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Increasing oxygen (O2) content and down‐regulating the concentration of glutathione (GSH) in tumor microenvironment (TME) by multiple approaches remain critical factors for the promotion of phototherapeutic effect, especially for photodynamic therapy (PDT). Herein, indocyanine green (ICG) laden dendritic mesoporous manganese‐silicon nanocomposite (NC) is designed and subsequently managed with calcification through in situ growth of calcium phosphate (IDMMS@CaP NC). As specific response behavior of the mildly acidic and GSH overexpressed TME, the IDMMS@CaP NC can rapidly collapse when accumulated at the tumor site, liberate Mn2+, Ca2+, and ICG, simultaneously reduce the concentration of GSH. Mn2+ can catalyze endogenous hydrogen peroxide to produce O2. Overloaded Ca2+ induces mitochondrial injury, and reduces cellular metabolism and O2 consumption. The photothermal effect from ICG with 808 nm laser irradiation can not only cause tumor cells necrosis but also accelerate blood flow to further improve the O2 content at the tumor site. Consequently, owing to effective GSH depletion and multiple O2 compensation, the PDT efficiency of ICG can be significantly increased. As proof of concept, the designed multifunctional nanocomposite will provide a general strategy for enhancing the role of phototherapy in cancer therapeutic area. [ABSTRACT FROM AUTHOR]

Highlights: Recent advancement in Type II nano-photosensitizers (AIE nanodots, carbon dots and metal nanoclusters) are reviewed. Nanoplasmonic strategies in enhancing singlet oxygen generation efficiency of different metal-photosensitizer (planar and colloidal) systems are discussed. Current challenges and future prospects of metal-enhanced nano-photosensitizers for advanced photodynamic therapy and theranostic treatment are highlighted.The great promise of photodynamic therapy (PDT) has thrusted the rapid progress of developing highly effective photosensitizers (PS) in killing cancerous cells and bacteria. To mitigate the intrinsic limitations of the classical molecular photosensitizers, researchers have been looking into designing new generation of nanomaterial-based photosensitizers (nano-photosensitizers) with better photostability and higher singlet oxygen generation (SOG) efficiency, and ways of enhancing the performance of existing photosensitizers. In this paper, we review the recent development of nano-photosensitizers and nanoplasmonic strategies to enhance the SOG efficiency for better PDT performance. Firstly, we explain the mechanism of reactive oxygen species generation by classical photosensitizers, followed by a brief discussion on the commercially available photosensitizers and their limitations in PDT. We then introduce three types of new generation nano-photosensitizers that can effectively produce singlet oxygen molecules under visible light illumination, i.e., aggregation-induced emission nanodots, metal nanoclusters (< 2 nm), and carbon dots. Different design approaches to synthesize these nano-photosensitizers were also discussed. To further enhance the SOG rate of nano-photosensitizers, plasmonic strategies on using different types of metal nanoparticles in both colloidal and planar metal-PS systems are reviewed. The key parameters that determine the metal-enhanced SOG (ME-SOG) efficiency and their underlined enhancement mechanism are discussed. Lastly, we highlight the future prospects of these nanoengineering strategies, and discuss how the future development in nanobiotechnology and theoretical simulation could accelerate the design of new photosensitizers and ME-SOG systems for highly effective image-guided photodynamic therapy. [ABSTRACT FROM AUTHOR]

Bark beetles mainly rely on detoxification enzymes to resist the host tree's defense against oleoresin terpenes. Cytochrome P450 enzymes (CYPs) play an important role in the detoxification of plant allelochemicals and pesticides in insect. One P450 gene (DaCYP4BQ1) is associated with the response of (+)-α-pinene in Dendroctonus armandi. However, the regulatory mechanism of this P450 gene response to (+)-α-pinene is still unknown. In this study, spatiotemporal expression profiling indicated that CYP4BQ1 was highly expressed in adult and larval stages of D. armandi, and it was predominantly expressed in fat body, midgut, and Malpighian tubules of adults. Moreover, the expression of CYP4BQ1 significantly increased after exposure to (+)-α-pinene, and depletion of it decreased the tolerance of adults to (+)-α-pinene. In addition, (+)-α-pinene treatment induced the expression of the transcription factors cap 'n' collar isoform C (CncC) and its binding factor muscle aponeurosis fibromatosis (Maf), elevated the level of hydrogen peroxide (H2O2), and increased the activities of antioxidant enzymes. Silencing CncC suppressed CYP4BQ1 expression and enhanced the susceptibility of beetles to (+)-α-pinene. Similarly, application of the reactive oxygen species (ROS) scavenger N-acetylcysteine reduced the production and accumulation of H2O2, suppressed the expression of CncC, Maf, and CYP4BQ1 and led to decreased tolerance of adults to (+)-α-pinene. In contrast, ingestion of the CncC agonist curcumin elevated CYP4BQ1 expression and enhanced (+)-α-pinene tolerance. The results demonstrate that, in D. armandi, (+)-α-pinene induces CYP4BQ1 via activation of the ROS/CncC signaling pathway. [ABSTRACT FROM AUTHOR]

Single‐atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task to precisely conduct catalysis at tumor sites after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations of SAzymes in the anticancer application are still in its infancy and need to be developed. Herein, an in situ synthesis strategy for Cu SAzyme was constructed to convert adsorbed copper ions into isolated atoms anchored by oxygen atoms (Cu−O2/Cu−O4) via GSH‐responsive deformability of supports. Our results suggest that the in situ activation process could further facilitate the dissociation of copper ions and the consumption of glutathione, thereby leading to copper deposition in cytoplasm and triggering cuproptosis. Moreover, the in situ synthesis of Cu SAzyme with peroxidase‐like activity enabled the intracellular reactive oxygen species production, resulting in specifically disturbance of copper metabolism pathway. Meanwhile, the in situ exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block the glycose uptake to boost cuproptosis efficacy. Overall, this in situ activation strategy effectively diminished the off‐target effects of SACs‐induced catalytic therapies and introduced a promising treatment paradigm for advancing cuproptosis‐associated therapies. [ABSTRACT FROM AUTHOR]

Single‐atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task to precisely conduct catalysis at tumor sites after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations of SAzymes in the anticancer application are still in its infancy and need to be developed. Herein, an in situ synthesis strategy for Cu SAzyme was constructed to convert adsorbed copper ions into isolated atoms anchored by oxygen atoms (Cu−O2/Cu−O4) via GSH‐responsive deformability of supports. Our results suggest that the in situ activation process could further facilitate the dissociation of copper ions and the consumption of glutathione, thereby leading to copper deposition in cytoplasm and triggering cuproptosis. Moreover, the in situ synthesis of Cu SAzyme with peroxidase‐like activity enabled the intracellular reactive oxygen species production, resulting in specifically disturbance of copper metabolism pathway. Meanwhile, the in situ exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block the glycose uptake to boost cuproptosis efficacy. Overall, this in situ activation strategy effectively diminished the off‐target effects of SACs‐induced catalytic therapies and introduced a promising treatment paradigm for advancing cuproptosis‐associated therapies. [ABSTRACT FROM AUTHOR]

We herein present an approach of photo‐induced disproportionation for preparation of Type‐I photodynamic agents. As a proof of concept, BODIPY‐based photosensitizers were rationally designed and prepared. The photo‐induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH4), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O2−⋅). One of our Type‐I photodynamic agents not only self‐assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O2), with a half‐maximal inhibitory concentration (IC50) of 0.96 μM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors. [ABSTRACT FROM AUTHOR]

We herein present an approach of photo‐induced disproportionation for preparation of Type‐I photodynamic agents. As a proof of concept, BODIPY‐based photosensitizers were rationally designed and prepared. The photo‐induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH4), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O2−⋅). One of our Type‐I photodynamic agents not only self‐assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O2), with a half‐maximal inhibitory concentration (IC50) of 0.96 μM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors. [ABSTRACT FROM AUTHOR]

With the rapid development of external minimally invasive or noninvasive therapeutic modalities, ultrasound‐based sonodynamic therapy (SDT) is a new alternative for treating deep tumors. However, inadequate sonosensitizer efficiency and poor biosecurity limit clinical applications. In this study, we prepared an oxygen‐vacancy‐engineered W18O49−x nanobrush with a band gap of 2.79 eV for highly efficient SDT using a simple solvothermal method. The suitable band structures of the W18O49−x nanobrush endows it with the potential to simultaneously produce singlet oxygen (1O2), superoxide anions (⋅O2−), and hydroxyl radicals (⋅OH) under ultrasound irradiation. Additionally, abundant oxygen vacancies that serve as further charge traps that inhibit electron‐hole recombination are incidentally introduced through one‐step thermal reduction. Collectively, the in vitro and in vivo results demonstrate that the oxygen‐vacancy‐engineered W18O49−x nanobrush delivers highly efficient reactive oxygen species (ROS) for SDT in a very biosafe manner. Overall, this study provides a new avenue for discovering and designing inorganic nanosonosensitizers with enhanced therapeutic efficiencies for use in SDT. [ABSTRACT FROM AUTHOR]

With the rapid development of external minimally invasive or noninvasive therapeutic modalities, ultrasound‐based sonodynamic therapy (SDT) is a new alternative for treating deep tumors. However, inadequate sonosensitizer efficiency and poor biosecurity limit clinical applications. In this study, we prepared an oxygen‐vacancy‐engineered W18O49−x nanobrush with a band gap of 2.79 eV for highly efficient SDT using a simple solvothermal method. The suitable band structures of the W18O49−x nanobrush endows it with the potential to simultaneously produce singlet oxygen (1O2), superoxide anions (⋅O2−), and hydroxyl radicals (⋅OH) under ultrasound irradiation. Additionally, abundant oxygen vacancies that serve as further charge traps that inhibit electron‐hole recombination are incidentally introduced through one‐step thermal reduction. Collectively, the in vitro and in vivo results demonstrate that the oxygen‐vacancy‐engineered W18O49−x nanobrush delivers highly efficient reactive oxygen species (ROS) for SDT in a very biosafe manner. Overall, this study provides a new avenue for discovering and designing inorganic nanosonosensitizers with enhanced therapeutic efficiencies for use in SDT. [ABSTRACT FROM AUTHOR]

[Display omitted] • A single-atom photocatalytic membrane (FeCN) was successfully fabricated. • The photocatalytic membrane achieved a reaction rate of 0.225 m·s−1 while maintaining 100% removal of pollutants. • Ultra-long term zero-fouling performance was obtained during ultra-low pressure filtration process for over 100 h. • The membrane fouling accumulation rate can reach to a relative balance with the catalytic degradation rate. Flow-through catalytic membrane reactors aim to achieve a long-term safe and stable operation through the catalytic performance of the membrane itself. However, applications are hindered by the easy deactivation of catalytic sites and insufficient catalytic efficiency in complex aqueous environments and long-term operation. Here, a model is proposed that anchors Fe single atoms to the 2D material g-C 3 N 4 and combines it with a gravity-driven ultra-low-pressure filtration system to enhance the membrane catalytic performance and reduce the pollutant accumulation rate, respectively. In addition, Fe sites have a stronger adsorption energy for acetylaminophenol (APAP) and reactive oxygen species, thus increasing their contact in the filtration catalysis process. The efficient catalytic layer combined with the restricted space between the membranes endowed the membrane with a 100% APAP removal efficiency and a reaction rate of 0.225 m s−1 which is 5–7 orders of magnitude higher than conventional photocatalytic reactions. Even after ultra-long filtration time (100 h), 85% APAP removal and zero fouling accumulation can be achieved in real water samples. Compared with the reported technology, the pollutant degradation capacity of this work is improved by 3 orders of magnitude and almost negligible energy consumption. This system has nearly 100% degradation efficiency for various water pollutants and can be combined with other AOPs processes, revealing the importance of ultra-low-pressure filtration and the introduction of single atoms for mobile catalytic systems. [ABSTRACT FROM AUTHOR]

Highlights • Ferroptosis is a new form of nonapoptotic programmed cell death. • Molecular mechanisms and pathways for ferroptosis regulation are presented. • Nanomaterials as inducers of ferroptosis for cancer specific therapy are reviewed. • System Xc−, GPX4 and iron metabolism are the major regulation targets of ferroptosis. Abstract Ferroptosis is a new form of nonapoptotic programmed cell death characterized by iron-dependent accumulation of lipid hydroperoxides to lethal levels. An increasing number of studies have in recent years revealed close relationships between ferroptosis and nanomedicine, which has been regarded as a new strategy for developing nanomaterial-based therapeutic agents for highly effective therapy of various cancers. In this review, the molecular mechanisms and pathways for ferroptosis regulation were first presented; then, various nanomaterials that induce ferroptosis for cancer specific therapy were systematically discussed; finally, the current challenges and constructive perspectives in this field were provided. [ABSTRACT FROM AUTHOR]

Zinc (Zn) is a fundamental trace element for cell viability and physiology, and concentrations above the physiological level may lead to cell damage. In order to explore the effect of zinc chloride (ZnCl 2 ) on murine photoreceptor cells, in this study, we investigated the alterations of murine photoreceptor cell proliferation and cell morphology after exposure to various concentrations of ZnCl 2 , determined the levels of hydrogen peroxide, hydroxyl radicals, cytochrome c , and ATP before and after cells exposure to different concentrations of ZnCl 2 , monitored the changes of mitochondrial membrane potential, and further explored the expressions of BCL2-associated X (Bax) and B cell CLL/lymphoma (Bcl)-2 at gene and protein levels. The results indicated that appropriate ZnCl 2 levels can enhance the cell proliferation, whereas high levels of ZnCl 2 could apparently inhibit cell growth, exaggerate the generation of both hydrogen peroxide and hydroxyl radicals, collapse the mitochondrial membrane potential, and accelerate cytochrome c release into cytosol, decrease the ATP production, elevate the Bax production, and reduce the Bcl-2 expression, thereby disrupting the mitochondrial homeostasis. Consequently, the disrupted mitochondrial homeostasis initiates the mitochondria-mediated apoptotic signaling pathway, leading to cell death. Taken together, the results suggest that the over generation of reactive oxygen species and the activated mitochondrial signaling pathway play an important role in ZnCl 2 -induced murine photoreceptor cell death. [ABSTRACT FROM AUTHOR]

NADPH oxidases (NOX) - derived reactive oxygen species (ROS) contribute to oxidative injury in hypoxia-induced pulmonary arterial hypertension. This study aims to evaluate the status of NOX in endothelial progenitor cells (EPCs) under hypoxic condition and to determine whether NOX inhibitors could attenuate hypoxia-induced dysfunctions of EPCs. EPCs were isolated from peripheral blood of SD rats and subjected to hypoxia (O 2 /N 2 /CO 2 , 1/94/5) for 24 h. The cells were collected for β-galactosidase or Hoechst staining, or for functional analysis (migration, adhesion and tube formation). The NOX expression, activity and H 2 O 2 content in EPCs were measured. The results showed that hypoxia treatment promoted EPC senescence and apoptosis, accompanied by the deteriorated functions of EPCs (the reduced abilities in adhesion, migration and tube formation), as well as an increase in NOX2 and NOX4 expression, NOX activity and H 2 O 2 production, these phenomena were attenuated by NOX inhibitors. Furthermore, administration of catalase could also improve the functions of hypoxia-treated EPCs. Based on these observations, we conclude that NOX-derived ROS contributes to the dysfunctions of EPCs under hypoxic condition. Thus, suppression of NOX may provide a novel strategy to improve endothelial functions in hypoxia-relevant diseases. [ABSTRACT FROM AUTHOR]

As a man-made additive, chromium picolinate Cr(pic) 3 has become a popular dietary supplement worldwide. In this paper Cr(pic) 3 and its new derivatives Cr(6-CH 3 -pic) 3 ( 1 ), [Cr(6-NH 2 -pic) 2 (H 2 O) 2 ]NO 3 ( 2 ) and Cr(3-NH 2 -pic) 3 ( 3 ) were synthesized, and complexes 1 and 2 were characterized by X-ray crystal structure (where pic = 2-carboxypyridine). The relationship between the chemical properties and biotoxicity of these complexes was fully discussed: (1) The dynamics stability of chromium picolinate complexes mainly depends on the Cr N bonds length. (2) There is a positive correlation between the dynamics stability, electrochemical potentials and generation of reactive oxygen species through Fenton-like reaction. (3) However, no biological toxicity was observed through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and sub-chronic oral toxicity study for these chromium picolinate compounds. Together, our findings establish a framework for understanding the structure-property-toxicity relationships of the chromium picolinate complexes. [ABSTRACT FROM AUTHOR]

Human gastric cancer is the fifth common cancer with considerable metastasis potential, and its high incidence and mortality rate threaten public health. In this study, we examined the anticancer effects of lobaplatin on the human gastric carcinoma cell line BGC-823 in vitro , and explored its relative mechanisms. The results of MTT assay showed dose- and time-dependent cytotoxicity in BGC-823 cells with lobaplatin. Flow cytometry (FCM) assay indicated that lobaplatin affected BGC-823 cells’ survival by inducing apoptosis. Western blot analysis also demonstrated that the occurrence of its apoptosis was associated with activation of Cleaved caspase-3 and Bax, downregulation of Bcl-2. Moreover, lobaplatin could also increase the reactive oxygen species (ROS) slightly and decrease the mitochondrial membrane potential (Δ Ym ) obviously, elucidating that lobaplatin may induce apoptosis via mitochondria-dependent apoptotic pathway. Furthermore, lobaplatin markedly blocked BGC-823 cells migration and invasion, and the reduction of matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed in vitro . Our findings demonstrated the chemotherapeutic potential of lobaplatin for treatment of human gastric carcinoma cell line BGC-823 by inhibiting proliferation, inducing apoptosis and attenuating cell migration and invasion. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) play an important role in signal transduction and metabolism. Over-produced ROS in cells or tissues, however, often leads to oxidation stress that has implications in a series of diseases including cancer, aging, atherosclerosis and inflammation. Driven by the need for on-demand drug delivery and fuelled by recent development of ROS-responsive materials and nanomedicine, responsive drug delivery systems (DDSs) have gained increasing research interest. ROS-responsive DDS is designed to release therapeutic agents only in targets of interest that produce excessive ROS, which may lead to both enhanced therapeutic efficiency and reduced side effects. Multiple-stimuli responsive DDSs that are also sensitive to other stimuli can further enhance controlled drug release in sites where multiple stimuli coexist. Beyond drug delivery, multifunctional DDSs have great potential in achieving simultaneous imaging, combinatorial therapy and targeting ability by introducing multifunctional elements such as signal reporter, targeting elements and photosensitizer. This review will summarize the latest development of ROS-responsive DDSs and discuss their design principle and biomedical applications. [ABSTRACT FROM AUTHOR]

Aims Recent studies suggest that proarrhythmic effects of cardiac glycosides (CGs) on cardiomyocyte Ca2+ handling involve generation of reactive oxygen species (ROS). However, the specific pathway(s) of ROS production and the subsequent downstream molecular events that mediate CG-dependent arrhythmogenesis remain to be defined. Methods and results We examined the effects of digitoxin (DGT) on Ca2+ handling and ROS production in cardiomyocytes using a combination of pharmacological approaches and genetic mouse models. Myocytes isolated from mice deficient in NADPH oxidase type 2 (NOX2KO) and mice transgenically overexpressing mitochondrial superoxide dismutase displayed markedly increased tolerance to the proarrhythmic action of DGT as manifested by the inhibition of DGT-dependent ROS and spontaneous Ca2+ waves (SCW). Additionally, DGT-induced mitochondrial membrane potential depolarization was abolished in NOX2KO cells. DGT-dependent ROS was suppressed by the inhibition of PI3K, PKC, and the mitochondrial KATP channel, suggesting roles for these proteins, respectively, in activation of NOX2 and in mitochondrial ROS generation. Western blot analysis revealed increased levels of oxidized CaMKII in WT but not in NOX2KO hearts treated with DGT. The DGT-induced increase in SCW frequency was abolished in myocytes isolated from mice in which the Ser 2814 CaMKII phosphorylation site on RyR2 is constitutively inactivated. Conclusion These results suggest that the arrhythmogenic adverse effects of CGs on Ca2+ handling involve PI3K- and PKC-mediated stimulation of NOX2 and subsequent NOX2-dependent ROS release from the mitochondria; mitochondria-derived ROS then activate CaMKII with consequent phosphorylation of RyR2 at Ser 2814. [ABSTRACT FROM AUTHOR]

The purpose of this article is to discuss whether gold nanoparticles (GNPs) play an auxo-action on ciprofloxacin (CIP)-mediated sonodynamic antimicrobial chemotherapy (SACT) in vitro. The measuring criterion of SACT, bactericidal efficiency, was measured by plate colony-counting methods. According to research findings, the duration of ultrasound (US) exposure, solution temperature and CIP:GNPs concentration were all critical influencing factors of SACT. Furthermore, scanning electron microscopy revealed that the group of CIP:GNPs combined with US showed the most severe damaged effect on Escherichia coli and Staphylococcus aureus , resulting in the loss of their typical microbial morphology and the disclosure of contents. Therefore, the above experimental results confirmed initially that GNPs could enhance the bacteriostasis of CIP-mediated SACT. And the intracellular reactive oxygen species (ROS) detection assays proved that this acceleration might be connected to the ROS generated through the ultrasonic mechanics. In conclusion, GNPs would be regarded as a promising auxiliary material for SACT, since they are both used to be the medication carriers and sonosensitizer accelerants. [ABSTRACT FROM AUTHOR]

Owing to the high depth of tissue penetration, non‐invasiveness, and controllability, ultrasound (US)‐mediated sonodynamic therapy (SDT) has shown broad application prospects for tumor treatment. However, the electron‐hole separation inefficiency of sonosensitizers and the tumor hypoxia remain two major challenges limiting the effect of SDT. Here, ultrafine photoetched bismuth vanadate (BiVO4) nanorods modified with DSPE‐PEG2000 (PEBVO@PEG NRs) were fabricated to achieve in situ self‐supply of oxygen (O2) and reactive oxygen species (ROS) for hypoxic tumor therapy. The photoetching approach could enhance the charge separation by inducing enriched oxygen vacancies on the surface of BiVO4, thereby improving the generation efficiency of ROS and O2. The PEBVO@PEG overcome the main obstacles of traditional sonosensitizers in the SDT process and show promising sonodynamic therapeutic effects, thus providing new strategies for improving the performance of sonosensitizer and hypoxic tumor elimination. [ABSTRACT FROM AUTHOR]

Owing to the high depth of tissue penetration, non‐invasiveness, and controllability, ultrasound (US)‐mediated sonodynamic therapy (SDT) has shown broad application prospects for tumor treatment. However, the electron‐hole separation inefficiency of sonosensitizers and the tumor hypoxia remain two major challenges limiting the effect of SDT. Here, ultrafine photoetched bismuth vanadate (BiVO4) nanorods modified with DSPE‐PEG2000 (PEBVO@PEG NRs) were fabricated to achieve in situ self‐supply of oxygen (O2) and reactive oxygen species (ROS) for hypoxic tumor therapy. The photoetching approach could enhance the charge separation by inducing enriched oxygen vacancies on the surface of BiVO4, thereby improving the generation efficiency of ROS and O2. The PEBVO@PEG overcome the main obstacles of traditional sonosensitizers in the SDT process and show promising sonodynamic therapeutic effects, thus providing new strategies for improving the performance of sonosensitizer and hypoxic tumor elimination. [ABSTRACT FROM AUTHOR]

The sonodynamic activities of gold nanoparticles (GNPs) with different morphologies, gold nanospheres (GNSs), gold nanoflowers (GNFs) and gold nanorods (GNRs), were explored by multi‐spectroscopic methods, in which the lesion degree of human serum albumin (HSA) was used as assessment index. The results revealed that three GNPs all had certain sonosensitivity but varying from different morphologies. It was also found that GNPs concentration and ultrasonic parameters were all critical influencing factors of sonodynamic injury HSA. Investigating the physical damage mechanism, the results indicated that the secondary and tertiary structure of HSA were compromised by ultrasound (US) combined with GNPs, so that the conformation of HSA was altered and the function was variously disturbed due to GNPs different morphologies. Studying the chemical damage mechanism, the results discovered that the yield of singlet oxygen (1O2) produced by GNPs with various morphologies combined with US was significant difference. Therefore, comprehensively analyzing the research results under different factors, the order of sonodynamic activities of GNPs was GNSs≈GNFs>GNRs. These findings may provide reference for the application of GNPs as sonosensitizers in sonodynamic therapy. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies demonstrate that alpha lipoic acid can prevent nitroglycerin tolerance by restoring aldehyde dehydrogenase 2 (ALDH2) activity and ALDH2-mediated detoxification of aldehydes is thought as an endogenous mechanism against ischemia–reperfusion injury. This study was performed to explore whether the cardioprotective effect of alpha lipoic acid was related to activation of ALDH2 and the underlying mechanisms. In a Langendorff model of ischemia–reperfusion in rats, cardiac function, activities of creatine kinase (CK) and ALDH2, contents of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. In a cell model of hypoxia–reoxygenation, the apoptosis, ALDH activity, reactive oxygen species level, 4-HNE and MDA contents were examined. In the isolated hearts, ischemia–reperfusion treatment led to cardiac dysfunction accompanied by an increase in 4-HNE and MDA contents. Pretreatment with lipoic acid significantly up-regulated myocardial ALDH2 activity concomitantly with an improvement of cardiac dysfunction and a decrease in 4-HNE and MDA contents, these effects were blocked by the inhibitor of ALDH2. Similarly, in the cultured cardiomyocytes, hypoxia–reoxygenation treatment induced apoptosis accompanied by an increase in the production of reactive oxygen species, 4-HNE and MDA. Administration of lipoic acid significantly up-regulated cellular ALDH2 activity concomitantly with a reduction in apoptosis, production of reactive oxygen species, 4-HNE and MDA, these effects were reversed in the presence of ALDH2 or PKCε inhibitors. Our results suggest that the cardioprotective effects of lipoic acid on ischemia–reperfusion injury are through a mechanism involving ALDH2 activation. The regulatory effect of lipoic acid on ALDH2 activity is dependent on PKCε signaling pathway. [Copyright &y& Elsevier]

Abstract: In this work, the antibacterial effect of fluoroquinolones (FQs) upon Escherichia coli (E.coli) was measured with and without application of 40kHz ultrasound (US) stimulation. The research results demonstrated that simultaneous application of 40kHz US apparently enhanced the antibacterial effectiveness of FQs. That is, the synergistic effect was observed and the bacterial viability was reduced when FQs and US were combined. In addition, various influencing factors, such as FQs drug concentration, US irradiation time and solution temperature, on the inhibition of E.coli were also investigated. The antibacterial activity was enhanced apparently with increasing of FQs drug concentration, US irradiation time and solution temperature. Furthermore, we discussed preliminarily the mechanism of US enhanced antibacterial activity. Results show that US can activate FQs to produce reactive oxygen species (ROS) indeed, which are mainly determined as superoxide radical anion (·O2 −) and hydroxyl radical (·OH). [Copyright &y& Elsevier]

A NIR-II light-actuated multifunctional nanoplatform based on ultrasmall CuCo 2 S 4 and Pt nanoparticles is developed for photothermal enhanced nanozyme catalytic and photodynamic therapy. [Display omitted] • CuCo 2 S 4 -Pt-PEG nanocomposites is ultrasmall, which facilitates cellular uptake, and improves the anticancer efficiency. • The nanocomposites have a high photothermal conversion efficiency of 78.46%, and can enhance nanozyme catalytic activities. • The CAT nanozyme activities of Pt enables CuCo 2 S 4 -Pt-PEG to produce more O 2 , and amplify its photodynamic properties. • CuCo 2 S 4 -Pt-PEG can stimulate the immune system to elicit immune response, and inhibited tumor metastasis. The clinical applications of the photothermal therapy (PTT) and photodynamic therapy (PDT) are restricted by the limited tissue penetration depth of excitation light, while the enzyme catalysis therapy is hindered on account of the low treatment efficiency. Herein, we modify artificial nanozyme Pt nanoparticles on the surface of CuCo 2 S 4 nanoparticles to prepare ultrasmall copper-based ternary bimetallic chalcogenides CuCo 2 S 4 -Pt-PEG nanocomposites for PTT/PDT/enzyme catalysis synergistic therapy. The as-fabricated CuCo 2 S 4 -Pt-PEG nanocomposites display peroxidase (POD)-like and catalase (CAT)-like activities, which can catalyze hydrogen peroxide to emerge highly toxic hydroxyl radicals and oxygen, respectively. The integration of Pt nanozyme significantly improves the POD-like and CAT-like activity of CuCo 2 S 4 −PEG that can produce more hydroxyl radicals and oxygen to improve the effects of PDT. Furthermore, the nanocomposites exhibit outstanding photothermal properties derived from the enhanced photothermal conversion efficiency (η = 78.46 %) exposed to 1064 nm NIR-II light irradiation with a low power density (0.8 W cm−2). In particular, the photothermal performance of CuCo 2 S 4 -Pt-PEG significantly enhances the enzyme-like activity. Additionally, the T 1 -weighted magnetic resonance and photoacoustic imaging endow CuCo 2 S 4 -Pt-PEG with the advantages of guiding the treatment process. The synergistic treatment demonstrates significant anticancer treatment efficiency while also elicits immune response that suppressed metastasis. This study could further promote the application of ternary bimetallic chalcogenides in cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) produced by activated microglia are deleterious to neurons. In this study, we studied the effect of Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a superoxide dismutase/catalase mimetic, on the lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons in rat mesencephalic neuroglia cultures. MnTMPyP exhibited a significantly protective effect against LPS (5 ng/ml)-induced neurotoxicity as determined by [3H]dopamine uptake and immunocytochemical analysis. MnTMPyP significantly attenuated LPS-induced production of superoxide free radical and prostaglandin E2 (PGE2) in microglia. These results indicate that MnTMPyP may potentially be used for the treatment of inflammation-related degenerative neurological disorders. [Copyright &y& Elsevier]

Photosensitizers (PSs) with effective reactive oxygen species generation ability against hypoxia are of great potential for clinical treatment of malignant tumors. However, complex tumor microenvironment, such as antioxidative responses and immunosuppression, would ineluctably limit the efficiency of photodynamic therapy (PDT). Herein, a molecular‐targeting photosensitizer QTANHOH is rationally designed for histone deacetylases (HDACs‐targeting photo‐immunotherapy application. The PS QTANHOH displays excellent type‐I/II PDT performance, exhibiting significant phototoxicity toward cancer cells with half maximal inhibitory concentration (IC50) less than 10 nm in both normoxia and hypoxia conditions under blue laser irradiation. Moreover, the bioactive compound could inhibit HDACs and activate the immune microenvironment to boost PDT efficacy on the immunocompetent BALB/c mice with breast cancer, leading to the eradication of solid tumor and inhibition of metastasis. Notably, the molecular‐targeting photosensitizer introduces an alternative strategy to achieve superior phototherapy for cancer therapy. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is endowed with a highly aggressive nature that results in distant metastases and high recurrence rates, yet limited success is realized in traditional chemotherapy. Activatable photosensitizers (PSs) may provide an effective and non‐invasive strategy to induce TNBC cell death in a precise way by offering stimuli‐responsive reactive oxygen species (ROS). However, the toxicity of ROS is often mitigated and even devitalized by the instinctive behavior of ROS resistance in TNBC cells. To address this issue, herein a small molecular self‐assembly nano‐prodrug is presented to co‐deliver an activatable PS and ROS resistance inhibitor. In TNBC cells, the overexpressed glutathione can disassemble the nano‐prodrug, thereby releasing ROS resistance inhibitor and activating the PS for photodynamic therapy and fluorescence imaging. A hybrid membrane coating‐assisted nanoparticle formation strategy is further demonstrated for efficient inhibition of tumor growth and distant metastases on both subcutaneous and orthotopic TNBC mice models. [ABSTRACT FROM AUTHOR]

The phototoxicity of photosensitizers (PSs) pre and post photodynamic therapy (PDT), and the hypoxic tumor microenvironment are two major problems limiting the application of PDT. While activatable PSs can successfully address the PS phototoxicity pre PDT, and type I PS can generate reactive oxygen species (ROS) effectively in hypoxic environment, very limited approaches are available for addressing the phototoxicity post PDT. There is virtually no solution available to address all these issues using a single design. Herein, we propose a proof‐of‐concept on‐demand switchable photosensitizer with quenched photosensitization pre and post PDT, which could be activated only in tumor hypoxic environment. Particularly, a hypoxia‐normoxia cycling responsive type I PS TPFN‐AzoCF3 was designed to demonstrate the concept, which was further formulated into TPFN‐AzoCF3 nanoparticles (NPs) using DSPE‐PEG‐2000 as the encapsulation matrix. The NPs could be activated only in hypoxic tumors to generate type I ROS during PDT treatment, but remain non‐toxic in normal tissues, pre or after PDT, thus minimizing side effects and improving the therapeutic effect. With promising results in in vitro and in vivo tumor treatment, this presented strategy will pave the way for the design of more on‐demand switchable photosensitizers with minimized side effects in the future. [ABSTRACT FROM AUTHOR]

The phototoxicity of photosensitizers (PSs) pre and post photodynamic therapy (PDT), and the hypoxic tumor microenvironment are two major problems limiting the application of PDT. While activatable PSs can successfully address the PS phototoxicity pre PDT, and type I PS can generate reactive oxygen species (ROS) effectively in hypoxic environment, very limited approaches are available for addressing the phototoxicity post PDT. There is virtually no solution available to address all these issues using a single design. Herein, we propose a proof‐of‐concept on‐demand switchable photosensitizer with quenched photosensitization pre and post PDT, which could be activated only in tumor hypoxic environment. Particularly, a hypoxia‐normoxia cycling responsive type I PS TPFN‐AzoCF3 was designed to demonstrate the concept, which was further formulated into TPFN‐AzoCF3 nanoparticles (NPs) using DSPE‐PEG‐2000 as the encapsulation matrix. The NPs could be activated only in hypoxic tumors to generate type I ROS during PDT treatment, but remain non‐toxic in normal tissues, pre or after PDT, thus minimizing side effects and improving the therapeutic effect. With promising results in in vitro and in vivo tumor treatment, this presented strategy will pave the way for the design of more on‐demand switchable photosensitizers with minimized side effects in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] Three ciprofloxacin derivatives (CPDs) were synthesized. Also, their sonodynamic antibacterial activities and possible mechanism under ultrasound (US) irradiation were preliminarily investigated. Staphylococcus aureus and Escherichia coli were selected as the research objects. The sonodynamic antibacterial effects of three CPDs and their structure-effective relationship were explored by the inhibition rate. The reactive oxygen species (ROS) produced under US irradiation were detected by oxidative extraction spectrophotometry and used to analyze the sonodynamic antibacterial mechanism of three CPDs. Research indicated that three CPDs, named compound 1 (C1), compound 2 (C2) and compound 3 (C3), separately all had strong sonodynamic antibacterial activities. In addition, C3 had the strongest effect relative to the other CPDs. The study also found that CPDs' concentration, US irradiation time, US solution temperature and US medium could disturb their sonodynamic antimicrobial effects. Moreover, 1O 2 and ·OH were the main types of ROS produced by C1 and C3; the ROS produced by C2 included 1O 2 , among other types. Results showed that all three CPDs could be activated to produce ROS after US irradiation. Among them, C3 displayed the highest ROS production and the utmost activity, which may be related to the introduction of the electron-giving group at the C-3 position of the quinoline backbone. [ABSTRACT FROM AUTHOR]

Abstract In this paper, brilliant cresyl blue (BCB) was selected as a sonosensitizer. The sonodynamic damage to human serum albumin (HSA) in the presence of BCB and the mechanism were studied by means of fluorescence and absorption spectra. Firstly, BCB could quench the intrinsic fluorescence of HSA obviously and the quenching mechanism was static quenching due to the formation of HSA-BCB complex. The results of the displacement experiments and the molecular modeling suggested that the binding site of BCB on HSA was site I, and hydrophobic forces and hydrogen bonds played major roles in the interaction between HSA and BCB. Secondly, the damage of HSA induced by the combined effects of ultrasonic irradiation and BCB was more efficient than that only BCB or ultrasound irradiation, which confirmed that BCB had sonodynamic activity. The damage degree of HSA was positively correlated with reactive oxygen species (ROS) produced in the system, which indicated that ultrasound could activate BCB to produce ROS, and the kinds of ROS produced by the combined effects of ultrasonic irradiation and BCB were mainly hydroxyl free radical, singlet oxygen and superoxide anion radical. [ABSTRACT FROM AUTHOR]

The designed H-TiO 2 @CPO/β-Lap@PAA nanoplatform (TCLP NPs) can downregulate HSPs to enhance MPTT efficiency by multiple cytotoxic reactive oxygen species (ROS) regulation. Moreover, the special tumor microenvironment with more H 2 O 2 , H+, and over expressed NQO1 enabled TCLP NPs with minimized safety risk on normal tissues. The enhanced MPTT can promote the intratumoral drug accumulation which further induce tumor necrosis. Therefore, the as-prepared TCLP NPs exhibits excellent antitumor efficiency in vitro and in vivo. The main procedure for the synthesis and antitumor mechanism of H-TiO 2 @CPO/β-Lap@PAA nanocomposite. [Display omitted] • The nanoplatform realizes tumor suppression through multi-model ROS regulation. • The nanoplatform resists the intracellular HSP expression to enhance MPTT efficiency. • The integration of two agents achieves a synergistic specific-antitumor effect. • The enhanced MPTT promotes the intratumoral drug accumulation. The tumor thermotolerance owing to the overexpression of heat shock proteins (HSPs) is the critical challenge in practical application of mild-temperature photothermal therapy (MPTT). Reactive oxygen species (ROS) can not only serve as a powerful weapon to kill cancer cells, but also a regulator to inhibit HSPs, thus improving the thermal sensitivity of tumors. Herein, a multi-model ROS regulation nano-platform based on TCLP nanocomposites consisting of polyacrylic acid encapsulated, chloroperoxidase (CPO) and β-Lapachone (β-Lap) loaded black mesoporous titanium (H-TiO 2) has been constructed for the ROS-enhanced MPTT. In this nano-platform, the H-TiO 2 acts as the NIR-Ⅱ light triggered photothermal agent and photosensitizer to contribute to deep tissue MPTT and PDT, the β-Lap acts as a H 2 O 2 amplifier to improve the 1O 2 production of CPO. The abundant ROS from TCLP NPs can limit the activity as well as the expression of HSPs, ultimately improving the antitumor efficacy of MPTT. Finally, excellent synergistic tumor inhibition based on TCLP NPs has been reached both in vitro and in vivo. This multi- model ROS enhanced MPTT nano-platform with low toxic side effects offers a promising strategy and enlightenments the clinical application of MPTT. [ABSTRACT FROM AUTHOR]

NADPH oxidase (NOX) is a major source of reactive oxygen species (ROS) in the body and it plays a key role in mediation of oxidative injury in the cardiovascular system. The purposes of this study are to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic rats and to determine whether NOX-derived ROS promotes the dysfunction of EPCs. The rats were fed on a high-fat diet for 8 weeks to establish a hyperlipidemic rat model, which showed the increased plasma lipids and the impaired functions of circulating EPCs (including the reduced abilities in migration and adhesion) accompanied by an increase in NOX activity and ROS production. Next, EPCs were isolated from normal rats and they were treated with oxidized low-density lipoprotein (ox-LDL) (100 μg/mL) for 24 h to induce a dysfunctional model in vitro. In agreement with our findings in vivo, ox-LDL treatment increased the dysfunctions of EPCs concomitant with an increase in NOX activity and ROS production; these phenomena were reversed by the NOX inhibitor. Based on these observations, we conclude that NOX-derived ROS involved in the dysfunctions of circulating EPCs in hyperlipidemic rats and inhibition of NOX might provide a novel strategy to improve EPC functions in hyperlipidemia. [ABSTRACT FROM AUTHOR]

Aims Diastolic Ca release (DCR) from sarcoplasmic reticulum (SR) Ca release channel ryanodine receptor (RyR2) has been linked to multiple cardiac pathologies, but its exact role in shaping divergent cardiac pathologies remains unclear. We hypothesize that the SR-mitochondria interplay contributes to disease phenotypes by shaping Ca signalling. Methods and results A genetic model of catecholaminergic polymorphic ventricular tachycardia (CPVT2 model of CASQ2 knockout) and a pre-diabetic cardiomyopathy model of fructose-fed mice (FFD), both marked by DCR, are employed in this study. Mitochondria Ca (mCa) is modulated by pharmacologically targeting mitochondria Ca uniporter (MCU) or permeability transition pore (mPTP), mCa uptake, and extrusion mechanisms, respectively. An MCU activator abolished Ca waves in CPVT2 but exacerbated waves in FFD cells. Mechanistically this is ascribed to mitochondria's function as a Ca buffer or source of reactive oxygen species (mtROS) to exacerbate RyR2 functionality, respectively. Enhancing mCa uptake reduced and elevated mtROS production in CPVT2 and FFD, respectively. In CPVT2, mitochondria took up more Ca in permeabilized cells, and had higher level of mCa content in intact cells vs. FFD. Conditional ablation of MCU in the CPVT2 model caused lethality and cardiac remodelling, but reduced arrhythmias in the FFD model. In parallel, CPVT2 mitochondria also employ up-regulated mPTP-mediated Ca efflux to avoid mCa overload, as seen by elevated incidence of MitoWinks (an indicator of mPTP-mediated Ca efflux) vs. FFD. Both pharmacological and genetic inhibition of mPTP promoted mtROS production and exacerbation of myocyte Ca handling in CPVT2. Further, genetic inhibition of mPTP exacerbated arrhythmias in CPVT2. Conclusion In contrast to FFD, which is more susceptible to mtROS-dependent RyR2 leak, in CPVT2 mitochondria buffer SR-derived DCR to mitigate Ca-dependent pathological remodelling and rely on mPTP-mediated Ca efflux to avoid mCa overload. SR-mitochondria interplay contributes to the divergent pathologies by disparately shaping intracellular Ca signalling. [ABSTRACT FROM AUTHOR]

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant of Sinomenium acutum (Thunb.) Rehd.et Wils. Currently, sinomenine hydrochloride (SIN) preparations, classified as a natural disease-modifying anti-rheumatic drug (nDMARD), have been used for therapy of rheumatoid arthritis (RA); however, the efficacy of SIN was seriously limited by its short half-life, low bioavailability, and dose-dependent adverse reactions. In this study, a biomimetic nanocomplex based on Prussian blue nanoparticles (PB NPs) was developed for overcoming clinical limitations of SIN and accordingly improving its efficacy. In vitro studies showed that the nanocomplexes significantly inhibited abnormal proliferation of fibroblast-like synoviocytes (FLSs) by scavenging reactive oxygen species (ROS) and inhibiting secretion of proinflammatory cytokines. In vivo imaging demonstrated that the improved immune-escape properties of the nanocomplexes resulted in markedly increased half-life of circulation and levels of accumulated drugs at arthritic sites of adjuvant-induced arthritis (AIA) rats. Notably, the nanocomplexes significantly suppressed joint inflammation and protected against bone destruction of AIA rats by inhibiting inflammatory cytokine secretion of the synovial macrophages and FLSs. These results indicate that the nanocomplexes provide an excellent carrier for controlled release and targeted accumulation of SIN within the arthritic sites, which consequently achieve disease-remitting effects of SIN on RA. The biomimetic Prussian blue nanocomplexes (PB NPs) loading sinomenine hydrochloride (SIN), termed as HA@M@PB@SIN NPs, were developed for efficient delivery of SIN to rheumatoid joints. HA@M@PB@SIN NPs suppressed joint inflammation and protected against bone destruction of rats with adjuvant-induced arthritis, a classical model of rheumatoid arthritis (RA), by targeting synovial macrophages and fibroblast-like synoviocytes to inhibit abundant production of various inflammatory cytokines. [Display omitted] • A biomimetic nanocomplex was successfully constructed for targeted delivery ofSIN to the affected joints ofRA. • HA@M@PB@SIN NPs demonstrated prolonged half-life of circulation and specific drug accumulation at the arthritic sites. • HA@M@PB@SIN NPs markedly suppressed joint inflammation and protected against bone destruction of AIA rats. [ABSTRACT FROM AUTHOR]

• A reverse filtration mode of catalytic membrane was proposed. • Reverse filtration can highly improve the flux and separation performance. • Algae body can firstly reject by the base membrane and keep integrity during reverse filtration. • The water quality was improved during the reverse filtration mode. During catalytic membrane filtration, algal cells and macromolecules in environmental aqueous conditions load on the surface of the catalytic material, leading to progressive deactivation of the catalytic membrane. Here, we synthesized catalytic membranes with outstanding water flux by anchoring catalyst (δ-MnO 2 and sulfur-doped g-C 3 N 4) on homoporous base membranes and immobilizing them by PIP-TMC interfacial polymerization. And the reverse filtration was used to pre-remove the hard-to-degrade foulings such as algal cells to enhance the degradation performance and antifouling performance of the catalyst membrane. The presence of reverse pre-filtration endowed the catalytic membrane to obtain 1.5 times higher water flux than normal filtration, reducing the contact of foulings with the catalyst and improving the catalytic efficiency and stability. Therefore, the operating conditions of the catalytic layer were optimized to obtain higher degradation rates and maintain long-term catalytic activity compared to normal filtration. Also, in the treatment of algae-laden water, reverse filtration allowed algal cells to be separated due to pore size sieving and catalytic material space, avoiding cell fragmentation and release of extracellular polymers caused by activated generated reactive oxygen species. In the catalytic removal of the refractory pollutants (APAP and SMX), the SK25 membrane was able to remove 100 % of the performance with degradation rates up to 0.36 mol·L−1·s−1. This study proposes a novel strategy for catalytic membrane filtration and promotes the application of catalytic membrane filtration technology in practical environmental problems. [ABSTRACT FROM AUTHOR]

Endo/lysosomal escape of gene vectors and the subsequent unpacking of nucleic acids in cytosol are two major challenges for efficient gene delivery. Herein, we report a polymeric gene delivery vector, which consists of a photosensitizer (PS) with aggregation-induced emission (AIE) characteristics and oligoethylenimine (OEI) conjugated via an aminoacrylate (AA) linker that can be cleaved by reactive oxygen species (ROS). In aqueous media, the polymer could self-assemble into bright red fluorescent nanoparticles (NPs), which can efficiently bind to DNA through electrostatic interaction for gene delivery. Upon visible light irradiation, the generated ROS can break the endo/lysosomal membrane and the polymer, resulting in light-controlled endo/lysosomal escape and unpacking of DNA for efficient gene delivery. The smart polymer represents the first successful gene vector to simultaneously address both challenges with a single light excitation process. [ABSTRACT FROM AUTHOR]

[Display omitted] • The mild sonothermal therapy is realized with red phosphorus nanoparticles. • The phosphorus nanoparticles have sonothermal conversion and sonodynamic effect. • The phosphorus nanoparticles are biodegradable and have long-term biosafety. Due to the shallow penetration depth of light in biological tissues, the effectiveness of photothermal therapy (PTT) in deep-seated tumors is limited. Conversely, ultrasonic wave has excellent tissue penetration depth. Using ultrasound (US) as an exogenous physical stimulus to trigger tumors thermotherapy is a promising alternative for deep-seated tumors to supersede conventional PTT. Here, we realized a mild sonothermal therapy (STT) using biodegradable red phosphorus nanoparticles (RP NPs) as sonothermal agents. Quite obvious sonothermal conversion of RP NPs is remarkable under low intensity US irradiation, with the temperature rise from 30 to 47 °C at tumor site. In terms of potential mechanism, under US excitation, the internal electrons of RP NPs undergo transition and release the energy by electrons and holes recombination process. This elicits the atom thermal vibration and raises the temperature around the RP NPs. Additionally, US irradiation can stimulate RP NPs to produce singlet oxygen (1O 2) and reduce intracellular energy levels that leads to downregulation of the heat shock proteins (HSPs) expression, providing an "escort" to mild STT. This work offers a new paradigm for the strategies of STT enhanced by sonodynamic effect. [ABSTRACT FROM AUTHOR]

This review provides both a systematic discussion and classification of the enhanced chemodynamic therapy (CDT) antitumor strategies that have emerged in recent years, as well as an in-depth review and summary of the stages of development in this highly attractive field. [Display omitted] • ROS, ROS-mediated CDT and the drawbacks and solutions of traditional Fenton response-based treatment strategies are presented. • The application of endogenous or exogenous stimulus-responsive nanoplatforms in enhancing CDT is discussed, respectively. • CDT nanoplatforms that internally modulate or respond to TME are introduced, as well as other responsive enhanced CDT nanoplatforms. • Several key issues facing the enhanced CDT nanoplatform and corresponding suggestions and comments are summarised and identified. In view of certain unique internalization features of the tumor microenvironment (TME) (mainly including hypoxia, acidity and higher concentrations of H 2 O 2 and GSH), advanced nanotechnology has been introduced to increase intracellular reactive oxygen species (ROS), mainly involving the Fenton and Fenton-like reactions of transition metals, metal-catalyzed reactions and peroxidase-catalyzed reactions for chemodynamic therapy (CDT) of tumors. However, there are many inevitable problems, such as the harsh conditions and low reaction efficiency for the Fenton reaction of iron-based materials, limited endogenous H 2 O 2 , neutralization of ROS produced by the antioxidant system, and unsatisfactory results of a single CDT mode of treatment, which seriously limit the application of CDT in the field of anticancer, while this has facilitated the generation and development of enhanced CDT nanoplatforms with better therapeutic effects in turn. The objective of this review article is to present representative and latest research progress of improving CDT antitumor effects, involving the amplification strategy of oxidative stress triggered by endogenous/exogenous stimuli. Endogenous stimuli mainly come from inside the TME or cancer cells (such as acidic pH, glucose, glutathione (GSH), some specific enzymes, etc.), and exogenous stimuli include light, heat, and US, etc. Here enhanced CDT nanomaterials are classified into three major categories based on the sources of these stimulations, namely endogenous stimulus-responsive nanomaterials, exogenous stimulus-responsive nanomaterials, and endogenous/exogenous co-stimuli-responsive nanomaterials. Representative examples in each type are dissected and discussed in terms of rational design and preparation of materials, mechanism of action and potential medical applications. Finally, the difficulties and bottlenecks encountered in the current development of CDT are summarized, and preliminary directions for the future development of the field are pointed out in an effort to maximize the potential power of scheduling and coordination of biology and chemistry. [ABSTRACT FROM AUTHOR]

Organochlorine pesticides (OCPs) are persistent pollutants linked to diverse adverse health outcomes. Environmental exposure to OCPs has been suggested to negatively impact the immune system but their effects on cellular antiviral responses remain unknown. Transcriptomic analysis of N27 rat dopaminergic neuronal cells unexpectedly detected high level expression of genes in the interferon (IFN)-related antiviral response pathways including the IFN-induced protein with tetratricopeptide repeats 1 and 2 (Ifit1/2) and the MX Dynamin Like GTPases Mx1 and Mx2. Interestingly, treatment of N27 cells with dieldrin markedly downregulated the expression of many of these genes. Dieldrin exterted a similar effect in inhibiting IFIT2 and MX1 gene expression in human SH-SY5Y neuronal cells induced by an RNA viral mimic, polyinosinic: polycytidylic acid (poly I:C) and IFIT2/3 gene expression in human pulmonary epithelial cells exposed to human influenza H1N1 virus. Mechanistically, dieldrin induced a rapid rise in levels of intracellular reactive oxygen species (iROS) and a decrease in intracellular glutathione (GSH) levels in SH-SY5Y cells. Treatment with N-acetylcysteine, an antioxidant and GSH biosynthesis precursor, effectively blocked both dieldrin-induced increases in iROS and its inhibition of poly I:C-induced upregulation of IFIT and MX gene expression, suggesting a role for intracellular oxidative status in dieldrin's modulation of antiviral gene expression. This study demonstrates that dieldrin modulates key genes of the cellular innate immune responses that are normally involved in the host's cellular defense against viral infections. Our findings have potential relevance to understanding the organismal effects of environmentally persistent organochlorine contaminants on the mammalian cellular immune system. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the bovine serum albumin (BSA) was selected as a target molecule, the sonodynamic damage to protein in the presence of promethazine hydrochloride (PMT) and its mechanism were studied by the means of absorption, fluorescence and circular dichroism (CD) spectra. The results of hyperchromic effect of absorption spectra and quenching of intrinsic fluorescence spectra indicate that the ultrasound-induced BSA molecules damage is enhanced by PMT. The damage degree of BSA molecules increases with the increase of ultrasonic irradiation time and PMT concentration. The results of synchronous fluorescence, three-dimensional fluorescence and CD spectra confirmed that the synergistic effects of ultrasound and PMT induced the damage of BSA molecules. The results of oxidation–extraction photometry with several reactive oxygen species (ROS) scavengers indicate that the damage of BSA molecules could be mainly due to the generation of ROS and both 1O2 and e important mediators of the ultrasound-induced BSA molecules damage in the presence of PMT. [Copyright &y& Elsevier]

The bovine serum albumin (BSA) was selected as a target molecule, the sonodynamic damage to protein in the presence of dioxopromethazine hydrochloride (DPZ) and its mechanism were studied by means of absorption and fluorescence spectra. The results of hyperchromic effect of absorption spectra and quenching of intrinsic fluorescence spectra indicated that the synergistic effects of ultrasound and DPZ could induce the damage of BSA molecules. The damage degree of BSA molecules increased with the increase of ultrasonic irradiation time and DPZ concentration. The results of synchronous fluorescence and three-dimensional fluorescence spectra further confirmed that the synergistic effects of ultrasound and DPZ induced the damage of BSA molecules. The results of oxidation-extraction photometry with several reactive oxygen species (ROS) scavengers indicated that the damage of BSA molecules could be mainly due to the generation of ROS, in which both O and ·OH were the important mediators of the ultrasound-inducing BSA molecules damage in the presence of DPZ. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, bovine serum albumin (BSA) was selected as a target molecule, and the sonodynamic damage to proteins in the presence of berberine (BER) and its mechanism were studied by means of absorption and fluorescence spectra. The results of hyperchromic effect of absorption spectra, and quenching of intrinsic fluorescence spectra indicated that the ultrasound-induced BSA molecules damage was enhanced by BER. The damage degree of BSA molecules increased with the increase in ultrasonic irradiation time and BER concentration. The results of synchronous fluorescence and three-dimensional fluorescence spectra confirmed that the synergistic effects of ultrasound and BER induced the damage of BSA molecules. The results of oxidation–extraction photometry with several reactive oxygen species (ROS) scavengers indicated that the damage of BSA molecules could be mainly due to the generation of ROS, and 1O2 was the major mediator of the ultrasound-induced BSA molecules damage in the presence of BER. [Copyright &y& Elsevier]

Abstract: Recently, the sonocatalytic technology using various semiconductors combined with ultrasonic irradiation has been received much attention to solve the environmental problems. In this paper, nano-sized titanium dioxide (TiO2) powder as a sonocatalyst was irradiated by ultrasound and the generation of reactive oxygen species (ROS) during sonocatalytic reaction process has been estimated by the method of Oxidation–Extraction Photometry (OEP). That is, the 1,5-diphenylcarbohydrazide (DPCI) can be oxidized by ROS into diphenylcarbonzone (DPCO), which can be extracted by the mixed solution of benzene and carbon tetrachloride and show the great absorbance at 563nm wavelength. The synergistic effect of TiO2 and ultrasonic irradiation was estimated and some influencing factors, such as ultrasonic irradiation time and TiO2 addition amount on the generation of ROS were reviewed. The results indicate that the quantities of generated ROS increase with the increase of ultrasonic irradiation time and TiO2 addition amount. Moreover, the relationship between quantities of generated ROS and DPCI concentration was also studied. And then, several quenchers were used to determine the kind of the generated ROS. At last, the researches on the sonocatalytic degradation of organic dyes and the corresponding reaction kinetics have also been performed, which is found to follow the pseudo first-order kinetics approximately. This paper may offer some important subjects for broadening the applications of sonocatalytic technology. [Copyright &y& Elsevier]

Abstract: Elevated exposure to manganese is known to cause neurodegeneration in the basal ganglia and to induce movement abnormalities called manganism. However, the underlying mechanism of action is not fully understood. Activation of the resident immune cells in the brain, microglia that release a variety of neurotoxic factors, has been implicated to contribute to neurodegeneration. Of the various neurotoxic factors released by activated microglia, reactive oxygen species such as superoxide and hydrogen peroxide are particularly detrimental to the survival of the oxidative damage-prone neurons. In this study, we report that exposure of rat microglia to manganese chloride (MnCl2) resulted in a time- and concentration-dependent release of hydrogen peroxide (H2O2). The MnCl2-stimulated microglial H2O2 release was sensitive to inhibitors of mitogen-activated protein kinases (MAPK) but not that of NADPH oxidase. MnCl2-induced a rapid activation of the extracellular signal-regulated kinase (ERK) and p38-MAPK in microglia that appeared to precede the MnCl2-induced H2O2 release, suggesting that ERK and p38-MAPK influenced the MnCl2-induced H2O2 release in microglia. In summary, these results demonstrate that manganese chloride is capable of activating microglia to release ROS and MAPK may, in part, be key regulators of the process. These findings may shed significant light on the potential role of microglia in the manganese-induced neurotoxicity. [Copyright &y& Elsevier]

Ferroptosis regulates cell death through reactive oxygen species (ROS)‐associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with no clear evidence. Herein, we report the first example of an LD/nucleus dual‐targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor–acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual‐targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis‐related diseases. [ABSTRACT FROM AUTHOR]

Ferroptosis regulates cell death through reactive oxygen species (ROS)‐associated lipid peroxide accumulation, which is expected to affect the structure and polarity of lipid droplets (LDs), but with no clear evidence. Herein, we report the first example of an LD/nucleus dual‐targeted ratiometric fluorescent probe, CQPP, for monitoring polarity changes in the cellular microenvironment. Due to the donor–acceptor structure of CQPP, it offers ratiometric fluorescence emission and fluorescence lifetime signals that reflect polarity variations. Using nucleus imaging as a reference, CQPP was applied to report the increase in LD polarity and the homogenization of polarity between LDs and cytoplasm in the ferroptosis model. This LD/nucleus dual‐targeted fluorescent probe shows the great potential of using fluorescence imaging to study ferroptosis and ferroptosis‐related diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • The 7−OH MTX was the main culprit for MTX nephrotoxicity. • PERK/CHOP mediated ER stress was screened as key pathway by RNA-seq analysis. • Nobiletin could ameliorate the nephrotoxicity of 7−OH MTX through PERK/CHOP pathway. • Nobiletin could maintain Ca2+ homeostasis and reduce the production of ROS. Drug-induced nephrotoxicity is a frequent adverse event that contributes to acute kidney injury with tubular and/or glomerular lesions. Methotrexate (MTX) is a folate analog used against a myriad of malignancies and autoimmune diseases. Unfortunately, ambiguous renal toxicology limits its safe clinical usage. Based on our previous studies, 7−OH MTX as an overlooked oxidative metabolite of MTX was proposed to be the main culprit responsible for nephrotoxicity, while nobiletin, a naturally occurring polymethoxylated flavonoid screened from our prepared total phenolic extracts of Citrus aurantium L. (TPE-CA), was employed as a therapeutic agent for drug-drug interactions. According to the present study, nobiletin can ameliorate the renal accumulation of 7−OH MTX through the interaction with aldehyde oxidase. RNA-seq analysis revealed that 7−OH MTX was mainly related to protein processing in endoplasmic reticulum (ER) stress, with the PERK/CHOP pathway selected as the most significant for metabolic nephrotoxicity. Meanwhile, the cross-linked proteins and conducted signals were investigated by western blotting and further verified by GSK inhibition analyses. These results indicated that nobiletin protected renal function from MTX-induced nephrotoxicity by modulating metabolism and ameliorated the metabolic toxicity of 7−OH MTX on ER stress-induced PERK/CHOP conduction by maintaining Ca2+ homeostasis and reducing the production of reactive oxygen species. [ABSTRACT FROM AUTHOR]

Intraplaque hemorrhage (IPH) plays a major role in the aggressive progression of vulnerable plaque, leading to acute cardiovascular events. We previously demonstrated that sonodynamic therapy (SDT) inhibits atherosclerotic plaque progression. In this study, we investigated whether SDT could also be applied to treat more advanced hemorrhagic plaque and addressed the underlying mechanism. SDT decreased atherosclerotic burden, positively altered atherosclerotic lesion composition, and alleviated iron retention in rabbit hemorrhagic plaques. Furthermore, SDT reduced iron retention by stimulating ferroportin 1 (Fpn1) expression in apolipoprotein E (ApoE)−/− mouse plaques with high susceptibility to IPH. Subsequently, SDT inhibited iron‐overload‐induced foam‐cell formation and pro‐inflammatory cytokines secretion in vitro. Moreover, SDT reduced levels of the labile iron pool and ferritin expression via the reactive oxygen species (ROS)‐nuclear factor erythroid 2‐related factor 2 (Nrf2)‐FPN1 pathway. SDT exerted therapeutic effects on hemorrhagic plaques and reduced iron retention via the ROS‐Nrf2‐FPN1 pathway in macrophages, thereby suggesting that it is a potential translational strategy for patients with advanced atherosclerosis in clinical practice. [ABSTRACT FROM AUTHOR]

To date, the mortality of tongue squamous cell carcinoma (TSCC) is still high, COX‐2 is highly expressed in the head and neck cancers, and targeting COX‐2 is a potential treatment for TSCC. Herein, a series of novel carborane compounds based on COX‐2 inhibitors have been developed for the effective treatment of TSCC by boron neutron capture therapy (BNCT). Notably, the compound 1 had high COX‐2 selectivity and low cytotoxicity against CAL27 cells. Meanwhile, the compound 1 had higher selectivity and uptake of CAL27 cells compared to the positive control group sodium borocaptate (BSH). The apoptosis of CAL27 cells treated with the compound 1 during BNCT was significantly induced by breaking DNA double strands and generating excess reactive oxygen species, and the proliferation of cancer cells was inhibited by down‐regulating the expression of cytokines associated with phosphatidylinositide 3‐kinases/protein kinase B (PI3K/Akt) and mitogen‐activated protein kinases (MAPKs) signaling pathways in BNCT. Thus, the carborane compounds based on COX‐2 inhibitors have the potential to effectively treat tongue squamous cell carcinoma through BNCT. [ABSTRACT FROM AUTHOR]