Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safet...Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.展开更多
Wearable biosensors have received great interest as patient-friendly diagnostic technologies because of their high flexibility and conformability.The growing research and utilization of novel materials in designing we...Wearable biosensors have received great interest as patient-friendly diagnostic technologies because of their high flexibility and conformability.The growing research and utilization of novel materials in designing wearable biosensors have accelerated the development of point-of-care sensing platforms and implantable biomedical devices in human health care.Among numerous potential materials,conjugated polymers(CPs)are emerging as ideal choices for constructing high-performance wearable biosensors because of their outstanding conductive and mechanical properties.Recently,CPs have been extensively incorporated into various wearable biosensors to monitor a range of target biomolecules.However,fabricating highly reliable CP-based wearable biosensors for practical applications remains a significant challenge,necessitating novel developmental strategies for enhancing the viability of such biosensors.Accordingly,this review aims to provide consolidated scientific evidence by summarizing and evaluating recent studies focused on designing and fabricating CP-based wearable biosensors,thereby facilitating future research.Emphasizing the superior properties and benefits of CPs,this review aims to clarify their potential applicability within this field.Furthermore,the fundamentals and main components of CP-based wearable biosensors and their sensing mechanisms are discussed in detail.The recent advancements in CP nanostructures and hybridizations for improved sensing performance,along with recent innovations in next-generation wearable biosensors are highlighted.CPbased wearable biosensors have been—and will continue to be—an ideal platform for developing effective and user-friendly diagnostic technologies for human health monitoring.展开更多
Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac...Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.展开更多
Osteoporosis remains incurable.The most widely used antiresorptive agents,bisphosphonates(BPs),also inhibit bone formation,while the anabolic agent,teriparatide,does not inhibit bone resorption,and thus they have limi...Osteoporosis remains incurable.The most widely used antiresorptive agents,bisphosphonates(BPs),also inhibit bone formation,while the anabolic agent,teriparatide,does not inhibit bone resorption,and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects.展开更多
Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with ...Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with histidine.After conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions.Notably,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus.CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity.Collectively,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.展开更多
Enhancing catalytic activity of multi-enzyme in vitro through substrate channeling effect is promis-ing yet challenging.Herein,conjugated microporous polymers(CMPs)-scaffolded integrated en-zyme cascade systems(I-ECSs...Enhancing catalytic activity of multi-enzyme in vitro through substrate channeling effect is promis-ing yet challenging.Herein,conjugated microporous polymers(CMPs)-scaffolded integrated en-zyme cascade systems(I-ECSs)are constructed through co-entrapping glucose oxidase(GOx)and horseradish peroxidase(HRP),in which hydrogen peroxide(H_(2)O_(2)) is the intermediate product.The interplay of low-resistance mass transfer pathway and appropriate pore wall-H_(2)O_(2) interactions facilitates the directed transfer of H_(2)O_(2),resulting in 2.4-fold and 5.0-fold elevation in catalytic activ-ity compared to free ECSs and separated ECSs,respectively.The substrate channeling effect could be regulated by altering the mass ratio of GOx to HRP.Besides,I-ECSs demonstrate excellent stabili-ties in harsh environments and multiple recycling.展开更多
By using one-dimensional tight-binding model modified to include electron-electric field interaction and electron-electron interaction,we theoretically explore the polarization process of exciton and biexciton in cis-...By using one-dimensional tight-binding model modified to include electron-electric field interaction and electron-electron interaction,we theoretically explore the polarization process of exciton and biexciton in cis-polyacetylene.The dynamical simulation is performed by adopting the non-adiabatic evolution approach.The results show that under the effect of moderate electric field,when the strength of electron-electron interaction is weak,the singlet exciton is stable but its polarization presents obvious oscillation.With the enhancement of interaction,it is dissociated into polaron pairs,the spin-flip of which can be observed through modulating the interaction strength.For the triplet exciton,the strong electron-electron interaction restrains its normal polarization,but it is still stable.In the case of biexciton,the strong electron-electron interaction not only dissociate it,but also flip its charge distribution.The yield of the possible states formed after the dissociation of exciton and biexciton is also calculated.展开更多
The 2022 M_(W)6.7 Menyuan earthquake ruptured the western end of the Tianzhu seismic gap,providing an opportunity to study the regional seismogenic characteristics and seismic hazards.Here we use interferometric synth...The 2022 M_(W)6.7 Menyuan earthquake ruptured the western end of the Tianzhu seismic gap,providing an opportunity to study the regional seismogenic characteristics and seismic hazards.Here we use interferometric synthetic aperture radar(InSAR)and seismic data to study the mainshock rupture,early afterslip and the second largest aftershock of the 2022 Menyuan earthquake sequences.Our modeling results show that the mainshock ruptured the Lenglongling fault and the Tuolaishan fault with a maximum slip of~3 m.Rapid postseismic transient deformation occurred at the center of the Lenglongling fault.Our afterslip modeling reveals that the majority of afterslip occurred in the deeper part of the Lenglongling fault.A high-angle conjugated faulting event is found at the middle section of the Lenglongling fault.We use the stress inversion to investigate the possible triggering mechanism of the conjugated rupture event.The results indicate the maximum principal stress direction is in~222°,forming a~22°angle between the conjugated fault of second largest aftershock and the mainshock.The calculated normal stress changes indicate the region is within a pull-apart stress field,which favors such a conjugated rupturing event.Our study will help understand the rupture behavior of such kind of conjugated fault in other regions.展开更多
As a generalization of the two-term conjugate gradient method(CGM),the spectral CGM is one of the effective methods for solving unconstrained optimization.In this paper,we enhance the JJSL conjugate parameter,initiall...As a generalization of the two-term conjugate gradient method(CGM),the spectral CGM is one of the effective methods for solving unconstrained optimization.In this paper,we enhance the JJSL conjugate parameter,initially proposed by Jiang et al.(Computational and Applied Mathematics,2021,40:174),through the utilization of a convex combination technique.And this improvement allows for an adaptive search direction by integrating a newly constructed spectral gradient-type restart strategy.Then,we develop a new spectral CGM by employing an inexact line search to determine the step size.With the application of the weak Wolfe line search,we establish the sufficient descent property of the proposed search direction.Moreover,under general assumptions,including the employment of the strong Wolfe line search for step size calculation,we demonstrate the global convergence of our new algorithm.Finally,the given unconstrained optimization test results show that the new algorithm is effective.展开更多
Heat transfers due to MHD-conjugate free convection from the isothermal horizontal circular cylinder while viscosity is a function of temperature is investigated. The governing equations of the flow and connected boun...Heat transfers due to MHD-conjugate free convection from the isothermal horizontal circular cylinder while viscosity is a function of temperature is investigated. The governing equations of the flow and connected boundary conditions are made dimensionless using a set of non-dimensional parameters. The governing equations are solved numerically using the finite difference method. Numerical results are obtained for various values of viscosity variation parameter, Prandtl number, magnetic parameter, and conjugate conduction parameter for the velocity and the temperature within the boundary layer as well as the skin friction coefficients and heat transfer rate along the surface.展开更多
Background:WHO currently recommends a single dose of typhoid conjugate vaccine(TCV)in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials.Given the decay of immunogenici...Background:WHO currently recommends a single dose of typhoid conjugate vaccine(TCV)in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials.Given the decay of immunogenicity,the protection beyond 2 years is unknown.We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination.展开更多
Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoi...Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.展开更多
Objective Ubiquitin conjugate enzyme E2O(UBE2O)is a ubiquitin-conjugating enzyme that has been reported to be involved in tumorigenesis.This study investigated the role of UBE2O in hepatocellular carcinoma(HCC).Method...Objective Ubiquitin conjugate enzyme E2O(UBE2O)is a ubiquitin-conjugating enzyme that has been reported to be involved in tumorigenesis.This study investigated the role of UBE2O in hepatocellular carcinoma(HCC).Methods The expression of UBE2O was detected using qRT-PCR,Western blotting,and immunohistochemical staining.Cell proliferation and Transwell assays were used to detect proliferation,migration,and invasion of HCC cells,respectively.Bioinformatic analysis was performed to analyze the relationship between UBE2O and the clinical features,prognosis,and immune cell infiltration of HCC.Results UBE2O was significantly over-expressed in HCC tissues.High expression of UBE2O was associated with poor tumor grade and poor prognosis.Functional experiments showed that down-regulation of UBE2O inhibited HCC cell proliferation,migration,and invasion.Co-expression gene analysis and gene set enrichment analysis showed that UBE2O was associated with protein hydrolysis,cell cycle,and cancer-related pathways in HCC.The results of immune analysis revealed that the expression of UBE2O was positively correlated with the immune infiltration and expression of immune-related chemokines of HCC.Conclusions UBE2O is significantly correlated with the prognosis of HCC and may be a valuable prognostic biomarker for HCC.展开更多
A three-dimensional conjugate tooth surface design method for Harmonic Drive with a double-circular-arc tooth profle is proposed. The radial deformation function of the fexspline (FS), obtained through Finite Element ...A three-dimensional conjugate tooth surface design method for Harmonic Drive with a double-circular-arc tooth profle is proposed. The radial deformation function of the fexspline (FS), obtained through Finite Element (FE) analysis, is incorporated into the kinematics model. By analyzing the FS tooth enveloping process, the optimization of the overlapping conjugate tooth profle is achieved. By utilizing the hobbing process, the three-dimensional machinable tooth surface of FS can be acquired. Utilizing the coning deformation of the FS, simulations are conducted to analyze the multi-section assembly and meshing motion of the machinable tooth surface. The FE method is utilized to analyze and compare the loaded contact characteristics. Results demonstrate that the proposed design method can achieve an internal gear pair consisting of a circular spline with a spur gear tooth surface and the FS with a machinable tooth surface. With the rated torque, approximately 24% of the FS teeth are engaged in meshing, and more than 4/5 of the tooth surface in the axial direction carries the load. The contact patterns, maximum contact pressure, and transmission error of the machinable tooth surface are 227.2%, 40.67%, and 71.24% of those on the spur gear tooth surface, respectively. It clearly demonstrates exceptional transmission performance.展开更多
Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity...Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.展开更多
Insulating polymers are characterized by a predominantlyσ-covalent structure,which localize electrons in the atoms and exhibit dielectricity.Insulating polymers typically adopt a more linear and extended conformation...Insulating polymers are characterized by a predominantlyσ-covalent structure,which localize electrons in the atoms and exhibit dielectricity.Insulating polymers typically adopt a more linear and extended conformation,as the repeating units are connected by single covalent bonds,resulting in a relatively straight and extended chain structure.For most insulating polymers,the contour length(L_(c))is significantly larger than their persistence length(Lp)due to the rotation of C−C single bonds(Fig.1(a)).Consequently,this leads to a flexible,random-coil chain conformation.This structural feature contributes to the great mechanical durability and resistance to crack initiation during stretching or bending processes.In contrast,conjugated polymers possess aπ-conjugated molecular structure,allowing electron mobility along the main chain,called delocalization,which imparts semiconducting properties[1,2].The presence of rigid,alternating single and multiple bonds results in comparable Lc and Lp,thereby yielding a stiff or semi-flexible conformation(Fig.1(b))[3,4].As a consequence,most conjugated polymers are prone to fracture under low strain levels(<10%)[5−7].展开更多
Lithium(Li)metal anodes have attracted extensive attention due to their ultrahigh theoretical capacity and low potential.However,the uneven deposition of Li near the unstable electrode/electrolyte interfaces leads to ...Lithium(Li)metal anodes have attracted extensive attention due to their ultrahigh theoretical capacity and low potential.However,the uneven deposition of Li near the unstable electrode/electrolyte interfaces leads to the growth of Li dendrites and the degradation of active electrodes.Herein,we directly fluorinate alkyne-containing conjugated microporous polymers(ACMPs)microspheres with fluorine gas(F_(2))to introduce a novel fluorinated interlayer as an interfacial stabilizer in lithium metal batteries.Using density functional theory methods,it is found that as-prepared fluorinated ACMP(FACMP)has abundant partially ionic C–F bonds.The C–F bonds with electrochemical lability yield remarkable lithiophilicity during cycling.The in situ reactions between the active C–F bonds and Li ions enable transfer of lithium fluoride microcrystals to the solid electrolyte interphase(SEI)layers,guaranteeing effective ionic distribution and smooth Li deposition.Consequently,Li metal electrodes with the fluorinated interlayers demonstrate excellent cycling performances in both half-batteries and full cells with a lithium bis(trifluoromethanesulfonyl)imide electrolyte as well as a nonfluorinated lithium bis(oxalate)borate electrolyte system.This strategy is highly significant in customizable SEI layers to stabilize electrode interfaces and ensure high utilization of Li metal anodes,especially in a nonfluorinated electrolyte.展开更多
With tunable local electronic environment,high mass density of MN4sites,and ease of preparation,metal-organic conjugated coordinative polymer(CCP) with inherent electronic conductivity provides a promising alternative...With tunable local electronic environment,high mass density of MN4sites,and ease of preparation,metal-organic conjugated coordinative polymer(CCP) with inherent electronic conductivity provides a promising alternative to the well-known M-N-C electrocatalysts.Herein,the coordination reaction between Cu^(2+)and 1,2,4,5-tetraaminobenzene(TAB) was conducted on the surface of metallic Cu nanowires,forming a thin layer of CuN4-based CCP(Cu-TAB) on the Cu nanowire.More importantly,interfacial transfer of electrons from Cu core to the CuN4-based CCP nanoshell was observed within the resulting CuTAB@Cu,which was found to enrich the local electronic density of the CuN4sites.As such,the CuTAB@Cu demonstrates much improved affinity to the*COOH intermediate formed from the rate determining step;the energy barrier for C-C coupling,which is critical to convert CO_(2)into C2products,is also decreased.Accordingly,it delivers a current density of-9.1 mA cm^(-2)at a potential as high as 0.558 V(vs.RHE) in H-type cell and a Faraday efficiency of 46.4% for ethanol.This work emphasizes the profound role of interfacial interaction in tuning the local electronic structure and activating the CuN4-based CCPs for efficient electroreduction of CO_(2).展开更多
Electrocatalytic conversion of carbon dioxide to high value-added chemicals is a promising method for solving the energy crisis and global warming.Electrochemical active metal-containing conjugated polymers have been ...Electrocatalytic conversion of carbon dioxide to high value-added chemicals is a promising method for solving the energy crisis and global warming.Electrochemical active metal-containing conjugated polymers have been widely studied for heterogeneous carbon dioxide reduction.In the present contribution,we designed and synthesized a stable cobalt phthalocyanine-based conjugated polymer,named CoPPc-TFPPy-CP,and also explored its electro-catalytic application in carbon dioxide reduction to liquid products in an aqueous solution.In the catalyst,cobalt phthalocyanine acts as building blocks connected with 1,3,6,8-tetrakis(4-formyl phenyl)pyrenes via imine-linkages,leading to mesoporous formation polymers with the pore size centered at 4.1nm.And the central co-balt atoms shifted to a higher oxidation state after condensation.With these chemical and structural natures,the catalyst displayed a remarkable electrocatalytic CO_(2) reduction performance with an ethanol Faradaic efficiency of 43.25%at-1.0V vs RHE.While at the same time,the electrochemical reduction process catalyzed by cobalt phthalocyanine produced only carbon monoxide and hydrogen.To the best of our knowledge,CoPPc-TFPPy-CP is the first example among organic polymers and metal-organic frameworks that produces ethanol from CO_(2) with a remarkable selectivity.展开更多
Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of...Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment.展开更多
基金The work was financially supported by the National Natural Science Foundation of China(No.52173135,22207024)Jiangsu Specially Appointed Professorship,Leading Talents of Innovation and Entrepreneurship of Gusu(ZXL2022496)the Suzhou Science and Technology Program(SKY2022039).
文摘Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)(No.NRF-2021R1A2C2004109)the Korea Institute for Advancement of Technology(KIAT)grant funded by the Korea Government(MOTIE)(No.P0020612,2022 The Competency Development Program for Industry Specialist).
文摘Wearable biosensors have received great interest as patient-friendly diagnostic technologies because of their high flexibility and conformability.The growing research and utilization of novel materials in designing wearable biosensors have accelerated the development of point-of-care sensing platforms and implantable biomedical devices in human health care.Among numerous potential materials,conjugated polymers(CPs)are emerging as ideal choices for constructing high-performance wearable biosensors because of their outstanding conductive and mechanical properties.Recently,CPs have been extensively incorporated into various wearable biosensors to monitor a range of target biomolecules.However,fabricating highly reliable CP-based wearable biosensors for practical applications remains a significant challenge,necessitating novel developmental strategies for enhancing the viability of such biosensors.Accordingly,this review aims to provide consolidated scientific evidence by summarizing and evaluating recent studies focused on designing and fabricating CP-based wearable biosensors,thereby facilitating future research.Emphasizing the superior properties and benefits of CPs,this review aims to clarify their potential applicability within this field.Furthermore,the fundamentals and main components of CP-based wearable biosensors and their sensing mechanisms are discussed in detail.The recent advancements in CP nanostructures and hybridizations for improved sensing performance,along with recent innovations in next-generation wearable biosensors are highlighted.CPbased wearable biosensors have been—and will continue to be—an ideal platform for developing effective and user-friendly diagnostic technologies for human health monitoring.
基金the National Natural Science Foundation of China(Grant No.:51803120).
文摘Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.
基金funded by National Institutes of Health,National Institute on Aging,grant numbers,R01AG076731,R01AG049994National Institute for Arthritis and Musculoskeletal and Skin Diseases,R01AR043510,and P30 AR069655。
文摘Osteoporosis remains incurable.The most widely used antiresorptive agents,bisphosphonates(BPs),also inhibit bone formation,while the anabolic agent,teriparatide,does not inhibit bone resorption,and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects.
基金supported by the grants from the National Natural Science Foundation of China(Nos.81773566 and 21602092)Innovation Project of Medicine and Health Science and Technology of Chinese Academy of Medical Sciences(2019-I2M-5-074)+1 种基金the Funds for Fundamental Research Creative Groups of Gansu Province(No.20JR5RA310)the Fundamental Research Funds for the Central Universities(No.lzujbky-2021-38).
文摘Melittin,a classical antimicrobial peptide,is a highly potent antitumor agent.However,its significant toxicity seriously hampers its application in tumor therapy.In this study,we developed novel melittin analogs with pH-responsive,cell-penetrating and membranelytic activities by replacing arginine and lysine with histidine.After conjugation with camptothecin(CPT),CPT-AAM-1 and CPT-AAM-2 were capable of killing tumor cells by releasing CPT at low concentrations and disrupting cell membranes at high concentrations under acidic conditions.Notably,we found that the C-terminus of the melittin analogs was more suitable for drug conjugation than the N-terminus.CPT-AAM-1 significantly suppressed melanoma growth in vivo with relatively low toxicity.Collectively,the present study demonstrates that the development of antitumor drugs based on pH-responsive antimicrobial peptide-drug conjugates is a promising strategy.
文摘Enhancing catalytic activity of multi-enzyme in vitro through substrate channeling effect is promis-ing yet challenging.Herein,conjugated microporous polymers(CMPs)-scaffolded integrated en-zyme cascade systems(I-ECSs)are constructed through co-entrapping glucose oxidase(GOx)and horseradish peroxidase(HRP),in which hydrogen peroxide(H_(2)O_(2)) is the intermediate product.The interplay of low-resistance mass transfer pathway and appropriate pore wall-H_(2)O_(2) interactions facilitates the directed transfer of H_(2)O_(2),resulting in 2.4-fold and 5.0-fold elevation in catalytic activ-ity compared to free ECSs and separated ECSs,respectively.The substrate channeling effect could be regulated by altering the mass ratio of GOx to HRP.Besides,I-ECSs demonstrate excellent stabili-ties in harsh environments and multiple recycling.
基金Project supported by the Natural Science Foundation of Shandong Province,China(Grant No.ZR2020MA070).
文摘By using one-dimensional tight-binding model modified to include electron-electric field interaction and electron-electron interaction,we theoretically explore the polarization process of exciton and biexciton in cis-polyacetylene.The dynamical simulation is performed by adopting the non-adiabatic evolution approach.The results show that under the effect of moderate electric field,when the strength of electron-electron interaction is weak,the singlet exciton is stable but its polarization presents obvious oscillation.With the enhancement of interaction,it is dissociated into polaron pairs,the spin-flip of which can be observed through modulating the interaction strength.For the triplet exciton,the strong electron-electron interaction restrains its normal polarization,but it is still stable.In the case of biexciton,the strong electron-electron interaction not only dissociate it,but also flip its charge distribution.The yield of the possible states formed after the dissociation of exciton and biexciton is also calculated.
基金the National Science Fund for Distinguished Young Scholars(No.41925016)National Key Research and Development Program(No.2022YFB3903602)+1 种基金National Natural Science Foundation of China(No.42174023)the Frontier Cross Research Project of Central South University(No.2023QYJC006).
文摘The 2022 M_(W)6.7 Menyuan earthquake ruptured the western end of the Tianzhu seismic gap,providing an opportunity to study the regional seismogenic characteristics and seismic hazards.Here we use interferometric synthetic aperture radar(InSAR)and seismic data to study the mainshock rupture,early afterslip and the second largest aftershock of the 2022 Menyuan earthquake sequences.Our modeling results show that the mainshock ruptured the Lenglongling fault and the Tuolaishan fault with a maximum slip of~3 m.Rapid postseismic transient deformation occurred at the center of the Lenglongling fault.Our afterslip modeling reveals that the majority of afterslip occurred in the deeper part of the Lenglongling fault.A high-angle conjugated faulting event is found at the middle section of the Lenglongling fault.We use the stress inversion to investigate the possible triggering mechanism of the conjugated rupture event.The results indicate the maximum principal stress direction is in~222°,forming a~22°angle between the conjugated fault of second largest aftershock and the mainshock.The calculated normal stress changes indicate the region is within a pull-apart stress field,which favors such a conjugated rupturing event.Our study will help understand the rupture behavior of such kind of conjugated fault in other regions.
基金supported by the National Natural Science Foundation of China (No.72071202)the Key Laboratory of Mathematics and Engineering ApplicationsMinistry of Education。
文摘As a generalization of the two-term conjugate gradient method(CGM),the spectral CGM is one of the effective methods for solving unconstrained optimization.In this paper,we enhance the JJSL conjugate parameter,initially proposed by Jiang et al.(Computational and Applied Mathematics,2021,40:174),through the utilization of a convex combination technique.And this improvement allows for an adaptive search direction by integrating a newly constructed spectral gradient-type restart strategy.Then,we develop a new spectral CGM by employing an inexact line search to determine the step size.With the application of the weak Wolfe line search,we establish the sufficient descent property of the proposed search direction.Moreover,under general assumptions,including the employment of the strong Wolfe line search for step size calculation,we demonstrate the global convergence of our new algorithm.Finally,the given unconstrained optimization test results show that the new algorithm is effective.
文摘Heat transfers due to MHD-conjugate free convection from the isothermal horizontal circular cylinder while viscosity is a function of temperature is investigated. The governing equations of the flow and connected boundary conditions are made dimensionless using a set of non-dimensional parameters. The governing equations are solved numerically using the finite difference method. Numerical results are obtained for various values of viscosity variation parameter, Prandtl number, magnetic parameter, and conjugate conduction parameter for the velocity and the temperature within the boundary layer as well as the skin friction coefficients and heat transfer rate along the surface.
文摘Background:WHO currently recommends a single dose of typhoid conjugate vaccine(TCV)in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials.Given the decay of immunogenicity,the protection beyond 2 years is unknown.We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination.
文摘Objective:This study aimed to describe,optimize and evaluate a method for preparing multivalent conjugate vaccines by simultaneous conjugation of two different bacterial capsular polysaccharides(CPs)with tetanus toxoid(TT)as bivalent conjugates.Methods:Different molecular weights(MWs)of polysaccharides,activating agents and capsular polysaccharide/protein(CP/Pro)ratio that may influence conjugation and immunogenicity were investigated and optimized to prepare the bivalent conjugate bulk.Using the described method and optimized parameters,a 20-valent pneumococcal conjugate vaccine and a bivalent meningococcal vaccine were developed and their effectiveness was compared to that of corresponding licensed vaccines in rabbit or mouse models.Results:The immunogenicity test revealed that polysaccharides with lower MWs were better for Pn1-TT-Pn3 and MenA-TT-MenC,while higher MWs were superior for Pn4-TT-Pn14,Pn6A-TT-Pn6B,Pn7F-TT-Pn23F and Pn8-TT-Pn11A.For activating polysaccharides,1-cyano-4-dimethylaminopyridinium tetrafluoroborate(CDAP)was superior to cyanogen bromide(CNBr),but for Pn1,Pn3 and MenC,N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride(EDAC)was the most suitable option.For Pn6A-TT-Pn6B and Pn8-TT-Pn11A,rabbits immunized with bivalent conjugates with lower CP/Pro ratios showed significantly stronger CP-specific antibody responses,while for Pn4-TT-Pn14,higher CP/Pro ratio was better.Instead of interfering with the respective immunological activity,our bivalent conjugates usually induced higher IgG titers than their monovalent counterparts.Conclusion:The result indicated that the described conjugation technique was feasible and efficacious to prepare glycoconjugate vaccines,laying a solid foundation for developing extended-valent multivalent or combined conjugate vaccines without potentially decreased immune function.
基金supported by grants from the National Natural Science Foundation of China(No.81670554 and No.8217113366)the Science and Technology Plan of Wuhan City(No.2020020601012208)+2 种基金the Natural Science Fund for Distinguished Young Scholars of Hubei Province(No.2017CFA068)the National Key R&D Program of China(No.2019YFC0121505)the Science and Technology Innovation Cultivation Fund of Zhongnan Hospital of Wuhan University(No.CXPY2020042).
文摘Objective Ubiquitin conjugate enzyme E2O(UBE2O)is a ubiquitin-conjugating enzyme that has been reported to be involved in tumorigenesis.This study investigated the role of UBE2O in hepatocellular carcinoma(HCC).Methods The expression of UBE2O was detected using qRT-PCR,Western blotting,and immunohistochemical staining.Cell proliferation and Transwell assays were used to detect proliferation,migration,and invasion of HCC cells,respectively.Bioinformatic analysis was performed to analyze the relationship between UBE2O and the clinical features,prognosis,and immune cell infiltration of HCC.Results UBE2O was significantly over-expressed in HCC tissues.High expression of UBE2O was associated with poor tumor grade and poor prognosis.Functional experiments showed that down-regulation of UBE2O inhibited HCC cell proliferation,migration,and invasion.Co-expression gene analysis and gene set enrichment analysis showed that UBE2O was associated with protein hydrolysis,cell cycle,and cancer-related pathways in HCC.The results of immune analysis revealed that the expression of UBE2O was positively correlated with the immune infiltration and expression of immune-related chemokines of HCC.Conclusions UBE2O is significantly correlated with the prognosis of HCC and may be a valuable prognostic biomarker for HCC.
基金Supported by Guangdong Provincial Key-Area Research and Development Program(Grant No.2019B090917002).
文摘A three-dimensional conjugate tooth surface design method for Harmonic Drive with a double-circular-arc tooth profle is proposed. The radial deformation function of the fexspline (FS), obtained through Finite Element (FE) analysis, is incorporated into the kinematics model. By analyzing the FS tooth enveloping process, the optimization of the overlapping conjugate tooth profle is achieved. By utilizing the hobbing process, the three-dimensional machinable tooth surface of FS can be acquired. Utilizing the coning deformation of the FS, simulations are conducted to analyze the multi-section assembly and meshing motion of the machinable tooth surface. The FE method is utilized to analyze and compare the loaded contact characteristics. Results demonstrate that the proposed design method can achieve an internal gear pair consisting of a circular spline with a spur gear tooth surface and the FS with a machinable tooth surface. With the rated torque, approximately 24% of the FS teeth are engaged in meshing, and more than 4/5 of the tooth surface in the axial direction carries the load. The contact patterns, maximum contact pressure, and transmission error of the machinable tooth surface are 227.2%, 40.67%, and 71.24% of those on the spur gear tooth surface, respectively. It clearly demonstrates exceptional transmission performance.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81974500,81773678)the CAMS Innovation Fund for Medical Sciences(Grant No.:2022-I2M-2-001).
文摘Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.
基金supported by Ministry of Science and Technology(2018YFA0208504)the Beijing Natural Science Foundation(JQ21006,2212045)+6 种基金National Natural Science Foundation of China(92163128,52073016)supported by the Fundamental Research Funds for the Central Universities(buctrc201828,XK1802-2)Open Project of State Key Laboratory of Organic-Inorganic Composites(oic-202201006)Open Project of State Key Laboratory of Supramolecular Structure and Materials(sklssm2023010)L.Ding thanks the National Key Research and Development Program of China(2022YFB3803300)the open research fund of Songshan Lake Materials Laboratory(2021SLABFK02)he National Natural Science Foundation of China(21961160720).
文摘Insulating polymers are characterized by a predominantlyσ-covalent structure,which localize electrons in the atoms and exhibit dielectricity.Insulating polymers typically adopt a more linear and extended conformation,as the repeating units are connected by single covalent bonds,resulting in a relatively straight and extended chain structure.For most insulating polymers,the contour length(L_(c))is significantly larger than their persistence length(Lp)due to the rotation of C−C single bonds(Fig.1(a)).Consequently,this leads to a flexible,random-coil chain conformation.This structural feature contributes to the great mechanical durability and resistance to crack initiation during stretching or bending processes.In contrast,conjugated polymers possess aπ-conjugated molecular structure,allowing electron mobility along the main chain,called delocalization,which imparts semiconducting properties[1,2].The presence of rigid,alternating single and multiple bonds results in comparable Lc and Lp,thereby yielding a stiff or semi-flexible conformation(Fig.1(b))[3,4].As a consequence,most conjugated polymers are prone to fracture under low strain levels(<10%)[5−7].
基金Science Foundation for Distinguished Young Scholars in Tianjin,Grant/Award Number:19JCJQJC61700National Natural Science Foundation of China,Grant/Award Numbers:51773147,51973151,52130303National Key R&D Program of China,Grant/Award Number:2022YFB3805702。
文摘Lithium(Li)metal anodes have attracted extensive attention due to their ultrahigh theoretical capacity and low potential.However,the uneven deposition of Li near the unstable electrode/electrolyte interfaces leads to the growth of Li dendrites and the degradation of active electrodes.Herein,we directly fluorinate alkyne-containing conjugated microporous polymers(ACMPs)microspheres with fluorine gas(F_(2))to introduce a novel fluorinated interlayer as an interfacial stabilizer in lithium metal batteries.Using density functional theory methods,it is found that as-prepared fluorinated ACMP(FACMP)has abundant partially ionic C–F bonds.The C–F bonds with electrochemical lability yield remarkable lithiophilicity during cycling.The in situ reactions between the active C–F bonds and Li ions enable transfer of lithium fluoride microcrystals to the solid electrolyte interphase(SEI)layers,guaranteeing effective ionic distribution and smooth Li deposition.Consequently,Li metal electrodes with the fluorinated interlayers demonstrate excellent cycling performances in both half-batteries and full cells with a lithium bis(trifluoromethanesulfonyl)imide electrolyte as well as a nonfluorinated lithium bis(oxalate)borate electrolyte system.This strategy is highly significant in customizable SEI layers to stabilize electrode interfaces and ensure high utilization of Li metal anodes,especially in a nonfluorinated electrolyte.
基金The National Key Research and Development Program of China(2021YFA1502000 and 2022YFA1505300)the National Natural Science Foundation of China (22288102, 22072124)+1 种基金support from Beijing Synchrotron Radiation Facility (1W1B, BSRF)China Scholarship Council for the financial support。
文摘With tunable local electronic environment,high mass density of MN4sites,and ease of preparation,metal-organic conjugated coordinative polymer(CCP) with inherent electronic conductivity provides a promising alternative to the well-known M-N-C electrocatalysts.Herein,the coordination reaction between Cu^(2+)and 1,2,4,5-tetraaminobenzene(TAB) was conducted on the surface of metallic Cu nanowires,forming a thin layer of CuN4-based CCP(Cu-TAB) on the Cu nanowire.More importantly,interfacial transfer of electrons from Cu core to the CuN4-based CCP nanoshell was observed within the resulting CuTAB@Cu,which was found to enrich the local electronic density of the CuN4sites.As such,the CuTAB@Cu demonstrates much improved affinity to the*COOH intermediate formed from the rate determining step;the energy barrier for C-C coupling,which is critical to convert CO_(2)into C2products,is also decreased.Accordingly,it delivers a current density of-9.1 mA cm^(-2)at a potential as high as 0.558 V(vs.RHE) in H-type cell and a Faraday efficiency of 46.4% for ethanol.This work emphasizes the profound role of interfacial interaction in tuning the local electronic structure and activating the CuN4-based CCPs for efficient electroreduction of CO_(2).
基金the financial support from the National Natural Science Foundation of China(22005099)。
文摘Electrocatalytic conversion of carbon dioxide to high value-added chemicals is a promising method for solving the energy crisis and global warming.Electrochemical active metal-containing conjugated polymers have been widely studied for heterogeneous carbon dioxide reduction.In the present contribution,we designed and synthesized a stable cobalt phthalocyanine-based conjugated polymer,named CoPPc-TFPPy-CP,and also explored its electro-catalytic application in carbon dioxide reduction to liquid products in an aqueous solution.In the catalyst,cobalt phthalocyanine acts as building blocks connected with 1,3,6,8-tetrakis(4-formyl phenyl)pyrenes via imine-linkages,leading to mesoporous formation polymers with the pore size centered at 4.1nm.And the central co-balt atoms shifted to a higher oxidation state after condensation.With these chemical and structural natures,the catalyst displayed a remarkable electrocatalytic CO_(2) reduction performance with an ethanol Faradaic efficiency of 43.25%at-1.0V vs RHE.While at the same time,the electrochemical reduction process catalyzed by cobalt phthalocyanine produced only carbon monoxide and hydrogen.To the best of our knowledge,CoPPc-TFPPy-CP is the first example among organic polymers and metal-organic frameworks that produces ethanol from CO_(2) with a remarkable selectivity.
文摘Over the past several decades, there has been a significant surge in the development of Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a multifaceted challenge, requiring the precise orchestration of various elements such as antigens, antibodies, linkers, and payloads. While ADCs aim to target tumor cells specifically, several antigens can also be found in regular tissues, potentially compromising the specificity of ADCs in therapeutic applications. The complexity extends to antibody selection, necessitating effective targeting of the desired antigen and ensuring compatibility with linkers for effective payload delivery. Additionally, the linker and payload combination are critical for the ADC’s therapeutic efficiency, balancing stability in circulation and timely payload release upon target binding. ADC doses must be safe for normal tissues while ensuring the released payloads are effective. The success of ADCs is attributed to their unmatched efficacy compared to traditional chemotherapy agents. The current research article aims to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer therapies. A brief discussion on the basics of ADCs, regulatory approach, overview, and technical complexities for quantification is presented. This review also summarizes recently approved ADCs and introduces the concepts of antibodies, linkers, and payloads. The article also outlines cancer-specific ADCs currently in late-stage clinical trials for cancer treatment.
