Temozolomide(TMZ)is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme.Despite being a highly potent molecule,TMZ poses several limitations,including short half-life,rapid metab...Temozolomide(TMZ)is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme.Despite being a highly potent molecule,TMZ poses several limitations,including short half-life,rapid metabolism,low brain bioavailability and dosedependent toxicities.Attempts have been made to improve the delivery of TMZ that mainly exhibited nominal therapeutic outcomes.In the current study,we have conjugated TMZ to mPEG-b-P(CB-{g-COOH})copolymer to obtain mPEG-b-P(CB-{g-COOH;g-TMZn})that demonstrated improvement in stability and efficacy.Further,a hybrid TMZ nanoconjugate formulation was developed using mPEG-b-P(CB-{g-COOH;g-TMZ_(40)})and mPEG-polylactic acid(mPEG-PLA)showed an average size of 105.7 nm with narrow PDI of<0.2 and TMZ loading of 21.6%.Stability was assessed under physiological conditions wherein TMZ was found to be stable with a half-life of∼194 h compared to 1.8 h for free TMZ.The Hybrid TMZ nanoconjugates showed improved intracellular uptake and reduced IC_(50)values in C6 and U87MG glioma cells.Furthermore,they exhibited better in vivo therapeutic outcome,i.e.,reduced brain weight,hemispherical width ratio and improved survival rate in C6-cell induced orthotropic glioma model in Sprague Dawley rats compared to the free TMZtreated and positive control animals.Histopathological evaluation also revealed reduced cell infiltration in the lungs and reduced toxicity in major organs.Overall,the hybrid nanoconjugates of TMZ significantly improved its stability and efficacy in the GBM model,thereby opening newer avenues for treatment.展开更多
The light-driven CO_(2)reduction reaction(CO_(2)RR)to CO is a very effective way to address global warming.To avoid competition with water photolysis,metal-free gas-solid CO_(2)RR catalysts should be investigated.Cova...The light-driven CO_(2)reduction reaction(CO_(2)RR)to CO is a very effective way to address global warming.To avoid competition with water photolysis,metal-free gas-solid CO_(2)RR catalysts should be investigated.Covalent organic frameworks(COFs)offer a promising approach for CO_(2)transformation but lack high efficiency and selectivity in the absence of metals.Here,we have incorporated a pyridine nitrogen component into the imine-COF conjugated structure(Tp Pym).This innovative system has set a record of producing a CO yield of 1565μmol g^(-1)within 6 h.The soft X-ray absorption fine structure measurement proves that Tp Pym has both better conjugation and electron cloud enrichment.The electronic structure distribution delays the charge-carrier recombination,as evidenced by femtosecond transient absorption spectroscopy.The energy band diagram and theoretical calculation show that the conduction-band potential of Tp Pym is lower and the reduction reaction of CO_(2)to CO is more likely to occur.展开更多
Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors c...Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors consume less power,but lack the capability to resolve static stimuli.Here,we address this issue by utilizing the unique polarization chemistry of conjugated polymers for the first time and propose a new type of bioinspired,passive,and bio-friendly tactile sensors for resolving both static and dynamic stimuli.Specifically,to emulate the polarization process of natural sensory cells,conjugated polymers(including poly(3,4-ethylenedioxythiophen e):poly(styrenesulfonate),polyaniline,or polypyrrole)are controllably polarized into two opposite states to create artificial potential differences.The controllable and reversible polarization process of the conjugated polymers is fully in situ characterized.Then,a micro-structured ionic electrolyte is employed to imitate the natural ion channels and to encode external touch stimulations into the variation in potential difference outputs.Compared with the currently existing tactile sensing devices,the developed tactile sensors feature distinct characteristics including fully organic composition,high sensitivity(up to 773 mV N^(−1)),ultralow power consumption(nW),as well as superior bio-friendliness.As demonstrations,both single point tactile perception(surface texture perception and material property perception)and two-dimensional tactile recognitions(shape or profile perception)with high accuracy are successfully realized using self-defined machine learning algorithms.This tactile sensing concept innovation based on the polarization chemistry of conjugated polymers opens up a new path to create robotic tactile sensors and prosthetic electronic skins.展开更多
In this paper,we propose a three-term conjugate gradient method for solving unconstrained optimization problems based on the Hestenes-Stiefel(HS)conjugate gradient method and Polak-Ribiere-Polyak(PRP)conjugate gradien...In this paper,we propose a three-term conjugate gradient method for solving unconstrained optimization problems based on the Hestenes-Stiefel(HS)conjugate gradient method and Polak-Ribiere-Polyak(PRP)conjugate gradient method.Under the condition of standard Wolfe line search,the proposed search direction is the descent direction.For general nonlinear functions,the method is globally convergent.Finally,numerical results show that the proposed method is efficient.展开更多
Small interfering RNA(siRNA),a promising revolutionary therapy,faces delivery obstacles due to its poor targeting,strong charge negativity and macromolecular nature.Clinical-approved siRNAs can now only be delivered t...Small interfering RNA(siRNA),a promising revolutionary therapy,faces delivery obstacles due to its poor targeting,strong charge negativity and macromolecular nature.Clinical-approved siRNAs can now only be delivered to the liver mediated by the chemically conjugated N-acetylgalactosamine(GalNAc)ligand,the conjugate can be effectively uptaken into cells through interaction with asialoglycoprotein receptor(ASGPR)highly expressed on liver hepatocytes.To further explore an efficient non-hepatic targeted delivery strategy,in this study,we designed a delivery system that chemically conjugated p53 siRNA to renal tubular cell-targeting peptides for targeting the kidney,which was suitable for industrial transformation.Results showed that peptide-siRNA conjugate could specifically enter renal tubular epithelial cells and silence target genes.In cisplatin-induced acute kidney injury(AKI)mice,peptide-siRNA conjugate blocked the p53-mediated apoptotic pathway and alleviated renal damage.The innovative proposed system to conjugate kidney-targeting peptides with siRNA achieved the efficient kidney-targeted delivery of si RNA and provided a prospective choice for treating AKI.展开更多
Bromocresol green(BCG)and malachite green(MG)are water-soluble toxic organic dyes with adverse health and environmental implications.This study presented a conjugate imprinted adsorbent(CIA)synthesized by incorporatin...Bromocresol green(BCG)and malachite green(MG)are water-soluble toxic organic dyes with adverse health and environmental implications.This study presented a conjugate imprinted adsorbent(CIA)synthesized by incorporating trimethoprim vanillin ligand into a highly crosslinked polymer,designed for the efficient removal of BCG and MG from wastewater.Characterization of CIA involved X-ray powder diffraction,Fourier transform infrared,and scanning electron microscopic analyses.Batch adsorption processes were conducted to evaluate the adsorption characteristics of CIA,with focuses on the effects of contact time,initial dye concentration,pH,and temperature.The molecularly imprinted polymers(MIPs)achieved removal efficiencies of 99.27%and 98.99%at equilibrium for BCG and MG adsorption,respectively.The non-imprinted polymers(NIPs)demonstrated BCG and MG adsorption efficiencies of 51.52%and 62.90%at equilibrium,respectively.Kinetic and isotherm models were employed to elucidate the BCG and MG adsorption mechanisms.The thermodynamic results indicated non-spontaneous and spontaneous reactions for BCG and MG adsorption on MIPs under the examined temperature conditions.The adsorbent exhibited sustained high removal efficiency through five reuse cycles,with no apparent reduction in adsorption performance.Validation of the adsorbent using real textile wastewater samples achieved BCG and MG removal efficiencies of 85.5%-87.5%.The adsorbent outperformed previously reported materials in BCG and MG adsorption.The synthesized CIA is a promising adsorbent for BCG and MG dye removal,contributing to water sustainability.展开更多
DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expressi...DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).展开更多
Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst m...Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst min-imising off-target effects.This review provides a comprehensive analysis of ADCs,encompassing their structural components,mechanisms of action,and clinical applications.It also examines recent technological advancements,particularly in antibody engineering and linker design,aimed at enhancing therapeutic efficacy and safety.The current clinical landscape is outlined,highlighting approved ADCs and promising candidates in clinical trials,while also addressing key challenges such as stability,half-life,and systemic toxicity.This review is based on an extensive literature survey from major databases such as Scopus and Web of Science,with a focus on keywords like“antibody-drug conjugates”,“ADC advancements”,and“next-generation ADC technologies”.By integrating insights from both preclinical and clinical perspectives,we highlight the transformative potential of ADCs in advancing modern cancer therapy.展开更多
Sonodynamic therapy(SDT)is garnering considerable attention as a promising treatment for deep-seated tumors because of its strong tissue penetration ability,non-invasiveness,and controllability.However,the SDT efficie...Sonodynamic therapy(SDT)is garnering considerable attention as a promising treatment for deep-seated tumors because of its strong tissue penetration ability,non-invasiveness,and controllability.However,the SDT efficiency of traditional sonosensitizers including porphyrins and their derivatives are limited due to their poor water dissolubility,high aggregation,and low reactive oxygen species(ROS)production efficiency.Consequently,it is crucial to develop novel sonosensitizers with high yields of ROS,outstanding water solubility,and good biocompatibility.Herein,we constructed a new platform for SDT based on unimolecular porphyrin derivatives OPV-C_(3)-TPP.The probe OPV-C_(3)-TPP was synthesized by covalently linking conjugated oligomers(OPV)with 5,10,15,20-tetra(4-aminophenyl)porphyrin(TAPP).The introduction of OPV greatly improves the water solubility of the porphyrins and reduces the self-aggregation of the porphyrins.In addition,OPV-C_(3)-TPP has good intramolecular energy transfer efficiency,thus enhancing the yield of ROS.The experimental results show that OPV-C_(3)-TPP exhibits excellent ROS generation capacity under ultrasound(US)irradiation,which leads to apoptosis and necrosis of tumor cells.In vivo tumor growth is also significantly inhibited in the OPV-C_(3)-TPP t US group,exhibiting better SDT effects than TAPP.Therefore,the unimolecular OPV-C_(3)-TPP can be used as a potential sonosensitizer,providing a promising SDT for deep-tissue tumors.展开更多
The global scarcity of clean water is an escalating issue due to climate change,population growth,and pollution.Traditional water purification technologies,while effective,often require significant energy input and co...The global scarcity of clean water is an escalating issue due to climate change,population growth,and pollution.Traditional water purification technologies,while effective,often require significant energy input and complex infrastructure,limiting their accessibility.This review explores the use of conjugated polymer hydrogels as a promising solution for solar water purification.Conjugated polymer hydrogels offer unique advantages,including high photothermal conversion efficiency,effective heat management,and rapid water transport,which are crucial for efficient solar-driven water evaporation.By leveraging the properties of these hydrogels,it is possible to significantly reduce the energy required for water evaporation,making them a cost-effective and scalable option for producing potable water from seawater or wastewater.This review discusses the principles of solar water purification using conjugated polymer hydrogels,strategies to enhance their performance through material and structural design,and their applications in pollutant removal and desalination.Additionally,it addresses the advantages and limitations of these materials,providing insights into their potential future development and applications in sustainable water purification technologies.展开更多
Precise control of luminescence in carbon quantum dots(CQDs),from single-color to full-color emission,is crucial for advancing their applications in biomedical imaging and display technologies.While CQDs luminescence ...Precise control of luminescence in carbon quantum dots(CQDs),from single-color to full-color emission,is crucial for advancing their applications in biomedical imaging and display technologies.While CQDs luminescence is primarily influenced by conjugated domains and surface states,the underlying interaction mechanisms remain poorly understood.This study explores a graded nitro-engineering approach to simultaneously regulate surface states and sp^(2)conjugated domains through nitro(-NO_(2))modulation,enabling comprehensive color tuning.Using o-phenylenediamine(o-PD)as the carbon source and adjusting nitric acid(HNO_(3))concentrations,we synthesized tricolor-emitting nitro-functionalized CQDs(NO_(2)-CQDs).At lower-NO_(2) concentrations,luminescence is mainly influenced by surface states,where the electron-withdrawing effect of-NO_(2) enhancesπ-electron delocalization and stabilizes sp^(2)conjugation.With increasing-NO_(2) content,the lowest unoccupied molecular orbital(LUMO)energy level decreases(-2.12 eV to-3.39 eV),resulting in a red-shift in fluorescence.At higher-NO_(2) concentrations,luminescence is primarily affected by the sp^(2)conjugated domain,where steric hindrance reduces molecular planarity and conjugation,leading to a blue-shift in fluorescence as the sp^(2)domain size decreases(4.03 nm to 2.83 nm).Combining experimental results with density functional theory(DFT)calculations,we reveal the dual role of-NO2in modulating CQDs luminescence,an approach rarely achieved through surface functionalization.This work presents a novel strategy for precise tuning of CQDs luminescence across the visible spectrum.展开更多
Conjugated polymers(CPs)have emerged as an interesting class of materials in modern electronics and photonics,characterized by their unique delocalizedπ-electron systems that confer high flexibility,tunable electroni...Conjugated polymers(CPs)have emerged as an interesting class of materials in modern electronics and photonics,characterized by their unique delocalizedπ-electron systems that confer high flexibility,tunable electronic properties,and solution processability.These organic polymers present a compelling alternative to traditional inorganic semiconductors,offering the potential for a new generation of optoelectronic devices.This review explores the evolving role of CPs,exploring the molecular design strategies and innovative approaches that enhance their optoelectronic properties.We highlight notable progress toward developing faster,more efficient,and environmentally friendly devices by analyzing recent advancements in CP-based devices,including organic photovoltaics,field-effect transistors,and nonvolatile memories.The integration of CPs in flexible sustainable technologies underscores their potential to revolutionize future electronic and photonic systems.As ongoing research pushes the frontiers of molecular engineering and device architecture,CPs are poised to play an essential role in shaping next-generation technologies that prioritize performance,sustainability,and adaptability.展开更多
Exploration of new green polymerization strategies for the construction of conjugated polymers is important but challengeable.In this work,a multicomponent polymerization of acetylarenes,alkynones and ammonium acetate...Exploration of new green polymerization strategies for the construction of conjugated polymers is important but challengeable.In this work,a multicomponent polymerization of acetylarenes,alkynones and ammonium acetate for in situ construction of conjugated poly(triarylpyridine)s was developed.The polymerization reactions of diacetylarenes,aromatic dialkynones and NH_(4)OAc were performed in dimethylsulfoxide(DMSO)under heating in the presence of potassium tert-butoxide(t-BuOK),affording four conjugated poly(2,4,6-triarylpyridine)s(PTAPs)in satisfactory yields.The resulting PTAPs have good solubility in common organic solvents and high thermal stability with 5%weight loss temperatures reaching up to 460℃.They are also electrochemically active.The PTAPs incorporating tetraphenylethene units manifest aggregation-induced emission features.Moreover,through simply being doped into poly(vinyl alcohol)(PVA)matrix,the polymer and model compound containing triphenylamine moieties exhibit room-temperature phosphorescence properties with ultralong lifetimes up to 696.2 ms and high quantum yields up to 28.7%.This work not only provides a facile green synthetic route for conjugated polymers but also offers new insights into the design of advanced materials with unique photophysical properties.展开更多
Adsorption-photocatalytic degradation of organic pollutants in water is an advantageous method for environmental purification.Herein,a feasible strategy is developed to construct a novel dual S-scheme heterojunctions ...Adsorption-photocatalytic degradation of organic pollutants in water is an advantageous method for environmental purification.Herein,a feasible strategy is developed to construct a novel dual S-scheme heterojunctions Cu_(7)S_(4)-TiO_(2)-conjugated polymer with a donor-acceptor structure.There are abundant adsorption active sites for adsorption in the porous structure of the composites,which can rapidly capture pollutants through hydrogen bonding and π-π interactions.In addition,the dual S-scheme heterojunctions effectively improve carrier separation while maintaining a strong redox ability.Thus,the optimized 1.5% CST-130 catalysts can adsorb 71% of 20 ppm BPA in 15 min and completely remove it within 30 min with high adsorption capacity and photodegradation efficiency.Therefore,this study provides a new inspiration for synergistic adsorption and degradation of BPA and the construction of dual S-scheme heterojunction.展开更多
The evolution of cancer therapies has highlighted the limitations of traditional chemotherapy,particularly its lack of specificity and off-target toxicities,driving the development of targeted treatments like small mo...The evolution of cancer therapies has highlighted the limitations of traditional chemotherapy,particularly its lack of specificity and off-target toxicities,driving the development of targeted treatments like small molecule-drug conjugates(SMDCs).SMDCs offer distinct advantages over antibody-drug conjugates(ADCs),including simpler synthesis,lower production costs,and improved solid tumor penetration due to their smaller size.However,challenges remain,such as a limited variety of targeting ligands and the complexity of optimizing selectivity and efficacy within the tumor microenvironment.This review focuses on key aspects such as mechanisms of action,biomarker selection,and the optimization of each component of SMDCs.It also covers SMDCs that have been approved or are currently under active clinical trials,while providing insights into future developments in this promising field of targeted cancer therapies.展开更多
A structural conjugate(HOC)of polysaccharide,hyaluronic acid(HA)with different ratios of oleic acid(OA)via cystamine(CYS)linker as a new ocular biomaterial was developed.The HOCs with controlled degrees of substitutio...A structural conjugate(HOC)of polysaccharide,hyaluronic acid(HA)with different ratios of oleic acid(OA)via cystamine(CYS)linker as a new ocular biomaterial was developed.The HOCs with controlled degrees of substitution of OA(4.6%,8.3%and 12.2%)were synthesized to form self-assembled HA-CYS-OA nanoparticles(HONs,HON1,HON2,HON3).A poorly water-soluble cyclosporine A(CsA)to be used for the treatment of multifactorial dry eye disease(DED)was chosen as model drug.CsA-loaded HONs exhibited improved solution transparency via solubilizing capacity of HON,and increased in vitro drug permeation compared to Restasis®.The physicochemical properties of CsA-loaded HONs such as nano behaviors,solution transparency,drug release,drug permeation and ocular cytocompatibility were highly variable according to the ratios of OA substitution.Interestingly,this CsA-loaded HON1 as optimal ocular nanoformulation showed markedly augmentedmacrophage polarization into the M2 phenotype,downregulated the expression of proinflammatory cytokines levels in LPS-induced M1 macrophage,and effectively inhibited VEGF-induced endothelial cell proliferation and capillary-like tube formation by the synergistic effect of CsA and HON1 containing OA at the same time.Collectively,the current fatty acid conjugated to HA,named fattigation platform,providing the roles and physicochemical properties via structural features of HA could be a promising co-delivery strategy of drug and fatty acid for DED and other ophthalmic disease treatments.展开更多
Urothelial carcinoma(UC)is the 9th most common and the 13th most deadly cancer worldwide1.Despite the availability of platinum-based chemotherapy and immune checkpoint inhib-itors(ICIs),the 5-year survival rate of pat...Urothelial carcinoma(UC)is the 9th most common and the 13th most deadly cancer worldwide1.Despite the availability of platinum-based chemotherapy and immune checkpoint inhib-itors(ICIs),the 5-year survival rate of patients with metastatic UC(mUC)remains poor(10-15%)2.展开更多
Exploration of efficient and stable photocatalysts to mimic natural leaves for the conversion of atmospheric CO_(2)into hydrocarbons utilizing solar light is very important but remains a major challenge.Herein,we repo...Exploration of efficient and stable photocatalysts to mimic natural leaves for the conversion of atmospheric CO_(2)into hydrocarbons utilizing solar light is very important but remains a major challenge.Herein,we report the design of four novel metal-salen-incorporated conjugated microporous polymers as robust artificial leaves for photoreduction of atmospheric CO_(2)with gaseous water.Owing to the rich nitrogen and oxygen moieties in the polymeric frameworks,they show a maximum CO_(2)adsorption capacity of 46.1 cm3 g^(−1)and adsorption selectivity for CO_(2)/N_(2)of up to 82 at 273 K.Under air atmosphere and simulated solar light(100mWcm^(−2)),TEPT-Zn shows an excellent CO yield of 304.96μmol h^(−1)g^(−1)with a selectivity of approximately 100%,which represents one of the best results in terms of organic photocatalysts for gas-phase CO_(2)photoreduction so far.Furthermore,only small degradation in the CO yield is observed even after 120-h continuous illumination.More importantly,a good CO yield of 152.52μmol g^(−1)was achieved by directly exposing the photocatalytic reaction of TEPT-Zn in an outdoor environment for 3 h(25-28℃,52.3±7.9mWcm^(−2)).This work provides an avenue for the continued development of advanced polymers toward gas-phase photoconversion of CO_(2)from air.展开更多
Discoidin domain receptor 1(DDR1)is overexpressed in various tumors,such as triple-negative breast cancer(TNBC),and is rarely expressed in normal tissues.These characteristics make DDR1 a preferable target candidate f...Discoidin domain receptor 1(DDR1)is overexpressed in various tumors,such as triple-negative breast cancer(TNBC),and is rarely expressed in normal tissues.These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate(ADC)for targeted therapy.Here,we investigated the preparation and preclinical efficacy of DDR1-DX8951,an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly(GGFG)linker.The anti-DDR1 monoclonal antibody was coupled to DX8951(i.e.,DDR1-DX8951),producing the targeted therapy ADC.The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models.DDR1-DX8951 can specifically target DDR1,be quickly internalized by TNBC cells,and reduce the viability of TNBC cells in vitro.The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models.Importantly,our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvironment(TME)of TNBC.Taken together,this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.展开更多
The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer i...The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer is the most common malignant tumor in women and one of the leading causes of cancer-related deaths.展开更多
基金support to DC through a research grant (BT/PR22123/NNT/28/1120/2016)support through DST-INSPIRE fellowship to PS (DST/INSPIRE Fellowship/2018/IF180652)
文摘Temozolomide(TMZ)is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme.Despite being a highly potent molecule,TMZ poses several limitations,including short half-life,rapid metabolism,low brain bioavailability and dosedependent toxicities.Attempts have been made to improve the delivery of TMZ that mainly exhibited nominal therapeutic outcomes.In the current study,we have conjugated TMZ to mPEG-b-P(CB-{g-COOH})copolymer to obtain mPEG-b-P(CB-{g-COOH;g-TMZn})that demonstrated improvement in stability and efficacy.Further,a hybrid TMZ nanoconjugate formulation was developed using mPEG-b-P(CB-{g-COOH;g-TMZ_(40)})and mPEG-polylactic acid(mPEG-PLA)showed an average size of 105.7 nm with narrow PDI of<0.2 and TMZ loading of 21.6%.Stability was assessed under physiological conditions wherein TMZ was found to be stable with a half-life of∼194 h compared to 1.8 h for free TMZ.The Hybrid TMZ nanoconjugates showed improved intracellular uptake and reduced IC_(50)values in C6 and U87MG glioma cells.Furthermore,they exhibited better in vivo therapeutic outcome,i.e.,reduced brain weight,hemispherical width ratio and improved survival rate in C6-cell induced orthotropic glioma model in Sprague Dawley rats compared to the free TMZtreated and positive control animals.Histopathological evaluation also revealed reduced cell infiltration in the lungs and reduced toxicity in major organs.Overall,the hybrid nanoconjugates of TMZ significantly improved its stability and efficacy in the GBM model,thereby opening newer avenues for treatment.
基金supported by the National Natural Science Foundation of China(Nos.22375031,22202037,22472023)the Fundamental Research Funds for the Central Universities(Nos.2412023YQ001,2412023QD019,2412024QD014)+1 种基金supported by grants from the seventh batch of Jilin Province Youth Science and Technology Talent Lifting Project(No.QT202305)Science and Technology Development Plan Project of Jilin Province,China(No.20240101192JC)。
文摘The light-driven CO_(2)reduction reaction(CO_(2)RR)to CO is a very effective way to address global warming.To avoid competition with water photolysis,metal-free gas-solid CO_(2)RR catalysts should be investigated.Covalent organic frameworks(COFs)offer a promising approach for CO_(2)transformation but lack high efficiency and selectivity in the absence of metals.Here,we have incorporated a pyridine nitrogen component into the imine-COF conjugated structure(Tp Pym).This innovative system has set a record of producing a CO yield of 1565μmol g^(-1)within 6 h.The soft X-ray absorption fine structure measurement proves that Tp Pym has both better conjugation and electron cloud enrichment.The electronic structure distribution delays the charge-carrier recombination,as evidenced by femtosecond transient absorption spectroscopy.The energy band diagram and theoretical calculation show that the conduction-band potential of Tp Pym is lower and the reduction reaction of CO_(2)to CO is more likely to occur.
基金financially supported by the Sichuan Science and Technology Program(2022YFS0025 and 2024YFFK0133)supported by the“Fundamental Research Funds for the Central Universities of China.”。
文摘Tactile perception plays a vital role for the human body and is also highly desired for smart prosthesis and advanced robots.Compared to active sensing devices,passive piezoelectric and triboelectric tactile sensors consume less power,but lack the capability to resolve static stimuli.Here,we address this issue by utilizing the unique polarization chemistry of conjugated polymers for the first time and propose a new type of bioinspired,passive,and bio-friendly tactile sensors for resolving both static and dynamic stimuli.Specifically,to emulate the polarization process of natural sensory cells,conjugated polymers(including poly(3,4-ethylenedioxythiophen e):poly(styrenesulfonate),polyaniline,or polypyrrole)are controllably polarized into two opposite states to create artificial potential differences.The controllable and reversible polarization process of the conjugated polymers is fully in situ characterized.Then,a micro-structured ionic electrolyte is employed to imitate the natural ion channels and to encode external touch stimulations into the variation in potential difference outputs.Compared with the currently existing tactile sensing devices,the developed tactile sensors feature distinct characteristics including fully organic composition,high sensitivity(up to 773 mV N^(−1)),ultralow power consumption(nW),as well as superior bio-friendliness.As demonstrations,both single point tactile perception(surface texture perception and material property perception)and two-dimensional tactile recognitions(shape or profile perception)with high accuracy are successfully realized using self-defined machine learning algorithms.This tactile sensing concept innovation based on the polarization chemistry of conjugated polymers opens up a new path to create robotic tactile sensors and prosthetic electronic skins.
基金Supported by the Science and Technology Project of Guangxi(Guike AD23023002)。
文摘In this paper,we propose a three-term conjugate gradient method for solving unconstrained optimization problems based on the Hestenes-Stiefel(HS)conjugate gradient method and Polak-Ribiere-Polyak(PRP)conjugate gradient method.Under the condition of standard Wolfe line search,the proposed search direction is the descent direction.For general nonlinear functions,the method is globally convergent.Finally,numerical results show that the proposed method is efficient.
基金supported by the National Key Technologies Research and Development Plan(No.2021YFE0106900)the National Natural Science Foundation of China(No.82173769)+1 种基金the Basic Research Cooperation Project of Beijing,Tianjin,Hebei from the Natural Science Foundation of Tianjin(No.20JCZXJC00070)the Applied Basic Research Multi-investment Foundation of Tianjin(No.21JCYBJC01540)。
文摘Small interfering RNA(siRNA),a promising revolutionary therapy,faces delivery obstacles due to its poor targeting,strong charge negativity and macromolecular nature.Clinical-approved siRNAs can now only be delivered to the liver mediated by the chemically conjugated N-acetylgalactosamine(GalNAc)ligand,the conjugate can be effectively uptaken into cells through interaction with asialoglycoprotein receptor(ASGPR)highly expressed on liver hepatocytes.To further explore an efficient non-hepatic targeted delivery strategy,in this study,we designed a delivery system that chemically conjugated p53 siRNA to renal tubular cell-targeting peptides for targeting the kidney,which was suitable for industrial transformation.Results showed that peptide-siRNA conjugate could specifically enter renal tubular epithelial cells and silence target genes.In cisplatin-induced acute kidney injury(AKI)mice,peptide-siRNA conjugate blocked the p53-mediated apoptotic pathway and alleviated renal damage.The innovative proposed system to conjugate kidney-targeting peptides with siRNA achieved the efficient kidney-targeted delivery of si RNA and provided a prospective choice for treating AKI.
文摘Bromocresol green(BCG)and malachite green(MG)are water-soluble toxic organic dyes with adverse health and environmental implications.This study presented a conjugate imprinted adsorbent(CIA)synthesized by incorporating trimethoprim vanillin ligand into a highly crosslinked polymer,designed for the efficient removal of BCG and MG from wastewater.Characterization of CIA involved X-ray powder diffraction,Fourier transform infrared,and scanning electron microscopic analyses.Batch adsorption processes were conducted to evaluate the adsorption characteristics of CIA,with focuses on the effects of contact time,initial dye concentration,pH,and temperature.The molecularly imprinted polymers(MIPs)achieved removal efficiencies of 99.27%and 98.99%at equilibrium for BCG and MG adsorption,respectively.The non-imprinted polymers(NIPs)demonstrated BCG and MG adsorption efficiencies of 51.52%and 62.90%at equilibrium,respectively.Kinetic and isotherm models were employed to elucidate the BCG and MG adsorption mechanisms.The thermodynamic results indicated non-spontaneous and spontaneous reactions for BCG and MG adsorption on MIPs under the examined temperature conditions.The adsorbent exhibited sustained high removal efficiency through five reuse cycles,with no apparent reduction in adsorption performance.Validation of the adsorbent using real textile wastewater samples achieved BCG and MG removal efficiencies of 85.5%-87.5%.The adsorbent outperformed previously reported materials in BCG and MG adsorption.The synthesized CIA is a promising adsorbent for BCG and MG dye removal,contributing to water sustainability.
文摘DB-1310 and trastuzumab synergistically inhibit breast cancer(BC)cell proliferation in vitro.HER3 overexpression has been described in patients with HER2-positive BC1.We determined the levels of HER2 and HER3 expression in BC using RNA-seq data from 1,082 BC patient samples in the TCGA dataset and 67 BC cell lines in the CCLE database(Supplementary material 1).
基金supported by the UCSI University under the Research Excellence and Innovation Grant(REIG)(grant numbers:REIG-FAS-2023/006,REIG-FAS-2024/001).
文摘Antibody-drug conjugates(ADCs)represent a promising approach in targeted cancer therapy,combining the tar-geted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst min-imising off-target effects.This review provides a comprehensive analysis of ADCs,encompassing their structural components,mechanisms of action,and clinical applications.It also examines recent technological advancements,particularly in antibody engineering and linker design,aimed at enhancing therapeutic efficacy and safety.The current clinical landscape is outlined,highlighting approved ADCs and promising candidates in clinical trials,while also addressing key challenges such as stability,half-life,and systemic toxicity.This review is based on an extensive literature survey from major databases such as Scopus and Web of Science,with a focus on keywords like“antibody-drug conjugates”,“ADC advancements”,and“next-generation ADC technologies”.By integrating insights from both preclinical and clinical perspectives,we highlight the transformative potential of ADCs in advancing modern cancer therapy.
基金supported by the National Natural Science Foundation of China(22274095 and 21974084)the Fundamental Research Funds for the Central Universities(GK202302004).
文摘Sonodynamic therapy(SDT)is garnering considerable attention as a promising treatment for deep-seated tumors because of its strong tissue penetration ability,non-invasiveness,and controllability.However,the SDT efficiency of traditional sonosensitizers including porphyrins and their derivatives are limited due to their poor water dissolubility,high aggregation,and low reactive oxygen species(ROS)production efficiency.Consequently,it is crucial to develop novel sonosensitizers with high yields of ROS,outstanding water solubility,and good biocompatibility.Herein,we constructed a new platform for SDT based on unimolecular porphyrin derivatives OPV-C_(3)-TPP.The probe OPV-C_(3)-TPP was synthesized by covalently linking conjugated oligomers(OPV)with 5,10,15,20-tetra(4-aminophenyl)porphyrin(TAPP).The introduction of OPV greatly improves the water solubility of the porphyrins and reduces the self-aggregation of the porphyrins.In addition,OPV-C_(3)-TPP has good intramolecular energy transfer efficiency,thus enhancing the yield of ROS.The experimental results show that OPV-C_(3)-TPP exhibits excellent ROS generation capacity under ultrasound(US)irradiation,which leads to apoptosis and necrosis of tumor cells.In vivo tumor growth is also significantly inhibited in the OPV-C_(3)-TPP t US group,exhibiting better SDT effects than TAPP.Therefore,the unimolecular OPV-C_(3)-TPP can be used as a potential sonosensitizer,providing a promising SDT for deep-tissue tumors.
基金funded by the National Natural Science Foundation of China,grant numbers 52373184&52473179the Key Research and Development Program of Jiangxi Province,grant number 20223BBE51023+1 种基金the Natural Science Foundation of Jiangxi Province,grant numbers 20232ACB204002&20232BAB202044the Jiangxi Provincial Key Laboratory of Flexible Electronics,grant numbers 20212BCD42004&20242BCC32010.
文摘The global scarcity of clean water is an escalating issue due to climate change,population growth,and pollution.Traditional water purification technologies,while effective,often require significant energy input and complex infrastructure,limiting their accessibility.This review explores the use of conjugated polymer hydrogels as a promising solution for solar water purification.Conjugated polymer hydrogels offer unique advantages,including high photothermal conversion efficiency,effective heat management,and rapid water transport,which are crucial for efficient solar-driven water evaporation.By leveraging the properties of these hydrogels,it is possible to significantly reduce the energy required for water evaporation,making them a cost-effective and scalable option for producing potable water from seawater or wastewater.This review discusses the principles of solar water purification using conjugated polymer hydrogels,strategies to enhance their performance through material and structural design,and their applications in pollutant removal and desalination.Additionally,it addresses the advantages and limitations of these materials,providing insights into their potential future development and applications in sustainable water purification technologies.
基金supported by National Natural Science Foundation of China(No.51873085)Natural Science Foundation of Liaoning Province-Outstanding Youth Foundation(No.2022-YQ-14)+2 种基金Liaoning Revitalization Talents Program(No.XLYC2007056)China Scholarship Council(CSC Scholarship,No.202006800009)the Shenyang Science and Technology Project(No.RC230707)。
文摘Precise control of luminescence in carbon quantum dots(CQDs),from single-color to full-color emission,is crucial for advancing their applications in biomedical imaging and display technologies.While CQDs luminescence is primarily influenced by conjugated domains and surface states,the underlying interaction mechanisms remain poorly understood.This study explores a graded nitro-engineering approach to simultaneously regulate surface states and sp^(2)conjugated domains through nitro(-NO_(2))modulation,enabling comprehensive color tuning.Using o-phenylenediamine(o-PD)as the carbon source and adjusting nitric acid(HNO_(3))concentrations,we synthesized tricolor-emitting nitro-functionalized CQDs(NO_(2)-CQDs).At lower-NO_(2) concentrations,luminescence is mainly influenced by surface states,where the electron-withdrawing effect of-NO_(2) enhancesπ-electron delocalization and stabilizes sp^(2)conjugation.With increasing-NO_(2) content,the lowest unoccupied molecular orbital(LUMO)energy level decreases(-2.12 eV to-3.39 eV),resulting in a red-shift in fluorescence.At higher-NO_(2) concentrations,luminescence is primarily affected by the sp^(2)conjugated domain,where steric hindrance reduces molecular planarity and conjugation,leading to a blue-shift in fluorescence as the sp^(2)domain size decreases(4.03 nm to 2.83 nm).Combining experimental results with density functional theory(DFT)calculations,we reveal the dual role of-NO2in modulating CQDs luminescence,an approach rarely achieved through surface functionalization.This work presents a novel strategy for precise tuning of CQDs luminescence across the visible spectrum.
基金Khalifa University,Abu Dhabi,for the generous support of this researchthe financial support from the Khalifa University Research&Innovation Grant(RIG-2023-005)。
文摘Conjugated polymers(CPs)have emerged as an interesting class of materials in modern electronics and photonics,characterized by their unique delocalizedπ-electron systems that confer high flexibility,tunable electronic properties,and solution processability.These organic polymers present a compelling alternative to traditional inorganic semiconductors,offering the potential for a new generation of optoelectronic devices.This review explores the evolving role of CPs,exploring the molecular design strategies and innovative approaches that enhance their optoelectronic properties.We highlight notable progress toward developing faster,more efficient,and environmentally friendly devices by analyzing recent advancements in CP-based devices,including organic photovoltaics,field-effect transistors,and nonvolatile memories.The integration of CPs in flexible sustainable technologies underscores their potential to revolutionize future electronic and photonic systems.As ongoing research pushes the frontiers of molecular engineering and device architecture,CPs are poised to play an essential role in shaping next-generation technologies that prioritize performance,sustainability,and adaptability.
基金supported by the National Natural Science Foundation of China(No.22071166)the Priority Academic Program Development of Jiangsu High Education Institutions(PAPD).
文摘Exploration of new green polymerization strategies for the construction of conjugated polymers is important but challengeable.In this work,a multicomponent polymerization of acetylarenes,alkynones and ammonium acetate for in situ construction of conjugated poly(triarylpyridine)s was developed.The polymerization reactions of diacetylarenes,aromatic dialkynones and NH_(4)OAc were performed in dimethylsulfoxide(DMSO)under heating in the presence of potassium tert-butoxide(t-BuOK),affording four conjugated poly(2,4,6-triarylpyridine)s(PTAPs)in satisfactory yields.The resulting PTAPs have good solubility in common organic solvents and high thermal stability with 5%weight loss temperatures reaching up to 460℃.They are also electrochemically active.The PTAPs incorporating tetraphenylethene units manifest aggregation-induced emission features.Moreover,through simply being doped into poly(vinyl alcohol)(PVA)matrix,the polymer and model compound containing triphenylamine moieties exhibit room-temperature phosphorescence properties with ultralong lifetimes up to 696.2 ms and high quantum yields up to 28.7%.This work not only provides a facile green synthetic route for conjugated polymers but also offers new insights into the design of advanced materials with unique photophysical properties.
基金supports provided by the National Key R&D Program of China (2020YFC1808401, 2020YFC1808403)National Natural Science Foundation of China (22078213, 21938006, 51973148)+3 种基金Basic Research Project of Cutting-Edge Technology in Jiangsu Province, China (BK20202012)Prospective Application Research Project of Suzhou, China (SYC2022042)Water Research and Technology Project of Suzhou, China (2022006)the Priority Academic Program Development of Jiangsu Higher Education Institutions, China (PAPD)。
文摘Adsorption-photocatalytic degradation of organic pollutants in water is an advantageous method for environmental purification.Herein,a feasible strategy is developed to construct a novel dual S-scheme heterojunctions Cu_(7)S_(4)-TiO_(2)-conjugated polymer with a donor-acceptor structure.There are abundant adsorption active sites for adsorption in the porous structure of the composites,which can rapidly capture pollutants through hydrogen bonding and π-π interactions.In addition,the dual S-scheme heterojunctions effectively improve carrier separation while maintaining a strong redox ability.Thus,the optimized 1.5% CST-130 catalysts can adsorb 71% of 20 ppm BPA in 15 min and completely remove it within 30 min with high adsorption capacity and photodegradation efficiency.Therefore,this study provides a new inspiration for synergistic adsorption and degradation of BPA and the construction of dual S-scheme heterojunction.
基金the financial support from the National Natural Science Foundation of China(Nos.82473781,82173652 and 81872728)the Natural Science Foundation of Jiangsu Province(No.BK20221522)Support from Jiangsu“333 High Level Talents Cultivation”Leading Talents(No.2022–3–16–203)。
文摘The evolution of cancer therapies has highlighted the limitations of traditional chemotherapy,particularly its lack of specificity and off-target toxicities,driving the development of targeted treatments like small molecule-drug conjugates(SMDCs).SMDCs offer distinct advantages over antibody-drug conjugates(ADCs),including simpler synthesis,lower production costs,and improved solid tumor penetration due to their smaller size.However,challenges remain,such as a limited variety of targeting ligands and the complexity of optimizing selectivity and efficacy within the tumor microenvironment.This review focuses on key aspects such as mechanisms of action,biomarker selection,and the optimization of each component of SMDCs.It also covers SMDCs that have been approved or are currently under active clinical trials,while providing insights into future developments in this promising field of targeted cancer therapies.
基金supported by a grant from the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(RS-2023-00208240),Republic of Korea.
文摘A structural conjugate(HOC)of polysaccharide,hyaluronic acid(HA)with different ratios of oleic acid(OA)via cystamine(CYS)linker as a new ocular biomaterial was developed.The HOCs with controlled degrees of substitution of OA(4.6%,8.3%and 12.2%)were synthesized to form self-assembled HA-CYS-OA nanoparticles(HONs,HON1,HON2,HON3).A poorly water-soluble cyclosporine A(CsA)to be used for the treatment of multifactorial dry eye disease(DED)was chosen as model drug.CsA-loaded HONs exhibited improved solution transparency via solubilizing capacity of HON,and increased in vitro drug permeation compared to Restasis®.The physicochemical properties of CsA-loaded HONs such as nano behaviors,solution transparency,drug release,drug permeation and ocular cytocompatibility were highly variable according to the ratios of OA substitution.Interestingly,this CsA-loaded HON1 as optimal ocular nanoformulation showed markedly augmentedmacrophage polarization into the M2 phenotype,downregulated the expression of proinflammatory cytokines levels in LPS-induced M1 macrophage,and effectively inhibited VEGF-induced endothelial cell proliferation and capillary-like tube formation by the synergistic effect of CsA and HON1 containing OA at the same time.Collectively,the current fatty acid conjugated to HA,named fattigation platform,providing the roles and physicochemical properties via structural features of HA could be a promising co-delivery strategy of drug and fatty acid for DED and other ophthalmic disease treatments.
基金supported by the Beijing Natural Science Foundation(Grant No.L244024)National Natural Science Foundation of China(Grant Nos.82172604 and 82473199)CSCO Clinical Oncology Research Foundation(Grant No.Y-2022HER2AZMS-0258).
文摘Urothelial carcinoma(UC)is the 9th most common and the 13th most deadly cancer worldwide1.Despite the availability of platinum-based chemotherapy and immune checkpoint inhib-itors(ICIs),the 5-year survival rate of patients with metastatic UC(mUC)remains poor(10-15%)2.
基金Research Foundation for Advanced Talents of East China University of Technology,Grant/Award Number:DHBK201927Excellent Youth Foundation of Jiangxi Scientific Committee,Grant/Award Number:20232ACB213012+2 种基金National Science Foundation for Young Scientists of China,Grant/Award Number:21905122National Science Foundation for Young Scientists,Grant/Award Number:21905147Jiangxi Talent Program,Grant/Award Number:DHSQT32022005.
文摘Exploration of efficient and stable photocatalysts to mimic natural leaves for the conversion of atmospheric CO_(2)into hydrocarbons utilizing solar light is very important but remains a major challenge.Herein,we report the design of four novel metal-salen-incorporated conjugated microporous polymers as robust artificial leaves for photoreduction of atmospheric CO_(2)with gaseous water.Owing to the rich nitrogen and oxygen moieties in the polymeric frameworks,they show a maximum CO_(2)adsorption capacity of 46.1 cm3 g^(−1)and adsorption selectivity for CO_(2)/N_(2)of up to 82 at 273 K.Under air atmosphere and simulated solar light(100mWcm^(−2)),TEPT-Zn shows an excellent CO yield of 304.96μmol h^(−1)g^(−1)with a selectivity of approximately 100%,which represents one of the best results in terms of organic photocatalysts for gas-phase CO_(2)photoreduction so far.Furthermore,only small degradation in the CO yield is observed even after 120-h continuous illumination.More importantly,a good CO yield of 152.52μmol g^(−1)was achieved by directly exposing the photocatalytic reaction of TEPT-Zn in an outdoor environment for 3 h(25-28℃,52.3±7.9mWcm^(−2)).This work provides an avenue for the continued development of advanced polymers toward gas-phase photoconversion of CO_(2)from air.
基金supported by Anhui Province Clinical Key Specialty Construction Project,China(Grant No.:2021sjlczdzk)the National Key Research and Development Program of China(Grants Nos.:2022YFC2304102 and 2022YFC2303300)the National Natural Science Foundation of China(Grant Nos.:82272301,32100745,and 31971129).
文摘Discoidin domain receptor 1(DDR1)is overexpressed in various tumors,such as triple-negative breast cancer(TNBC),and is rarely expressed in normal tissues.These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate(ADC)for targeted therapy.Here,we investigated the preparation and preclinical efficacy of DDR1-DX8951,an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly(GGFG)linker.The anti-DDR1 monoclonal antibody was coupled to DX8951(i.e.,DDR1-DX8951),producing the targeted therapy ADC.The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models.DDR1-DX8951 can specifically target DDR1,be quickly internalized by TNBC cells,and reduce the viability of TNBC cells in vitro.The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models.Importantly,our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvironment(TME)of TNBC.Taken together,this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81672638)。
文摘The“Global Cancer Statistics Report 2022”estimates that there were approximately 20 million new cancer cases worldwide,including 9.7 million in females,of which 2.31 million were breast cancer cases1.Breast cancer is the most common malignant tumor in women and one of the leading causes of cancer-related deaths.
