[Objective] This study aimed to clone ubiquitin-conjugating enzyme gene TaUBC4 from different wheat cultivars and thus analyze their phylogenetic relationship.[Method] The UBC4 coding sequences were cloned through rev...[Objective] This study aimed to clone ubiquitin-conjugating enzyme gene TaUBC4 from different wheat cultivars and thus analyze their phylogenetic relationship.[Method] The UBC4 coding sequences were cloned through reverse transcription PCR （RT-PCR） from 21 wheat varieties.After sequencing,the UBC4 sequence in wheat cultivar Zhongguochun （GenBank accession No：M28059） was selected as the reference gene,to analyze the mutation frequency and evolutionary distance in the CDSs and corresponding amino acid sequences of the different wheat cultivars.Moreover,the phylogenetic tree based on the amino acid sequences of these TaUBC4 genes were constructed,involving the homologous sequences of TaUBC4 in eight other monocots.[Result] TaUBC4 sequence was highly conserved because the similarity in DNA sequences of the wheat varieties was over 94％,while that in amino acid sequence was over 96％.And the amino acid sequence difference only can be seen at two sites among some varieties.Phylogenetic tree constructed revealed the evolutionary relationships among these wheat varieties.[Conclusion] This study reveals the polymorphism and evolutionary characteristics in the nucleotide and amino acid sequences in different wheat varieties,which lays foundation for investigating the evolution and biological function of TaUBC4 gene.In addition,the phylogenetic tree constructed provides theoretical references for the classification of the wheat varieties with complicated background.展开更多
BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect t...BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect the mouse liver against the hepatocarcinogen diethylnitrosamine(DEN)-dependent acute liver injury and carcinogenesis.While there exists an established pathologic connection between fibrosis and hepatocellular carcinoma(HCC),DEN exposure alone does not induce robust hepatic fibrosis.Further studies are warranted to identify new suppressive mechanisms contributing to DEN-induced fibrosis and HCC.AIM To investigate the suppressive mechanisms of BRUCE in hepatic fibrosis and HCC development.METHODS Male C57/BL6/J control mice[loxp/Loxp;albumin-cre(Alb-cre)-]and BRUCE Alb-Cre KO mice(loxp/Loxp;Alb-Cre+)were injected with a single dose of DEN at postnatal day 15 and sacrificed at different time points to examine liver disease progression.RESULTS By using a liver-specific BRUCE knockout(LKO)mouse model,we found that BRUCE deficiency,in conjunction with DEN exposure,induced hepatic fibrosis in both premalignant as well as malignant stages,thus recapitulating the chronic fibrosis background often observed in HCC patients.Activated in fibrosis and HCC,β-catenin activity depends on its stabilization and subsequent translocation to the nucleus.Interestingly,we observed that livers from BRUCE KO mice demonstrated an increased nuclear accumulation and elevated activity ofβ-catenin in the three stages of carcinogenesis:Pre-malignancy,tumor initiation,and HCC.This suggests that BRUCE negatively regulatesβ-catenin activity during liver disease progression.β-catenin can be activated by phosphorylation by protein kinases,such as protein kinase A(PKA),which phosphorylates it at Ser-675(pSer-675-β-catenin).Mechanistically,BRUCE and PKA were colocalized in the cytoplasm of hepatocytes where PKA activity is maintained at the basal level.However,in BRUCE deficient mouse livers or a human liver cancer cell line,both PKA activity and pSer-675-β-catenin levels were observed to be elevated.CONCLUSION Our data support a“BRUCE-PKA-β-catenin”signaling axis in the mouse liver.The BRUCE interaction with PKA in hepatocytes suppresses PKA-dependent phosphorylation and activation ofβ-catenin.This study implicates BRUCE as a novel negative regulator of both PKA andβ-catenin in chronic liver disease progression.Furthermore,BRUCE-liver specific KO mice serve as a promising model for understanding hepatic fibrosis and HCC in patients with aberrant activation of PKA andβ-catenin.展开更多
Small ubiquitin-like modifier （SUMO） conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and...Small ubiquitin-like modifier （SUMO） conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and in vitro a SUMO conjugating enzyme with a Cys to Ser change in the active site, and show that it has a dominant negative effect. In planta expression significantly perturbs normal development, leading to growth retardation, early flowering and gene expression changes. We suggest that the mutant protein can serve as a probe to investigate sumoylation, also in plants for which poor genetic infrastructure precludes analysis via loss-of-function mutants.展开更多
Formamidinium lead iodide(FAPbI_(3))perovskite exhibits an impressive X-ray absorption coefficient and a large carrier mobility-lifetime product(μτ),making it as a highly promising candidate for X-ray detection appl...Formamidinium lead iodide(FAPbI_(3))perovskite exhibits an impressive X-ray absorption coefficient and a large carrier mobility-lifetime product(μτ),making it as a highly promising candidate for X-ray detection application.However,the presence of larger FA^(+)cation induces to an expansion of the Pb-I octahedral framework,which unfortunately affects both the stability and charge carrier mobility of the corresponding devices.To address this challenge,we develop a novel low-dimensional(HtrzT)PbI_(3) perovskite featuring a conjugated organic cation(1H-1,2,4-Triazole-3-thiol,HtrzT^(+))which matches well with theα-FAPbI_(3) lattices in two-dimensional plane.Benefiting from the matched lattice between(HtrzT)PbI_(3) andα-FAPbI_(3),the anchored lattice enhances the Pb-I bond strength and effectively mitigates the inherent tensile strain of theα-FAPbI_(3) crystal lattice.The X-ray detector based on(HtrzT)PbI_(3)(1.0)/FAPbI_(3) device achieves a remarkable sensitivity up to 1.83×10^(5)μC Gy_(air)^(−1) cm^(−2),along with a low detection limit of 27.6 nGy_(air) s^(−1),attributed to the release of residual stress,and the enhancement in carrier mobility-lifetime product.Furthermore,the detector exhibits outstanding stability under X-ray irradiation with tolerating doses equivalent to nearly 1.17×10^(6) chest imaging doses.展开更多
The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI ...The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI with NIR-II window excitation (1064nm/other wavelength beyond 1000nm) can afford deeper tissue penetration depth with high clarity due to the merits of suppressed photon scattering and diminished autofluorescence. In this review, we have summarized NIR-II window excitable/emissive organic/polymeric fluorophores recently developed. The characteristics of these fluorophores such as chemical structures and photophysical properties have also been critically discussed. Furthermore, the latest development of noninvasive in vivo FLI with NIR-II excitation was highlighted. The ideal imaging results emphasized the importance of NIR-II excitation of these fluorophores in enabling deep tissue penetration and high-resolution imaging. Finally, a perspective on the challenges and prospects of NIR-II excitable/emissive organic/polymeric fluorophores was also discussed. We expected this review will be served as a source of inspiration for researchers, stimulating the creation of novel NIR-II excitable fluorophores and fostering the development of bioimaging applications.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
The demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and...The demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and PhDO-Aze as a case study to emphasize the pivotal role of cross conjugation in tuning the optical structure-property relationship.Na DC-Aze and PhDO-Aze,formed by hybridizing two distinct conjugated systems in a single naphthalene molecule,exhibit spectral characteristics from both conjugated systems.Experimental data and theoretical calculations demonstrate the coexistence of two electron-delocalization systems in a cross-conjugation manner in both Na DC-Aze and PhDO-Aze.The cross-conjugation fluorophores exhibit high brightness,large Stokes shift,and a broad absorption wavelength range by combining distinct spectral properties from its parent fluorophores.These spectral properties will be advantageous for certain applications(i.e.,panchromatic absorption in organic solar cells,and fluorophores compatible with a wide range of excitation wavelengths).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
π-Conjugated donor-acceptor-donor-acceptor-donor(D-A-D-A-D)type pyrenoviologens(PyV^(2+)),with the 2,7 positions of pyrene serving as connection bridges,were synthesized through SN2 reactions.Specifically,pyrenoviolo...π-Conjugated donor-acceptor-donor-acceptor-donor(D-A-D-A-D)type pyrenoviologens(PyV^(2+)),with the 2,7 positions of pyrene serving as connection bridges,were synthesized through SN2 reactions.Specifically,pyrenoviologen 3c was modified with a methylnaphthalene group,while 3a and 3b were modified with methyl and benzyl groups,respectively,for comparison.These pyrenoviologens exhibit reversible redox properties and strong fluorescence emission.Electrochromic devices(ECDs)were prepared using pyrenoviologens as the active materials.Notably,naphthalene-containing pyrenoviologen 3c,with its DA-D-A-D conjugated structure,possesses more stable free radicals,enabling it to maintain the radical color for a longer duration after power loss.A series of color-changing devices were successfully assembled.Due to the strong fluorescence of pyrenoviologens and the unique electron transfer effect between them and picric acid(PA),a sensor film with good selectivity and high sensitivity for PA in aqueous solution was prepared using pyrenoviologens as the fluorescent probe.Specifically,3c exhibited the highest sensitivity to PA due to its lowest energy gap.The introduction of the D-A-D-A-D structure is a strategic approach to enhancing photoelectric performance and broadening the application of viologens.展开更多
Tuning the conjugated bridges between the electron-donor and electron-acceptor moieties plays a crucial role in enhancing the memristive properties of organic materials,yet it is rarely reported.Herein,we designed and...Tuning the conjugated bridges between the electron-donor and electron-acceptor moieties plays a crucial role in enhancing the memristive properties of organic materials,yet it is rarely reported.Herein,we designed and synthesized four donor-acceptor(D-A)organic small molecules,namely 4,7-bis(4-((9H-fluoren-9-ylidene)(phenyl)methyl)phenyl)benzo[c][1,2,5]thiadiazole(DF-BT),4,7-bis((4-((9H-fluoren-9-ylidene)(phenyl)methyl)phenyl)ethynyl)benzo[c][1,2,5]thiadiazole(DF-ynl-BT),4,7-bis(5-(4-((9H-fluoren-9-ylidene)(phenyl)methyl)phenyl)thiophen-2-yl)benzo[c][1,2,5]thiadiazole(DF-Th-BT),and 4,7-bis((5-(4-((9H-fluoren-9-ylidene)(phenyl)methyl)phenyl)thiophen-2-yl)ethynyl)benzo[c][1,2,5]thiadiazole(DF-Th-ynl-BT),featuring unique conjugated bridges.These molecules were employed as active layers in resistive random-access memory(RRAM)devices to systematically investigate the influence of conjugation bridges on the electrical parameters.The results revealed that devices based on DF-BT,DF-ynl-BT,and DF-Th-BT exhibited write-once-read-many-times(WORM)characteristics,while the DF-Th-ynl-BT-based device demonstrated stable Flash-type switching behavior.Compared to DF-BT,memory devices utilizing DF-ynl-BT,DF-Th-BT,and DF-Th-ynl-BT,which incorporate additional conjugated bridges,exhibited nonvolatile memory properties with reduced threshold voltages,an improved ON/OFF current ratio,enhanced stability,and better uniformity.These findings demonstrated that tailoring the conjugated bridges in D-A molecules can effectively modulate resistive memory behavior and enhance device performance.Furthermore,the DF-Th-ynl-BT-based device was successfully integrated into logic gate circuits and display functions,highlighting its significant potential for applications in artificial intelligence(AI)neural networks.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
Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttra...Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.展开更多
Diradicaloid polycyclic hydrocarbons(PHs)own unique open-shell electronic structures and exhibit potential utility in the fields of organic electronics and spintronics.Herein,we disclose precise fusion of B/O-heterocy...Diradicaloid polycyclic hydrocarbons(PHs)own unique open-shell electronic structures and exhibit potential utility in the fields of organic electronics and spintronics.Herein,we disclose precise fusion of B/O-heterocycles onto PHs for control over their electronic structures and diradical properties.We designed and synthesized four B/O-containing diradicaloid isomers that feature the fluoreno[3,2-b]fluorene and fluoreno[2,1-a]fluoreneπ-skeletons,respectively.The precise B/O-heterocycle fusion modes along with the changed conjugation patterns lead to their modulated electronic structures and properties,such as diradical and aromatic structures,energy levels and band gaps,as well as magnetic,electrochemical and photophysical properties.Notably,the mode A may decrease the open-shell extent,whereas the mode B can enhance the diradical nature,leading to their well-tuned diradical characters in the range of0.46-0.70.Moreover,the mode A stabilizes the LUMOs and the mode B obviously increases the HOMO levels,which are remarkably contributed by the B and O atoms,respectively,further giving rise to the decreased band gaps and redshifted absorptions.This study clearly illustrates the electronic effects of B/O-heterocycle fusion on PHs and gains insight into B/O-type organic diradicaloids.These findings will provide an important guideline for the design of more fascinating heteroatom-containing diradicaloids.展开更多
Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obes...Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.展开更多
Encapsulation and protection of hesperidin(HES)in mung bean protein isolate(MPI)-dextran(DX)conjugatestabilized nanoemulsions(MDC NEs)were investigated in this study.The degree of grafting of MDC prepared by a dry-hea...Encapsulation and protection of hesperidin(HES)in mung bean protein isolate(MPI)-dextran(DX)conjugatestabilized nanoemulsions(MDC NEs)were investigated in this study.The degree of grafting of MDC prepared by a dry-heating method reached 39.70%±0.01% under the optimal conditions of MPI/DX mass ratio 1:2.3,reaction temperature 58.8℃,and reaction time 4 d.Moreover,the analyses of Fourier infrared spectroscopy,intrinsic fluorescence spectroscopy,surface hydrophobicity,and thermal stability further confirmed the covalent grafting of dextran onto MPI molecules.When encapsulated in MDC NEs at 80 MPa for three times by highpressure homogenization,the encapsulation efficiency and loading capacity of HES were 63.62%±0.01%and 0.40±0.00 g/g,respectively.The encapsulated HES exhibited higher antioxidant activity and stronger light and storage stability than the free HES.Additionally,the incorporation of HES inhibited the formation of lipid peroxides in the nanoemulsions.The findings suggest that glycosylation combined with high-pressure homogenization is an effective strategy for enhancing the stability of MPI-based emulsions and improving their encapsulation of HES.This study provides a promising approach for the development of innovative food and beverage products based on MPI emulsions or new materials for encapsulating fat-soluble bioactive compounds.展开更多
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
With prolonged exposure in the human body,titanium alloy implants face challenges associated with bacterial attachment and proliferation,leading to implant failure and severe complications.Photothermal therapy(PTT)eme...With prolonged exposure in the human body,titanium alloy implants face challenges associated with bacterial attachment and proliferation,leading to implant failure and severe complications.Photothermal therapy(PTT)emerges as an efficient strategy for biofilm elimination.However,the local high temperature of PTT and incomplete bacteria ablation in low-temperature PTT pose risks of damage to normal tissues and biofilm recalcitrance,respectively.In this study,we synergistically combined photothermal therapy and chemotherapy to mildly disrupt biofilms of Staphylococcus aureus(S.aureus)to enhance the efficiency of biofilm ablation.The synergistic nanoplatform comprises near-infrared-light responsive con-jugated polymers,heat-sensitive liposomes,and the antibiotic daptomycin for biofilm elimination.The heat generated by conjugated polymers,stimulated with 808 nm light,alters biofilm permeability and releases antibiotics locally to eradicate biofilm.The nanoparticles exhibit biofilm dispersion activity and can effectively inhibit biofilm growth for up to 5 days.Consequently,this nanoplatform based on conjugated polymers offers a reliable method for ablating biofilms on titanium alloy implant and exhibits potential in drug-resistant clinical applications.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
基金Supported by the Natural Science Foundation of Shandong Province(ZR2011CQ035)Scientific and Technological Innovation Fund for the Undergraduates of Liaocheng University(F2013274)~~
文摘[Objective] This study aimed to clone ubiquitin-conjugating enzyme gene TaUBC4 from different wheat cultivars and thus analyze their phylogenetic relationship.[Method] The UBC4 coding sequences were cloned through reverse transcription PCR （RT-PCR） from 21 wheat varieties.After sequencing,the UBC4 sequence in wheat cultivar Zhongguochun （GenBank accession No：M28059） was selected as the reference gene,to analyze the mutation frequency and evolutionary distance in the CDSs and corresponding amino acid sequences of the different wheat cultivars.Moreover,the phylogenetic tree based on the amino acid sequences of these TaUBC4 genes were constructed,involving the homologous sequences of TaUBC4 in eight other monocots.[Result] TaUBC4 sequence was highly conserved because the similarity in DNA sequences of the wheat varieties was over 94％,while that in amino acid sequence was over 96％.And the amino acid sequence difference only can be seen at two sites among some varieties.Phylogenetic tree constructed revealed the evolutionary relationships among these wheat varieties.[Conclusion] This study reveals the polymorphism and evolutionary characteristics in the nucleotide and amino acid sequences in different wheat varieties,which lays foundation for investigating the evolution and biological function of TaUBC4 gene.In addition,the phylogenetic tree constructed provides theoretical references for the classification of the wheat varieties with complicated background.
基金Supported by NIH(Du CY),No.R21CA241025-01NIH(Du CY),No.RO1CA158323+3 种基金NCI RO1 Diversity Supplement(Du CY),No.R01CA158323-05SNational Center for Advancing Translational Sciences of the National Institutes of Health(Du CY),No.2UL1TR001425-05A1University of Cincinnati Center for Environmental Genetics-NIH/NIEHS Award(Du CY),No.P30 ES006096Pathways to Cancer Therapeutics T32(Du CY and Vilfranc CL),No.CA117846-12.
文摘BACKGROUND BIR repeat-containing ubiquitin conjugating enzyme(BRUCE)is a liver tumor suppressor,which is downregulated in a large number of patients with liver diseases.BRUCE facilitates DNA damage repair to protect the mouse liver against the hepatocarcinogen diethylnitrosamine(DEN)-dependent acute liver injury and carcinogenesis.While there exists an established pathologic connection between fibrosis and hepatocellular carcinoma(HCC),DEN exposure alone does not induce robust hepatic fibrosis.Further studies are warranted to identify new suppressive mechanisms contributing to DEN-induced fibrosis and HCC.AIM To investigate the suppressive mechanisms of BRUCE in hepatic fibrosis and HCC development.METHODS Male C57/BL6/J control mice[loxp/Loxp;albumin-cre(Alb-cre)-]and BRUCE Alb-Cre KO mice(loxp/Loxp;Alb-Cre+)were injected with a single dose of DEN at postnatal day 15 and sacrificed at different time points to examine liver disease progression.RESULTS By using a liver-specific BRUCE knockout(LKO)mouse model,we found that BRUCE deficiency,in conjunction with DEN exposure,induced hepatic fibrosis in both premalignant as well as malignant stages,thus recapitulating the chronic fibrosis background often observed in HCC patients.Activated in fibrosis and HCC,β-catenin activity depends on its stabilization and subsequent translocation to the nucleus.Interestingly,we observed that livers from BRUCE KO mice demonstrated an increased nuclear accumulation and elevated activity ofβ-catenin in the three stages of carcinogenesis:Pre-malignancy,tumor initiation,and HCC.This suggests that BRUCE negatively regulatesβ-catenin activity during liver disease progression.β-catenin can be activated by phosphorylation by protein kinases,such as protein kinase A(PKA),which phosphorylates it at Ser-675(pSer-675-β-catenin).Mechanistically,BRUCE and PKA were colocalized in the cytoplasm of hepatocytes where PKA activity is maintained at the basal level.However,in BRUCE deficient mouse livers or a human liver cancer cell line,both PKA activity and pSer-675-β-catenin levels were observed to be elevated.CONCLUSION Our data support a“BRUCE-PKA-β-catenin”signaling axis in the mouse liver.The BRUCE interaction with PKA in hepatocytes suppresses PKA-dependent phosphorylation and activation ofβ-catenin.This study implicates BRUCE as a novel negative regulator of both PKA andβ-catenin in chronic liver disease progression.Furthermore,BRUCE-liver specific KO mice serve as a promising model for understanding hepatic fibrosis and HCC in patients with aberrant activation of PKA andβ-catenin.
基金supported by the Max Planck Societythe German Research Foundation DFG (SFB 635 to G.C., and SPP 1365 and grant BA1158/3–1 to A.B.)+1 种基金the Austrian Research Foundation FWF (grant P 21215 to A.B.)pre-doctoral fellowships from the International Max Planck Research School to R.B. and R.H
文摘Small ubiquitin-like modifier （SUMO） conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and in vitro a SUMO conjugating enzyme with a Cys to Ser change in the active site, and show that it has a dominant negative effect. In planta expression significantly perturbs normal development, leading to growth retardation, early flowering and gene expression changes. We suggest that the mutant protein can serve as a probe to investigate sumoylation, also in plants for which poor genetic infrastructure precludes analysis via loss-of-function mutants.
基金supports from the National Natural Science Foundation of China(22375220,U2001214,22471302)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020101)Open Project Fund from State Key Laboratory of Optoelectronic Materials and Technologies(OEMT-2024-KF-08).
文摘Formamidinium lead iodide(FAPbI_(3))perovskite exhibits an impressive X-ray absorption coefficient and a large carrier mobility-lifetime product(μτ),making it as a highly promising candidate for X-ray detection application.However,the presence of larger FA^(+)cation induces to an expansion of the Pb-I octahedral framework,which unfortunately affects both the stability and charge carrier mobility of the corresponding devices.To address this challenge,we develop a novel low-dimensional(HtrzT)PbI_(3) perovskite featuring a conjugated organic cation(1H-1,2,4-Triazole-3-thiol,HtrzT^(+))which matches well with theα-FAPbI_(3) lattices in two-dimensional plane.Benefiting from the matched lattice between(HtrzT)PbI_(3) andα-FAPbI_(3),the anchored lattice enhances the Pb-I bond strength and effectively mitigates the inherent tensile strain of theα-FAPbI_(3) crystal lattice.The X-ray detector based on(HtrzT)PbI_(3)(1.0)/FAPbI_(3) device achieves a remarkable sensitivity up to 1.83×10^(5)μC Gy_(air)^(−1) cm^(−2),along with a low detection limit of 27.6 nGy_(air) s^(−1),attributed to the release of residual stress,and the enhancement in carrier mobility-lifetime product.Furthermore,the detector exhibits outstanding stability under X-ray irradiation with tolerating doses equivalent to nearly 1.17×10^(6) chest imaging doses.
基金supported by the National Nature Science Foundation of China(Nos.62075079,62305127,61975200)the Natural Science Foundation of Jilin Province(20230508135RC)the Science and Technology Development Foundation of Changchun City(23GZZ15).
文摘The fluorescence imaging (FLI) in the second near-infrared window (NIR-II, 1000–1700nm) has attracted considerable attention in the past decade. In contrast to conventional NIR-I window excitation (808nm/980nm), FLI with NIR-II window excitation (1064nm/other wavelength beyond 1000nm) can afford deeper tissue penetration depth with high clarity due to the merits of suppressed photon scattering and diminished autofluorescence. In this review, we have summarized NIR-II window excitable/emissive organic/polymeric fluorophores recently developed. The characteristics of these fluorophores such as chemical structures and photophysical properties have also been critically discussed. Furthermore, the latest development of noninvasive in vivo FLI with NIR-II excitation was highlighted. The ideal imaging results emphasized the importance of NIR-II excitation of these fluorophores in enabling deep tissue penetration and high-resolution imaging. Finally, a perspective on the challenges and prospects of NIR-II excitable/emissive organic/polymeric fluorophores was also discussed. We expected this review will be served as a source of inspiration for researchers, stimulating the creation of novel NIR-II excitable fluorophores and fostering the development of bioimaging applications.
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 Natural Science Foundation of China(Nos.22225806,22078314,21908216,22378385)Dalian Institute of Chemical Physics(Nos.DICPI202142,DICPI202436)+1 种基金Agency for Science,Technology and Research(No.A*STAR,Singapore)under its Advanced Manufacturing and Engineering Program(No.A2083c0051)SUTD Kickstarter Initiative(No.SKI 2021_03_10)。
文摘The demand for enhanced optical properties in advanced fluorescence technologies has driven research into the structure-property relationship of fluorophores.In this paper,we use naphthalene fluorophores Na DC-Aze and PhDO-Aze as a case study to emphasize the pivotal role of cross conjugation in tuning the optical structure-property relationship.Na DC-Aze and PhDO-Aze,formed by hybridizing two distinct conjugated systems in a single naphthalene molecule,exhibit spectral characteristics from both conjugated systems.Experimental data and theoretical calculations demonstrate the coexistence of two electron-delocalization systems in a cross-conjugation manner in both Na DC-Aze and PhDO-Aze.The cross-conjugation fluorophores exhibit high brightness,large Stokes shift,and a broad absorption wavelength range by combining distinct spectral properties from its parent fluorophores.These spectral properties will be advantageous for certain applications(i.e.,panchromatic absorption in organic solar cells,and fluorophores compatible with a wide range of excitation wavelengths).
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 Shaanxi Province Technological Innovation Guidance Special(No.2022QFY08-01)the National Key Research and Development Program of China(No.2021YFB3200702)+5 种基金Natural Science Foundation of China(Nos.22201228,22205172,52203240 and 22175138)China Postdoctoral Science Foundation(Nos.2022M712530,2023T160506,and 2022M712497)Fundamental Research Funds for the Central Universities(No.xzy012022017)Young Talent Fund of Association for Science and Technology in Shaanxi(No.20230624)Shaanxi Province Postdoctoral Science Foundation(No.2023b SHTBZZ04)the Youth Innovation Team of Shaanxi Universities。
文摘π-Conjugated donor-acceptor-donor-acceptor-donor(D-A-D-A-D)type pyrenoviologens(PyV^(2+)),with the 2,7 positions of pyrene serving as connection bridges,were synthesized through SN2 reactions.Specifically,pyrenoviologen 3c was modified with a methylnaphthalene group,while 3a and 3b were modified with methyl and benzyl groups,respectively,for comparison.These pyrenoviologens exhibit reversible redox properties and strong fluorescence emission.Electrochromic devices(ECDs)were prepared using pyrenoviologens as the active materials.Notably,naphthalene-containing pyrenoviologen 3c,with its DA-D-A-D conjugated structure,possesses more stable free radicals,enabling it to maintain the radical color for a longer duration after power loss.A series of color-changing devices were successfully assembled.Due to the strong fluorescence of pyrenoviologens and the unique electron transfer effect between them and picric acid(PA),a sensor film with good selectivity and high sensitivity for PA in aqueous solution was prepared using pyrenoviologens as the fluorescent probe.Specifically,3c exhibited the highest sensitivity to PA due to its lowest energy gap.The introduction of the D-A-D-A-D structure is a strategic approach to enhancing photoelectric performance and broadening the application of viologens.
基金supported by the financial support from the National Natural Science Foundation of China(Grant Nos.:62174116 and 61774109)the start-up fund from Shanghai University.
文摘Tuning the conjugated bridges between the electron-donor and electron-acceptor moieties plays a crucial role in enhancing the memristive properties of organic materials,yet it is rarely reported.Herein,we designed and synthesized four donor-acceptor(D-A)organic small molecules,namely 4,7-bis(4-((9H-fluoren-9-ylidene)(phenyl)methyl)phenyl)benzo[c][1,2,5]thiadiazole(DF-BT),4,7-bis((4-((9H-fluoren-9-ylidene)(phenyl)methyl)phenyl)ethynyl)benzo[c][1,2,5]thiadiazole(DF-ynl-BT),4,7-bis(5-(4-((9H-fluoren-9-ylidene)(phenyl)methyl)phenyl)thiophen-2-yl)benzo[c][1,2,5]thiadiazole(DF-Th-BT),and 4,7-bis((5-(4-((9H-fluoren-9-ylidene)(phenyl)methyl)phenyl)thiophen-2-yl)ethynyl)benzo[c][1,2,5]thiadiazole(DF-Th-ynl-BT),featuring unique conjugated bridges.These molecules were employed as active layers in resistive random-access memory(RRAM)devices to systematically investigate the influence of conjugation bridges on the electrical parameters.The results revealed that devices based on DF-BT,DF-ynl-BT,and DF-Th-BT exhibited write-once-read-many-times(WORM)characteristics,while the DF-Th-ynl-BT-based device demonstrated stable Flash-type switching behavior.Compared to DF-BT,memory devices utilizing DF-ynl-BT,DF-Th-BT,and DF-Th-ynl-BT,which incorporate additional conjugated bridges,exhibited nonvolatile memory properties with reduced threshold voltages,an improved ON/OFF current ratio,enhanced stability,and better uniformity.These findings demonstrated that tailoring the conjugated bridges in D-A molecules can effectively modulate resistive memory behavior and enhance device performance.Furthermore,the DF-Th-ynl-BT-based device was successfully integrated into logic gate circuits and display functions,highlighting its significant potential for applications in artificial intelligence(AI)neural networks.
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the National Natural Science Foundation of China(Nos.82373722,22077144)Hunan Provincial Natural Science Foundation of China(No.2023JJ30527)+2 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023B1515040006)Guangdong Provincial Key Laboratory of Construction Foundation(No.2023B1212060022)Key Research and Development Program of Guangdong Province(No.2020B1111110003).
文摘Chemical modification of native peptides and proteins is a versatile strategy to facilitate late-stage diversification for functional studies.Among the proteogenic amino acids,lysine is extensively involved in posttranslational modifications and the binding of ligands to target proteins,making its selective modification attractive.However,lysine’s high natural abundance and solvent accessibility,as well as its relatively low reactivity to cysteine,necessitate addressing chemoselectivity and regioselectivity for the Lys modification of native proteins.Although Lys chemoselective modification methods have been well developed,achieving site-selective modification of a specific Lys residue remains a great challenge.In this review,we discussed the challenges of Lys selective modification,presented recent examples of Lys chemoselective modification,and summarized the currently known methods and strategies for Lys site-selective modification.We also included an outlook on potential solutions for Lys site-selective labeling and its potential applications in chemical biology and drug development.
基金supported by National Natural Science Foundation of China(Nos.52373182 and 22175074)Jilin Scientific and Technological Development Program(No.20220101054JC)Department of Education of Jilin Province(No.JJKH20221046KJ)。
文摘Diradicaloid polycyclic hydrocarbons(PHs)own unique open-shell electronic structures and exhibit potential utility in the fields of organic electronics and spintronics.Herein,we disclose precise fusion of B/O-heterocycles onto PHs for control over their electronic structures and diradical properties.We designed and synthesized four B/O-containing diradicaloid isomers that feature the fluoreno[3,2-b]fluorene and fluoreno[2,1-a]fluoreneπ-skeletons,respectively.The precise B/O-heterocycle fusion modes along with the changed conjugation patterns lead to their modulated electronic structures and properties,such as diradical and aromatic structures,energy levels and band gaps,as well as magnetic,electrochemical and photophysical properties.Notably,the mode A may decrease the open-shell extent,whereas the mode B can enhance the diradical nature,leading to their well-tuned diradical characters in the range of0.46-0.70.Moreover,the mode A stabilizes the LUMOs and the mode B obviously increases the HOMO levels,which are remarkably contributed by the B and O atoms,respectively,further giving rise to the decreased band gaps and redshifted absorptions.This study clearly illustrates the electronic effects of B/O-heterocycle fusion on PHs and gains insight into B/O-type organic diradicaloids.These findings will provide an important guideline for the design of more fascinating heteroatom-containing diradicaloids.
基金supported by the National Natural Science Foundation of China(No.22101086)Guangzhou Basic and Applied Basic Research Project(No.202201010052)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515140030).
文摘Iron overload has been evidenced to contribute to obesity-associated metabolic disorders,including insulin resistance.Strategies to reduce iron levels might help manage the metabolic complications associated with obesity.Here,it is demonstrated that the specific accumulation of oleic acid-modified polyoxovanadates(OPOVs)in adipose tissue leads to the reduction of iron concentrations in adipocytes in mice fed with a high-fat diet(HFD).Conjugation of oleic acids to polyoxovanadates enables tissue-specific depletion of iron from white adipose tissue(WAT)by OPOVs,protecting mice from HFD-induced obesity and obesity-associated metabolic deteriorations.Glucose tolerance and insulin sensitivity are improved in OPOV-treated mice,which demonstrates that the OPOV-induced iron depletion can reverse the metabolic degeneration caused by HFD-induced obesity.Furthermore,a decrease in expression of the marker genes of iron overload suggests the participation of OPOVs in maintaining iron homeostasis and a potential medical application of vanadium clusters in targeting the iron overload caused by obesity.These findings underscore the potential of vanadate-based clusters tailored to address the complex interplay between iron metabolism and metabolic health.
基金financially supported by the National Natural Science Foundation of China(Grant No.32101981)the cooperation project between Ya’an city and Sichuan Agricultural University(23ZDF0003)。
文摘Encapsulation and protection of hesperidin(HES)in mung bean protein isolate(MPI)-dextran(DX)conjugatestabilized nanoemulsions(MDC NEs)were investigated in this study.The degree of grafting of MDC prepared by a dry-heating method reached 39.70%±0.01% under the optimal conditions of MPI/DX mass ratio 1:2.3,reaction temperature 58.8℃,and reaction time 4 d.Moreover,the analyses of Fourier infrared spectroscopy,intrinsic fluorescence spectroscopy,surface hydrophobicity,and thermal stability further confirmed the covalent grafting of dextran onto MPI molecules.When encapsulated in MDC NEs at 80 MPa for three times by highpressure homogenization,the encapsulation efficiency and loading capacity of HES were 63.62%±0.01%and 0.40±0.00 g/g,respectively.The encapsulated HES exhibited higher antioxidant activity and stronger light and storage stability than the free HES.Additionally,the incorporation of HES inhibited the formation of lipid peroxides in the nanoemulsions.The findings suggest that glycosylation combined with high-pressure homogenization is an effective strategy for enhancing the stability of MPI-based emulsions and improving their encapsulation of HES.This study provides a promising approach for the development of innovative food and beverage products based on MPI emulsions or new materials for encapsulating fat-soluble bioactive compounds.
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 Key R&D Program of China(No.2023YFE0105200)the National Natural Science Foundation of China(Nos.21905072,22077025,22207029,U20A20260)+3 种基金the Natural Science Foundation of Hebei Province(Nos.B2020202086,B2023202024,B2021202041,B2020202062)the Financial Support Project of Central Government for Promoting Development of Science and Technology of Hebei Province(No.236Z2705G)the Excellent Young Scientist Fund of the Natural Science Foundation of Hebei Province(No.B2022202027)the Science Research Project of Hebei Education Department(No.ZD2021032).
文摘With prolonged exposure in the human body,titanium alloy implants face challenges associated with bacterial attachment and proliferation,leading to implant failure and severe complications.Photothermal therapy(PTT)emerges as an efficient strategy for biofilm elimination.However,the local high temperature of PTT and incomplete bacteria ablation in low-temperature PTT pose risks of damage to normal tissues and biofilm recalcitrance,respectively.In this study,we synergistically combined photothermal therapy and chemotherapy to mildly disrupt biofilms of Staphylococcus aureus(S.aureus)to enhance the efficiency of biofilm ablation.The synergistic nanoplatform comprises near-infrared-light responsive con-jugated polymers,heat-sensitive liposomes,and the antibiotic daptomycin for biofilm elimination.The heat generated by conjugated polymers,stimulated with 808 nm light,alters biofilm permeability and releases antibiotics locally to eradicate biofilm.The nanoparticles exhibit biofilm dispersion activity and can effectively inhibit biofilm growth for up to 5 days.Consequently,this nanoplatform based on conjugated polymers offers a reliable method for ablating biofilms on titanium alloy implant and exhibits potential in drug-resistant clinical applications.
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.
