A Functional "Key" Amplified Piezoelectric Effect Modulates ROS Storm with an Open Source for Multimodal Synergistic Cancer Therapy.

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.

An Active Strategy Based on Different Droplet Removal Modes on Polydimethylsiloxane Magnetic Microstructures.

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.

Defect-Engineered Tin Disulfide Nanocarriers as "Precision-Guided Projectile" for Intensive Synergistic Therapy.

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.

Synergizing Pyroelectric Catalysis and Enzyme Catalysis: Establishing a Reciprocal and Synergistic Model to Enhance Anti-Tumor Activity.

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 (V2 CTx nanosheets), is developed. Here, the V2 CTx nanosheets exhibit enhanced peroxidase activity by reacting V3+ with H2 O2 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 V2 CTx 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.

Three-Step Depletion Strategy of Glutathione: Tunable Metal-Organic-Framework-Engineered Nanozymes for Driving Oxidative/Nitrative Stress to Maximize Ferroptosis Therapy.

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.

Architecture of Vanadium-Based MXene Dysregulating Tumor Redox Homeostasis for Amplified Nanozyme Catalytic/Photothermal Therapy.

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.

Biomineralized RuO2 Nanozyme with Multi-Enzyme Activity for Ultrasound-Triggered Peroxynitrite-Boosted Ferroptosis.

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.

Revealing of Intracellular Antioxidants in Dendrobium nobile by High Performance Liquid Chromatography-Tandem Mass Spectrometry.

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.

Application of omics technology to investigate the mechanism underlying the role of San Hua Tang in regulating microglia polarization and blood-brain barrier protection following ischemic stroke.

ETHNOPHARMACOLOGY RELEVANCE: San Hua Tang (SHT) was first mentioned in the book "The Collection of Plain Questions about Pathogenesis, Qi, and Life." SHT has the effect of dispelling wind and dredging collaterals, dredging viscera, and guiding stagnation, and is used in the treatment of ischemic stroke (IS). SHT is composed of Rheum palmatum L., Magnolia officinalis Rehder & E.H.Wilson, Citrus assamensis S.Dutta & S.C.Bhattacharya, and Notopterygium tenuifolium M.L.Sheh & F.T.Pu, which is the traditional prescription of the Tongxia method for the treatment of stroke. Tongxia is one of the "eight methods" used in traditional Chinese medicine, which plays a role in treating diseases by promoting gastrointestinal peristalsis and defecation. Studies have demonstrated a close relationship between gut microbiota metabolism and cerebral stroke; however, the role of SHT in IS treatment through gut microbiota or intestinal metabolites is unclear. AIM OF THE STUDY: To explore the connotation of the Xuanfu theory and clarify the mechanism underlying SHT-mediated opening Xuanfu methods. Through metabolomics, 16S rRNA gene sequencing, and molecular biology techniques, research on the changes in the gut microbiota and blood-brain barrier (BBB) will highlight greater strategies for the treatment of stroke. MATERIALS AND METHODS: We used pseudo-germ-free (PGF) rats combined with an ischemia/reperfusion (I/R) rat model for the follow-up experimental research. PGF rats were prepared by the intragastric administration of an antibiotic cocktail for 6 days, following which SHT was administered for 5 consecutive days. The I/R model was performed 1 day following the concluding administration of SHT. We detected the neurological deficit score, cerebral infarct volume, serum inflammatory factor levels (interleukin IL-6, IL-10, IL-17, and tumor necrosis factor alpha), tight junction-related proteins (Zonula occludens-1, Occludin, and Claudin-5), and small glue plasma cell-associated proteins (Cluster of Differentiation 16/Cluster of Differentiation 206, Matrix metalloproteinase, ionized calcium-binding adapter molecule 1, and C-X3-C Motif Chemokine Ligand 1) 24 h following I/R. Using 16S rRNA gene sequencing and non-targeted metabolomics analysis, we explored the relationship between fecal microecology and serum metabolites. Eventually, we analyzed the correlation between the gut microbiota and plasma metabolic profile as well as the mechanism underlying the SHT-mediated regulation of gut microbiota to protect the BBB following stroke. RESULTS: In IS treatment, SHT is principally involved in reducing neurological injury and the volume of cerebral infarction; protecting the intestinal mucosal barrier; increasing the levels of acetic acid, butyric acid, and propionic acid; promoting the transformation of microglia to the M2 state; reducing inflammatory reactions; and enhancing tight junctions. These therapeutic effects were not observed in the group treated with antibiotics alone or that treated with SHT in combination with antibiotics, thereby indicating SHT plays a therapeutic role through the gut microbiota. CONCLUSION: SHT regulates the gut microbiota, inhibits pro-inflammatory factors in rats with IS, alleviates an inflammatory injury of the BBB, and plays a protective role in the brain.

2D Piezoelectric BiVO4 Artificial Nanozyme with Adjustable Vanadium Vacancy for Ultrasound Enhanced Piezoelectric/Sonodynamic Therapy.

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 •- 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.

Paenibacillus dendrobii sp. nov., an indole-3-acetic acid-producing endophytic bacterium isolated from Dendrobium nobile.

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 1.0 % 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 98.2 % sequence similarity. The DNA-DNA hybridization values between strain HJL G12T and the two reference strains were 23.6 % and 24.9 %, respectively. Menaquinone-7 was the only respiratory quinone and meso-diaminopimelic acid was present in the cell-wall peptidoglycan. Antesio-C15 : 0 and iso-C16 : 0 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.

Dual Nanozyme-Driven PtSn Bimetallic Nanoclusters for Metal-Enhanced Tumor Photothermal and Catalytic Therapy.

Specific generation of reactive oxygen species (ROS) within tumors in situ catalyzed by nanozymes is a promising strategy for cancer therapeutics. However, it remains a significant challenge to fabricate highly efficient nanozymes acting in the tumor microenvironment. Herein, we develop a bimetallic nanozyme (Pt50Sn50) with the photothermal enhancement of dual enzymatic activities for tumor catalytic therapy. The structures and activities of PtSn bimetallic nanoclusters (BNCs) with different Sn content are explored and evaluated systematically. Experimental comparisons show that the Pt50Sn50 BNCs exhibit the highest activities among all those investigated, including enzymatic activity and photothermal property, due to the generation of SnO2-x with oxygen vacancy (Ovac) sites on the surface of Pt50Sn50 BNCs. Specifically, the Pt50Sn50 BNCs exhibit photothermal-enhanced peroxidase-like and catalase-like activities, as well as a significantly enhanced anticancer efficacy in both multicellular tumor spheroids and in vivo experiments. Due to the high X-ray attenuation coefficient and excellent light absorption property, the Pt50Sn50 BNCs also show dual-mode imaging capacity of computed tomography and photoacoustic imaging, which could achieve in vivo real-time monitoring of the therapeutic process. Therefore, this work will advance the development of noble-metal nanozymes with optimal composition for efficient tumor catalytic therapy.

Tumor-Specific NIR-Activatable Nanoreactor for Self-Enhanced Multimodal Imaging and Cancer Phototherapy.

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 ABTS•+. ABTS•+ 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.

Designable Electrical/Thermal Coordinated Dual-Regulation Based on Liquid Metal Shape Memory Polymer Foam for Smart Switch.

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.

As a novel anticancer candidate, ether extract of Dendrobium nobile overstimulates cellular protein biosynthesis to induce cell stress and autophagy.

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.

Fatty Acid Biosynthesis Pathways Are Downregulated during Stigma Development and Are Critical during Self-Incompatible Responses in Ornamental Kale.

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.

Quantitative Identification of Antioxidant Basis for Dendrobium Nobile Flower by High Performance Liquid Chromatography-Tandem Mass Spectrometry.

Dendrobium nobile is a beautiful orchid and a widely used medicinal plant. In vitro antioxidant assays suggested that D. noblie flower extracts showed significantly higher 2, 2'-azinobis-3-ethylbenzthiazoline-6-sulfonate (ABTS) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging rates and much more ferric-reducing power than those of root, stem, leaf and fruit. To better understand the antioxidant basis of D. nobile flower, high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was used for metabolic identification and quantification. Finally, there were 72 metabolites among the total of 712 identified components showed significant association (coefficient >0.8, p < 0.05) with ABTS scavenging rates, DPPH scavenging rates, and ferric-reducing power. The three enriched classes of flower metabolites, including amino acids and their derivatives, organic acids and their derivatives, and flavonoids, formed the main antioxidant basis. The significantly accumulated rutin, astragalin, isomucronulatol-7-O-glucoside, quercetin 4'-O-glucoside, methylquercetin O-hexoside, caffeic acid, caffeic acid O-glucoside, and p-coumaric acid (Log2(fold change) >2, p < 0.01, distribution in flower >0.1%) made a key contribution to the higher antioxidant activities in flower. The relative quantification results of HPLC-MS/MS were verified by the common quantification methods. The antioxidant basis revealed of D. nobile flower will be helpful in the production of healthy or beauty products.

Dual Glutathione Depletion Enhanced Enzyme Catalytic Activity for Hyperthermia Assisted Tumor Therapy on Semi-Metallic VSe2/Mn-CS.

Semimetallic nanomaterials as photothermal agents for bioimaging and cancer therapy have attracted tremendous interest. However, the poor photothermal stability, low biocompatibility, and single component limit their therapeutic efficiency in cancer treatment. Here, manganese-doped VSe2 semimetallic nanosheets were prepared and subsequently modified with chitosan (named VSe2/Mn-CS NSs) for combined enzyme catalytic and photothermal therapy. VSe2/Mn-CS NSs show high photothermal property with a photothermal conversion efficiency of 34.61% upon 808 nm near-infrared laser irradiation. In the tumor microenvironment, VSe2/Mn-CS NSs can convert endogenous H2O2 into lethal hydroxyl radicals (•OH) to induce cancer cell apoptosis. The interaction between glutathione (GSH) and Se-Se bonds in VSe2/Mn-CS NSs results in the depletion of GSH level, and the valence states transition of manganese ions is also beneficial for the GSH consumption. This dual depletion of GSH markedly enhances the peroxidase (POD) activity, leading to the high •OH production and the improved therapeutic effect. What is more, the T1-weighted magnetic resonance and photoacoustic imaging endow VSe2/Mn-CS NSs with the ability to guide and track the treatment process. Our study provides a research strategy for the application of semimetallic nanomaterials in cancer diagnosis and treatment.

Engineering oxygen vacancy of MoOx nanoenzyme by Mn doping for dual-route cascaded catalysis mediated high tumor eradication.

There is an urgent need to develop photosensitive nanoenzymes with better phototherapeutic efficiency through simple processes. By exploiting semiconductor catalysis and defect chemistry principles, herein, a MnMoOx composite semiconductor nanoenzyme was developed to achieve a fully integrated theranostic nanoenzyme for highly efficient photo/chemo-enzyme-dynamic eradication of deep tumors. Relative to iron oxides, manganese oxides offer ideal catalytic performance under near-neutral conditions, which helps to broaden the suitable pH range of the MnMoOx nanoenzyme for antitumor therapy. Furthermore, with the assistance of glutathione depletion, Mn4+/Mo6+ was successfully converted to Mn2+/Mo5+, inhibiting the scavenging of reactive oxygen species (ROS) and promoting cycling. Therefore, MnMoOx has favorable catalase (CAT)-like activity and oxidase (OXD)-like activity in the tumor microenvironment (TME) for promoting the "H2O2O2O2-" and "H2O2OH" cascade reactions. The abundant oxygen vacancy defects also promote the surface plasmon resonance (SPR) effect in the second near-infrared (NIR-II) window of MnMoOx, which significantly enhanced its photothermal therapy (PTT) effect and catalytic activity. In detail, ROS production was significantly enhanced due to the adsorption of water and oxygen molecules by the rich oxygen vacancies of MnMoOx. MnMoOx also exhibited excellent multi-modal imaging activity (including computed tomography (CT), magnetic resonance imaging (MRI), and photoacoustic (PA)), which can be exploited to better guide the administration of medication.

Myricetin Restores Aß-Induced Mitochondrial Impairments in N2a-SW Cells.

Alzheimer's disease (AD) is the most common type of dementia that occurs in the elderly. Amyloid hypothesis is one of the most studied pathological mechanisms, and ß-amyloid (Aß) is the drug target for most clinical trials. Mitochondrial dysfunction induced by the Aß-precursor protein (APP)/Aß has been suggested to play a key role in the development of AD. Here, we explored the effects of myricetin, a polyphenol compound abundant in fruits and vegetables, on mitochondrial damages in N2a-SW cells. After the treatment of myricetin, mitochondrial depolarization was improved by increasing the mitochondrial membrane potential. Mitochondrial biogenesis as well as mitochondrial genome integrity was enhanced via increased levels of PGC-1α, Nrf1, TFAM, and the copy number of mtDNA. Mitochondrial functions were restored as represented by the increased levels of proteins involved in the electron transport chain and the adenosine 5'-triphosphate (ATP) content and the decreased concentration of ROS. Mitochondrial dynamics and mitophagy were ameliorated through the regulation of proteins involved in fusion (OPA1 and Mfn2), fission (Drp1 and Fis1), and mitophagy (PINK1 and Parkin). Thus, it is summarized that myricetin could recover the mitochondrial impairments in N2a-SW cells, exhibiting the potential to promote neuroprotection for APP/Aß-related diseases, including AD.