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Piezoelectric dynamic therapy (PzDT) is an effective method of tumor treatment by using piezoelectric polarization to generate reactive oxygen species. In this paper, two-dimensional Cu-doped BiOCl nanosheets with surface vacancies are produced by the photoetching strategy. Under ultrasound, a built-in electric field is generated to promote the electron and hole separation. The separated carriers achieve O2 reduction and GSH oxidation, inducing oxidative stress. The bandgap of BiOCl is narrowed by introducing surface oxygen vacancies, which act as charge traps and facilitate the electron and hole separation. Meanwhile, Cu doping induces chemodynamic therapy and depletes GSH via the transformation from Cu(II) to Cu(I). Both in vivo and in vitro results confirmed that oxidative stress can be enhanced by exogenous ultrasound stimulation, which can cause severe damage to tumor cells. This work emphasizes the efficient strategy of doping engineering and defect engineering for US-activated PzDT under exogenous stimulation.
Assuntos
Cobre , Nanoestruturas , Oxigênio , Oxigênio/química , Cobre/química , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Animais , Camundongos , Neoplasias/terapia , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular Tumoral , Bismuto/química , Espécies Reativas de Oxigênio/metabolismo , Glutationa/químicaRESUMO
Ferroptosis is a novel type of nonapoptotic programmed cell death involving the accumulation of lipid peroxidation (LPO) to a lethal threshold. Herein, we propose tunable zeolitic imidazolate framework (ZIFs)-engineered biodegradable nanozymes for ferroptosis mediated by both reactive oxygen species (ROS) and nitrogen species (RNS). l-Arginine is utilized as an exogenous nitric oxide donor and loaded into hollow ZIFs@MnO2 artificial nanozymes, which are formed by etching ZIFs with potassium permanganate and simultaneously generating a MnO2 shell in situ. The constructed nanozymes with multienzyme-like activities including peroxidase, oxidase, and catalase can release satisfactory ROS and RNS through a cascade reaction, consequently promoting the accumulation of LPO. Furthermore, it can improve the efficiency of ferroptosis through a three-step strategy of glutathione (GSH) depletion; that is, the outer MnO2 layer consumes GSH under slightly acidic conditions and RNS downregulates SLC7A11 and glutathione reductase, thus directly inhibiting GSH biosynthesis and indirectly preventing GSH regeneration.
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Ferroptose , Estruturas Metalorgânicas , Espécies Reativas de Oxigênio , Compostos de Manganês/farmacologia , Óxidos , Estresse Oxidativo , GlutationaRESUMO
The efficient removal of droplets on solid surfaces holds significant importance in the field of fog collection, condensation heat transfer, and so on. However, on current typical surfaces, droplets are characterized by a passive and single removal mode, contingent on the traction force (e.g., capillary force, Laplace pressure, etc.) generated by the surface's physics and chemistry design, posing challenges for enhancing the efficiency of droplet removal. In this paper, an effective active strategy based on different removal modes is demonstrated on magnetic responsive polydimethylsiloxane (PDMS) superhydrophobic microplates (RM-MPSM). By regulating the parameters of microplates and droplet volume, different effective departure modes (top jumping and side departure) can be induced to facilitate the removal of droplets. Moreover, the removal volume of droplets through the side departure mode exhibits a significant reduction compared to that observed in the top jumping mode. The exceptional removal ability of RM-MPSM demonstrates adaptability to diverse functional applications: efficient fog collection, removal of condensation droplets and micro-particles. The efficient modes of droplet removal demonstrated in this work hold significant implications for broadening its application in many fields, such as droplet collection, heat transfer, and anti-icing.
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Chemodynamic therapy (CDT) is a non-invasive strategy for generating reactive oxygen species (ROS) and is promising for cancer treatment. However, increasing ROS in tumor therapy remains challenging. Therefore, exogenous excitation and inhibition of electron-hole pair recombination are attractive for modulating ROS storms in tumors. Herein, a Ce-doped BiFeO3 (CBFO) piezoelectric sonosensitizer to modulate ROS generation and realize a synergistic mechanism of CDT/sonodynamic therapy and piezodynamic therapy (PzDT) is proposed. The mixed Fe2+ and Ce3+ can implement a circular Fenton/Fenton-like reaction in the tumor microenvironment. Abundant ·OH can be generated by ultrasound (US) stimulation to enhance CDT efficacy. As a typical piezoelectric sonosensitizer, CBFO can produce O2 - owing to the enhanced polarization by the US, resulting in the motion of charge carriers. In addition, CBFO can produce a piezoresponse irradiated upon US, which accelerates the migration rate of electrons/holes in opposite directions and results in energy band bending, further achieving toxic ROS production and realizing PzDT. Density functional theory calculations confirmed that Ce doping shortens the diffusion of electrons and improves the conductivity and catalytic activity of CBFO. This distinct US-enhanced strategy emphasizes the effects of doping engineering and piezoelectric-optimized therapy and shows great potential for the treatment of malignant tumors.
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Dendrobium nobile is an important orchid plant that has been used as a traditional herb for many years. For the further pharmaceutical development of this resource, a combined transcriptome and metabolome analysis was performed in different parts of D. nobile. First, saccharides, organic acids, amino acids and their derivatives, and alkaloids were the main substances identified in D. nobile. Amino acids and their derivatives and flavonoids accumulated strongly in flowers; saccharides and phenols accumulated strongly in flowers and fruits; alkaloids accumulated strongly in leaves and flowers; and a nucleotide and its derivatives and organic acids accumulated strongly in leaves, flowers, and fruits. Simultaneously, genes for lipid metabolism, terpenoid biosynthesis, and alkaloid biosynthesis were highly expressed in the flowers; genes for phenylpropanoids biosynthesis and flavonoid biosynthesis were highly expressed in the roots; and genes for other metabolisms were highly expressed in the leaves. Furthermore, different members of metabolic enzyme families like cytochrome P450 and 4-coumarate-coA ligase showed differential effects on tissue-specific metabolic accumulation. Members of transcription factor families like AP2-EREBP, bHLH, NAC, MADS, and MYB participated widely in differential accumulation. ATP-binding cassette transporters and some other transporters also showed positive effects on tissue-specific metabolic accumulation. These results systematically elucidated the molecular mechanism of differential accumulation in different parts of D. nobile and enriched the library of specialized metabolic products and promising candidate genes.
Assuntos
Dendrobium , Regulação da Expressão Gênica de Plantas , Transcriptoma , Dendrobium/genética , Dendrobium/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica/métodos , Metaboloma , Flores/genética , Flores/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Frutas/metabolismo , Frutas/genética , Flavonoides/metabolismo , Flavonoides/biossíntese , Alcaloides/metabolismoRESUMO
Increasing the yield of reactive oxygen species (ROS) to enhance oxidative stress in cells is an eternal goal in cancer therapy. In this study, BiVO4 artificial nanozyme is developed with adjustable vanadium vacancy for ultrasound (US) enhanced piezoelectric/sonodynamic therapy. Under US excitation, the vanadium vacancy-rich BiVO4 nanosheets (abbreviated Vv -r BiVO4 NSs) facilitate the generation of a large number of electrons to improve the ROS yield. Meanwhile, the mechanical strain imposed by US irradiation makes the Vv -r BiVO4 NSs display a typical piezoelectric response, which tilts the conduction band to be more negative and the valance band more positive than the redox potentials of O2 /O2 â¢- and H2 O/·OH, boosting the efficiency of ROS generation. Both density functional theory calculations and experiments confirm that the introduction of cationic vacancy can improve the sonodynamic effect. As expected, Vv -r BiVO4 NSs have better peroxidase enzyme catalytic and glutathione depletion activities, resulting in increased intracellular oxidative stress. This triple amplification strategy of oxidative stress induced by US substantially inhibits the growth of cancer cells. The work may open an avenue to achieve a synergetic therapy by introducing cationic vacancy, broadening the biomedical use of piezoelectric materials.
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Corantes , Vanádio , Espécies Reativas de Oxigênio , Ultrassonografia , CatáliseRESUMO
Ferroptosis, as a non-apoptotic cell death pathway, has attracted increasing attention for cancer therapy. However, the clinical application of ferroptosis-participated modalities is severely limited by the low efficiency owing to the intrinsic intracellular regulation pathways. Herein, chlorin e6 (Ce6) and N-acetyl-l-cysteine-conjugated bovine serum albumin-ruthenium dioxide is elaborately designed and constructed for ultrasound-triggered peroxynitrite-mediated ferroptosis. Upon ultrasound stimulation, the sonosensitizers of Ce6 and RuO2 exhibit highly efficient singlet oxygen (1 O2 ) generation capacity, which is sequentially amplified by superoxide dismutase and catalase-mimicking activity of RuO2 with hypoxia relief. Meanwhile, the S-nitrosothiol group in BCNR breaks off to release nitric oxide (NO) on-demand, which then reacts with 1 O2 forming highly cytotoxic peroxynitrite (ONOO- ) spontaneously. Importantly, BCNR nanozyme with glutathione peroxidase-mimicking activity can consume glutathione (GSH), along with the generated ONOO- downregulates glutathione reductase, avoiding GSH regeneration. The two-parallel approach ensures complete depletion of GSH within the tumor, resulting in the boosted ferroptosis sensitization of cancer cells. Thus, this work presents a superior paradigm for designing peroxynitrite-boosted ferroptosis sensitization cancer therapeutic.
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Antineoplásicos , Ferroptose , Neoplasias , Humanos , Ácido Peroxinitroso/farmacologia , Antineoplásicos/farmacologia , Ultrassonografia , Óxido Nítrico/metabolismo , Glutationa/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismoRESUMO
A novel rod-shaped, Gram-stain-positive, spore-forming and motile by peritrichous flagella strain, designated HJL G12T, was isolated from the root of Chinese herb Dendrobium nobile. Strain HJL G12T grew optimally at pH 7.0, 30 °C and in the presence of 1.0â% NaCl (w/v). Phylogenetic analysis based on 16S rRNA gene and genomic sequences showed that HJL G12T clustered with Paenibacillus chibensis NBRC 15958T and Paenibacillus dokdonensis YH-JAE5T with 98.3 and 98.2â% sequence similarity. The DNA-DNA hybridization values between strain HJL G12T and the two reference strains were 23.6â% and 24.9 %, respectively. Menaquinone-7 was the only respiratory quinone and meso-diaminopimelic acid was present in the cell-wall peptidoglycan. Antesio-C15â:â0 and iso-C16â:â0 were detected to be the major cellular fatty acids. The cellular polar lipid profile contained diphosphatidyglycerol, phosphatidylglycerol, phosphatidylethanolamine, lysyl-phospatidylglycerol and three unidentified aminophospholipids. Based on these results, strain HJL G12T is considered to represent a novel species within the genus Paenibacillus, for which the name Paenibacillus dendrobii sp. nov. is proposed, with HJL G12T (=NBRC 115617T=CGMCC 1.18520T) as the type strain.
Assuntos
Dendrobium , Paenibacillus , Ácidos Graxos/química , Fosfolipídeos/análise , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Composição de Bases , DNA Bacteriano/genética , Técnicas de Tipagem BacterianaRESUMO
Increasing data has confirmed the potential anticancer properties of Dendrobium, a traditional Chinese herb. However, most anticancer compositions from the plant of Dendrobium were usually extracted by high polar solvent, while weak polar compositions with excellent anticancer activity remained largely unexplored. In this study, the differences between ether extract and ethanol extract of Dendrobium nobile Lindl. on chemical components and anticancer activities were investigated, as well as the anticancer mechanisms among different extracts. The results demonstrated that the ether extract exhibited a stronger anticancer effect than ethanol extract, and its anticancer effect was mainly due to weak polar compounds rather than polysaccharides and alkaloids. Quantitative proteomics suggested that the ether extract significantly stimulated the over-expression of immature proteins, the endoplasmic reticulum stress and unfolded protein response were subsequently induced, the intracellular reactive oxygen species level was seriously elevated, and oxidative stress occurred in the meanwhile. Eventually, autophagy and apoptosis were activated to cause cell death. Our findings demonstrate that the ether extract of D. nobile is a potential candidate for anticancer drug development, and that future research on anticancer drugs derived from medicinal plants should also concentrate on weak polar compounds.
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Antineoplásicos , Dendrobium , Éter , Dendrobium/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Autofagia , Biossíntese de Proteínas , Antineoplásicos/farmacologia , EtanolRESUMO
In Brassicaceae, the papillary cells of the stigma are the primary site of the self-incompatibility (SI) responses. SI preserves the genetic diversity by selectively rejecting irrelevant or incompatible pollen, thus promoting cross fertilization and species fitness. Mechanisms that regulate SI responses in Brassica have been studied mainly on the mature stigma that often undermines how stigma papillary cells attain the state of SI during development. To understand this, we integrated PacBio SMRT-seq with Illumina RNA-seq to construct a de novo full-length transcriptomic database for different stages of stigma development in ornamental kale. A total of 48,800 non-redundant transcripts, 31,269 novel transcripts, 24,015 genes, 13,390 alternative splicing, 22,389 simple sequence repeats, 21,816 complete ORF sequences, and 4591 lncRNAs were identified and analyzed using PacBio SMRT-seq. The Illumina RNA-seq revealed 15,712 differentially expressed genes (DEGs) and 8619 transcription factors. The KEGG enrichment analysis of 4038 DEGs in the "incompatibility" group revealed that the flavonoid and fatty acid biosynthesis pathways were significantly enriched. The cluster and qRT-PCR analysis indicated that 11 and 14 candidate genes for the flavonoid and fatty acid biosynthesis pathways have the lowest expression levels at stigma maturation, respectively. To understand the physiological relevance of the downregulation of fatty acid biosynthesis pathways, we performed inhibitor feeding assays on the mature stigma. The compatible pollination response was drastically reduced when mature stigmas were pre-treated with a fatty acid synthase inhibitor. This finding suggested that fatty acid accumulation in the stigmas may be essential for compatible pollination and its downregulation during maturity must have evolved as a support module to discourage the mounting of self-incompatible pollen.
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Brassica , Brassica/genética , Brassica/metabolismo , Polinização/genética , Pólen/genética , Flavonoides/metabolismo , Ácidos Graxos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
The present study aimed to explore the correlation between agronomic traits and quality indexes of Dendrobium nobile and its application value in agricultural breeding. The cultivated strains of D. nobile in Hejiang-Chishui producing areas were extensively collected,and the main agronomic traits and quality indexes were measured. The agronomic traits with significant correlation with quality indexes were screened out by the correlation analysis,and then the parental lines and self-bred F_1 generation plants were furtherverified. Among 96 lines of D. nobile,the content of soluble polysaccharides showed a significant negative correlation with dendrobine( P < 0. 01),and no significant correlation with agronomic traits in stems and leaves. The content of dendrobine exhibited a significant positive correlation with the stem width-thickness ratio( at the largest cross section; P < 0. 01),and no significant correlation with other agronomic traits. Regression analysis further verified the positive correlation between dendrobine content and stem width-thickness ratio( R2> 0. 9). Two lines,JC-10 and JC-35,with significant differences in stem width-thickness ratio were screened out( P <0. 05). The corresponding F1 generation plants by self-pollination both showed that the dendrobine content was higher with greater stem width-thickness ratio( P < 0. 01). The experimental results suggested that within a certain range,the dendrobine content was higher in D. nobile with flatter stem. Therefore,in the breeding of D. nobile,this specific trait could be used for screening plants with high content of quality indexes such as dendrobine.
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Dendrobium , Agricultura , Dendrobium/genética , Melhoramento Vegetal , Folhas de Planta/genética , PolissacarídeosRESUMO
Dendrobium denneanum have been used for a long time as rare medicinal herbs in traditional Chinese medicine. Our previous works found that ether extract of D. denneanum had higher anticancer activities than alcohol or water extract,thus with better development prospects. Quantitative proteomics based on SILAC technique was used to investigate the anticancer mechanism of D. denneanum on lung tumor cell line A549,and 4 855 proteins were detected in A549 cells. Quantitative proteomics experiments found that 193 proteins of A549 cells were up-regulated,and 44 proteins were down-regulated by ether extract of D. denneanum. Those proteins are associated with synthesis,transport and metabolism of biological macromolecules,chaperone,DNA repair,oxidoreductase,cell adhesion,cell cycle,apoptosis and autophagy. Through the function analysis of differentially expressed proteins,it was inferred that ether extract of D. denneanum caused cell protein metabolism disorder,endoplasmic reticulum stress response,abnormal self-repair mechanism of cells,damage of cell adhesion and proliferation; besides,it caused a dramatic increase in ROS level in A549 cells,and upset the balance of intracellular oxidation reduction system. Affected by the above factors,lung cancer cells initiated apoptosis and autophagy,which accelerated cell death. This research explains the anticancer mechanism of D. denneanum from the perspective of quantitative proteomics,and lays a foundation for future research and development of new anticancer drugs based on ether extract of D. denneanum.
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Dendrobium , Neoplasias Pulmonares , Células A549 , Animais , Apoptose , Éter , Humanos , ProteômicaRESUMO
MAIN CONCLUSION: This review summarizes current knowledge of chromosome characterization, genetic mapping, genomic sequencing, quality formation, floral transition, propagation, and identification in Dendrobium. The widely distributed Dendrobium has been studied for a long history, due to its important economic values in both medicine and ornamental. In recent years, some species of Dendrobium and other orchids had been reported on genomic sequences, using the next-generation sequencing technology. And the chloroplast genomes of many Dendrobium species were also revealed. The chromosomes of most Dendrobium species belong to mini-chromosomes, and showed 2n = 38. Only a few of genetic studies were reported in Dendrobium. After revealing of genomic sequences, the techniques of transcriptomics, proteomics and metabolomics could be employed on Dendrobium easily. Some other molecular biological techniques, such as gene cloning, gene editing, genetic transformation and molecular marker developing, had also been applied on the basic research of Dendrobium, successively. As medicinal plants, insights into the biosynthesis of some medicinal components were the most important. As ornamental plants, regulation of flower related characteristics was the most important. More, knowledge of growth and development, environmental interaction, evolutionary analysis, breeding of new cultivars, propagation, and identification of species and herbs were also required for commercial usage. All of these studies were improved using genomic sequences and related technologies. To answer some key scientific issues in Dendrobium, quality formation, flowering, self-incompatibility and seed germination would be the focus of future research. And genome related technologies and studies would be helpful.
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Dendrobium/genética , Genoma de Planta/genética , Genômica , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Dendrobium/classificação , Dendrobium/fisiologia , Genoma de Cloroplastos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Plantas Medicinais , Reprodução , Análise de Sequência de DNARESUMO
Coordinated regulation of various acid survival systems in response to environmental stimuli is crucial for the adaptation of enteropathogenic bacteria to acidic environments such as the stomach. In this study, we demonstrated that the RovM protein, a central regulator of the CsrABC-RovM-RovA cascade, conversely regulates the expression of two acid survival systems in Yersinia pseudotuberculosis by acting as a dual transcriptional regulator. RovM activated the expression of T6SS4, which is essential for bacterial survival under mild acidic conditions, by binding upstream of the T6SS4 promoter. On the contrary, RovM repressed the expression of a functional arginine-dependent acid resistance system (AR3), which is crucial for bacterial survival under strong acidic conditions, by directly binding to the -35 element in the AR3 promoter. Consistent with previous findings that rovM expression responds to the availability of nutrients, the expression of T6SS4 and AR3 was differentially regulated by nutritional status. Based on these results, a dynamic model whereby RovM coordinately regulates the expression of AR3 and T6SS4 in response to the availability of nutrients in the environment was proposed.
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Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Sistemas de Secreção Tipo VI/metabolismo , Yersinia pseudotuberculosis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Yersinia pseudotuberculosis/genéticaRESUMO
Taking the significance of the special microenvironment for tumor cell survival into account, disrupting tumor redox homeostasis is highly prospective for improving therapeutic efficacy. Herein, a multifunctional 2D vanadium-based MXene nanoplatform, V4 C3 /atovaquone@bovine albumin (V4 C3 /ATO@BSA, abbreviated as VAB) has been elaborately constructed for ATO-enhanced nanozyme catalytic/photothermal therapy. The redox homeostasis within the tumor cells is eventually disrupted, showing a remarkable anti-tumor effect. The VAB nanoplatform with mixed vanadium valence states can induce a cascade of catalyzed reactions in the tumor microenvironment, generating plenty of reactive oxygen species (ROS) with effective glutathione consumption to amplify oxidative stress. Meanwhile, the stable and strong photothermal effect of VAB under near-infrared irradiation not only causes the necrosis of tumor cells, but also improves its peroxidase-like activity. In addition, the release of ATO can effectively alleviate endogenous oxygen consumption to limit triphosadenine formation and inhibit mitochondrial respiration. As a result, the expression of heat shock proteins is effectively suppressed to overcome thermoresistance and the production of ROS can be further promoted due to mitochondrial injury. Moreover, VAB also presents high photoacoustic and photothermal imaging performances. In brief, the multifunctional nanoplatform can provide ATO-enhanced nanozyme catalytic/photothermal therapy with broadening the biomedical applications of vanadium-based MXene.
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Neoplasias , Nitritos , Terapia Fototérmica , Elementos de Transição , Animais , Bovinos , Vanádio , Estudos Prospectivos , Espécies Reativas de Oxigênio , Homeostase , Oxirredução , Neoplasias/terapia , Catálise , Microambiente Tumoral , Linhagem Celular Tumoral , Peróxido de HidrogênioRESUMO
Nanozyme activity is greatly weakened by the microenvironment and multidrug resistance of tumor cells. Hence, a bi-catalytic nanoplatform, which promotes the anti-tumor activity through "charging empowerment" and "mutual complementation" processes involved in enzymatic and pyroelectric catalysis, by loading ultra-small nanoparticles (USNPs) of pyroelectric ZnSnO3 onto MXene nanozyme (V2CTx nanosheets), is developed. Here, the V2CTx nanosheets exhibit enhanced peroxidase activity by reacting V3+ with H2O2 to generate toxic ·OH, accelerated by the near-infrared (NIR) light mediated heat effect. The resulting V4+ is then converted to V3+ by oxidizing endogenous glutathione (GSH), realizing an enzyme-catalyzed cycle. However, the cycle will lose its persistence once GSH is insufficient; nevertheless, the pyroelectric charges generated by ZnSnO3 USNPs continuously support the V4+/V3+ conversion and ensure nanoenzyme durability. Moreover, the hyperthermia arising from the V2CTx nanosheets by NIR irradiation results in an ideal local temperature gradient for the ZnSnO3 USNPs, giving rise to an excellent pyroelectric catalytic effect by promoting band bending. Furthermore, polarized charges increase the tumor cell membrane permeability and facilitate nanodrug accumulation, thereby resolving the multidrug resistance issue. Thus, the combination of pyroelectric and enzyme catalysis together with the photothermal effect solves the dilemma of nanozymes and improves the antitumor efficiency.
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Antineoplásicos , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Catálise , Linhagem Celular Tumoral , Raios Infravermelhos , Nanopartículas/química , Glutationa/química , Glutationa/metabolismo , Animais , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , CamundongosRESUMO
Nanoformulations with endogenous/exogenous stimulus-responsive characteristics show great potential in tumor cell elimination with minimal adverse effects and high precision. Herein, an intelligent nanotheranostic platform (denoted as TPZ@Cu-SnS2-x /PLL) for tumor microenvironment (TME) and near-infrared light (NIR) activated tumor-specific therapy is constructed. Copper (Cu) doping and the resulting sulfur vacancies can not only improve the response range of visible light but also improve the separation efficiency of photogenerated carriers and increase the carrier density, resulting in the ideal photothermal and photodynamic performance. Density functional theory calculations revealed that the introduction of Cu and resulting sulfur vacancies can induce electron redistribution, achieving favorable photogenerated electrons. After entering cells through endocytosis, the TPZ@Cu-SnS2-x /PLL nanocomposites show the pH responsivity property for the release of the TPZ selectively within the acidic TME, and the released Cu2+ can first interact with local glutathione (GSH) to deplete GSH with the production of Cu+ . Subsequently, the Cu+ -mediated Fenton-like reaction can decompose local hydrogen peroxide into hydroxyl radicals, which can also be promoted by hyperthermia derived from the photothermal effect for tumor cell apoptosis. The integration of photoacoustic/computed tomography imaging-guided NIR phototherapy, TPZ-induced chemotherapy, and GSH-elimination/hyperthermia enhanced chemodynamic therapy results in synergistic therapeutic outcomes without obvious systemic toxicity in vivo.
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The medicinal plant Dendrobium nobile is an important natural antioxidant resource. To reveal the antioxidants of D. nobile, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed for metabolic analysis. The H2O2-induced oxidative damage was used in human embryonic kidney 293T (H293T) cells to assess intracellular antioxidant activities. Cells incubated with flower and fruit extracts showed better cell survival, lower levels of reactive oxygen species (ROS), and higher catalase and superoxide dismutase activities than those incubated with root, stem, and leaf extracts (p < 0.01). A total of 13 compounds were newly identified as intracellular antioxidants by association analysis, including coniferin, galactinol, trehalose, beta-D-lactose, trigonelline, nicotinamide-N-oxide, shikimic acid, 5'-deoxy-5'-(methylthio)adenosine, salicylic acid, isorhamnetin-3-O-neohespeidoside, methylhesperidin, 4-hydroxybenzoic acid, and cis-aconitic acid (R2 > 0.8, Log2FC > 1, distribution > 0.1%, and p < 0.01). They showed lower molecular weight and higher polarity, compared to previously identified in vitro antioxidants in D. nobile (p < 0.01). The credibility of HPLC-MS/MS relative quantification was verified by common methods. In conclusion, some saccharides and phenols with low molecular weight and high polarity helped protect H293T cells from oxidative damage by increasing the activities of intracellular antioxidant enzymes and reducing intracellular ROS levels. The results enriched the database of safe and effective intracellular antioxidants in medicinal plants.
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Electronic components with tunable resistance, especially with synergistic regulation of thermal conductivity, play important roles in the fields of electronics, smart switch, soft robots, and so on. However, it is still a challenge to get the material with various resistance and thermal conductivity stably without lasting external force. Herein, a liquid metal shape memory polymer foam (LM-SMF) is developed by loading electrically and thermally conductive liquid metal (LM) on deformable foam skeleton. Based on thermal response shape memory effect, the foam skeleton can be reversibly pressed, the process of which enables LM to transfer between connected and disconnected states. As a result, obtained LM-SMF shows that the resistance stably changes from 0.8 Ω (conductor) to 200 MΩ (insulator), and the thermal conductivity difference is up to 4.71 times (0.108 to 0.509 W m-1 K-1 ), which indicates that LM-SMF can achieve the electrical and thermal dual-regulation. Moreover, LM-SMF can be used as a designable self-feedback/-warning integrated smart switch or tunable infrared stealth switch. This work proposes a novel strategy to get the material with electrical-thermal coordinated dual-regulation, which is possibly applied in intelligent heating system with real-time monitoring function, electrothermal sensor in the future.
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Responsive nanosystems for tumor treatment with high specificity and sensitivity have aroused great attention. Herein, we develop a tumor microenvironment responsive and near-infrared (NIR)-activatable theranostic nanoreactor for imaging-guided anticancer therapy. The nanoreactor (SnO2-x@AGP) is comprised of poly(vinylpyrrolidine) encapsulated hollow mesoporous black SnO2-x nanoparticles coloaded with glucose oxidase (GOx) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The constructed nanoreactor can be specifically activated through endogenous H2O2 by an NIR-mediated "bursting-like" process to enhance its imaging and therapeutic functions. Black SnO2-x with abundant oxygen vacancies expedites effective separation of electron-hole pairs from energy-band structure and endows them with strong hyperthermia effect upon NIR laser irradiation. The generating toxic H2O2 with the assistance of GOx provides SnO2-x@AGP with the capacity of oxidative stress therapy. Ascended H2O2 can activate ABTS into ABTSâ¢+. ABTSâ¢+ not only possesses significant NIR absorption properties, but also disrupts intracellular glutathione to generate excessive reactive oxygen species for improved phototherapy, leading to more effective treatment together with oxidative stress therapy. Thus, SnO2-x@AGP with NIR-mediated and H2O2-activated performance presents tumor inhibition efficacy with minimized damage to normal tissues. These outstanding characteristics of SnO2-x@AGP bring an insight into the development of activatable nanoreactors for smart, precise, and non-invasive cancer theranostics.