On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sortin...On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.展开更多
Probability theory and mathematical statistics are fundamental courses for various majors in science and engineering.In response to the current teaching situation,we should integrate theory with practice,implement tea...Probability theory and mathematical statistics are fundamental courses for various majors in science and engineering.In response to the current teaching situation,we should integrate theory with practice,implement teaching reform,and carry out teaching innovation.The article carries out blended teaching with deep integration of online and offline modes and within and outside of class,constructing innovative measures of“four integrations and four reshaping.”The article conducts diversified evaluations to stimulate learning motivation and help achieve talent cultivation goals.Through the close integration of probability theory and mathematical statistics course teaching with professional education and practical application,the“three-in-one”teaching goal of value shaping,ability cultivation,and knowledge exploration is achieved.The fundamental task of“cultivating morality and talents”is implemented.展开更多
Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the pre...Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.展开更多
Intercalation of atomic species is a practicable method for epitaxial graphene to adjust the electronic band structure and to tune the coupling between graphene and Si C substrate. In this work, atomically flat epitax...Intercalation of atomic species is a practicable method for epitaxial graphene to adjust the electronic band structure and to tune the coupling between graphene and Si C substrate. In this work, atomically flat epitaxial graphene is prepared on 4H-SiC(0001) using the flash heating method in an ultrahigh vacuum system. Scanning tunneling microscopy, Raman spectroscopy and electrical transport measurements are utilized to investigate surface morphological structures and transport properties of pristine and Er-intercalated epitaxial graphene. It is found that Er atoms are intercalated underneath the graphene layer after annealing at 900℃, and the intercalation sites of Er atoms are located mainly at the bufferlayer/monolayer-graphene interface in monolayer domains. We also report the different behaviors of Er intercalation in monolayer and bilayer regions, and the experimental results show that the diffusion barrier for Er intercalated atoms in the buffer-layer/monolayer interface is at least 0.2 eV higher than that in the first/second graphene-layer interface. The appearance of Er atoms is found to have distinct impacts on the electronic transports of epitaxial graphene on SiC(0001).展开更多
To investigate the structure-activity relationship of polysaccharide and obtain a better antidepressant polysaccharide,the antidepressant-like activity of a carboxymethyl polysaccharide(C-MEPS2)subjected to submerged ...To investigate the structure-activity relationship of polysaccharide and obtain a better antidepressant polysaccharide,the antidepressant-like activity of a carboxymethyl polysaccharide(C-MEPS2)subjected to submerged fermentation was systematically studied.PC12-H cell and Kunming mice were used to investigate the differences and their mechanism in the antidepressant effects of C-MEPS2 and MEPS2.Cell experiments have showed that C-MEPS2 has a better antidepressant effect than MEPS2.C-MEPS2 could exert antidepressant effects related to catecholamine synthesis with specifi c sites of TH,D2DR,and P-CAMKII.In addition,C-MEPS2 could repair the Res-induced damage in PC12-H cell,stabilize the mitochondrial membrane potential and regulate intracellular Ca^(2+) concentration,thus reducing cell apoptosis caused by RES.Antagonists common dosing experiments on animals further proved that CMEPS2 could signifi cantly improve the antidepressant effect of derivatives without affecting the antidepressant mechanism of MEPS2.It is speculated that it may be related to carboxymethylated modifi cation.展开更多
In response to the limitations of the traditional education and teaching model,this article proposes a smart education model based on ChatGPT.The model actively breaks the constraint of time and space and the design p...In response to the limitations of the traditional education and teaching model,this article proposes a smart education model based on ChatGPT.The model actively breaks the constraint of time and space and the design patterns of traditional education,providing smart education services including personalized learning,smart tutoring and evaluation,educational content creation support,and education big data analysis.Through constructing an open and inclusive learning space and creating flexible and diverse educational models,ChatGPT can help to meet students’individuality and overall development,as well as assist teachers in keeping up with the students’learning performance and developmental requirements in real-time.This provides an important basis for optimizing teaching content,offering personalized and accurate cultivation,and planning the development path of students.展开更多
Time-frequency-based methods are proven to be effective for parameter estimation of linear frequency modulation (LFM) signals.The smoothed pseudo Winger-Ville distribution (SPWVD) is used for the parameter estimation ...Time-frequency-based methods are proven to be effective for parameter estimation of linear frequency modulation (LFM) signals.The smoothed pseudo Winger-Ville distribution (SPWVD) is used for the parameter estimation of multi-LFM signals,and a method of the SPWVD binarization by a dynamic threshold based on the Otsu algorithm is proposed.The proposed method is effective in the demand for the estimation of different parameters and the unknown signal-to-noise ratio (SNR) circumstance.The performance of this method is confirmed by numerical simulation.展开更多
Liposomes hold great potential in anti-cancer drug delivery and the targeting treatment of tumors.However,the clinical therapeutic efficacy of liposomes is still limited by the complexity of tumor microenvironment(TME...Liposomes hold great potential in anti-cancer drug delivery and the targeting treatment of tumors.However,the clinical therapeutic efficacy of liposomes is still limited by the complexity of tumor microenvironment(TME)and the insufficient accumulation in tumor sites.Meanwhile,the application of cholesterol and polyethylene glycol(PEG),which are usually used to prolong the blood circulation and stabilize the structure of liposomes respectively,has been questioned due to various disadvantages.Herein,we developed a ginsenoside Rh2-based multifunctional liposome system(Rh2-lipo)to effectively address these challenges once for all.Different with the conventional’wooden’liposomes,Rh2-lipo is a much more brilliant carrier with multiple functions.In Rh2-lipo,both cholesterol and PEG were substituted by Rh2,which works as membrane stabilizer,long-circulating stealther,active targeting ligand,and chemotherapy adjuvant at the same time.Firstly,Rh2 could keep the stability of liposomes and avoid the shortcomings caused by cholesterol.Secondly,Rh2-lipo showed a specifically prolonged circulation behavior in the blood.Thirdly,the accumulation of the liposomes in the tumor was significantly enhanced by the interaction of glucose transporter of tumor cells with Rh2.Fourth,Rh2-lipo could remodel the structure and reverse the immunosuppressive environment in TME.When tested in a 4T1 breast carcinoma xenograft model,the paclitaxel-loaded Rh2-lipo realized high efficient tumor growth suppression.Therefore,Rh2-lipo not only innovatively challenges the position of cholesterol as a liposome component,but also provides another innovative potential system with multiple functions for anti-cancer drug delivery.展开更多
Nanotechnologies have been successfully applied to the treatment of various diseases.Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in d...Nanotechnologies have been successfully applied to the treatment of various diseases.Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in drug-delivery. PENs are minimally cytotoxic to healthy tissues, with which they show excellent biocompatibility, and are biased towards tumors by targeting specific tissues through special endocytosis mechanisms. Thus, the use of these PENs may expand the scope of drug therapies while reducing the off-target effects.In this review, we summarize the fundamental features and bioactivities of PENs extracted from the grape, grapefruit, ginger, lemon, and broccoli and discuss the applications of these particles as therapeutics and nanocarriers.展开更多
To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and...To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.展开更多
Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has al...Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor microenvironment.Previous studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell infiltration.FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies.Thus,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of PDAC.Methods:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT.Results:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to RT.Antitumor activity of the combination of FAKi and RT is T cell dependent.FAKi in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(P<0.05).FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(P<0.01).Conclusions:These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.展开更多
The dividing wall column(DWC) is considered as a major breakthrough in distillation technology and has good prospect of industrialization. Model predictive control(MPC) is an advanced control strategy that has acquire...The dividing wall column(DWC) is considered as a major breakthrough in distillation technology and has good prospect of industrialization. Model predictive control(MPC) is an advanced control strategy that has acquired extensive applications in various industries. In this study, MPC is applied to the process for separating ethanol,n-propanol, and n-butanol ternary mixture in a fully thermally coupled DWC. Both composition control and temperature inferential control are considered. The multiobjective genetic algorithm function "gamultiobj" in Matlab is used for the weight tuning of MPC. Comparisons are made between the control performances of MPC and PI strategies. Simulation results show that although both MPC and PI schemes can stabilize the DWC in case of feed disturbances, MPC generally behaves better than the PI strategy for both composition control and temperature inferential control, resulting in a more stable and superior performance with lower values of integral of squared error(ISE).展开更多
The satellite-based automatic identification system(AIS) receiver has to encounter the frequency offset caused by the Doppler effect and the oscillator instability. This paper proposes a non-coherent sequence detectio...The satellite-based automatic identification system(AIS) receiver has to encounter the frequency offset caused by the Doppler effect and the oscillator instability. This paper proposes a non-coherent sequence detection scheme for the satellite-based AIS signal transmitted over the white Gaussian noise channel.Based on the maximum likelihood estimation and a Viterbi decoder, the proposed scheme is capable of tolerating a frequency offset up to 5% of the symbol rate. The complexity of the proposed scheme is reduced by the state-complexity reduction, which is based on per-survivor processing. Simulation results prove that the proposed non-coherent sequence detection scheme has high robustness to frequency offset compared to the relative scheme when messages collision exists.展开更多
In this study,an optical setup for generating terahertz(THz)pulses through a two-color femtosecond laser filament was carefully designed to achieve a precise overlap of two-color laser pulses in space and time.β-bari...In this study,an optical setup for generating terahertz(THz)pulses through a two-color femtosecond laser filament was carefully designed to achieve a precise overlap of two-color laser pulses in space and time.β-barium borate(BBO),α-BBO,and a dual-wavelength plate were used to compensate the phase delay of the two-color lasers.Tilting ofα-BBO could further realize the precise spatial overlap of the two beams by counteracting the walk-off effect.The maximum out-put THz pulse energy reached 21μJ in argon gas when using a commercial Ti:sapphire laser with a pulse energy of 6 mJ at a 1 kHz repetition rate.The corresponding conversion efficiency exceeded 0.35%.展开更多
Archaea regulate the biogeochemical processes of ocean systems.The Changjiang(Yangtze)River estuary(CRE) is a complex and dynamic area strongly affected by seawaters and ocean currents.In this study,the planktonic arc...Archaea regulate the biogeochemical processes of ocean systems.The Changjiang(Yangtze)River estuary(CRE) is a complex and dynamic area strongly affected by seawaters and ocean currents.In this study,the planktonic archaeal communities in the surface and bottom seawaters of the CRE were investigated.Significant differences in the archaeal community composition were found between the surface and bottom seawaters(P<0.001).Marine Group Ⅱ(MG-Ⅱ) was dominant in the surface layers,and Nitrosopumilales was enriched in the bottom layers.Marine Group Ⅲ(MG-Ⅲ) was more abundant in the bottom layers than in the surface ones(P<0.001).These results were completely different from previous findings in the CRE seawater.Instead of dissolved oxygen(DO),temperature and salinity were the most vital environmental variations in the distribution of the archacal communities.According to the predicted metabolic pathways,the following functional subcategories were enriched in the hypoxic condition:replication and repair,membrane transport,glycan biosynthesis and metabolism,amino acid metabolism,metabolism of cofactors and vitamins,and xenobiotics biodegradation and metabolism(P<0.001),which indicated the strong adaptability of archaea to the harsh environment in the bottom seawater.These findings expand the understanding on archaeal structure and functions in the surface and bottom seawaters,including the hypoxic zones in the CRE,and may contribute to further works of the archaeal community in the CRE.展开更多
Hardware Trojan(HT) refers to a special module intentionally implanted into a chip or an electronic system. The module can be exploited by the attacker to achieve destructive functions. Unfortunately the HT is difficu...Hardware Trojan(HT) refers to a special module intentionally implanted into a chip or an electronic system. The module can be exploited by the attacker to achieve destructive functions. Unfortunately the HT is difficult to detecte due to its minimal resource occupation. In order to achieve an accurate detection with high efficiency, a HT detection method based on the electromagnetic leakage of the chip is proposed in this paper. At first, the dimensionality reduction and the feature extraction of the electromagnetic leakage signals in each group(template chip, Trojan-free chip and target chip) were realized by principal component analysis(PCA). Then, the Mahalanobis distances between the template group and the other groups were calculated. Finally, the differences between the Mahalanobis distances and the threshold were compared to determine whether the HT had been implanted into the target chip. In addition, the concept of the HT Detection Quality(HTDQ) was proposed to analyze and compare the performance of different detection methods. Our experiment results indicate that the accuracy of this detection method is 91.93%, and the time consumption is 0.042s in average, which shows a high HTDQ compared with three other methods.展开更多
The prokaryotic microbial communities in the sediments play crucial roles in the ecological functions of mangrove ecosystems.Therefore,the environmental factors that affect the structures of these prokaryotic microbia...The prokaryotic microbial communities in the sediments play crucial roles in the ecological functions of mangrove ecosystems.Therefore,the environmental factors that affect the structures of these prokaryotic microbial communities could indirectly participate in the regulation of mangrove functions,which is of great value for mangrove studies.The particle size(PS)of soils is recently demonstrated as a key environmental factor for shaping the microbial communities;however,this hypothesis has rarely been tested for mangrove environments.A case study of three tropical mangroves from Sanya,China was performed in this work to assess the influence of PS on the prokaryotic microbial community structures of bacteria,archaea,diazotrophs,and denitrifiers in the sediments.Results showed the variability in the spatial scale and the stability in the temporal scale for the prokaryotic communities,indicating that the tropical mangrove sediments could be a versatile but stable environment.Among the collected environmental factors,PS,salinity,and humidity had the greatest impacts,and PS mostly affected the structures of these prokaryotic communities based on its highest R^2 values of canonical correspondence analysis,Mental test,and linear fitting(p≤0.05).Furthermore,PS was positively correlated with the diversity and abundance of diazotrophic communities and negatively correlated with the abundances of methanogenic communities including Methanobacteriaceae,Methanospirillaceae,Methanoregulaceae,and Methanosaetaceae.Former studies show the increasing trend of PS caused by the rise of sea level and the intensification of human activities.Therefore,our findings indicate that PS could be a potential intermediate that links climate change and human activities with the possible ecological function migration of mangroves;meanwhile,the increase of PS could in turn release the stress of these environmental changes by increasing the abundance and diversity of the diazotrophic community and decreasing the abundances of methanogens.展开更多
A cost-effective technique,including nanocrystalline powder preparation using a modified Pechini method and a two-step low-temperature sintering route,was developed for the synthesis of high performance La_2Mo_2O_9- b...A cost-effective technique,including nanocrystalline powder preparation using a modified Pechini method and a two-step low-temperature sintering route,was developed for the synthesis of high performance La_2Mo_2O_9- based oxide-ion conductors.The optimum parameters of the compaction pressure,the first step and the second step sintering temperatures for the synthesis of fine grained,high density and uniform La_2Mo_2O_9- based oxide-ion conductors were determined by a series of sintering experiments.High density and uniform sintered La_2Mo_2O_9 samples with average grain size from 0.8 to 5μm and La_(1.96)K_(0.04)Mo_2O_(8.96) sample with average grain size as small as 500 nm were synthesized by using this cost-effective method.The impedance measurement results show that the as-fabricated La_2Mo_2O_9-based ceramics possess much higher ionic con- ductivity than that obtained by solid state reaction method.It is found that in the range of 0.8-5μm the grain size of dense La_2Mo_2O_9 samples prepared from the nanocrystalline powders has little influence on their conductivities.展开更多
The Changjiang River Estuary(CRE)in the East China Sea suffers from seasonal hypoxia in summer.The vertical distributions and seasonal changes of microbial communities in the CRE were well documented.However,little is...The Changjiang River Estuary(CRE)in the East China Sea suffers from seasonal hypoxia in summer.The vertical distributions and seasonal changes of microbial communities in the CRE were well documented.However,little is known about the diurnal changes of bacterial communities in the hypoxic zone of the CRE.Here,16 S rRNA gene analysis was used to explore the changes of bacterial communities in the oxic surface and hypoxic middle seawater layers during 24 h in the CRE.Significant differences between the hypoxic and oxic layers were observed:the phyla Cyanobacteria,Bacteroidetes and Acidimicrobiia were enriched in the oxic layer,whereas the phylum SAR406 and the class Deltaproteobacteria were more abundant in the hypoxic layer.In addition,some subtle diurnal variations of the bacterial relative abundance were found in both two layers.The relative abundance of Synechococcus increased at night,and this change was more obvious in the hypoxic layer.The similar trend was also found in some phototrophic and several heterotrophic bacteria,such as Rhodobacteraceae,OM60 and Flavobacteriaceae.Their relative abundances peaked at 16:00 in the oxic layer,while the relative abundances peaked at around 7:00 and decreased until 13:00 in the hypoxic layer.Together,the results of the present study suggest that some photosynthetic bacteria and several heterotrophic bacteria have similar diurnal variations implying the light and physicochemical heterogeneity in the course of a day are important for bacterial diurnal changes in the CRE.展开更多
基金The authors acknowledge the financial support from the NationalNatural Science Foundation ofChina(No.52275562)the Technology Innovation Fund of Huazhong University of Science and Technology(No.2022JYCXJJ015).
文摘On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.
文摘Probability theory and mathematical statistics are fundamental courses for various majors in science and engineering.In response to the current teaching situation,we should integrate theory with practice,implement teaching reform,and carry out teaching innovation.The article carries out blended teaching with deep integration of online and offline modes and within and outside of class,constructing innovative measures of“four integrations and four reshaping.”The article conducts diversified evaluations to stimulate learning motivation and help achieve talent cultivation goals.Through the close integration of probability theory and mathematical statistics course teaching with professional education and practical application,the“three-in-one”teaching goal of value shaping,ability cultivation,and knowledge exploration is achieved.The fundamental task of“cultivating morality and talents”is implemented.
基金This research was funded by the National Natural Science Foundation of China(No.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).
文摘Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.
基金Project supported by the Natural Science Foundation of Shanghai Science and Technology Committee (Grant No. 18ZR1403300)。
文摘Intercalation of atomic species is a practicable method for epitaxial graphene to adjust the electronic band structure and to tune the coupling between graphene and Si C substrate. In this work, atomically flat epitaxial graphene is prepared on 4H-SiC(0001) using the flash heating method in an ultrahigh vacuum system. Scanning tunneling microscopy, Raman spectroscopy and electrical transport measurements are utilized to investigate surface morphological structures and transport properties of pristine and Er-intercalated epitaxial graphene. It is found that Er atoms are intercalated underneath the graphene layer after annealing at 900℃, and the intercalation sites of Er atoms are located mainly at the bufferlayer/monolayer-graphene interface in monolayer domains. We also report the different behaviors of Er intercalation in monolayer and bilayer regions, and the experimental results show that the diffusion barrier for Er intercalated atoms in the buffer-layer/monolayer interface is at least 0.2 eV higher than that in the first/second graphene-layer interface. The appearance of Er atoms is found to have distinct impacts on the electronic transports of epitaxial graphene on SiC(0001).
基金funded by the Natural Science Foundation of China(32072203)the Tianjin Municipal Education Commission(TD13-5013)+4 种基金the Open Project of State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science&Technology(SKLFNS-KF-202102)Natural Science Foundation of Shanxi(201901D211130)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(2017105)Tianjin synthetic biotechnology innovation capacity improvement project(TSBICIP-KJGG-016)Tianjin Science and Technology Plan Project(21ZYJDJC00030).
文摘To investigate the structure-activity relationship of polysaccharide and obtain a better antidepressant polysaccharide,the antidepressant-like activity of a carboxymethyl polysaccharide(C-MEPS2)subjected to submerged fermentation was systematically studied.PC12-H cell and Kunming mice were used to investigate the differences and their mechanism in the antidepressant effects of C-MEPS2 and MEPS2.Cell experiments have showed that C-MEPS2 has a better antidepressant effect than MEPS2.C-MEPS2 could exert antidepressant effects related to catecholamine synthesis with specifi c sites of TH,D2DR,and P-CAMKII.In addition,C-MEPS2 could repair the Res-induced damage in PC12-H cell,stabilize the mitochondrial membrane potential and regulate intracellular Ca^(2+) concentration,thus reducing cell apoptosis caused by RES.Antagonists common dosing experiments on animals further proved that CMEPS2 could signifi cantly improve the antidepressant effect of derivatives without affecting the antidepressant mechanism of MEPS2.It is speculated that it may be related to carboxymethylated modifi cation.
基金Ministry of Education of New Engineering Project Research and Practice(No.E-AQGABQ20202704)Undergraduate Teaching Reform and Innovation Project of Beijing Higher Education(No.202110018002)+3 种基金First-Class Discipline Construction Project of Beijing Electronic Science and Technology Institute(No.20210064Z0401,No.20210056Z0402)Fundamental Research Funds for the Central Universities(No.328202205,No.328202271,No.328202269)Research on Graphical Development Platform of Reconfigurable Cryptographic Chip Based on Model Driven(No.20220153Z0114)National Key Research and Development Program Funded Project(No.2017YFB0801803)。
文摘In response to the limitations of the traditional education and teaching model,this article proposes a smart education model based on ChatGPT.The model actively breaks the constraint of time and space and the design patterns of traditional education,providing smart education services including personalized learning,smart tutoring and evaluation,educational content creation support,and education big data analysis.Through constructing an open and inclusive learning space and creating flexible and diverse educational models,ChatGPT can help to meet students’individuality and overall development,as well as assist teachers in keeping up with the students’learning performance and developmental requirements in real-time.This provides an important basis for optimizing teaching content,offering personalized and accurate cultivation,and planning the development path of students.
基金supported by the National Natural Science Foundation of China (61302188)the Nanjing University of Science and Technology Research Foundation (2010ZDJH05)
文摘Time-frequency-based methods are proven to be effective for parameter estimation of linear frequency modulation (LFM) signals.The smoothed pseudo Winger-Ville distribution (SPWVD) is used for the parameter estimation of multi-LFM signals,and a method of the SPWVD binarization by a dynamic threshold based on the Otsu algorithm is proposed.The proposed method is effective in the demand for the estimation of different parameters and the unknown signal-to-noise ratio (SNR) circumstance.The performance of this method is confirmed by numerical simulation.
基金supported by National Natural Science Foundation of China(Nos.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20150407)。
文摘Liposomes hold great potential in anti-cancer drug delivery and the targeting treatment of tumors.However,the clinical therapeutic efficacy of liposomes is still limited by the complexity of tumor microenvironment(TME)and the insufficient accumulation in tumor sites.Meanwhile,the application of cholesterol and polyethylene glycol(PEG),which are usually used to prolong the blood circulation and stabilize the structure of liposomes respectively,has been questioned due to various disadvantages.Herein,we developed a ginsenoside Rh2-based multifunctional liposome system(Rh2-lipo)to effectively address these challenges once for all.Different with the conventional’wooden’liposomes,Rh2-lipo is a much more brilliant carrier with multiple functions.In Rh2-lipo,both cholesterol and PEG were substituted by Rh2,which works as membrane stabilizer,long-circulating stealther,active targeting ligand,and chemotherapy adjuvant at the same time.Firstly,Rh2 could keep the stability of liposomes and avoid the shortcomings caused by cholesterol.Secondly,Rh2-lipo showed a specifically prolonged circulation behavior in the blood.Thirdly,the accumulation of the liposomes in the tumor was significantly enhanced by the interaction of glucose transporter of tumor cells with Rh2.Fourth,Rh2-lipo could remodel the structure and reverse the immunosuppressive environment in TME.When tested in a 4T1 breast carcinoma xenograft model,the paclitaxel-loaded Rh2-lipo realized high efficient tumor growth suppression.Therefore,Rh2-lipo not only innovatively challenges the position of cholesterol as a liposome component,but also provides another innovative potential system with multiple functions for anti-cancer drug delivery.
基金supported by the National Natural Science Foundation of China (No. 81773911, 81690263 and 81573616)the Development Project of Shanghai Peak DisciplinesIntegrated Medicine (No. 20180101)。
文摘Nanotechnologies have been successfully applied to the treatment of various diseases.Plant-derived exosome-like nanoparticles (PENs) are expected to become effective therapeutic modalities for treating disease or in drug-delivery. PENs are minimally cytotoxic to healthy tissues, with which they show excellent biocompatibility, and are biased towards tumors by targeting specific tissues through special endocytosis mechanisms. Thus, the use of these PENs may expand the scope of drug therapies while reducing the off-target effects.In this review, we summarize the fundamental features and bioactivities of PENs extracted from the grape, grapefruit, ginger, lemon, and broccoli and discuss the applications of these particles as therapeutics and nanocarriers.
基金supported by the National Natural Science Foundation of China (No. 82074277 and 81773911)the Development Project of Shanghai Peak Disciplines-Integrated Medicine (No. 20180101)
文摘To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.
文摘Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor microenvironment.Previous studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell infiltration.FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies.Thus,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of PDAC.Methods:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT.Results:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to RT.Antitumor activity of the combination of FAKi and RT is T cell dependent.FAKi in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(P<0.05).FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(P<0.01).Conclusions:These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.
基金Supported by the National Natural Science Foundation of China(21676299,21476261and 21606255)
文摘The dividing wall column(DWC) is considered as a major breakthrough in distillation technology and has good prospect of industrialization. Model predictive control(MPC) is an advanced control strategy that has acquired extensive applications in various industries. In this study, MPC is applied to the process for separating ethanol,n-propanol, and n-butanol ternary mixture in a fully thermally coupled DWC. Both composition control and temperature inferential control are considered. The multiobjective genetic algorithm function "gamultiobj" in Matlab is used for the weight tuning of MPC. Comparisons are made between the control performances of MPC and PI strategies. Simulation results show that although both MPC and PI schemes can stabilize the DWC in case of feed disturbances, MPC generally behaves better than the PI strategy for both composition control and temperature inferential control, resulting in a more stable and superior performance with lower values of integral of squared error(ISE).
文摘The satellite-based automatic identification system(AIS) receiver has to encounter the frequency offset caused by the Doppler effect and the oscillator instability. This paper proposes a non-coherent sequence detection scheme for the satellite-based AIS signal transmitted over the white Gaussian noise channel.Based on the maximum likelihood estimation and a Viterbi decoder, the proposed scheme is capable of tolerating a frequency offset up to 5% of the symbol rate. The complexity of the proposed scheme is reduced by the state-complexity reduction, which is based on per-survivor processing. Simulation results prove that the proposed non-coherent sequence detection scheme has high robustness to frequency offset compared to the relative scheme when messages collision exists.
基金National Natural Science Foundation of China(12061131010,12074198)Russian Science Foundation(21-49-00023).
文摘In this study,an optical setup for generating terahertz(THz)pulses through a two-color femtosecond laser filament was carefully designed to achieve a precise overlap of two-color laser pulses in space and time.β-barium borate(BBO),α-BBO,and a dual-wavelength plate were used to compensate the phase delay of the two-color lasers.Tilting ofα-BBO could further realize the precise spatial overlap of the two beams by counteracting the walk-off effect.The maximum out-put THz pulse energy reached 21μJ in argon gas when using a commercial Ti:sapphire laser with a pulse energy of 6 mJ at a 1 kHz repetition rate.The corresponding conversion efficiency exceeded 0.35%.
基金Supported by the National Key R&D Program of China(No.2019YFD0901305)the Science and Technology Program of Zhoushan(No.2019C21011)+4 种基金the Research Project of Ecological Environment Protection and Restoration of Yangtze River in Zhoushan(No.SZGXZS2020068)the National Natural Science Foundation of China(Nos.31270160,J1310037)the Natural Science Foundation of Zhejiang Province,China(No.LY12C03003)the Zhejiang Public Welfare Technology Application Research Project(No.2016C33084)the Province Key Research and Development Program of Zhejiang(No.2021C02047)。
文摘Archaea regulate the biogeochemical processes of ocean systems.The Changjiang(Yangtze)River estuary(CRE) is a complex and dynamic area strongly affected by seawaters and ocean currents.In this study,the planktonic archaeal communities in the surface and bottom seawaters of the CRE were investigated.Significant differences in the archaeal community composition were found between the surface and bottom seawaters(P<0.001).Marine Group Ⅱ(MG-Ⅱ) was dominant in the surface layers,and Nitrosopumilales was enriched in the bottom layers.Marine Group Ⅲ(MG-Ⅲ) was more abundant in the bottom layers than in the surface ones(P<0.001).These results were completely different from previous findings in the CRE seawater.Instead of dissolved oxygen(DO),temperature and salinity were the most vital environmental variations in the distribution of the archacal communities.According to the predicted metabolic pathways,the following functional subcategories were enriched in the hypoxic condition:replication and repair,membrane transport,glycan biosynthesis and metabolism,amino acid metabolism,metabolism of cofactors and vitamins,and xenobiotics biodegradation and metabolism(P<0.001),which indicated the strong adaptability of archaea to the harsh environment in the bottom seawater.These findings expand the understanding on archaeal structure and functions in the surface and bottom seawaters,including the hypoxic zones in the CRE,and may contribute to further works of the archaeal community in the CRE.
基金supported by the Special Funds for Basic Scientific Research Business Expenses of Central Universities No. 2014GCYY0the Beijing Natural Science Foundation No. 4163076the Fundamental Research Funds for the Central Universities No. 328201801
文摘Hardware Trojan(HT) refers to a special module intentionally implanted into a chip or an electronic system. The module can be exploited by the attacker to achieve destructive functions. Unfortunately the HT is difficult to detecte due to its minimal resource occupation. In order to achieve an accurate detection with high efficiency, a HT detection method based on the electromagnetic leakage of the chip is proposed in this paper. At first, the dimensionality reduction and the feature extraction of the electromagnetic leakage signals in each group(template chip, Trojan-free chip and target chip) were realized by principal component analysis(PCA). Then, the Mahalanobis distances between the template group and the other groups were calculated. Finally, the differences between the Mahalanobis distances and the threshold were compared to determine whether the HT had been implanted into the target chip. In addition, the concept of the HT Detection Quality(HTDQ) was proposed to analyze and compare the performance of different detection methods. Our experiment results indicate that the accuracy of this detection method is 91.93%, and the time consumption is 0.042s in average, which shows a high HTDQ compared with three other methods.
基金Natural Science Foundation of Zhejiang under contract No.LQ22D060004the Scientific Research Foundation of Third Institute of Oceanography,Ministry of Natural Resources under contract No.2019013the Science and Technology Program of Zhoushan under contract No.2019C21011。
文摘The prokaryotic microbial communities in the sediments play crucial roles in the ecological functions of mangrove ecosystems.Therefore,the environmental factors that affect the structures of these prokaryotic microbial communities could indirectly participate in the regulation of mangrove functions,which is of great value for mangrove studies.The particle size(PS)of soils is recently demonstrated as a key environmental factor for shaping the microbial communities;however,this hypothesis has rarely been tested for mangrove environments.A case study of three tropical mangroves from Sanya,China was performed in this work to assess the influence of PS on the prokaryotic microbial community structures of bacteria,archaea,diazotrophs,and denitrifiers in the sediments.Results showed the variability in the spatial scale and the stability in the temporal scale for the prokaryotic communities,indicating that the tropical mangrove sediments could be a versatile but stable environment.Among the collected environmental factors,PS,salinity,and humidity had the greatest impacts,and PS mostly affected the structures of these prokaryotic communities based on its highest R^2 values of canonical correspondence analysis,Mental test,and linear fitting(p≤0.05).Furthermore,PS was positively correlated with the diversity and abundance of diazotrophic communities and negatively correlated with the abundances of methanogenic communities including Methanobacteriaceae,Methanospirillaceae,Methanoregulaceae,and Methanosaetaceae.Former studies show the increasing trend of PS caused by the rise of sea level and the intensification of human activities.Therefore,our findings indicate that PS could be a potential intermediate that links climate change and human activities with the possible ecological function migration of mangroves;meanwhile,the increase of PS could in turn release the stress of these environmental changes by increasing the abundance and diversity of the diazotrophic community and decreasing the abundances of methanogens.
基金the National Natural Science Foundation of China(Grant No.50672100)the Anhui Provincial Natural Science Foundation,China(Grant No.050440901)the Ningbo Civic Natural Science Foundation,China(Grant No.2006A610057).
文摘A cost-effective technique,including nanocrystalline powder preparation using a modified Pechini method and a two-step low-temperature sintering route,was developed for the synthesis of high performance La_2Mo_2O_9- based oxide-ion conductors.The optimum parameters of the compaction pressure,the first step and the second step sintering temperatures for the synthesis of fine grained,high density and uniform La_2Mo_2O_9- based oxide-ion conductors were determined by a series of sintering experiments.High density and uniform sintered La_2Mo_2O_9 samples with average grain size from 0.8 to 5μm and La_(1.96)K_(0.04)Mo_2O_(8.96) sample with average grain size as small as 500 nm were synthesized by using this cost-effective method.The impedance measurement results show that the as-fabricated La_2Mo_2O_9-based ceramics possess much higher ionic con- ductivity than that obtained by solid state reaction method.It is found that in the range of 0.8-5μm the grain size of dense La_2Mo_2O_9 samples prepared from the nanocrystalline powders has little influence on their conductivities.
基金The National Key R&D Program of China under contract No.2019YFD0901305the Science and Technology Program of Zhoushan under contract No.2019C21011+4 种基金the National Natural Science Foundation of China under contract Nos31270160 and J1310037the Natural Science Foundation of Zhejiang ProvinceChina under contract No.LY12C03003the Zhejiang Public Welfare Technology Application Research Project under contract No.2016C33084the Research Project of Ecological Environment Protection and Restoration of Yangtze River in Zhoushan under contract No.SZGXZS2020068。
文摘The Changjiang River Estuary(CRE)in the East China Sea suffers from seasonal hypoxia in summer.The vertical distributions and seasonal changes of microbial communities in the CRE were well documented.However,little is known about the diurnal changes of bacterial communities in the hypoxic zone of the CRE.Here,16 S rRNA gene analysis was used to explore the changes of bacterial communities in the oxic surface and hypoxic middle seawater layers during 24 h in the CRE.Significant differences between the hypoxic and oxic layers were observed:the phyla Cyanobacteria,Bacteroidetes and Acidimicrobiia were enriched in the oxic layer,whereas the phylum SAR406 and the class Deltaproteobacteria were more abundant in the hypoxic layer.In addition,some subtle diurnal variations of the bacterial relative abundance were found in both two layers.The relative abundance of Synechococcus increased at night,and this change was more obvious in the hypoxic layer.The similar trend was also found in some phototrophic and several heterotrophic bacteria,such as Rhodobacteraceae,OM60 and Flavobacteriaceae.Their relative abundances peaked at 16:00 in the oxic layer,while the relative abundances peaked at around 7:00 and decreased until 13:00 in the hypoxic layer.Together,the results of the present study suggest that some photosynthetic bacteria and several heterotrophic bacteria have similar diurnal variations implying the light and physicochemical heterogeneity in the course of a day are important for bacterial diurnal changes in the CRE.
