This study aimed to investigate the effect of varying pyrite(Py)content on copper(Cu)in the presence of different regrinding conditions,which were altered using different types of grinding media:iron,ceramic balls,and...This study aimed to investigate the effect of varying pyrite(Py)content on copper(Cu)in the presence of different regrinding conditions,which were altered using different types of grinding media:iron,ceramic balls,and their mixture,followed by flotation in the cleaner stage.The flotation performance of rough Cu concentrate can be improved by changing the regrinding conditions based on the Py content.Scanning electron microscopy,X-ray spectrometry,ethylenediaminetetraacetic acid disodium salt extraction,and X-ray photoelectron spectroscopy studies illustrated that when the Py content was high,the use of iron media in regrinding promoted the generation of hydrophilic Fe OOH on the surface of Py and improved the Cu grade.The ceramic medium with a low Py content prevented excessive Fe OOH from covering the surface of chalcopyrite(Cpy).Electrochemical studies further showed that the galvanic corrosion current of Cpy-Py increased with the addition of Py and became stronger with the participation of iron media.展开更多
In the context of the new era of education,advanced mathematics not only undertakes the function of knowledge transmission but also plays a vital role in cultivating logical thinking,scientific spirit,and value orient...In the context of the new era of education,advanced mathematics not only undertakes the function of knowledge transmission but also plays a vital role in cultivating logical thinking,scientific spirit,and value orientation.However,traditional teaching has overemphasized knowledge instillation while neglecting value guidance,making it difficult to meet the demands of cultivating interdisciplinary talents.This study introduces the OBE concept and constructs a“knowledge–ability–value”teaching framework,integrating outcome orientation,backward design,and diversified evaluation to promote the systematic incorporation of ideological and political education into the curriculum.Taking limits,definite integrals,and series as representative knowledge points,the paper designs case-based pathways to foster dialectical thinking,patriotism,and scientific spirit.Practice has shown that this model effectively unifies knowledge education and value education,enhancing students’logical reasoning,sense of responsibility,and scientific literacy.The study provides an operational pathway for the reform of ideological and political education in advanced mathematics courses and carries practical significance for implementing the goal of“all-round education.”展开更多
As a tool for quantifying individuals’visual attention and information processing,eye-tracking technology is gradually being applied in the reform of higher education.This paper focuses on issues in university mathem...As a tool for quantifying individuals’visual attention and information processing,eye-tracking technology is gradually being applied in the reform of higher education.This paper focuses on issues in university mathematics teaching,such as heavy cognitive load,delayed feedback,and insufficient adaptability.Based on theories of cognitive psychology,the study explores application pathways of this technology in cognitive diagnosis,instructional optimization,classroom regulation,personalized support,and teaching assessment.Research shows that eye-tracking data can reveal key cognitive features during the learning process,enhance the visualization of instructional feedback,and improve the scientific basis of decision-making.This provides both theoretical support and practical reference for data-driven and precise transformation in university mathematics education.展开更多
Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodie...Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodies.This highlights a critical need to discover new therapeutic agents to overcome the variants mutations.Despite the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-Co V-2 variants infection.Here,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H121)protected K18-h ACE2 mice against lethal challenge with SARS-Co V-2 variants.The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200or 1000 TCID_(50),and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also evaluated with delta and omicron challenge.Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining normal.Furthermore,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron infection.Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-Co V-2 variants infection.展开更多
In this paper, we use Lax-Oleinik formula to study the asymptotic behavior for the initial problem of scalar conservation law u_t + F(u)_x = 0. First, we prove a simple but useful property of Lax-Oleinik formula(Lemma...In this paper, we use Lax-Oleinik formula to study the asymptotic behavior for the initial problem of scalar conservation law u_t + F(u)_x = 0. First, we prove a simple but useful property of Lax-Oleinik formula(Lemma 2.7). In fact, denote the Legendre transform of F(u) as L(σ), then we can prove that the quantity F(q)-′qF(q) + L(′F(q)) is a constant independent of q. As a simple application, we first give the solution of Riemann problem without using of Rankine-Hugoniot condition and entropy condition. Then we study the asymptotic behavior of the problem with some special initial data and prove that the solution contains only a single shock for t > T~*. Meanwhile, we can give the equation of the shock and an explicit value of T~*.展开更多
In this paper,we study the global existence of periodic solutions to an isothermal relativistic Euler system in BV space.First,we analyze some properties of the shock and rarefaction wave curves in the Riemann invaria...In this paper,we study the global existence of periodic solutions to an isothermal relativistic Euler system in BV space.First,we analyze some properties of the shock and rarefaction wave curves in the Riemann invariant plane.Based on these properties,we construct the approximate solutions of the isothermal relativistic Euler system with periodic initial data by using a Glimm scheme,and prove that there exists an entropy solution V(x,t)which belongs to L^(∞)∩BV_(loc)(R×R_(+)).展开更多
In this article, we give the existence of global L^(∞)bounded entropy solutions to the Cauchy problem of a generalized n × n hyperbolic system of Le Roux type. The main difficulty lies in establishing some compa...In this article, we give the existence of global L^(∞)bounded entropy solutions to the Cauchy problem of a generalized n × n hyperbolic system of Le Roux type. The main difficulty lies in establishing some compactness estimates of the viscosity solutions because the system has been generalized from 2×2 to n×n and more linearly degenerate characteristic fields emerged, and the emergence of singularity in the region {v1= 0} is another difficulty.We obtain the existence of the global weak solutions using the compensated compactness method coupled with the construction of entropy-entropy flux and BV estimates on viscous solutions.展开更多
In this paper,we study the global existence of BV solutions of the initial value problem for the isentropic p-system,where the state equation of the gas is given by P=Av^(-γ).Forγ>1,the general existence result f...In this paper,we study the global existence of BV solutions of the initial value problem for the isentropic p-system,where the state equation of the gas is given by P=Av^(-γ).Forγ>1,the general existence result for large initial data has not been obtained.By using the Glimm scheme,Nishida,Smoller and Diperna successively obtained the global existence results for(γ-1)TV(v_(0)(x),u_(0)(x))being small.In the present paper,by adopting a rescaling technique,we improve these results and obtain the global existence result under the condition that(γ-1)^(γ+1)(TV(v_(0)(x)))~(γ-1)(TV(u_(0)(x)))^(2) is small,which implies that,for fixedγ>1,either TV(v_(0)(x))or TV(u_(0)(x))can be arbitrarily large.展开更多
Transmembrane water exchange(TWE)including transcytolemmal water exchange and transvascular water exchange is involved in many in vivo measurements and makes different contributions to the measuring results.In this st...Transmembrane water exchange(TWE)including transcytolemmal water exchange and transvascular water exchange is involved in many in vivo measurements and makes different contributions to the measuring results.In this study,we focus on the potential influence of TWE on the cell density parameter,intracellular water mole fraction pi,derived by dynamic contrast enhanced-magnetic resonance imaging(DCE-MRI)which has been reported as a technique to characterize perfusion and vascularization of tissues,but its accuracy in measuring cell density(or interstitial space)has been questioned.Sixteen patients with glioblastoma multiforme(GBM)were enrolled since GBM shows strong intratumor heterogeneity in both cell density and TWE.All the subjects were collected with DCE-MRI and apparent diffusion coefficient(ADC)map.The latter was considered as a valid surrogate of cell density.Extended Tofts(eTofts)model considering TWE as infinitely large variables and shutter-speed model(SSM)considering TWE as finite ones were used to fit DCE-MRI data.Monte Carlo(MC)and finite difference(FD)methods were used to simulate the influence of TWE on DCE-MRI-derived pi and ADC,respectively.The eTofts model shows a significant overestimation of pi in comparison with SSM in GBM(P<0.001),which is in accordance with MC simulations,and this overestimation shows dependence on the intra-to-extracellular water exchange rate constant(kio).Significant negative correlations between ADC and SSM-derived pi were found in both voxel-wise analyses(t-test P<0.001,average r=-0.74)and inter-subject comparisons(r=-0.63,P=0.009).But no consistent voxel-wise correlations(P>0.05)and a weaker inter-subject negative correlation(r=-0.56,P=0.02)were found between ADC and eTofts-derived pi.Further experimental and FD results revealed that kio made a limited contribution to ADC values in the physiological kio range in GBM,supporting ADC as a valid biomarker of cell density.These results suggest that the DCE-MRI pharmacokinetic shutter-speed model could significantly improve its accuracy in cell density estimation because of the considering transmembrane water exchange.展开更多
Precision treatment,which targets the molecular-based pathogenesis or the specific microenvironment of the focus,has become an established paradigm in current therapeutic agent development and delivery strategy design...Precision treatment,which targets the molecular-based pathogenesis or the specific microenvironment of the focus,has become an established paradigm in current therapeutic agent development and delivery strategy design.However,current therapeutics lack spatial and temporal control,resulting in systemic side effects and suboptimal patient outcomes.Drug delivery systems that are site-specific,ratespecific,and time-specific can be designed to improve therapeutic precision by optimizing pharmacokinetics,developing stimulus-sensitive switches,and creating novel responsive biomaterials.Here,we discuss the engineering of stimulus switches at various scales to improve spatial-temporal precision in therapeutic delivery systems,release drugs in a controlled manner,and reduce adverse reactions.We further outline the use of biomaterials that respond to endogenous stimuli(pH,enzymes,prodrugs,and redox potential),and summarized the three key controllable release mechanisms of these stimulus switches:time,site and rate-specific.We also anticipate that the strategies summarized in this review will contribute to the development of neotype drug delivery strategies.展开更多
Cancer immunotherapy has appeared as a prospective therapeutic modality.Therapeutic antibodies induced in an in vitro expression system act as"targeting missiles"against tumor-associated binding sites,and su...Cancer immunotherapy has appeared as a prospective therapeutic modality.Therapeutic antibodies induced in an in vitro expression system act as"targeting missiles"against tumor-associated binding sites,and subsequently,immune system attack on tumors is restored or boosted.These antibody regimens are engineered towards enhanced Fc efficacy,humanization,and fragmentation to specifically recognize and bind to effective tumor-associated targets.The challenge lies in obtaining efficient therapeutic regimens with low response rates,acquisition of resistance,and immune-related undesirable effects of artificially designed therapeutic antibodies,which is crucial for enhancing clinical efficacy.This review provides an in-depth introduction to antibodies that perform direct/indirect roles in cancer treatment by binding to immune checkpoints,costimulatory receptors,and extracellular membrane receptors.It also discusses how antibodies kill tumors and modulate microenvironment of tumor through these targets.The classification of expression systems for antibody production is summarized to guide appropriate selection based on different specificities.Understanding antibody sources,ongoing evaluation of engineered antibodies,and tumor-associated antigen research pave the way for designing appropriate antibody-based immunotherapy regimens.展开更多
Organic donor-acceptor semiconductors exhibit great potential in photothermal conversion.However,it is still challenging to achieve pure organic materials with broad absorption comparable with inorganic materials such...Organic donor-acceptor semiconductors exhibit great potential in photothermal conversion.However,it is still challenging to achieve pure organic materials with broad absorption comparable with inorganic materials such as graphene.Herein,two D-AD type DPA-BT-O4 and NDI-TPA-O4 and three D-A-π-A-D type Th-O4,Th2-O4,and IDT-O4 were readily prepared via two high-yield steps and simple air oxidization.The stability can be attributed to their multiple resonance structures based on the aromatic nitric acid radical mechanism.Compared with the D-A-D radicals,the conjugation extension of the D-A-π-A-D radicals endows them with a narrowed band gap and broad absorption in powder.Interestingly,the IDT-O4 powder with aggregation-induced radical effect exhibits broad absorption between 300 and 2500 nm,which is comparable with graphene and other inorganic materials.Under irradiation of 0.9 W/cm^(2)(808 nm),the temperature of IDT-O4 powder rises to 250℃within 60 s.The water evaporation conversion efficiency of 94.38%and an evaporation rate of 1.365 kg/m^(2)h^(−1)under one sun illumination were achieved.IDT-O4 stands as one of the most efficient photothermal conversion materials among pure organic materials via a rational design strategy.展开更多
Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polye...Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.展开更多
Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of re...Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of rectal cancer.In recent years,the proportion of rectal cancer has trended downward,however the incidence of rectal cancer inyounger adults is increasing.The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were editedto help improve the diagnosis and comprehensive treatment in China.Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal CancerSociety,based on a careful review of the latest evidence including China’s studies,and referred to domestic and internationalrelative guidelines,also considered China’s specific national conditions and clinical practice.Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectalcancer,prevention and screening,diagnosis,treatment of nonmetastatic and metastatic rectal cancer,follow-up,and whole-course rehabilitation management.Conclusion Committee of Colorectal Cancer Society,Chinese Anti-Cancer Association,standardizes the diagnosisand treatment of rectal cancer in China through the formulation of the CACA Guidelines.展开更多
With the rapid development of minimally invasive surgery for the treatment of colorectal diseases,novel surgical techniques aiming at reducing surgical trauma have become frequently discussed issues[1].Natural orifice...With the rapid development of minimally invasive surgery for the treatment of colorectal diseases,novel surgical techniques aiming at reducing surgical trauma have become frequently discussed issues[1].Natural orifice specimen extraction surgery(NOSES),including transvaginal specimen extraction(TVSE)and transanal specimen extraction(TASE),have been considered well-established surgical approaches for avoiding abdominal incision[2.3].NOSES represents one of the least invasive options in the treatment of colorectal cancer(CRC),but most relevant studies are singlecentered with limited sample sizes.Whether previous findings can be generalized to a wider patient population remains unclear[3.4).Therefore,we performed the first nationwide large-scale study with the aim of confirming the safety and feasibility of NOSES for CRC by analyzing the short-term and long-term oncological outcomes.展开更多
In this paper,the authors use Glimm scheme to study the global existence of BV solutions to Cauchy problem of the pressure-gradient system with large initial data.To this end,some important properties of the shock cur...In this paper,the authors use Glimm scheme to study the global existence of BV solutions to Cauchy problem of the pressure-gradient system with large initial data.To this end,some important properties of the shock curves of the pressure-gradient system in the Riemann invariant coordinate system and verify that the shock curves satisfy Diperna’s conditions(see[Diperna,R.J.,Existence in the large for quasilinear hyperbolic conservation laws,Arch.Ration.Mech.Anal.,52(3),1973,244–257])are studied.Then they construct the approximate solution sequence through Glimm scheme.By establishing accurate local interaction estimates,they prove the boundedness of the approximate solution sequence and its total variation.展开更多
基金financially supported by the National Key Research and Development Plan of China(No.2022YFC2904603)the National Natural Science Foundation of China(No.52174268)。
文摘This study aimed to investigate the effect of varying pyrite(Py)content on copper(Cu)in the presence of different regrinding conditions,which were altered using different types of grinding media:iron,ceramic balls,and their mixture,followed by flotation in the cleaner stage.The flotation performance of rough Cu concentrate can be improved by changing the regrinding conditions based on the Py content.Scanning electron microscopy,X-ray spectrometry,ethylenediaminetetraacetic acid disodium salt extraction,and X-ray photoelectron spectroscopy studies illustrated that when the Py content was high,the use of iron media in regrinding promoted the generation of hydrophilic Fe OOH on the surface of Py and improved the Cu grade.The ceramic medium with a low Py content prevented excessive Fe OOH from covering the surface of chalcopyrite(Cpy).Electrochemical studies further showed that the galvanic corrosion current of Cpy-Py increased with the addition of Py and became stronger with the participation of iron media.
基金2024 Education and Teaching Reform Project(Project No.:JG2024047)Basic Scientific Research Funding of the Xinjiang Uygur Autonomous Region(Project No.:XQZX20250005)。
文摘In the context of the new era of education,advanced mathematics not only undertakes the function of knowledge transmission but also plays a vital role in cultivating logical thinking,scientific spirit,and value orientation.However,traditional teaching has overemphasized knowledge instillation while neglecting value guidance,making it difficult to meet the demands of cultivating interdisciplinary talents.This study introduces the OBE concept and constructs a“knowledge–ability–value”teaching framework,integrating outcome orientation,backward design,and diversified evaluation to promote the systematic incorporation of ideological and political education into the curriculum.Taking limits,definite integrals,and series as representative knowledge points,the paper designs case-based pathways to foster dialectical thinking,patriotism,and scientific spirit.Practice has shown that this model effectively unifies knowledge education and value education,enhancing students’logical reasoning,sense of responsibility,and scientific literacy.The study provides an operational pathway for the reform of ideological and political education in advanced mathematics courses and carries practical significance for implementing the goal of“all-round education.”
基金The 2024 Education and Teaching Reform Project,“Exploration and Practice of University Mathematics Teaching Reform Driven by Eye-Tracking Technology”(Project No.:JG2024047)。
文摘As a tool for quantifying individuals’visual attention and information processing,eye-tracking technology is gradually being applied in the reform of higher education.This paper focuses on issues in university mathematics teaching,such as heavy cognitive load,delayed feedback,and insufficient adaptability.Based on theories of cognitive psychology,the study explores application pathways of this technology in cognitive diagnosis,instructional optimization,classroom regulation,personalized support,and teaching assessment.Research shows that eye-tracking data can reveal key cognitive features during the learning process,enhance the visualization of instructional feedback,and improve the scientific basis of decision-making.This provides both theoretical support and practical reference for data-driven and precise transformation in university mathematics education.
基金supported by National Key Research and Development Program of China(2021YFC2600200,2017YFA0205100)。
文摘Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodies.This highlights a critical need to discover new therapeutic agents to overcome the variants mutations.Despite the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-Co V-2 variants infection.Here,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H121)protected K18-h ACE2 mice against lethal challenge with SARS-Co V-2 variants.The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200or 1000 TCID_(50),and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also evaluated with delta and omicron challenge.Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining normal.Furthermore,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron infection.Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-Co V-2 variants infection.
基金supported in part by NSFC(11671193)the Fundamental Research Funds for the Central Universities(NE2015005)supported in part by NSFC(11271182 and 11501290)
文摘In this paper, we use Lax-Oleinik formula to study the asymptotic behavior for the initial problem of scalar conservation law u_t + F(u)_x = 0. First, we prove a simple but useful property of Lax-Oleinik formula(Lemma 2.7). In fact, denote the Legendre transform of F(u) as L(σ), then we can prove that the quantity F(q)-′qF(q) + L(′F(q)) is a constant independent of q. As a simple application, we first give the solution of Riemann problem without using of Rankine-Hugoniot condition and entropy condition. Then we study the asymptotic behavior of the problem with some special initial data and prove that the solution contains only a single shock for t > T~*. Meanwhile, we can give the equation of the shock and an explicit value of T~*.
基金supported by NSFC(11671193)the Fundamental Research Funds for the Central Universities NE2015005。
文摘In this paper,we study the global existence of periodic solutions to an isothermal relativistic Euler system in BV space.First,we analyze some properties of the shock and rarefaction wave curves in the Riemann invariant plane.Based on these properties,we construct the approximate solutions of the isothermal relativistic Euler system with periodic initial data by using a Glimm scheme,and prove that there exists an entropy solution V(x,t)which belongs to L^(∞)∩BV_(loc)(R×R_(+)).
基金supported by the National Science Foundation of China(11572148,11671193)the National Research Foundation for the Doctoral Program of Higher Education of China(20133218110025)
文摘In this article, we give the existence of global L^(∞)bounded entropy solutions to the Cauchy problem of a generalized n × n hyperbolic system of Le Roux type. The main difficulty lies in establishing some compactness estimates of the viscosity solutions because the system has been generalized from 2×2 to n×n and more linearly degenerate characteristic fields emerged, and the emergence of singularity in the region {v1= 0} is another difficulty.We obtain the existence of the global weak solutions using the compensated compactness method coupled with the construction of entropy-entropy flux and BV estimates on viscous solutions.
基金partially the NSFC(11671193)Fangqi Chen was partially the NSFC(12172166,11872201)。
文摘In this paper,we study the global existence of BV solutions of the initial value problem for the isentropic p-system,where the state equation of the gas is given by P=Av^(-γ).Forγ>1,the general existence result for large initial data has not been obtained.By using the Glimm scheme,Nishida,Smoller and Diperna successively obtained the global existence results for(γ-1)TV(v_(0)(x),u_(0)(x))being small.In the present paper,by adopting a rescaling technique,we improve these results and obtain the global existence result under the condition that(γ-1)^(γ+1)(TV(v_(0)(x)))~(γ-1)(TV(u_(0)(x)))^(2) is small,which implies that,for fixedγ>1,either TV(v_(0)(x))or TV(u_(0)(x))can be arbitrarily large.
基金the National Natural Science Foundation of China(NSFC)(Grant No.81873894,Grant No.21922410)Natural Science Foundation of Zhejiang Province,China(Grant No.LR20H180001,Grant No.LR19B050001)Taishan Scholars Program(No.tsqn20161070).
文摘Transmembrane water exchange(TWE)including transcytolemmal water exchange and transvascular water exchange is involved in many in vivo measurements and makes different contributions to the measuring results.In this study,we focus on the potential influence of TWE on the cell density parameter,intracellular water mole fraction pi,derived by dynamic contrast enhanced-magnetic resonance imaging(DCE-MRI)which has been reported as a technique to characterize perfusion and vascularization of tissues,but its accuracy in measuring cell density(or interstitial space)has been questioned.Sixteen patients with glioblastoma multiforme(GBM)were enrolled since GBM shows strong intratumor heterogeneity in both cell density and TWE.All the subjects were collected with DCE-MRI and apparent diffusion coefficient(ADC)map.The latter was considered as a valid surrogate of cell density.Extended Tofts(eTofts)model considering TWE as infinitely large variables and shutter-speed model(SSM)considering TWE as finite ones were used to fit DCE-MRI data.Monte Carlo(MC)and finite difference(FD)methods were used to simulate the influence of TWE on DCE-MRI-derived pi and ADC,respectively.The eTofts model shows a significant overestimation of pi in comparison with SSM in GBM(P<0.001),which is in accordance with MC simulations,and this overestimation shows dependence on the intra-to-extracellular water exchange rate constant(kio).Significant negative correlations between ADC and SSM-derived pi were found in both voxel-wise analyses(t-test P<0.001,average r=-0.74)and inter-subject comparisons(r=-0.63,P=0.009).But no consistent voxel-wise correlations(P>0.05)and a weaker inter-subject negative correlation(r=-0.56,P=0.02)were found between ADC and eTofts-derived pi.Further experimental and FD results revealed that kio made a limited contribution to ADC values in the physiological kio range in GBM,supporting ADC as a valid biomarker of cell density.These results suggest that the DCE-MRI pharmacokinetic shutter-speed model could significantly improve its accuracy in cell density estimation because of the considering transmembrane water exchange.
基金supported by the Liaoning Revitalization Talents Program(No.XLYC2203019)the Fundamental Research Funds for the Central Universities(No.N2405005)+1 种基金the Joint Fund of the Natural Science Foundation of Liaoning Province(No.2023-MSBA-058)for Z.J.W.and F.Zsupported by the Kuni Foundation,Collins Medical Trust,and start-up package from Providence Cancer Institute for D.W.
文摘Precision treatment,which targets the molecular-based pathogenesis or the specific microenvironment of the focus,has become an established paradigm in current therapeutic agent development and delivery strategy design.However,current therapeutics lack spatial and temporal control,resulting in systemic side effects and suboptimal patient outcomes.Drug delivery systems that are site-specific,ratespecific,and time-specific can be designed to improve therapeutic precision by optimizing pharmacokinetics,developing stimulus-sensitive switches,and creating novel responsive biomaterials.Here,we discuss the engineering of stimulus switches at various scales to improve spatial-temporal precision in therapeutic delivery systems,release drugs in a controlled manner,and reduce adverse reactions.We further outline the use of biomaterials that respond to endogenous stimuli(pH,enzymes,prodrugs,and redox potential),and summarized the three key controllable release mechanisms of these stimulus switches:time,site and rate-specific.We also anticipate that the strategies summarized in this review will contribute to the development of neotype drug delivery strategies.
基金This work was supported by National Natural Science Foundation of China(22204015)Shenyang Young and Middle-aged Scientific and Technological Innovation Talents Project(RC220478)the Fundamental Research Funds for the Central Universities(N2405010).
文摘Cancer immunotherapy has appeared as a prospective therapeutic modality.Therapeutic antibodies induced in an in vitro expression system act as"targeting missiles"against tumor-associated binding sites,and subsequently,immune system attack on tumors is restored or boosted.These antibody regimens are engineered towards enhanced Fc efficacy,humanization,and fragmentation to specifically recognize and bind to effective tumor-associated targets.The challenge lies in obtaining efficient therapeutic regimens with low response rates,acquisition of resistance,and immune-related undesirable effects of artificially designed therapeutic antibodies,which is crucial for enhancing clinical efficacy.This review provides an in-depth introduction to antibodies that perform direct/indirect roles in cancer treatment by binding to immune checkpoints,costimulatory receptors,and extracellular membrane receptors.It also discusses how antibodies kill tumors and modulate microenvironment of tumor through these targets.The classification of expression systems for antibody production is summarized to guide appropriate selection based on different specificities.Understanding antibody sources,ongoing evaluation of engineered antibodies,and tumor-associated antigen research pave the way for designing appropriate antibody-based immunotherapy regimens.
基金National Natural Science Foundation of China,Grant/Award Number:51973063Tip-top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program,Grant/Award Number:2019TQ05C890+3 种基金Opening Project of Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of EducationJianghan University,Grant/Award Number:JDGD-202010Pearl River S&T Nova Program of Guangzhou,Grant/Award Number:201710010194Fund of Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates,Grant/Award Number:2019B030301003。
文摘Organic donor-acceptor semiconductors exhibit great potential in photothermal conversion.However,it is still challenging to achieve pure organic materials with broad absorption comparable with inorganic materials such as graphene.Herein,two D-AD type DPA-BT-O4 and NDI-TPA-O4 and three D-A-π-A-D type Th-O4,Th2-O4,and IDT-O4 were readily prepared via two high-yield steps and simple air oxidization.The stability can be attributed to their multiple resonance structures based on the aromatic nitric acid radical mechanism.Compared with the D-A-D radicals,the conjugation extension of the D-A-π-A-D radicals endows them with a narrowed band gap and broad absorption in powder.Interestingly,the IDT-O4 powder with aggregation-induced radical effect exhibits broad absorption between 300 and 2500 nm,which is comparable with graphene and other inorganic materials.Under irradiation of 0.9 W/cm^(2)(808 nm),the temperature of IDT-O4 powder rises to 250℃within 60 s.The water evaporation conversion efficiency of 94.38%and an evaporation rate of 1.365 kg/m^(2)h^(−1)under one sun illumination were achieved.IDT-O4 stands as one of the most efficient photothermal conversion materials among pure organic materials via a rational design strategy.
基金We would like to dedicate this article to Professor Qing Huang. This work was supported by National Natural Science Foundation of China （Nos. 31771102, 31371015, 21675167, U1532119, 31470970, 31371493, and 31571498）, the National Basic Research Program of China （Nos. 2013CB932803, 2013CB933802, 2016YFA0400900, and 2016YFA0201200）, the Youth Innovation Promotion Association from Chinese Academy of Sciences （No. 2015211）, Key Research Program of Frontier Sciences, CAS （Nos. QYZDJ-SSW-SLH019 and QYZDJ-SSW-SLH031）.
文摘Magnetite nanoparticles （Fe3O4 NPs） are a well proven biocompatible nanomaterial, which hold great promise in various biomedical applications. Interestingly, unlike conventional biocompatible materials （e.g., polyethylene glycol （PEG）） that are chemically and biologically inert in nature, Fe3O4 NPs are known to be catalytically active and exhibit prominent physiological effects. Herein, we report an ＂active＂, dynamic equilibrium mechanism for maintaining the cellular amenity of Fe3O4 NPs. We examined the effects of two types of iron oxide （magnetite and hematite） NPs in rat pheochromocytoma （PC12） cells and found that both induced stress responses. However, only Fe2O3 NPs caused significant programmed cell death; whereas Fe3O4 NPs are amenable to cells. We found that intrinsic catalase-like activity of Fe3O4 NPs antagonized the accumulation of toxic reactive oxygen species （ROS） induced by themselves, and thereby modulated the extent of cellular oxidative stress, autophagic activity, and programmed cell death. In line with this observation, we effectively reversed severe autophagy and cell death caused by Fe2O3 NPs via co-treatment with natural catalase. This study not only deciphers the distinct intrinsic antagonism of Fe3O4 NPs, but opens new routes to designing biocompatible theranostic nanoparticles with novel mechanisms.
文摘Purpose Colorectal cancer is a common malignant tumor worldwide.In China,the ratio of rectal cancer to coloncancer in terms of incidence is close to 1:1.Low rectal cancer accounts for more than half of all cases of rectal cancer.In recent years,the proportion of rectal cancer has trended downward,however the incidence of rectal cancer inyounger adults is increasing.The CACA Guidelines for Holistic Integrative Management of Rectal Cancer were editedto help improve the diagnosis and comprehensive treatment in China.Methods This guideline has been prepared by consensuses reached by the CACA Committee of Colorectal CancerSociety,based on a careful review of the latest evidence including China’s studies,and referred to domestic and internationalrelative guidelines,also considered China’s specific national conditions and clinical practice.Results The CACA Guidelines for Holistic Integrative Management of Rectal Cancer include the epidemiology of rectalcancer,prevention and screening,diagnosis,treatment of nonmetastatic and metastatic rectal cancer,follow-up,and whole-course rehabilitation management.Conclusion Committee of Colorectal Cancer Society,Chinese Anti-Cancer Association,standardizes the diagnosisand treatment of rectal cancer in China through the formulation of the CACA Guidelines.
基金supported by the Beijing Municipal Science&Technology Commission(D171100002617004)。
文摘With the rapid development of minimally invasive surgery for the treatment of colorectal diseases,novel surgical techniques aiming at reducing surgical trauma have become frequently discussed issues[1].Natural orifice specimen extraction surgery(NOSES),including transvaginal specimen extraction(TVSE)and transanal specimen extraction(TASE),have been considered well-established surgical approaches for avoiding abdominal incision[2.3].NOSES represents one of the least invasive options in the treatment of colorectal cancer(CRC),but most relevant studies are singlecentered with limited sample sizes.Whether previous findings can be generalized to a wider patient population remains unclear[3.4).Therefore,we performed the first nationwide large-scale study with the aim of confirming the safety and feasibility of NOSES for CRC by analyzing the short-term and long-term oncological outcomes.
基金supported by the National Natural Science Foundation of China(No.11671193)。
文摘In this paper,the authors use Glimm scheme to study the global existence of BV solutions to Cauchy problem of the pressure-gradient system with large initial data.To this end,some important properties of the shock curves of the pressure-gradient system in the Riemann invariant coordinate system and verify that the shock curves satisfy Diperna’s conditions(see[Diperna,R.J.,Existence in the large for quasilinear hyperbolic conservation laws,Arch.Ration.Mech.Anal.,52(3),1973,244–257])are studied.Then they construct the approximate solution sequence through Glimm scheme.By establishing accurate local interaction estimates,they prove the boundedness of the approximate solution sequence and its total variation.
