis was conducted on the problem of rescue vehicle scheduling and the evacuation of trapped persons in the process of fire rescue.Methods The intelligent fire visualization platform based on the three-dimensional(3D)Geographic Information Science(GIS)covers project overview,equipment status,equipment classification,equipment alarm information,alarm classification,alarm statistics,equipment account information,and other modules.The live video accessed through the visual interface can clearly identify the stage of the fire,which facilitates the arrangement of rescue equipment and personnel.The vehicle scheduling model in the system primarily used two objective functions to solve the Pareto Non-Dominated Solution Set Optimization:emergency rescue time and the number of vehicles.In addition,an evacuation path optimization method based on the Improved Ant Colony(IAC)algorithm was designed to realize the dynamic optimization of building fire evacuation paths.Results The experimental results indicate that all the values of detection signals were significantly larger in the smoldering fire scene at t=17s than the initial value.In addition,the probability of smoldering fire and the probability of open fire were relatively large according to the probability function of the corresponding fire situation,demonstrating that this model could detect fire.Conclusions The IAC algorithm reported here avoided the passages near the fire and spreading areas as much as possible and took the safety of the trapped persons as the premise when planning the evacuation route.Therefore,the IoT-based fire information system has important value for ensuring fire safety and carrying out emergency rescue and is worthy of popularization and application.
基金financially supported by the National Natural Science Foundation of China (Grant No.41961144023)the Israeli Science Foundation (Grant No.3195/19)。
文摘Methane dominated gas is one of the cleanest energy resources;however, there is no direct method to determine its source rock. Natural gases produced from the eastern Sichuan Basin together with seismic data were studied for their sources and secondary alteration by thermochemical sulfate reduction(TSR). Our results demonstrate that Upper Permian to Lower Triassic(P_(3)ch-T_(1)f) gases in the surrounding of the Kaijiang-Liangping area show volatile organic sulfur compounds(VOSCs) δ^(34)S values close to those of the associated H_(2)S, and may have been altered by methane-dominated TSR, resulting in positive shift in methane δ^(13)C_(1)values with increasing TSR extents. Other(or group 2) gases produced from the P_(3)ch-T_(1)f reservoirs from the southern area and the Upper Carboniferous to Middle Permian(C_(2)h-P_(2)q) from the eastern Sichuan Basin are not significantly changed by TSR, show similar δ^(34)S values between the kerogens and some VOSCs, and may have been derived from the Lower Silurian and Middle Permian source rocks. This study demonstrates a case for the first time showing the δ^(34)S values of VOSCs can be used as a tool for direct correlation between non-TSR altered gas and source rocks. Methane-dominated gas pools can be found using gas and source rock geochemistry combined with seismic data.
基金National Key R&D Program of China,Grant/Award Number:2022YFA1203304Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20220288Suzhou Institute of Nano-Tech and Nano-Bionics,Chinese Academy of Sciences,Grant/Award Number:E1552102。
文摘Prussian blue analogs(PBAs)are potential contestants for aqueous Mg-ion batteries(AMIBs)on account of their high discharge voltage and threedimensional open frameworks.However,the low capacity arising from single reaction site severely restricts PBAs'practical applications in highenergy-density AMIBs.Here,an organic acid co-coordination combined with etching method is reported to fabricate defect-rich potassium-free copper hexacyanoferrate with structural water on carbon nanotube fiber(DCuHCF@CNTF).Benefiting from the high-valence-state reactive sites,arrayed structure and defect effect,the well-designed D-CuHCF@CNTF exhibits an extraordinary reversible capacity of 146.6 mAh g1 with two-electron reaction,nearly close to its theoretical capacity.It is interesting to unlock the reaction mechanism of the Fe2+/Fe3+and Cu+/Cu2+redox couples via x-ray photoelectron spectroscopy.Furthermore,density functional theory calculations reveal that Fe and Cu in potassium-free D-CuHCF participate in charge transfer during the Mg2+insertion/extraction process.As a proof-of-concept demonstration,a rocking-chair fiber-shaped AMIBs was constructed via coupling with the NaTi2(PO4)3/CNTF anode,achieving high energy density and impressive mechanical flexibility.This work provides new possibilities to develop potassium-free PBAs with dual-active sites as high-capacity cathodes for wearable AMIBs.
基金the National Key Research and Development Program of China(No.2016YFB0301102)the Postgraduate Education Fund of Chongqing University(No.201704020).
文摘In general,different extrusion conditions will affect the microstructure of magnesium alloys and further determine the mechanical properties.The effects of extrusion parameters and heat treatment processes such as extrusion speed,pre-forging,annealing time,extrusion ratio and cooling rate on the microstructure,texture evolution and tensile properties of Mg-2Gd-0.3Zr alloys were investigated in this study.Compared with the as-cast alloy,the extrusion process significantly refines the grains and exhibit the rare earth texture.With the increase of extrusion speed and annealing time,the growth of recrystallized grains is accelerated,leading to the increase of elongation.Large pre-forging deformation achieves to refine the grains by promoting recrystallization nucleation,resulting in increased strength of Mg-2Gd-0.3Zr alloy.Decreasing the extrusion ratio or increasing the cooling rate will introduce coarse un-DRXed grains,which transformed the texture into the basal texture.In particular,the effect of rapid cooling on refining the recrystallized grains is also obvious.Different extrusion conditions influence the mechanical properties of the Mg-2Gd-0.3Zr alloy through the grain size,proportion of non-recrystallization region and texture type.
基金supported by the National Key R&D Program of China(2017YFA0205600)the National Natural Science Foundation of China(81690264,81821004).
文摘Currently,the cancer immunotherapy has made great progress while antitumor vaccine attracts substantial attention.Still,the selection of adjuvants as well as antigens are always the most crucial issues for better vaccination.In this study,we proposed a biomimetic antitumor nanovaccine based on biocompatible nanocarriers and tumor cell membrane antigens.Briefly,endogenous calcium pyrophosphate nanogranules with possible immune potentiating effect are designed and engineered,both as delivery vehicles and adjuvants.Then,these nanocarriers are coated with lipids and B16-OVA tumor cell membranes,so the biomembrane proteins can serve as tumor-specific antigens.It was found that calcium pyrophosphate nanogranules themselves were compatible and possessed adjuvant effect,while membrane proteins including tumor associated antigen were transferred onto the nanocarriers.It was demonstrated that such a biomimetic nanovaccine could be well endocytosed by dendritic cells,promote their maturation and antigen-presentation,facilitate lymph retention,and trigger obvious immune response.It was confirmed that the biomimetic vaccine could induce strong T-cell response,exhibit excellent tumor therapy and prophylactic effects,and simultaneously possess nice biocompatibility.In general,the present investigation might provide insights for the further design and application of antitumor vaccines.
基金supported by the National Natural Science Foundation of China[81690264]the National Basic Research Program of China[2015CB932100,2017YFA0205600]the Innovation Team of the Ministry of Education[BMU20110263]。
文摘Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells.It plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significant events in cells,such as the interaction with foreign particles.Therefore,it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay,since more and more nanomedicine are supposed to be used in biomedical field.However,there is no review in this aspect.This review summarizes the small GTPases in terms of the structure,biological function and its interaction with nanoparticles.We briefly introduced the various nanoparticles such as gold/silver nanoparticles,SWCNT,polymeric micelles and other nano delivery systems that interacted with different GTPases.These current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases study.This will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research direction.It is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines.