Search

Phototherapeutic nanoplatforms that combine photodynamic therapy (PDT) and photothermal therapy (PTT) with the guidance of photoacoustic (PA) imaging are an effective strategy for the treatment of tumors, but establishing a universal method for this strategy has been challenging. In this study, we present a supramolecular assembly strategy based on Förster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent (PcDA) via the anion and cation supramolecular interaction between two water‐soluble phthalocyanine ramifications, PcD and PcA. This approach promotes the absorption of energy, thus enhancing the generation of reactive oxygen species (ROS) and heat by PcDA, improving its therapeutic efficacy, and overcoming the low photon utilization efficiency of conventional PSs. Notably, after the intravenous injection of PcDA, neoplastic sites could be clearly visualized using PA imaging, with a PA signal‐to‐liver ratio as high as 11.9. Due to these unique features, PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light irradiation. This study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging. [ABSTRACT FROM AUTHOR]

Glufosinate‐ammonium (GLA) is a widely used herbicide, but less research has been done on its harmful effects on non‐target organisms, especially aquatic organisms. In this study, 600 adult zebrafish were exposed to different concentration of GLA (0, 1.25, 2.5, 5, 10, and 20 mg/L) for 7 days, and the livers were dissected on the eighth day to examine the changes in liver structure, function, oxidative stress, inflammation, apoptosis, and Nrf2 pathway, and finally to clarify the mechanism of GLA induced liver injury in zebrafish. The levels of alanine aminotransferase, aspartate aminotransferase, reactive oxygen species, malondialdehyde, inflammatory factors (IL‐6 and TNF‐α), and caspase‐3 gradually increased, while the levels of superoxide dismutase, catalase, glutathione, and glutathione peroxidase gradually decreased with the increase of GLA concentration. The Nrf2 pathway was activated at low concentrations (1.25–5 mg/L) and significantly inhibited at high concentrations (10 and 20 mg/L). These results suggested that GLA could cause oxidative stress, inflammation, and apoptosis in zebrafish liver. Therefore, GLA can cause liver injury in zebrafish, and at high concentrations, the inhibition of Nrf2 pathway is one of the important causes of liver injury. [ABSTRACT FROM AUTHOR]

Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O2∙−) and singlet oxygen (1O2) in water under light irradiation, which were 2.6-fold and 15.4-fold higher than those of free PcSA, respectively. Furthermore, PcSA@Lip was able to accumulate selectively in tumors after intravenous injection with the fluorescence intensity ratio of tumors to livers was 4.1:1. The significant tumor inhibition effects resulted in a 98% tumor inhibition rate after PcSA@Lip was injected intravenously at an ultra-low PcSA@Lip dose (0.8 nmol g−1 PcSA) and light dose (30 J cm−2). Therefore, the liposomal PcSA@Lip is a prospective nanophotosensitizer possessing hybrid type I and type II photoreactions with efficient photodynamic anticancer effects. [ABSTRACT FROM AUTHOR]

While light is the basic element for inducing vision and modulating circadian rhythms, excessive light has been reported to have a negative effect on the survival of various types of retinal cells. Among them photoreceptors and retinal pigment epithelial (RPE) cells degeneration after light exposure is widely observed, but light-induced retinal ganglion cell (RGC) damage achieves relatively little attention. The purpose of this article is to summarize the experimental evidence for the possible negative effects of excessive light on RGCs. By searching the database, twenty-six related articles have been included. Taken together, excessive light may insult RGCs through the three main ways: (i) directly action on RGC mitochondria, as well as DNA, resulting in an upregulation of reactive oxygen species (ROS) and subsequently caspase-dependent or -independent cell death; (ii) mediation in gliotransmitters or relevant receptors of retinal glial cells; and (iii) a secondary event to photoreceptors and RPE cells degeneration and subsequent retinal remodeling. So RGCs can certainly be injured by excessive light, especially when they are already energetically compromised in some diseases. And more attentions should be paid to this topic to take timely measures to protect these frail RGCs from being damaged by excessive light. [ABSTRACT FROM AUTHOR]

A multifunctional PC10A/DOX/MoS2 hydrogel was designed and prepared for chemotherapy/photothermal therapy/photodynamic therapy of 4T1 tumor, and the immune responses triggered by photothermal and photodynamic effect of MoS2 nanosheet in the hydrogel were also studied. Positively charged DOX and negatively charged PC10A were loaded on the surface of MoS2 nanosheet through layer-by-layer method to prepare hybrid PC10A/DOX/MoS2 nanoparticles. PC10A/DOX/MoS2 nanoparticles were dispersed in PC10A hydrogel to prepare PC10A/DOX/MoS2 hydrogel. 2D MoS2 nanosheet in the hydrogel was simultaneously utilized as photothermal agent and photodynamic agent for the generation of hyperthermia and reactive oxygen species, respectively. This PC10A/DOX/MoS2 hydrogel was injectable and possessed excellent biocompatibility. The results of in vivo tumor-bearing mice experiments showed that a remarkably enhance tumor inhibition was observed by the combination of chemo-photothermal-photodynamic therapy compared with photothermal therapy, photodynamic therapy, or chemotherapy alone. In addition, the results of in vivo therapy exhibited that the PC10A/DOX/MoS2 hydrogel with laser irradiation could activate antitumor immune effects to suppress the growth of primary 4T1 breast tumors and distal lung metastatic nodules. Therefore, these results demonstrated that the PC10A/DOX/MoS2 hydrogel was promising to be utilized in antitumor immunity therapy triggered by photothermal therapy and photodynamic therapy for malignant tumor. [ABSTRACT FROM AUTHOR]

[Display omitted] • A self-degradable phthalocyanine nano-assembly (NanoPcDA2) was developed for photothermal therapy. • NanoPcDA2 possessed excellent photothermal effect and biosecurity capability. • NanoPcDA2 could be degraded by singlet oxygen produced by itself and lose photoactivity after PTT. • The photo-degradation products of NanoPcDA2 showed negligible cytotoxicity. Photothermal therapy (PTT) possesses a great promise for tumor therapy due to its effective tumor inhibition and minimal invasiveness. Nevertheless, most of organic photothermal agents (PTAs) suffer from poor photothermal conversion efficiency, and the residues of PTAs may cause the problem of side effects. Herein, we utilize a molecular surgery approach to develop a self-degradable nanostructured PTA (NanoPcDA2). NanoPcDA2 exhibited a remarkable photothermal conversion efficiency. In addition, NanoPcDA2 showed an outstanding tumor accumulation after intravenous injection, and 92% tumor growth was suppressed in the mice tumor model at a low light dose of 300 J cm−2 and a NanoPcDA2 dose of 0.8 nmol g−1. Moreover, NanoPcDA2 can be degraded by singlet oxygen (1O 2) produced by itself and lose its photoactivity after PTT. Notably, the photo-degradation products of NanoPcDA2 have negligible cytotoxicity. In this way, it not only contributes to resolve the potential phototoxicity problems of residual PTAs, but also can expedite the metabolism of PTAs to avert the potential biotoxicity of drug accumulation. [ABSTRACT FROM AUTHOR]

In order to reduce the intramolecular charge-transfer (ICT) effect of amine groups on the photophysical properties of zinc (II) phthalocyanine (ZnPc), tertiary amines were covalently connected with ZnPc ring via ethyl p-hydroxybenzoate or diethyl 5-hydroxyisophthalate. Six new tertiary amine-modified ZnPcs were therefore synthesized and characterized. Meanwhile, the corresponding quaternary ammonium ZnPcs were also synthesized. The effects of different substitution ways (mono-substitutions, symmetrical tetra-substitutions, or asymmetric tetra-substitutions) and the numbers of different substitutions on the photophysical and physicochemical properties of these ZnPcs were studied. All twelve ZnPcs had relatively high singlet oxygen quantum yields (Φ Δ = 0.32–0.68) and fluorescence quantum yields (Φ F = 0.23–0.40), where the amine-containing substituents did not show obvious ICT effect. All ZnPcs showed effective phototoxicity towards breast cancer cells (IC 50 = 63–366 nmol/L). Among them, three tetra-substituted ZnPcs containing quaternary ammonium groups (4aN , 4bN and 4cN) showed the best in vitro anticancer photodynamic activities with IC 50 = 64–76 nmol/L, which owned to their relatively high cellular uptake. The tumor inhibition rate of 4aN on H22 tumor-bearing mice reached 87% (4aN dose: 3 nmol/g; light dose: 685 nm, 135 J/cm2). • 12 new amine-modified zinc (II) phthalocyanines were synthesized and characterized. • The effects of different substitution ways of 12 ZnPcs were studied. • 12 ZnPcs showed relatively high Φ Δ = 0.32–0.68 and Φ F = 0.23–0.40. • 12 ZnPcs showed significant PDT effect on cancer cells (IC 50 = 63–366 nmol/L). • The tumor inhibition rate of 4aN on H22 tumor-bearing mice reached 87%. [ABSTRACT FROM AUTHOR]

Given their superior penetration depths, photosensitizers with longer absorption wavelengths present broader application prospects in photodynamic therapy (PDT). Herein, Ag2S quantum dots were discovered, for the first time, to be capable of killing tumor cells through the photodynamic route by near‐infrared light irradiation, which means relatively less excitation of the probe compared with traditional photosensitizers absorbing short wavelengths. On modification with polydopamine (PDA), PDA‐Ag2S was obtained, which showed outstanding capacity for inducing reactive oxygen species (increased by 1.69 times). With the addition of PDA, Ag2S had more opportunities to react with surrounding O2, which was demonstrated by typical triplet electron spin resonance (ESR) analysis. Furthermore, the PDT effects of Ag2S and PDA‐Ag2S achieved at longer wavelengths were almost identical to the effects produced at 660 nm, which was proved by studies in vitro. PDA‐Ag2S showed distinctly better therapeutic effects than Ag2S in experiments in vivo, which further validated the enhanced regulatory effect of PDA. Altogether, a new photosensitizer with longer absorption wavelength was developed by using the hitherto‐unexplored photodynamic function of Ag2S quantum dots, which extended and enhanced the regulatory effect originating from PDA. [ABSTRACT FROM AUTHOR]

Summary: Cold, a major environmental stress for plants, has been studied intensively for decades. Its response system has been revealed, especially at the transcriptional level. The mechanisms underlying recovery growth and environmental adaptation, however, remain unknown.Taking advantage of a naturally existing system, two subspecies of Asian cultivated rice (Oryza sativa) with significant divergence in chilling tolerance, we analyzed representative japonica and indica varieties, Nipponbare and 93‐11, using comparative metabolomic analysis at six time points covering chilling treatment and recovery.In total, 223 known metabolites were detected. During chilling treatment, significant biochemical changes were centered on antioxidation. During recovery, a wide‐ranging chilling response was observed. Large‐scale amino acid accumulation occurred, consistent with the appearance of chilling injury. At the mid‐treatment stage, the accumulation of antioxidation‐related compounds appeared earlier in Nipponbare than in 93‐11, consistent with the higher reactive oxygen species (ROS) levels in japonica vs indica varieties. A significant contribution of ROS‐mediated gene regulation, rather than the C‐repeat binding factor/dehydration‐responsive‐element binding factor (CBF/DREB) regulon, to the more vigorous transcriptional stress response in Nipponbare was revealed by RNA‐seq. Accordingly, during recovery, the induction of stress‐tolerant‐related metabolites was more active in the chilling‐tolerant variety Nipponbare. Senescence‐related compounds accumulated only in the chilling‐sensitive variety 93‐11.Our study uncovers the dynamic metabolic models underlying chilling response and recovery, and reveals a ROS‐dominated rice adaptation mechanism to low‐temperature environments. [ABSTRACT FROM AUTHOR]

Heme proteins perform diverse biological functions, of which myoglobin (Mb) is a representative protein. In this study, the O 2 carrier Mb was shown to cleave double stranded DNA upon aerobic dithiothreitol-induced reduction, which is fine-tuned by an additional distal histidine, His29 or His43, engineered in the heme active center. Spectroscopic (UV–vis and EPR) and inhibition studies suggested that free radicals including singlet oxygen and hydroxyl radical are responsible for efficient DNA cleavage via an oxidative cleavage mechanism. On the other hand, L29E Mb, with a distinct heme active center involving three water molecules in the met form, was found to exhibit an excellent DNA cleavage activity that was not depending on O 2 . Inhibition and ligation studies demonstrated for the first time that L29E Mb cleaves double stranded DNA into both the nicked circular and linear forms via a hydrolytic cleavage mechanism, which resembles native endonucleases. This study provides valuable insights into the distinct mechanisms for DNA cleavage by heme proteins, and lays down a base for creating artificial DNA endonucleases by rational design of heme proteins. Moreover, this study suggests that the diverse functions of heme proteins can be fine-tuned by rational design of the heme active center with a hydrogen-bonding network. [ABSTRACT FROM AUTHOR]

An integrative method based on the combination of electrochemical reduction (ECR) and in-situ electrochemiluminescence (ECL) detection was developed for the sensitive detection of the nitroaromatic compounds (NACs), including 4-nitrotoluene (4-NT), 2,4-dinitrotoluene (2,4-DNT), 2,4,6-trinitrotoluene (TNT). An electrochemical flow cell including two working electrodes was fabricated with poly(dimethylsiloxane) (PDMS) to achieve the dual functions. The first one is a copper mesh electrode, acting as the reductor to convert the NACs to aminoaromatic compounds (AACs). Electrochemical deposition of copper nanoparticles on the surface of the copper mesh was conducted to further increase the reduction efficiency. The second one is an ECL electrode, which was used for in-situ detection of the reduced products. The ECL electrode was fabricated by the immobilization of Ru(bpy) 3 2+ on a glassy carbon electrode (GCE) with the Nafion/the multi-wall carbon nanotubes (MWCNTs) composite film. The copper mesh electrode was arranged directly underneath the ECL electrode to ensure the reduced products could be immediately detected in-situ. An electrolytic solution consists of 33.3 mmol/L Na 2 SO 4 and 16.7 mmol/L phosphate buffer solution (PBS, pH7.0) was found to be optimum for both the electrochemical reduction of the NACs and the ECL detection. The ECL intensities were proportional to the concentrations of 4-NT, 2,4-DNT and TNT in the range from 1.0 × 10 −9 to 1.0 × 10 −5 , 3.5 × 10 −9 to 1.0 × 10 −5 and 7.5 × 10 −9 to 1.0 × 10 −5 mol/L respectively. The limit of detections (LOD) were 4.0 × 10 −10 , 1.7 × 10 −9 and 3.1 × 10 −9 mol/L respectively for 4-NT, 2,4-DNT and TNT. The reduction mechanism was preliminarily investigated and it was found that the presence of oxygen was critical for the reduction process, suggesting that the reductive oxygen species O 2 − , O H could be involved in the NACs reduction process. [ABSTRACT FROM AUTHOR]

Due to the significance of reactive oxygen species (ROS) in numerous physiological processes including pathogen response, apoptosis, and induction of defense genes, various methods have been developed for their quantitative analysis. However, the conventional methods using exogenous tracers lack the capability to conduct real-time in vivo measurements. The electrochemical biosensors have shown their potentials for in vivo applications with the rapid and reagentless detection processes. In this article, electrochemical biosensors that are capable of making in vivo ROS detections are reviewed. The different configurations of these biosensors with corresponding strategies to enhance sensitivity and selectivity are discussed in detail. With further studies to promote the biosensor performance, these devices promise to provide more facile ways for ROS research in life sciences. [ABSTRACT FROM AUTHOR]

The NLR family pyrin domain containing 3 (NLRP3) inflammasome is a widely studied inflammasome that plays a critical role in inflammatory responses. Many triggers, including microbial pathogens (ie, bacteria and viruses) and other signals (ie, reactive oxygen species, adenosine triphosphate, urate, silicon, and asbestos), can stimulate the NLRP3 inflammasome. Liver ischemia/reperfusion (I/R) injury is a common pathologic process during liver surgery and shock and can induce severe liver damage. Although its pathogenesis is still unclear, oxidative stress and overproduction of the inflammatory response are likely to contribute to I/R injury. The NLRP3 inflammasome is activated during the I/R process, resulting in further recruitment and activation of caspase-1. Activated caspase-1 cleaves the pro-forms of interleukin-1β and interleukin-18 and results in their maturation, triggering a proinflammatory cytokine cascade and causing liver damage. Bruton's tyrosine kinase is a critical molecule involved in diverse cellular pathways, such as proliferation, apoptosis, inflammation, and angiogenesis. Intrahepatic Bruton's tyrosine kinase is mainly expressed on Kupffer cells and sinusoidal endothelial cells, and the inflammasome is activated in Kupffer cells. Our study found that inhibition of Bruton's tyrosine kinase effectively attenuated liver I/R injury by suppressing activation of the NLRP3 inflammasome in Kupffer cells. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Oxidative phosphorylation (OXPHOS) has attracted a considerable attention in CRC. It is of great interest to explore novel therapies that inhibit OXPHOS for CRC treatment. Compound 6c is a novel naphthalimide derivative. However, the effects of 6c on CRC and the underlying mechanism are unclear. In this study, 6c suppressed CRC tumor growth and metastasis. RNA-seq data showed that 6c triggered the inhibition of OXPHOS and tricarboxylic acid cycle. 6c specifically inhibited mitochondrial complex III activity and the expression of isocitrate dehydrogenase 2 (IDH2), resulting in oxidative stress. Antioxidants reversed 6c-induced cell death, senescence, and autophagosomes formation. 6c inhibited autophagy flux; however, pretreatment with autophagy inhibitors resulted in the reduction of 6c-induced cytoplasmic vacuolization and proliferation inhibition. Moreover, combinatory treatment of 6c and mitoxantrone (MIT) showed stronger inhibitory effects on CRC compared with the single agent. Downregulation of IDH2 induced reactive oxygen species production, leading to MIT accumulation and autophagic cell death after co-treatment with 6c and MIT. In summary, our findings indicated 6c as a promising candidate for CRC treatment. [ABSTRACT FROM AUTHOR]

Abscess wound caused by bacterial infection is usually difficult to heal, thus greatly affect people's quality of life. In this study, a biodegradable drug-loaded microneedle patch (MN) is designed for targeted eradication of S. aureus infection and repair of abscess wound. Firstly, the bacterial responsive composite nanoparticle (Ce6@GNP-Van) with a size of about 182.6 nm is constructed by loading the photosensitizer Ce6 into gelatin nanoparticle (GNP) and coupling vancomycin (Van), which can specifically target S. aureus and effectively shield the phototoxicity of photosensitizer during delivery. When Ce6@GNP-Van is targeted and enriched in the infected regions, the gelatinase secreted by the bacteria can degrade GNP in situ and release Ce6, which can kill the bacteria by generating ROS under laser irradiation. In vivo experiments show that the microneedle is basically degraded in 10 min after inserting into skin, and the abscess wound is completely healed within 13 d after applying Ce6@GNP-Van-loaded MN patch to the abscess wound of the bacterial infected mice with laser irradiation, which can simultaneously achieve the eradication of biofilm and subsequent wound healing cascade activation, showing excellent synergistic antibacterial effect. In conclusion, this work establishes a synergistic treatment strategy to facilitate the repair of chronic abscess wound. The biodegradable MN patch is loaded with enzyme-responsive antimicrobial nanoparticle Ce6@GNP-Van was developed in this study for eradicating traumatic bacterial infection and promoting stalled healing of abscess wound. The responsive MN system has the following features: (1) the MN patch can physically penetrate and disrupt the bacterial biofilm structure after being applied to the infected site to facilitate the release of the antimicrobial agent; (2) the loading of Ce6 into GNP nanoparticle significantly inhibits the ability of singlet oxygen production and avoids phototoxicity during delivery; (3) Ce6@GNP-Van can target the bacterial community and release the drug only in response to the gelatinase secreted by the bacterial community, and generate a large amount of ROS under laser irradiation, which enhances the specific killing to bacteria by the nanoparticle and thus promotes the wound repairation. The experimental results show that the combination of antimicrobial therapy and MN drug delivery system can meet the requirements of precise targeting of bacteria and stimulation of responsive drug release through rational design, which is expected to achieve wider application in wound healing. [Display omitted] [ABSTRACT FROM AUTHOR]

• HPT with anti-inflammatory and high thermal conversion properties was prepared. • The photothermal conversion efficiency of HPT is as high as 43.18%. • HPT can significantly reduce inflammatory response by removing various ROS. • HPT can effectively relieve the RA disease symptoms and inhibit bone erosion. Rheumatoid arthritis (RA) is an autoimmune disease, in which inflammatory macrophages play a crucial role by secreting a large number of proinflammatory factors to aggravate inflammatory response. In addition, reactive oxygen species (ROS) are abundant in hypoxic joints, inducing chondrocyte apoptosis and causing irreversible bone destruction. In this work, we synthesized hyaluronic acid-modified platinum-tellurium nanorods (HPT) as a photothermal agent to target RA joints, ablating inflammatory macrophages and scavenging ROS in the microenvironment. Hyaluronic acid can specifically bind to the CD44 receptors, which are over-expressed on the surface of inflammatory macrophages, achieving active targeting and improving therapy effectiveness. Under the irradiation of an 808 nm laser, thermal energy produced by HPT, which has high photothermal conversion efficiency is sufficient to induce apoptosis of inflammatory macrophages. Simultaneously, platinum particles on the surface of tellurium nanorods can effectively remove a variety of ROS, reducing oxidative stress and alleviating inflammatory response in RA joints. Collagen-induced arthritis (CIA) mice had been used to study the therapeutic potential of HPT. The results revealed that the clinical scores in CIA mice injected with HPT and irradiated with a near-infrared laser were significantly reduced. The inflammatory response was also obviously relieved, when compared with CIA mice injected with PBS. Micro-CT imaging revealed that bone erosion was visibly reduced in the HPT + Laser group. These results demonstrate that multifunctional HPT is promising to serve as a therapeutic platform for the treatment of RA. [ABSTRACT FROM AUTHOR]

Three novel neonicotinoids (cycloxaprid, flupyradifurone and sulfoxaflor) were designed to reduce the biotoxicity for non-target organisms. These neonicotinoids were photolyzed under light radiation, but it was unclear for the photo-enhanced toxicity and influences of the novel modifying group of the three neonicotinoids. The photolysis and photo-enhanced toxicity experiments were performed for the three neonicotinoids, coupled with quantum chemistry calculation, the mechanisms of photolysis, photo-enhanced toxicity and the influences of novel modifying groups were analyzed. The results showed the photolysis pathways were enriched as compared with previous neonicotinoids due to the composition of modifying groups, singlet oxygen and hydroxyl participated the photolysis of cycloxaprid and flupyradifurone. All tested neonicotinoids exhibited photo-enhanced toxicity to Vibrio fischeri. Due to the difference of photolysis mechanism and toxicity to V. fischeri , the photo-enhanced toxicity curves showed diverse variation when histidine, tert -butanol or dissolved organic matters was in presence of the test solutions. The impact of novel modifying groups over photolysis and photo-enhanced toxicity were analyzed based on the comparison with previous neonicotinoids, theoretically predicted UV-Vis spectra and photo-physical/chemical property descriptors. The data showed the composition of novel modifying group increased the light absorption and photo-chemical activities for the three neonicotinoids. [Display omitted] • Photolysis and photo-enhanced toxicity of three neonicotinoids were determined. • Mechanisms of photolysis and photo-enhanced toxicity were investigated. • Solutes influenced the photolysis and photo-enhanced toxicity of neonicotinoids. • Novel modifying groups improved the photochemical response of neonicotinoids. [ABSTRACT FROM AUTHOR]

TMEM126A is a mitochondrial transmembrane protein, and its functions in breast cancer progression remain unclear. In this study, via the iTRAQ assay using primary and metastatic breast cancer cell models, we found that TMEM126A expression decreased in metastatic cells. We further confirmed that low TMEM126A expression correlated with tumor progression and poor prognosis in patients. The downregulation of TMEM126A in breast cancer cell lines significantly enhanced the metastatic properties in vitro and in vivo, whereas its overexpression decreased the metastatic potential of cell lines. Mechanistic studies based on RNA-sequencing indicated that TMEM126A might regulate cell metastasis via ECM-receptor interaction, focal adhesions, and actin cytoskeleton, among other processes. Furthermore, the loss of TMEM126A activated extracellular matrix (ECM) remodeling and promoted epithelial-to-mesenchymal transition (EMT). Moreover, TMEM126A silencing induced reactive oxygen species (ROS) production and mitochondrial membrane potential depolarization. The ROS scavengers reversed ECM remodeling and EMT mediated by TMEM126A. Collectively, our findings show that the loss of TMEM126A induces mitochondrial dysfunction and subsequently metastasis by activating ECM remodeling and EMT. These findings suggest that TMEM126A is a novel suppressor of metastasis and that it can be a potential prognostic indicator for patients with breast cancer. [ABSTRACT FROM AUTHOR]

• All four neonicotinoids exhibit photo-enhanced toxicity to V. fischeri with different toxic responses because of diverse photolysis mechanism for different main structure. • ROSs play important roles in the photolysis process and photo-enhanced toxicity. • A developed theoretical equation can well explain the toxicity variations of four neonicotinoids. Neonicotinoids are widely used pesticides that contaminate aquatic environments. Although these chemicals can be photolyzed under sunlight radiation, it is unclear for the relationship between photolysis mechanism and toxicity change in aquatic organisms. This study aims to determine the photo-enhanced toxicity of four neonicotinoids with different main structures (acetamiprid, and thiacloprid for cyano-amidine structure, imidacloprid and imidaclothiz for nitroguanidine). To Achieve the goal, photolysis kinetics, effect of dissolved organic matter (DOM) and reactive oxygen species (ROSs) scavengers on photolysis rates, photoproducts, and photo-enhanced toxicity to Vibrio fischeri were investigated for four neonicotinoids. The results showed direct photolysis plays a key role in the photo-degradation of imidacloprid and imidaclothiz (photolysis rate constants are 7.85 × 10−3 and 6.48 × 10−3 min−1, respectively), while the photosensitization process of acetamiprid and thiacloprid was dominated by ·OH reactions and transformation (photolysis rate constants are 1.16 × 10−4 and 1.21 × 10−4 min−1, respectively). All four neonicotinoid insecticides exerted photo-enhanced toxicity to Vibrio fischeri , indicating photolytic product(s) posed greater toxicity than their parent compounds. The addition of DOM and ROS scavengers influenced photo-chemical transformation rates of parent compounds and their intermediates, leading to diverse effects on photolysis rates and photo-enhanced toxicity for the four insecticides as a result of different photo-chemical transformation processes. Based upon the detection of chemical structures of intermediates and Gaussian calculations, we observed different photo-enhanced toxicity mechanisms for the four neonicotinoid insecticides. Molecular docking was used to analyze the toxicity mechanism of parent compounds and photolytic products. A theoretical model was subsequently employed to describe the variability of toxicity response to each of the four neonicotinoids. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: In this paper, poly-o-phenylenediamine and Pt microparticle modified Pt electrode (POPD/Pt-MP/Pt) as microbiosensor has been developed to monitor in vivo oxidative burst induced by ultraviolet A (UV-A) and ultraviolet C (UV-C) radiation stress in oilseed rape (Brassica napus L.). Twice oxidative bursts were detected, appearing at 2 and 25h, respectively. According to the peak area of amperometry, the amount of H2O2 induced by UV stress was estimated to be 6.2×10−10 and 3.1×10−10 mol for such two oxidative bursts in detected leafstalk, respectively. This novel microbiosensor provides an effective tool for studying the defense reaction of the plant in the situation of UV stress and probing the antioxidative mechanism of the antioxidative enzyme. [Copyright &y& Elsevier]

• Engineered polypeptide was firstly used as a nanoreactor for in situ synthesis of Te-NRs. • Engineered polypeptide was used to improve the biocompatibility of Te nanorods. • P-TeNRs possessed excellent photothermal conversion performance and sonodynamic property. • The use of Te nanorods for sonodynamic therapy of tumors was firstly reported. Nanoparticles containing elemental tellurium (Te) have been aroused extensive attention in biomedical applications. However, the ideal synthesis methods and effective anti-cancer strategies of Te nanoparticles remain great challenges. In this study, genetically engineered polypeptide (PC 10 ARGD)-capped Te nanorods (P-TeNRs) was in situ synthesized. The excellent dispersion of P-TeNRs with average lengths of 25.2 ± 4.65 nm and diameters of 6.5 ± 0.83 nm were confirmed by TEM. PC 10 ARGD was integrated onto the surface of Te nanorods to enhance the stability and biocompatibility of P-TeNRs. P-TeNRs exhibited the excellent photothermal conversion performance under irradiation of NIR laser and the reactive oxygen species (ROS) generating capacity under ultrasound (US) irradiation, which can achieve photothermal therapy and sonodynamic therapy of tumors. Compared with single photothermal therapy and sonodynamic therapy, the results of in vitro and in vivo experiments showed that the combination therapy has a synergistic effect on breast 4T1 tumors. In addition, the results of in vivo toxicity assay suggested that synthesized P-TeNRs presented negligible toxicity. These results demonstrate that this P-TeNRs can be engineered as a novel theranostic nanoplatform for synergistic photothermal-sonodynamic therapy of tumors. [ABSTRACT FROM AUTHOR]

Abstract: Peroxiredoxins (Prxs) are believed to play an important role in insects for protection against the toxicity of reactive oxygen species (ROS). A gene encoding a novel 1-Cys Prx was firstly identified and characterized from an expressed sequence tag database (EST) in the lepidopteran insect, Bombyx mori. The 1-Cys Prx of B. mori (BmPrx) cDNA contained an open reading frame of 672 bp encoding a protein of 223 amino acid residues with calculated molecular mass of 25 kDa and included conserved cysteine residues signature motifs (PVCT) in the N-terminus amino acid. Sequence comparison showed that BmPrx shared 53 to 64% identity with other species 1-Cys proteins. RT-PCR revealed that the BmPrx transcripts were present in all tissues and developmental stages. The coding sequence was cloned and expressed as a 30-kDa protein in Escherichia coli. The purified enzyme acted as a catalyst in ferrithiocyanate system and protected supercoiled form of plasmid DNA from damage in metal-catalyzed oxidation (MCO) system in vitro. In addition, real-time PCR analysis indicated that significant rise of the transcripts level of BmPrx was induced by temperature stress including low and high temperature stimuli. [Copyright &y& Elsevier]

Phthalocyanines are promising photosensitizers for photodynamic therapy (PDT), but the inherent tendency of aggregation generally leads to the decrease or even quenching of photoactivities. To address this issue and realize the desirable photodynamic therapeutic effect of phthalocyanines, herein, we report a folate-modified phthalocyanine-based liposomal nanophotosensitizer (PcN@Lip-FA), which can be prepared through a facile "one-pot" method. An analogue (PcN@Lip) without folate was also prepared as a negative control. The liposomal nanophotosnesitizers greatly prevented the aggregation of the zinc(II) phthalocyanine (PcN) and showed highly efficient photoactivities (fluorescence and singlet oxygen generation) in aqueous solutions, although the free PcN is severely aggregated and its photoactivities are nearly quenched. The in vitro results demonstrate that PcN@Lip-FA can be taken in by folate receptor (FR)-positive HeLa cells through FR-mediated process, and exhibits significantly higher cellular uptake and photocytotoxicity against HeLa cells than both PcN@Lip and PcN , but for FR-negative MCF-7 cells, PcN@Lip-FA and PcN@Lip show comparable photocytotoxicity. In addition, with the folate vector, PcN@Lip-FA has highly efficient tumor targeting and PDT effect on the S180 rat ascitic tumor-bearing mice with a tumor inhibition rate up to 98.0%. Therefore, the liposomal nanophotosensitizer PcN@Lip-FA can serve as a promising nanoplatform for cancer diagnosis and targeted PDT. Image 1 • A folate-modified phthalocyanine-based liposomal nanophotosnesitizer was prepared. • The liposomal carrier reduced aggregation and enhanced photoactivities of free PcN. • PcN@Lip-FA could selectively kill HeLa cells with enhanced photodynamic activity. • PcN@Lip-FA had highly efficient tumor targeting and in vivo photodynamic efficacy. • Its tumor inhibition rate on the S180 rat ascitic tumor-bearing mice was up to 98.0%. [ABSTRACT FROM AUTHOR]

Nanocarrier for augmenting the efficacy of reactive oxygen species (ROS) by tumor microenvironment (TME) has become an emerging strategy for cancer treatment. Herein, a smart biodegradable drug delivery nanoplatform with mitochondrial-targeted ability, pH-responsive drug release and enzyme-like catalytic function is designed. This efficient ROS-generating platform uses ultrasound with deeper penetration capability as excitation source for combined chemotherapy and sonodynamic therapy (SDT) of tumor. In vitro experiments show that the nanoplatform can co-load Ce6 and DOX and be degraded in slight acid environment, and the DOX release rate is 63.91 ± 1.67%. In vivo experiments show that the nanoplatform has extremely biosafety and can be enriched in tumor site and excluded from body after 24 h. More significantly, after combined treatment, the tumors are eliminated and the mice still survive healthily without recurrence after 60 d. This is because not only it can achieve mitochondrial targeting and use platinum particle to increase oxygen content in TME to enhance the effect of SDT, but also it can use weak acidic TME to accelerate drug release to achieve the combination of chemotherapy and SDT. The probe provides a new strategy for designing ROS-based nanoplatform for the treatment of malignant tumor. [ABSTRACT FROM AUTHOR]