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Alzheimer's disease (AD) is one of the most common neurodegenerative diseases that characterized by the accumulation of β-amyloid peptide (Aβ). Overexpressions of Aβ could induce oxidative stress that might be a key insult to initiate the cascades of Aβ accumulation. As a result, anti-oxidative stress and attenuating Aβ accumulation might be one promising intervention for AD treatment. Tanshinone IIA (Tan IIA), a major component of lipophilic tanshinones in Danshen, is proven to be effective in several diseases, including AD. Due to the poor solubility in water, the clinical application of Tan IIA was limited. Therefore, a great number of nanoparticles were designed to overcome this issue. In the current study, we choose chitson as delivery carrier to load Tanshinone IIA (CS@Tan IIA) and explore the protective effects of CS@Tan IIA on the CL2006 strain, a transgenic C. elegans of AD model organism. Compared with Tan IIA monomer, CS@Tan IIA could significantly prolong the lifespan and attenuate the AD-like symptoms, including reducing paralysis and the Aβ deposition by inhibiting the oxidative stress. The mechanism study showed that the protection of CS@Tan IIA was attenuated by knockdown of daf-16 gene, but not skn-1. The results indicated that DAF-16/SOD-3 pathway was required in the protective effects of CS@Tan IIA. Besides DAF-16/SOD-3 pathway, the Tan IIA-loaded CS nanoparticles might protect the C. elegans against the AD insults via promoting autophagy. All the results consistently suggested that coating by chitosan could improve the solubility of Tan IIA and effectively enhance the protective effects of Tan IIA on AD, which might provide a potential drug loading approach for the hydrophobic drugs as Tan IIA.

Maddock mixers are ubiquitous in plastics processing for single-screw extruders and injection molding plasticators due to their low cost to build and their ability to provide a uniform level of dispersive mixing. If the mixer is designed properly, all entering solid polymer fragments and certain types of gels can be trapped and dispersed into the matrix resin. Many mixers that are used commercially, however, provide lower levels of dispersive stress mixing than required by the process and they can degrade polyethylene (PE) resins. This paper will describe the mechanisms that are occurring in a Maddock mixer and develop guidelines for obtaining optimal mixing stresses while mitigating resin degradation.

Ischemic stroke is the leading cause of disability and death worldwide. Currently, the only proven treatment for ischemic stroke is restoring the cerebral blood supply. In addition, some of the tissue is damaged during the subsequent reperfusion because of the overproduction of reactive oxygen species (ROS). Furthermore, antioxidant therapies have shown promise in preclinical studies for the treatment of ischemia-reperfusion injury. However, their therapeutic efficacy has been limited because of their low bioavailability in brain. To resolve this issue, we synthesized ROS-responsive, fan-shaped dendrimer nanoparticles (NPs) and conjugated them with a blood-brain barrier (BBB)-targeting peptide, COG1410, and salvianic acid A (SA), which is an effective antioxidant in ischemic stroke. The BBB targeting peptide acts as a ligand of the nanocarrier system and penetrates the BBB through the endocytosis of the ligand receptor. The results showed that T-SA-NPs not only target and accumulate in the infarct area, they also reduce over 2 times of the infarct area and reverse the behavioral deficits in MCAO mice, which illustrates that these NPs have an effective therapeutic effect on the ischemic stroke. In addition, these NPs had no toxicity in any organs of the body. Importantly, the present study provides an alternative strategy for delivering antioxidants to the brain and achieving targeted therapy of ischemic stroke.

Electrochemical doping is a promising method to modify the photoelectrochemical performance of semiconductors. The published works using H ions as compensated cations have shown increased photocurrents, but theories vary about the causes of the improvement of photoelectrochemical performance. In this paper, we present the effects of cation ion and the key factors of enhancement using alkali sulfates ((Li/Na/K)2SO4) as the electrolyte for electrochemical doping. The effective electrode surface area (ECSA) was increased for the WO3 film after electrochemical doping. The Li-ion, with the smallest radius and thereby the highest potential to insert into the WO3 cell, results in the Li ion inserted WO3 with the highest photocurrent in the three electrochemically doped samples. To investigate the possible factors affecting the photoelectrochemical performance, the electrochemically doped samples and a control sample were annealed under inert gas (Ar). The lower photocurrents were observed for the electrochemically doped samples after annealing, confirming that the key factors are the increase of the effective electrode surface area caused by electrochemical doping and ion compensation, rather than the ions themselves and the chemical bonds between alkali ions and W or O.

The photoelectrochemical water splitting of monoclinic bismuth vanadate (BiVO4) suffers from sluggish charge mobility as well as substantial charge recombination losses. Here, we treated the BiVO4 ...

Because of their biocompatibility and biosafety, pegylated Au NPs (Au@PEG), as a nanodrug-carrier, have been widely applied in different biomedical applications, including imaging and drug delivery systems. Under such conditions, the biosafety of Au@PEG has attracted tremendous attention. However, only a small number of studies focused on the neurotoxicity of Au@PEG used as drug delivery carriers not to mention reducing the neurotoxicity of Au@PEG. To address this issue, the adverse effects of Au@PEG on human neuroblastoma SHSY5Y cells were first investigated. The results showed that 4.5 nm Au@PEG significantly induced cell apoptosis through upregulating reactive oxygen species (ROS) production and disordering the mitochondrial membrane potential. To further evaluate whether the neurotoxicity of Au@PEG could be improved through conjugating antioxidants on the surface of Au@PEG, Trolox (a vitamin E analogue)-functionalized Au@PEG (Au@Trolox) was synthesized. The results showed that the neurotoxicity of Au@PEG on SHSY5Y cells could be significantly improved by Au@Trolox. Next, mice were subjected to administration of 4.5 nm Au@PEG and Au@Trolox for 3 months. An increase of oxidative stress and a decrease in the activity of key antioxidant enzymes including glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were observed after long-term injection of Au@PEG. More importantly, both the apoptosis of neurons and the activation of astrocytes were observed in the hippocampus of mice injected with Au@PEG. In contrast, the adverse effects of Au@PEG could be improved when injected with Au@Trolox. In short, the present study provided new insights into the toxicity evaluation of nanoparticles and would help to better understand and prevent the neurotoxicity of nanomaterials used in pharmaceutics.

Nonviral vectors have been attracting more attention for several advantages in gene delivery and the development of nonviral gene carriers with high delivery efficiency and low cytotoxicity has long been a key project. Starburst polyamidoamine dendrimers are a class of synthetic polymers with unique structural and physical characteristics. However, when they are used as gene carrier, the gene transfection efficiency is not satisfactory. Herein, a novel thioketal-core polyamidoamine dendrimer (i.e., ROS-PAMAM) was synthesized and characterized. Compared to ethylenediamine-core dendrimers or widely used cationic polymers of polyetherimide, ROS-PAMAM showed lower cytotoxicity. Moreover, ROS-PAMAM demonstrated reactive oxygen species responsive characteristics, which can facilitate the release of siRNA in the tumor microenvironment. In vitro gene transfection experiments based on A549 cells confirmed that siRNA/ROS-PAMAM exhibits high gene transfection efficiency. It is concluded that ROS-PAMAM shows great potential as a generalizable vehicle for gene therapy applications.

As well as their ion transportation function, the voltage-dependent potassium channels could act as the cell signal inducer in a variety of pathogenic processes. However, their roles in neurogenesis after stroke insults have not been clearly illustrated. In our preliminary study, the expressions of voltage-dependent potassium channels Kv4.2 was significantly decreased after stroke in cortex, striatum and hippocampus by real-time quantitative PCR assay. To underlie the neuroprotection of Kv4.2 in stroke rehabilitation, recombinant plasmids encoding the cDNAs of mouse Kv4.2 was constructed. Behavioral tests showed that the increased Kv4.2 could be beneficial to the recovery of the sensory, the motor functions and the cognitive deficits after stroke. Temozolomide (TMZ), an inhibitor of neurogenesis, could partially abolish the mentioned protections of Kv4.2. The immunocytochemical staining showed that Kv4.2 could promote the proliferations of neural stem cells and induce the neural stem cells to differentiate into neurons in vitro and in vivo. And Kv4.2 could up-regulate the expressions of ERK1/2, p-ERK1/2, p-STAT3, NGF, p-TrkA, and BDNF, CAMKII and the concentration of intracellular Ca2+. Namely, we concluded that Kv4.2 promoted neurogenesis through ERK1/2/STAT3, NGF/TrkA, Ca2+/CAMKII signal pathways and rescued the ischemic impairments. Kv4.2 might be a potential drug target for ischemic stroke intervention.

Monitoring superoxide anion radical (O2•-) in live cells and in vivo is of great significance since O2•- is the precursor of other reactive oxygen species and has been closely associated with various physiological and pathological processes. Herein, we developed a novel mitochondria-targeted fluorescent probe PF-MitoSOX Green in which the phosphinate moiety is utilized to recognize O2•- with high sensitivity and selectivity. Confocal imaging results illustrated that PF-MitoSOX Green can not only detect intracellular O2•-, but also can conveniently visualize its production in cells and Caenorhabditis elegans. The present study illustrates that PF-MitoSOX Green provides a novel approach for imaging and detecting O2•- in live cells and in vivo.

Background Gold nanoparticles (AuNPs) have been widely studied for biomedical applications, although their safety and potential toxicity in pregnancy remains unknown. The aim of this study is to explore the effect of AuNPs maternal exposure at different gestational ages on fetal survival and development, as well as the potential mechanism of AuNPs affecting embryos and fetuses. Methods Thirty nm polyethylene glycol (PEG)-coated AuNPs (A30) were administered to pregnant mice via intravenous injection (5 μg Au/g body weight) over three days at either early or late pregnancy. Fetal abortion rate and morphological development in E16.5 were then detected in detail. The pregnant mice physiological states with A30 exposure were examined by biochemical, histological or imaging methods; and materno-fetal distribution of gold elements was assayed by electron microscopy and mass spectrometry. Murine embryonic stem cells derived embryoid-bodies or neuroectodermal cells were treated with A30 (0.0025 to 0.25 μg Au/mL) to examine A30 effects on expression levels of the germ differentiation marker genes. Tukey’s method was used for statistical analysis. Results Exposure to A30 during early (A30E) but not late (A30L) pregnancy caused a high abortion rate (53.5%), lower fetal survival rate and abnormal decidualization compared with non-exposed counterparts. The developmental damage caused by A30 followed an “all-or-nothing” pattern, as the non-aborted fetuses developed normally and pregnancies maintained normal endocrine values. A30 caused minor impairment of liver and kidney function of A30E but not A30L mice. TEM imaging of fetal tissue sections confirmed the transfer of A30 into fetal brain and live as aggregates. qPCR assays showed A30 suppressed the expression of ectodermal, but not mesodermal and endodermal differentiation markers. Conclusions These results illustrate that maternal A30 exposure in early pregnant results in A30 transfer into embryonic tissues, inhibiting ectodermal differentiation of embryonic stem cells, leading to abnormal embryonic development and abortion. While exposure to A30 during late pregnancy had little or no impact on dams and fetuses. These findings suggest the safety of biomedical applications employing AuNPs during pregnancy is strongly influenced by fetal maturity and gestational age at exposure and provide the clues for AuNPs safe application period in pregnancy. Electronic supplementary material The online version of this article (10.1186/s10020-018-0061-2) contains supplementary material, which is available to authorized users.

We here report a facile synthesis of chitosan shelled quantum dot (QD/fGC) that holds essential properties requisite for biological applications, such as excellent water solubility, super colloidal stability, and low nonspecific adsorption as well as ease of functionalization. In this method, the amphiphilic glycol chitosan fragment (MW 1.0-1.7 kDa) was assembled on the top of CdSeS/ZnS nanocrystal through hydrophobic interaction in aqueous solution, without displacing the native coordinating ligands, which result in a higher quantum yield of about 0.26, 46% of the uncoated CdSeS/ZnS QDs in chloroform (0.57). In addition, the prepared QD/fGC composes an individual semiconductor core and presents an extremely small size of about 6.03 ± 1.50 nm (n = 399) in diameter. By conjugation with bioactive amines via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-based hydroxyl activation approach, the functionalized QD/fGC presented excellent recognition of specific cells in fluorescent imaging. Our work provides a new general method of chitosan modification of hydrophobic nanoparticles for biomedical applications.

Epicatechin gallate (ECG) is a main effective catechin widely existing in natural plants and food, with well-known health benefits. The present study first designed a new exosome-based delivery system for ECG and examined its neuroprotective effects on a rotenone (Rot)-induced Parkinson's disease (PD) model in vitro. Exosomes (Exo) were isolated from fresh bovine milk, and their average size was 85.15 ± 2.00 nm. ECG was encapsulated into Exo by a sonication method, and the loading efficiency of ECG-loaded exosomes (ECG-Exo) was 25.96 ± 0.45%. The neuroprotective effects of ECG-Exo were evaluated on Rot-induced SHSY5Y cells and compared with free ECG. Cell viability, cellular reactive oxygen species, apoptosis rate, and the expressions of caspase-3, Bax, Bcl-2, parkin, PINK1, and Atg5 were determined. Our results showed that Exo delivered ECG successfully into SHSY5Y cells and exhibited enhanced neuroprotective effects. ECG-Exo might inhibit SHSY5Y cell damage induced by Rot through antiapoptosis and antimitophagy.

The enhancement in reactivity of the antioxidant functionalized gold nanoparticles is closely related to the rate constant and activation energy, which were significantly affected by the chain length of the PEG ligands that capped the gold nanoparticles. Meanwile, the enhancement could be attributed to the π-π stacking interaction between the adjacent phenol groups coated on gold nanoparticles' surface.

All-in-one drug delivery nanovehicles with low cytotoxicity, high clinical imaging tracking capability, and targeted- and controlled-releasing performances are regarded as promising nanoplatforms for tumor theranostics. Recently, the design of these novel nanovehicles by low molecular weight amphiphilic chitosan (CS) was proposed. Based on fluorescent gold nanoclusters (AuNCs), a tumor-targeting nanovehicle (i.e. AuNCs-CS–AS1411) was prepared via electrostatic attraction between AuNC-conjugated chitosan (i.e. AuNCs-CS) and the anti-nucleolin aptamer, AS1411. After that, the anticancer drug methotrexate (MTX) was encapsulated into the nanovehicles and then the dual-functional nano-drug (i.e. MTX@AuNCs-CS–AS1411) was comparatively supplied to the human hepatocellular carcinoma cell line HepG2 and the human normal liver cell line LO2, to exhibit its “all in one” behavior. Under the conditions of the same concentration of MTX, MTX@AuNCs-CS–AS1411 demonstrates more intensive cytotoxicity and apoptosis-inducing activity against HepG2 cells than those against normal LO2 cells, mainly due to the targeting effect of AS1411 on the nucleolins that were found at high levels on the surface of tumor cells, but are at low levels or absent on normal cells. On the other hand, the MTX release from the MTX@AuNCs-CS–AS1411 was much faster in mildly acidic solution than that in neutral pH. Thus, it may provide a possibility to more significantly release MTX in intracellular lysosome of tumor cells, rather than let loose MTX during transport of the drug from blood vessels to tumor tissue. In conclusion, our dual-functional nanovehicle possesses high fluorescence efficiency and photostability, low cytotoxicity, pH-dependent controlled release, high sensitivity and target-specificity to cancer cells which allowed concurrent targeted imaging and delivery in cancer chemotherapies.

Parkinson's disease (PD) is the second most common neurodegenerative disease around the world. Current treatments alleviate the symptoms through the administration of drugs, including dopamine precursors, dopamine metabolism inhibitors, and activated dopamine agonists, but they cannot prevent the ongoing dopaminergic damage. One of the pivotal factors is the poor drug transport efficiency of crossing the blood-brain barrier, while studies reveal that exosomes are endogenous vesicles that are useful for drug delivery and disease diagnosis. As drug carriers, exosomes can not only deliver effective therapeutic drugs but also conquer difficulties such as biocompatibility, blood-brain barrier penetrability, metabolic stability, and target specificity. Exosomes have been successfully loaded with catalase, dopamine, catalase mRNA, and small interfering RNA for PD treatment and shown significant therapeutic effects. As diagnostic indicators (biomarkers), exosomes are more sensitive and reliable. They can reflect the pathological conditions and monitor disease progression. Exosomes from cerebrospinal fluid, plasma, serum, saliva, and urine are valuable biomarkers for PD diagnosis. This review mainly illuminates the association between exosomes and PD, sums up the therapeutic and diagnostic applications of exosomes in PD, and raises some critical remaining questions on the field. It is proposed that future investigations could be dedicated to exploiting a standard procedure to prepare large-scale exosomal carriers with high loading efficiency and new components of exosomes as biomarkers (mRNA; receptors), for better therapeutic and diagnostic options of PD.

Engineered nanoparticles could trigger inflammatory responses and potentiate a desired innate immune response for efficient immunotherapy. Here we report size-dependent activation of innate immune signaling pathways by gold (Au) nanoparticles. The ultrasmall-size (10 nm) trigger the NF-κB signaling pathway. Ultrasmall (4.5 nm) Au nanoparticles (Au4.5) activate the NLRP3 inflammasome through directly penetrating into cell cytoplasm to promote robust ROS production and target autophagy protein-LC3 (microtubule-associated protein 1-light chain 3) for proteasomal degradation in an endocytic/phagocytic-independent manner. LC3-dependent autophagy is required for inhibiting NLRP3 inflammasome activation and plays a critical role in the negative control of inflammasome activation. Au4.5 nanoparticles promote the degradation of LC3, thus relieving the LC3-mediated inhibition of the NLRP3 inflammasome. Finally, we show that Au4.5 nanoparticles could function as vaccine adjuvants to markedly enhance ovalbumin (OVA)-specific antibody production in an NLRP3-dependent pattern. Our findings have provided molecular insights into size-dependent innate immune signaling activation by cell-penetrating nanoparticles and identified LC3 as a potential regulatory target for efficient immunotherapy.

Chemotherapy-based treatment for cancer has made great progress in the past decades. However, there is still a big challenge for the treatment of lung cancer. Herein, a multifunctional nanocarrier was developed through electrostatic interaction between the fluorescent gold nanocluster-conjugated chitosan and the nucleolin targeting AS1411 aptamer. Then methotrexate was loaded into the multifunctional nanocarrier through hydrophobic interaction to obtain the nanodrug carrier systems. The prepared nanodrug carrier systems have an average nanoparticle size of 200 nm with 13.8% drug loading efficiency. The drug release is pH-dependent. The in vitro results demonstrated that the nanodrug carrier systems were selectively taken up by cancer cells in a time-dependent manner and exhibited significantly enhanced anticancer activity in a model of lung cancer A549 cells. The in vivo results showed that intravenous administration of nanodrug carrier systems into BALB/c mice led to accumulation of methotrexate at the tumor site and significantly inhibited the tumor growth but without overt toxicity. The present study suggests that the prepared multifunctional nanocarrier can be used as an effective drug delivery system for anticancer drugs and exhibits great potential in clinical applications.

Carbon dots have attracted considerable attention in the field of biosensors and bioimaging because of their excellent optical performance and low toxicity. However, the cellular uptake of the reported carbon dots generally has a low efficiency, which limits their practical applications. In this study, we reported a novel red fluorescent sulfur and nitrogen co-doped carbon dots with small molecular phenylboronic acid tags (i.e. S, N-CDs-PBA). The S, N-CDs-PBA can be taken up rapidly by PC12 cells in twenty minutes and showed high sensitivity for the detection of Fe3+ ions. The maximum emission wavelength is at 593 nm under the excitation of 550 nm. The absolute fluorescence quantum yield is 23% in water. The fluorescence can be effectively and selectively quenched by Fe3+ ions and the linear response range of Fe3+ ions was obtained from 0.3 µM to 5.0 µM with a detection limit as low as 0.1 µM. It could be concluded that the rapid uptake of S, N-CDs-PBA into cells and high photoluminescence quantum yield of red emission are beneficial for quick detection of Fe3+ ions.

Introduction: Psoriasis is a common, recurrent, immune skin disease, which seriously affects patients’ quality of life. In clinical practice, modified Runji ointment can effectively treat mild-to-moderate psoriasis with blood dryness syndrome, but there is a lack of high-quality evidence-based medical evidence. This trial aims to evaluate the efficacy and safety of nano-modified Runji ointment in the treatment of mild-to-moderate psoriasis with blood dryness syndrome. Methods/design: This study will be a randomized double-blind placebo-controlled trial. A total of 80 patients will be recruited and randomly divided into an intervention group (nano-modified Runji ointment group) and a placebo group at a ratio of 1:1. All included patients will receive 8 weeks of nano-modified Runji ointment or placebo ointment respectively, twice a day. The primary outcome will be the change in psoriasis area and disease severity index score at week 8 compared to baseline. The secondary outcomes will be rash area score, pruritus score, Dermatology Life Quality Index score, traditional Chinese medicine symptom score and adverse events. Discussion: This study may provide high-quality evidence for the efficacy of nano-modified Runji ointment in the treatment of mild to moderate psoriasis with blood dryness syndrome. The results of this study will be published in peer-reviewed journals. Trial registration: ChiCTR, ChiCTR2000034292. Registered July 1, 2020, https://www.chictr.org.cn/edit.aspx?pid=55884&htm=4

The sensitive and selective analytical methods for real-time monitoring of sulfur dioxide and its derivatives are significant for human health, pollution-control and food safety. Herein, we report a new nanocomposite (Hex-FGO-DPS) consisting of cyanine dye and fluorescent graphene oxide with unique reactive properties for ratiometric fluorescent detection of bisulfite. The ratiometric fluorescence of Hex-FGO-DPS in aqueous solution can be sensitively, selectively and efficiently tuned by bisulfite through a specific nucleophilic addition reaction. In the presence of bisulfite, the ratiometric fluorescence intensity of Hex-FGO-DPS (F 470nm /F 580nm ) changes up to 25 folds, accompanied by a distinct color change from yellow to blue which can be visually identified. The detection limit was measured to be 0.44 μM. The probe can be further applied for sensing intracellular bisulfite through the ratiometric fluorescence imaging analysis in living cells. In addition, the probe Hex-FGO-DPS also can be used for selective determination of gaseous sulfur dioxide in atmosphere and aqueous solution. The simple, sensitive and effective strategy reported here could facilitate the development of portable and reliable sensor for visual identification applications.

The sensitive and selective fluorescence probe for hydroxyl radical analysis is of significance because hydroxyl radical plays key roles in many physiological and pathological processes. In this work, a novel organic fluorescence molecular probe OHP for hydroxyl radical is synthesized by a two-step route. The probe employs 4-bora-3a,4a-diaza-s-indacene (difluoroboron dipyrromethene, BODIPY) as the fluorophore and possesses relatively high fluorescence quantum yields (77.14%). Hydroxyl radical can rapidly react with the probe and quench the fluorescence in a good linear relationship (R2=0.9967). The limit of detection is determined to be as low as 11 nM. In addition, it has been demonstrated that the probe has a good stability against pH and light illumination, low cytotoxicity and high biocompatibility. Cell culture experimental results show that the probe OHP is sensitive and selective for imaging and tracking endogenous hydroxyl radical in live cells.

Extensive health studies had declared that exposure to particulate matter (PM) was closely associated with neurodegenerative diseases, i.e. Parkinson’s disease (PD). Our aim was to clarify the potential molecular mechanism by which PM2.5 aggravated PD symptoms using in vitro and in vivo PD models. In this study, PC12 cells treated with rotenone (1 μM) and/or PM2.5 (50 μg/mL) for 4 days was used as the in vitro model. C57BL/6 J mice expored to PM2.5 (inhalation, 2.5 mg/kg) and rotenone (intraperitoneal injection, 30 mg/kg) for 28 days was used as the in vivo model. Rapamycin was used to promote the level of autophagy. The results showed that after exposure to PM2.5, the apoptosis of rotenone-treated PC12 cells were increased by increasing the ROS levels and decreasing the levels of mitochondrial membrane potential. In rotenone-treated PC12 cells, exposure to PM2.5 could decrease the expression levels of LC3II and Atg5, and increase the expression level of mTOR, suggesting that PM2.5 exposure inhibited autophagy. Furthermore, the mitophagy related genes, including PINK1 and Parkin, were decreased. At the same time, inhalation of PM2.5 could relieve the behavioral abnormalities of PD mouse induced by rotenone. The levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were significantly increased. Inhalation of PM2.5 could induce the oxidative stress and apoptosis in the substantia nigra of PD mouse, as well as the key markers of autophagy and mitophagy were also changed, which was consistent with the cell model. Besides, rapamycin would relieve the damaging effect of PM2.5 by triggering autophagy and mitophagy in rotenone-induced PD models. These results indicated that exposure to PM2.5 aggravated the behavioral abnormalities of PD symptoms through increasing oxidative stress, decreasing autophagy and mitophagy, and inducing mitochondria-mediated neuronal apoptosis. These findings not only revealed the effects and mechanism of PM2.5 exposure on PD, but also provided fundamental data that can be exploited to develop environmental safety policies.

The 1.5 wt% CNT/6061 composite was produced by the flake powder metallurgy process and treated by five intensities of shot peening (SP). After SP, the surface 3-D topography, the residual stress fields, microstructure, and microhardness of the deformed layers were investigated. Additionally, the microstructure included the domain size, microstrain density, and dislocation density, which were calculated by the Rietveld refinement method in MAUD software. Results showed that the depths of the projectile indentation increased and the surface roughness became larger with increasing SP intensity. The compressive residual stress field was introduced after SP. The average domain size decreased, whereas the microstrain became greater and the dislocation density increased as the SP intensity increased. The microhardness and depth of the strengthened layer increased with the increasing SP intensity. This investigation can prove that the effects of SP on the CNT/6061 composite were distinct. Keywords: Shot peening, CNT, Residual stress, Microstructure, Reinforcement, X-ray

Thermal management is critical to the performance, lifetime, and reliability of electronic devices. With the miniaturization, integration and functionalization of electronics and the emergence of new applications such as light emitting diodes, thermal dissipation becomes a challenging problem. Addressing this challenge requires the development of novel polymer-based composite materials with enhanced thermal conductivity. In this review, the fundamental design principles of highly thermally conductive composites were discussed. The key factors influencing the thermal conductivity of polymers, such as chain structure, crystallinity, crystal form, orientation of polymer chains, and orientation of ordered domains in both thermoplastics and thermosets were addressed. The properties of thermally conductive fillers (carbon nanotubes, metal particles, and ceramic particles such as boron nitride or aluminum oxide) are summarized at length. The dependence of thermal conductivity of composites on the filler loading, filler aggregate morphology and overall composite structure is also discussed. Special attention is paid to recent advances in controlling the microstructure of polymer composites to achieve high thermal conductivity (novel approaches to control filler orientation, special design of filler agglomerates, formation of continuous filler network by self-assembly process, double percolation approach, etc.). The review also summarizes some emerging applications of thermally conductive polymer composites. Finally, we outline the challenges and outlook for thermally conductive polymer composites.

Bismuth vanadate (BiVO4) is one of the most studied photoanodes whose photoelectrochemical (PEC) performance is limited by the sluggish charge mobility and substantial recombination losses. Here, a high porosity Mo doped BiVO4 film was synthesized by excess Mo doping and following vanadium re-substitution. The as-prepared BiVO4 based photoanode has large contact area between the electrolyte and the film due to the dissolution of excess Mo, shown by the results of electrochemically active surface area tests. As a result, the photocurrent of VMo-BiVO4 is 6.12 mA/cm2 at 1.23 V vs. the reversible hydrogen electrode (RHE) in 0.2 M KPi + 0.2 M Na2SO3 with the charge separation efficiency of ~96%, and the photocurrent of VMo-BiVO4 (3.18 mA/cm2 at 1.23 V vs. RHE) is 6.91 times of pristine BiVO4 in 0.2 M KPi. This approach demonstrated that a reasonable doping structure design could guarantee PEC water splitting with high performance.

Water splitting driven by sunlight is considered to be a promising strategy for solving energy crisis and environment pollution. But the sluggish kinetics of oxygen evolution reaction (OER) is quite limited for improving the efficiency of solar conversion. In this study, a core-shell nanostructure film of WCoFe oxyhydroxide coated BiVO4 (WCoFe/BiVO4) was constructed by solvothermal method, which exhibits better photoelectrochemical (PEC) properties compared with the bare BiVO4. A high quality-interface is formed between WCoFe oxyhydroxide and BiVO4 junctions, which further facilitates the separation and transport of photogenerated carriers. Notably, WCoFe/BiVO4 photoanode shows a low onset potential of 0.28 V vs. reversible hydrogen electrode (RHE) and a significant enhancement of photocurrent density, reaching 4.35 mA cm−2 at 1.23 VRHE, which is mainly attributed to the improved OER kinetics. In addition, the charge injection efficiency of WCoFe/BiVO4 photoanode also increases to 84.75%, more than twice as much as that of bare BiVO4 photoanode. Photoelectrochemical measurements and optical studies have demonstrated that the high PEC performance can be contributed to the reduced OER barriers and charge recombination, as well as the excellent optical transparency of WCoFe oxyhydroxide.

Peroxynitrite is a short-lived endogenous reactive species and plays important roles in many physiological and pathological processes. In this work, we synthesized a near-infrared probe based on the structure of benzothiazole derived cyanine for determination of peroxynitrite (ONOO-). The designed probe specifically reacted with ONOO- through oxidative cleavage of conjugated C˭C double bonds and generating the non-fluorescent product. Meanwhile, the characteristic absorption of the probe at 630 nm greatly decreased after reaction with ONOO-, accompanied by drastic color change from bright blue to green yellow, which exhibited a distinct visual feature. It was demonstrated that the probe could be used to measure ONOO- in a dose-response manner and had a detection limit lower as 26 nM. Furthermore, the probe Cy-SN was applied for the imaging of endogenous ONOO- in living cells by confocal microscopy, which showed good cell permeability and low cytotoxicity. Successful application of probe for exogenous colorimetric detection and endogenous fluorescence imaging of ONOO- is suggesting its great potential applications in biological analysis.

Because of the synergistic effects of drugs and minimal drug dose for cancer therapy, combination chemotherapy is frequently used in the clinic. In this study, hyaluronic acid-modified amine-terminated fourth-generation polyamidoamine dendrimer nanoparticles were synthesized for systemic co-delivery of cisplatin and doxorubicin (HA@PAMAM-Pt-Dox). In vitro data showed that HA@PAMAM-Pt-Dox can enter the cells through the lysosome mediated-pathway in a time-dependent manner. Cell viability studies indicated that HA@PAMAM-Pt-Dox exhibited a higher anticancer activity on MCF-7 and MDA-MB-231 breast cancer cells at a relative low concentration. HA@PAMAM-Pt-Dox not only efficiently inhibited tumor growth but also significantly reduced the toxicity of Dox. Moreover, intravenous administration of HA@PAMAM-Pt-Dox to MDA-MB-231 tumor-bearing BALB/c nude mice resulted in the accumulation of HA@PAMAM-Pt-Dox at the tumor site, thereby significantly inhibiting tumor growth without apparent toxicity. These results suggested that HA@PAMAM-Pt-Dox has great potential to improve the chemotherapeutic efficacy of cisplatin and doxorubicin in breast cancer. STATEMENT OF SIGNIFICANCE: One of the main problems in cancer treatment is the development of drug resistance. To date, it is believed that combination chemotherapy might be an effective strategy for the above problem. However, for two completely different drugs, combination chemotherapy faces huge difficulties including the antagonistic nature of drugs, variations in drugs in terms of solubility, and limited tumor targeting. Recent developments in nanoscience and nanotechnology provide an effective approach for such disadvantages. Considering the advantages of dendrimers such as control of size and molecular weight, bioavailability, and biosafety, we used fourth-generation dendrimers modified by HA as drug vectors by covalently conjugating them with anticancer drugs (cisplatin and doxorubicin) to form a nanodrug delivery system, named HA@PAMAM-Pt-Dox. We observed that the HA@PAMAM-Pt-Dox system can effectively kill breast cancer cells both in vitro and in vivo, which showed a favorable synergistic effect. This strategy can be extended to other drugs, thus providing a highly effective strategy for cancer treatment.

Macrophage apoptosis occurs throughout all stages of atherosclerosis, mainly induced by oxidized low density lipoproteins (Ox LDLs), leading to the formation of necrotic cores. Nevertheless, the mechanism of macrophage apoptosis induced by Ox LDLs is not yet clearly understood. In this study, a model of RAW264.7 macrophages exposed to an Ox LDL analogue, i.e. tert-butylhydroperoxide (t-BHP), was established. We thoroughly evaluated the viability and apoptosis of RAW264.7 cells treated with t-BHP at different time intervals. t-BHP treatment decreases the viability of RAW264.7 cells in a dose- and time-dependent manner (IC(50): 400 μM) and also induces a loss of the mitochondrial membrane potential (MMP) in RAW264.7 cells. Moreover, the activation of Bid, up-regulation of Bcl-2, and down-regulation of Bax, as well as the proteolysis of pro-caspase 3 and cleavage of PARP, were all also observed in t-BHP treated RAW264.7 cells. Finally, we concluded that t-BHP induces the apoptosis of macrophages via a mitochondria-mediated signaling pathway.

The gold nanoparticles (AuNPs) have been widely used as drug delivery systems at several biomedical fields. However, the effect of AuNPs on the components of human blood is not well characterized. AuNPs firstly interacted with blood when using AuNPs as the drug delivery carries. Therefore, it is urgent to investigate the effect of AuNPs (including the ligands of AuNPs) on human blood, especially its components. In this study, we investigated the possible effects of polyethylene glycol-coated AuNPs (PEG@AuNPs) and citric acid-coated AuNPs (CT-AuNPs) on the blood cell function and distribution of those nanoparticles in blood components including erythrocytes, leukocytes, platelets (PLTs) cells and plasma. We found that the amount of CT-AuNPs engulfed by leukocytes was four folds more compared to PEG@AuNPs, indicating that PEGylation might have the ability to escape the immune system. We found that each individual leukocyte uptaked more AuNPs particles than individual platelet. However, there are more PLTs than leukocytes in the blood. The total amount of AuNPs including PEG@AuNPs and CT-AuNPs accumulation in PLTs were more than in leukocytes. Moreover, we found that both CT-AuNPs and PEG@AuNPs-induced PLTs activation at high concentration. We therefore concluded that the interactions between nanodrug delivery systems (AuNPs) and human blood components, especially the PLTs should be careful evaluated prior to their clinical applications.

Lysosome fluorescent imaging has been widely used in the field of biological staining and diagnostics, which plays a key role in understanding intracellular metabolism and various physiological processes. However, for most currently used small-molecule lysotrackers, the photostability is often unsatisfactory when used for long-term and real-time visualization of lysosomal dynamics. Herein, we reported a new lysosome-targetable photostable fluorescent probe (i.e. MPL-NPA), and results showed that MPL-NAP possesses superior photostability, appreciable tolerance to pH change, low cytotoxicity and high lysosome targeting ability. These findings confirm that MPL-NAP is a well-suited imaging agent for targeting lysosome and enables long-term and real-time monitor of lysosome morphological changes under physiological processes.

Neuron loss is one fundamental features of neurodegenerative diseases. Stimulating endogenous neurogenesis, especially neuronal differentiation, might potentially provide therapeutic effects to these diseases. In this study, tanshinone II A (TIIA), a multiple target neuroprotectant, was demonstrated to promote dose-dependent neuronal differentiation in three cell models of immortalized C17.2 neuronal stem cells, rat embryonic cortical neural stem cells (NSCs) and rat PC12 pheochromocytoma cells. In particular, TIIA exerted promising effects on NSCs even at the dose of 3 nM. In PC12 cells, TIIA activated mitogen-activated protein kinase 42/44 (MAPK42/44) and its downstream transcription factor, cAMP response element-binding protein (CREB). In addition, TIIA up-regulated the expressions of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). The MEK inhibitor and the antagonist to the receptors of NGF and BDNF could partially attenuate the differentiation effects, indicating that MAPK42/44 mediated BDNF and NGF signals were involved in TIIA's differentiation effects. Caveolin-1 (CAV-1), the major functional protein of membrane caveolae, plays critical roles in the endocytosis of exogenous materials. CAV1, which was activated by TIIA, might help TIIA transport across cell membrane to initiate its differentiation effects. It was proven by the evidences that suppressing the function of caveolin inhibited the differentiation effects of TIIA. Therefore, we concluded that TIIA promoted neuronal differentiation partially through MAPK42/44 mediated BDNF and NGF signals in a caveolae-dependent manner.

The examination of top-cited studies is a useful method for identify and monitoring outstanding scientific research. The objective of this study was to identify and analyse the characteristics of the top 100 cited research studies on tuberculosis (TB) based on the Web of Knowledge. Overall, the top 100 cited studies were cited between 366 and 4443 times, and were published between 1995 and 2010, with the largest number of publications in 2003 and in 1995. Four studies were attributed to a single author and 10 to two authors; the number of authors exceeded six in 50 studies. Nine authors had more than one study as the first author and 18 authors had more than one study as the corresponding author. The United States contributed the largest number of studies, followed by the United Kingdom and France. The institutions with the largest number of articles were the Institut National de la Santé et de la Recherche Médicale in France and the University of California in the United States. The studies appeared in 35 journals, with 11 published in Science, followed by PNAS and NEJM. The majority of TB articles have been published in those medical journals with the highest impact factors, and are from the most industrialised countries.

The detection of free radicals and related species has attracted considerable attention in recent years due to their critical roles in physiological and pathological processes. Among the various methods for the detection of free radicals, electron spin resonance coupled with spin-trapping technique has been an effective approach for the characterization and quantification of free radicals due to its high specificity. In this study, we designed and synthesized a novel amphiphilic spin trap, 2-(diethoxyphosphoryl)-2-heptadecanyl-3,4-dihydro-2H-pyrrole-1-oxide (DEPHdPO), from 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide with a long hydrocarbon chain at the C-5 position of the pyrroline ring, providing the amphiphilic character. The free-radical-trapping ability of DEPHdPO was evaluated by capturing hydroxyl radicals (·OH), superoxide anions ( $$ {\text{O}}_{2}^{ \cdot - } $$ ), and carbon-centered free radicals in a model membrane prepared from sodium dodecyl sulfate (SDS). The results indicate that the hydrophobic hydrocarbon chain of DEPHdPO can be inserted into the inner core of SDS micelles, and the hydrophilic nitronyl functional moiety is located on the surface layer. Thus, various free radicals, including ·OH radicals, $$ {\text{O}}_{2}^{ \cdot - } $$ anions, and carbon-centered radicals could be site-specifically detected near the membrane surface. Moreover, DEPHdPO could be successfully located on the surface of thylakoid membranes, and the nearby photo-initiated $$ {\text{O}}_{2}^{ \cdot - } $$ anions could be trapped site-specifically.

Antioxidants are believed to have great potential for the treatment of diseases that are induced by oxidative stress. However, their pharmaceutical application is severely limited by their poor bioavailability and low biocompatibility. To solve this problem, the antioxidants can be encapsulated or covalently linked with nanomaterials to form nanoantioxidants. In this review, we aim to summarize the use of nanocarriers for antioxidant delivery and discuss their enhancement of antioxidant activity. We also suggest future research directions toward bringing nanoantioxidants into the realm of clinical applications.

Due to mitochondria involved in both apoptotic and necrotic cell death, labeling and imaging mitochondria has attracted considerable interest. However, conventional organic dyes used for mitochondrial imaging are limited because of their poor photostability. Considering that gold nanoclusters (AuNCs) possess some advantages over considerable interest, such as excellent photostability and strong fluorescence emission, we herein prepared a mitochondria-targeted fluorescent probe, AuNCs@CS-TPP, based on a covalent link between triphenylphosphonium (TPP) cations and chitosan-coated AuNCs (AuNCs@CS). The as-prepared AuNCs@CS-TPP exhibited a bluish fluorescence emission at 440 nm with a quantum yield of 8.5%. Meanwhile, the fluorescence intensity of AuNCs@CS-TPP labeled HeLa cells did not show apparent decrease after 8 min irradiation. Cytotoxicity assay showed that AuNCs@CS-TPP did not display any appreciable cytotoxicity on cells even at a concentration of 60 μg mL(-1). In addition, the result of fluorescence co-localization imaging in vitro indicated that AuNCs@CS-TPP could selectively accumulate into mitochondria of HeLa cells and HepG2 cells. These findings demonstrated that AuNCs@CS-TPP possessed superior photostability, low cytotoxicity, high sensitivity and target-specificity to mitochondria, allowing labeling and imaging of the mitochondria in living cells.

Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure.

The clinical application of antioxidants as pharmaceutical agents has been limited in general because of their poor aqueous solubility and inferior stability. According to previous studies, nanocarrier drug delivery systems may provide an alternative way to solve the above problems. In this study, nanoparticle carriers consisting of 6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (Trolox) encapsulating hydroxy-terminated poly (amidoamine) dendrimer (PAMAM-OH) were prepared by a self-assembly method and characterized by size, size distribution and morphology. A drug release assay showed that the Trolox release from PAMAM-OH/Trolox exhibits pH dependence. Moreover, the effects of PAMAM-OH/Trolox on cells damaged by tert-butylhydroperoxide were determined by 3-(4, 5-dimethylthizaol-2-yl)-2, 5-diphenyl tetrazolium bromide assay for cell viability, and malonaldehyde assay for membrane lipid peroxidation. The results illustrated that the PAMAM-OH/Trolox can significantly improve cell viability and reduce MDA content compared with those of cells pretreated with free Trolox.

The enhanced antioxidant ac- tivity of surface-functionalized gold nanoparticles (AuNPs) synthesized by self-assembly has attracted great atten- tion, but little is known about the mechanism behind the enhanced activi- ty. To address this challenge, the anti- oxidant activity of Au@PEG3SA (i.e., surface-functionalization of spherical AuNPs with the antioxidant salvianic acid A) was used as an example to il- lustrate the mechanism of the en- hanced activity. Evaluation of the anti- oxidant activity was performed in a radical-scavenging reaction between Au@PEG3SA and 2,2-diphenyl-1-pic- rylhydrazyl (DPPH) radical. As expect- ed, the rate constant for the reaction of Au@PEG3SA with DPPH was about nine times greater than that for the sal- vianic acid A monomer. A comparative analysis of the spectral characteristics of Au@PEG3SA and the salvianic acid A monomer further imply that the enhancement of the antioxidative re- A kinetics may be ascribed to the variation in the transition state for the DPPH-radical scavenging reaction through p-p stacking interactions be- tween and among adjacent groups on the surface of Au@PEG3SA. On the other hand, the kinetic enhancement of Au@PEG3SA on reactive-oxygen-spe- cies (ROS) scavenging can be observed in living cells and in vivo, which possi- bly provides new insight for the bioap- plication of self-assembly of surface- functionalized AuNPs.

It is still a huge challenge to find a new strategy for rationally designing covalent drugs because most of them are discovered by serendipity. Considering that the effect of covalent drugs is closely associated with the kinetics of the reaction between drug molecule and its target protein, here we first demonstrate an example of the kinetic effect of pi-stacking of drug molecules on covalent antimicrobial drug design. When PEGylated 7-aminocephalosporanic acid (PEG-ACA) is used as a substrate drug, pi-stacking of the ACA group via the self-assembly of PEG-ACA on the surface of gold nanoparticles (i.e. Au@ACA) exhibits antibacterial activity against E. coli fourfold higher than a PEG-ACA monomer does. The reason can be reasonably attributed to the kinetic rate enhancement for the covalent reaction between Au@ACA and penicillin binding proteins. We believe that the self-assembly of functional groups onto the surface of gold nanoparticles represents a new strategy for covalent drug design.

It is crucial to monitor intracellular pH values and their fluctuation since the organelles of cells have different pH distribution. Herein we construct a new small molecule fluorescent probe HBT-O for monitoring the subtle pH values within the scope of neutral to acid in living cells. The probe exhibited good water solubility, a marked turquoise to olivine emission color change in response to pH, and tremendous fluorescence hypochromatic shift of ∼50nm (1718cm-1) as well as the increased fluorescence intensity when the pH value changed from neutral to acid. Thus, the probe HBT-O can distinguish the subtle changes in the range of normal pH values from neutral to acid with significant fluorescence changes. These properties can be attributed to the intramolecular charge transfer (ICT) process of the probe upon protonation in buffer solutions at varied pH values. Moreover, the probe was reversible and nearly non-toxic for living cells. Then the probe was successfully used to detect pH fluctuation in living cells by exhibiting different fluorescence colors and intensity. These findings demonstrate that the probe will find useful applications in biology and biomedical research.

In this paper, we report a benzothiazole-functionalized cyanine fluorescence probe and demonstrate that it is selectively reactive to bisulfite, an intermediate indicator for oxidative stress. The selective reaction can be monitored by distinct ratiometric fluorescence variation favorable for cell imaging and visualization. The original probe can be regenerated in high yield through the elimination of bisulfite from the product by peroxides such as hydrogen peroxide, accompanied by fluorescence turning on at 590 nm, showing a potential application for the detection of peroxides. We successfully applied this probe for fluorescence imaging of bisulfite in cancer cells (MCF-7) treated with bisulfite and hydrogen peroxide as well as a selective detection limit of 0.34 μM bisulfite in aqueous solution.

A nanocarrier, namely, hydroxylethyl-chitosan nanoparticles was developed in this research for delivering antioxidants with 6-hydroxy-2, 5, 7, 8-tetra-methylchromane-2-carboxylic acid (trolox) as a model antioxidant. The trolox-encapsulated chitosan nanoparticles (trolox-CS NPs) were prepared by modifying chitosan with epoxyethane, which self-assembled into NPs and entrapped trolox, and then characterized by their size, size distribution, morphology and in vitro trolox release profile. Intracellular trafficking of CS NPs was observed. The anti-oxidant effect and potential mechanism of trolox-CS NPs were subsequently investigated in RAW264.7 cells. The effects of trolox-CS NPs on RAW264.7 cells damaged by tert-butylhydroperoxide (t-BHP) were determined by MTT assay for cell viability, MDA assay for membrane lipid peroxidation, JC-1 probe and Annexin V-FITC/PI double staining for mitochondria membrane potential (MMP) and RAW264.7 apoptosis, respectively. The trolox-CS NPs significantly improved cell viability and reduced MDA content compared with those of cells treated with free trolox. The trolox-CS NPs treatment inhibited MMP collapse and RAW264.7 apoptosis more obviously than free trolox. Molecular basis of apoptosis studied by western blotting revealed that trolox-CS NPs may block mitochondria-mediated apoptosis pathway through up-regulation of Bcl-2 and down-regulation of Bax and inhibiting the activation of pro-caspase 3, PARP and Bid.

So far it is unclear whether the release of oxygen-evolving complex (OEC) subunits including PsbO, PsbP, and PsbQ proteins is affected by the phosphorylation of photosystem II (PSII) membranes under light stress. In this work, different phosphorylated PSII membranes were obtained from spinach. Phosphorylation partially suppressed the release of PsbO, PsbP, and PsbQ proteins from PSII membranes under light stress. Reactive oxygen species including superoxide anion, hydrogen peroxide and hydroxyl radical, were involved in the release of a small part of PsbO protein, but not in the release of PsbP and PsbQ proteins in the non-phosphorylated and phosphorylated PSII membranes. All of the results suggested that the release of PsbO, PsbP, and PsbQ proteins was partially regulated by phosphorylation in PSII membranes, and the role of reactive oxygen species in the release of OEC subunits in non-phosphorylated PSII membranes was the same as in phosphorylated PSII membranes.