Effect of Rhythmically Cued Exercise Interventions on Functions in Patients With Parkinson Disease: A Meta-Analysis.

OBJECTIVE: The purpose of this review was to investigate the efficacy of rhythmically cued exercise interventions on motor function, cognition, and mental state in patients with Parkinson disease. METHODS: PubMed, Cochrane Database, Web of Science, Embase, and CINAHL were searched June 15, 2023. Original studies investigating the efficacy of rhythmically cued exercise interventions on the functions of patients with Parkinson disease were included. The Cochrane risk-of-bias assessment tool was used to evaluate the risk of bias. The protocol was registered in PROSPERO (CRD42022371203). RESULTS: A total of 38 original studies involving 1486 participants were included. Rhythmically cued exercise interventions demonstrated superior effects on motor function compared to exercise therapy without rhythm (standardized mean difference [SMD] = -0.31). However, no significant improvements were observed in cognition and mental state. Overall, significant improvements were observed in motor examination (SMD = -0.61), Timed "Up & Go" Test (mean difference [MD] = -0.91), activities of daily living (SMD = -0.49), balance (SMD = 0.59), walking velocity (MD = 0.06), step length (MD = 2.65), and stride length (MD = 0.04) following rhythmically cued exercise interventions. No significant improvements were observed in freezing of gait and cadence. Assessment of publication bias showed no significant evidence of publication bias. Meta-regression analyses revealed a significant association between treatment duration and improvement in motor function. Furthermore, adverse events and dropout rates did not significantly differ between the 2 groups. CONCLUSION: Rhythmically cued exercise interventions are effective in improving motor function in the early to middle stages of Parkinson disease. More than 10 weeks of intervention yielded better results. However, these interventions do not have a significant impact on cognition and mental states. Importantly, rhythmically cued exercise interventions are safe and well tolerated. Large-scale trials are needed for further confirmation. IMPACT: This study contributes to the development of safe and reliable home rehabilitation programs, aiming to enhance the quality of life for patients with Parkinson disease.

Adhesive Ergothioneine Hyaluronate Gel Protects against Radiation Gastroenteritis by Alleviating Apoptosis, Inflammation, and Gut Microbiota Dysbiosis.

Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients' life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.

Effect of phytic acid combined with lactic acid on color and texture deterioration of ready-to-eat shrimps during storage.

To retard the deterioration of texture and color of ready-to-eat (RTE) shrimps during storage, phytic acid (PA) and lactic acid (LA) were used to soak the shrimp prior to cooking. The factors affecting texture (water holding capacity, protein oxidation and degradation, and microstructure) and color (Maillard reaction and lipid oxidation) were determined separately. The free radical and copper ion content were also determined in order to investigate the regulation mechanism of phytic acid and lactic acid on the texture and color of RTE shrimps. It was found that the inhibitor-treated RTE shrimps showed better texture and color properties than the control group, and the compound inhibitor (PA + LA) showed a better inhibition effect than single inhibitor. In addition, PA and LA prevented the oxidation of RTE shrimps by scavenging free radicals and chelating copper ions, which in turn enabled the regulation of color and texture deterioration.

Biocompatible Tantalum Nanoparticles as Radiosensitizers for Enhancing Therapy Efficacy in Primary Tumor and Metastatic Sentinel Lymph Nodes.

Metastasis of breast carcinoma is commonly realized through lymphatic circulation, which seriously threatens the lives of breast cancer patients. Therefore, efficient therapy for both primary tumor and metastatic sentinel lymph nodes (SLNs) is highly desired to inhibit cancer growth and metastasis. During breast cancer treatment, radiotherapy (RT) is a common clinical method. However, the efficacy of RT is decreased by the radioresistance to a hypoxic microenvironment and inevitable side effects for healthy issues at high radiation doses. Considering the above-mentioned, we provide high biocompatible poly(vinylpyrrolidone) coated Ta nanoparticles (Ta@PVP NPs) for photothermal therapy (PTT) assisted RT for primary tumor and metastatic SLNs. On the one hand, for primary tumor treatment, Ta@PVP NPs with a high X-ray mass attenuation coefficient (4.30 cm2/kg at 100 keV) can deposit high radiation doses within tumors. On the other hand, for metastatic SLNs treatment, the effective delivery of Ta@PVP NPs from the primary tumor into SLNs is monitored by computed tomography and photoacoustic imaging, which greatly benefit the prognosis and treatment for metastatic SLNs. Moreover, Ta@PVP NPs-mediated PTT could enhance the RT effect, and immunogenic cell death caused by RT/PTT could induce an immune response to improve the therapeutic effect of metastatic SLNs. This study not only explores the potential of Ta@PVP NPs as effective radiosensitizers and photothermal agents for combined RT and PTT but also offers an efficient strategy to cure both primary tumor and metastatic SLNs in breast carcinoma.

Remanufacturing an evaluation system for electrical control systems of drilling rig based on the improved FCE and ANN.

The decision process of different remanufacturing schemes in an electronic control system has great fuzziness and uncertainty. Therefore, it is essential to use an appropriate method to show the characteristics of different schemes and support the users' decision. Based on the concepts of the artificial neural network theory and the improved comprehensive evaluation method, the decision-making system of the electronic control remanufacturing scheme was constructed in the present study. In the first step, a classification method of parts is proposed from the perspective of manufacturing enterprises. Moreover, an artificial neural network model is used to determine parts of remanufacturing value. Then the pricing strategy is divided according to the users' needs, and then a decision model is constructed. The combined subjective and objective methods are used to solve the compound weight of different equipment, and a set of improved fuzzy comprehensive decision methods is formed. Then the proposed model was applied to an electronic control transformation project as an example to evaluate the performance of different schemes. The evaluation results were consistent with the results of a third-party organization. It was concluded that the proposed scheme can be used as the theoretical basis to choose the best remanufacturing scheme to ensure the efficient operation of each part in an ECS.

Ultrathin, Transparent, and High Density Perovskite Scintillator Film for High Resolution X-Ray Microscopic Imaging.

Inorganic perovskite quantum dots CsPbX3 (X = Cl, Br, and I) has recently received extensive attention as a new promising class of X-ray scintillators. However, relatively low light yield (LY) of CsPbX3 and strong optical scattering of the thick opaque scintillator film restrict their practical applications for high-resolution X-ray microscopic imaging. Here, the Ce3+ ion doped CsPbBr3 nanocrystals (NCs) with enhanced LY and stability are obtained and then the ultrathin (30 µm) and transparent scintillator films with high density are prepared by a suction filtration method. The small amount Ce3+ dopant greatly enhances the LY of CsPbBr3 NCs (about 33 000 photons per MeV), which is much higher than that of bare CsPbBr3 NCs. Moreover, the scintillator films made by these NCs with high density realize a high spatial resolution of 862 nm thanks to its thin and transparent feature, which is so far a record resolution for perovskite scintillator-based X-ray microscopic imaging. This strategy not only provides a simple way to increase the resolution down to nanoscale but also extends the application of as-prepared CsPbBr3 scintillator for high resolution X-ray microscopic imaging.

Metabolic Profiling and Gene Expression Analysis Unveil Differences in Flavonoid and Lipid Metabolisms Between 'Huapi' Kumquat (Fortunella crassifolia Swingle) and Its Wild Type.

To elucidate the mechanism underlying special characteristic differences between a spontaneous seedling mutant 'Huapi' kumquat (HP) and its wild-type 'Rongan' kumquat (RA), the fruit quality, metabolic profiles, and gene expressions of the peel and flesh were comprehensively analyzed. Compared with RA, HP fruit has distinctive phenotypes such as glossy peel, light color, and few amounts of oil glands. Interestingly, HP also accumulated higher flavonoid (approximately 4.1-fold changes) than RA. Based on metabolomics analysis, we identified 201 differential compounds, including 65 flavonoids and 37 lipids. Most of the differential flavonoids were glycosylated by hexoside and accumulated higher contents in the peel but lower in the flesh of HP than those of RA fruit. For differential lipids, most of them belonged to lysophosphatidycholines (LysoPCs) and lysophosphatidylethanolamines (LysoPEs) and exhibited low abundance in both peel and flesh of HP fruit. In addition, structural genes associated with the flavonoid and lipid pathways were differentially regulated between the two kumquat varieties. Gene expression analysis also revealed the significant roles of UDP-glycosyltransferase (UGT) and phospholipase genes in flavonoid and glycerophospholipid metabolisms, respectively. These findings provide valuable information for interpreting the mutation mechanism of HP kumquat.

X-ray-facilitated redox cycling of nanozyme possessing peroxidase-mimicking activity for reactive oxygen species-enhanced cancer therapy.

Nanomaterials with shifting or mixed redox states is one of the most common studied nanozyme with peroxidase-like activity for chemodynamic therapy (CDT), which can decompose hydrogen peroxide (H2O2) of tumor microenvironment into highly toxic reactive oxygen species (ROS) by a nano-catalytic way. However, most of them exhibit an insufficient catalytic efficiency due to their dependence on catalytic condition. Herein, a potential methodology is proposed to enhance their enzymatic activity by accelerating the redox cycling of these nanomaterials with shifting or mixed redox states in the presence of X-ray. In this study, the nanocomposite consisting of SnS2 nanoplates and Fe3O4 quantum dots with shifting or mixed redox states (Fe2+/Fe3+) is used to explore the strategy. Under external X-ray irradiation, SnS2 cofactor as electron donor can be triggered to transfer electrons to Fe3O4, which promotes the regeneration of Fe2+ sites on the surface of the Fe3O4. Consequently, the regenerated Fe2+ sites react with the overexpressed H2O2 to persistently generate ROS for enhanced tumor therapy. The designed nanocomposite displays the synergistic effects of radiotherapy and CDT. The strategy provides a new avenue for the development of artificial nanozymes with shifting or mixed redox states in precise cancer treatments based on X-ray-enhanced enzymatic efficacy.

Photothermal Killing of A549 Cells and Autophagy Induction by Bismuth Selenide Particles.

With a highly efficient optical absorption capability, bismuth selenide (Bi2Se3) can be used as an outstanding photothermal agent for anti-tumor treatment and shows promise in the field of nanotechnology-based biomedicine. However, little research has been completed on the relevant mechanism underlying the photothermal killing effect of Bi2Se3. Herein, the photothermal effects of Bi2Se3 particles on A549 cells were explored with emphasis put on autophagy. First, we characterized the structure and physicochemical property of the synthesized Bi2Se3 and confirmed their excellent photothermal conversion efficiency (35.72%), photostability, biocompatibility and ability of photothermal killing on A549 cells. Enhanced autophagy was detected in Bi2Se3-exposed cells under an 808 nm laser. Consistently, an elevated expression ratio of microtubule-associated protein 1 light chain 3-II (LC3-II) to LC3-I, a marker of autophagy occurrence, was induced in Bi2Se3-exposed cells upon near infrared (NIR) irradiation. Meanwhile, the expression of cleaved-PARP was increased in the irradiated cells dependently on the exposure concentrations of Bi2Se3 particles. Pharmacological inhibition of autophagy by 3-methyladenine (3-MA) further strengthened the photothermal killing effect of Bi2Se3. Meanwhile, stress-related signaling pathways, including p38 and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), were activated, coupled with the attenuated PI3K/Akt signaling. Our study finds that autophagy and the activation of stress-related signaling pathways are involved in the photothermal killing of cancerous cells by Bi2Se3, which provides a more understanding of photothermal materials.

The efficacy of internet-based cognitive behavioural therapy for social anxiety disorder: A systematic review and meta-analysis.

Social anxiety disorder (SAD) is one of the most common lifelong anxiety disorders. Although cognitive behavioural therapy (CBT) has proven to be effective in treating people with SAD, it may not be available for a considerable proportion of patients. Internet-based CBT (ICBT) is more accessible than face-to-face treatment. This meta-analysis evaluated the efficacy of ICBT in patients with SAD. We searched five databases, PubMed, Cochrane Central Register of Controlled Trials, Health Management Information Consortium, Ovid MEDLINE and EMBASE, and identified 20 eligible randomized controlled trials published from inception to 25 July 2020, with the outcome data from 1,743 participants. The results indicated that ICBT had a significant positive effect on patients with SAD compared with the control groups (g = -0.55). A subgroup analysis revealed that ICBT and CBT had an equal effect on treating patients with SAD (g = -0.18). There was also no difference between ICBT and ICBT plus other therapies in the treatment of patients with SAD (g = -0.07). The effect size of ICBT on patients with SAD was maintained at the 6-month follow-up (g = -0.08) and at the 12-month follow-up (g = -0.17). The findings of this review demonstrated that ICBT can significantly reduce SAD symptoms and that ICBT and face-to-face CBT produce equivalent effects. The results of this meta-analysis contributed to the literature on ICBT for the treatment of patients with SAD, although numerous aspects of ICBT were identified for future investigations.

A Heterojunction Structured WO2.9-WSe2 Nanoradiosensitizer Increases Local Tumor Ablation and Checkpoint Blockade Immunotherapy upon Low Radiation Dose.

Radiotherapy (RT) in practical use often suffers from off-target side effects and ineffectiveness against hypoxic tumor microenvironment (TME) as well as remote metastases. With regard to these problems, herein, we provide semiconductor heterojunction structured WO2.9-WSe2-PEG nanoparticles to realize a synergistic RT/photothermal therapy (PTT)/checkpoint blockade immunotherapy (CBT) for enhanced antitumor and antimetastatic effect. Based on the heterojunction structured nanoparticle with high Z element, the nanosystem could realize non-oxygen-dependent reactive oxygen species generation by catalyzing highly expressed H2O2 in TME upon X-ray irradiation, which could further induce immunogenic cell death. Meanwhile, this nanosystem could also induce hyperthermia upon near-infrared irradiation to enhance RT outcome. With the addition of anti-PD-L1 antibody-based CBT, our results give potent evidence that local RT/PTT upon mild temperature and low radiation dose could efficiently ablate local tumors and inhibit tumor metastasis as well as prevent tumor rechallenge. Our study provides not only one kind of radiosensitizer based on semiconductor nanoparticles but also a versatile nanoplatform for simultaneous triple-combined therapy (RT/PTT/CBT) for treating both local and metastasis tumors.

Clinically Approved Carbon Nanoparticles with Oral Administration for Intestinal Radioprotection via Protecting the Small Intestinal Crypt Stem Cells and Maintaining the Balance of Intestinal Flora.

The exploration of an old drug for new biomedical applications has an absolute predominance in shortening the clinical conversion time of drugs for clinical application. In this work, carbon nanoparticles suspension injection (CNSI), the first clinically approved carbon nanoparticles in China, is explored as a new nano-radioprotective agent for potent intestinal radioprotection. CNSI shows powerful radioprotective performance in the intestine under oral administration, including efficient free radical scavenging ability, good biosafety, high chemical stability, and relatively long retention time. For example, CNSI shows high reactive oxygen species (ROS) scavenging activities, which effectively alleviates the mitochondrial dysfunction and DNA double-strand breaks to protect the cells against radiation-induced damage. Most importantly, this efficient ROS scavenging ability greatly helps restrain the apoptosis of the small intestinal epithelial and crypt stem cells, which decreases the damage of the mechanical barrier and thus relieves radiation enteritis. Moreover, CNSI helps remove the free radicals in the intestinal microenvironment and thus maintain the balance of intestinal flora so as to mitigate the radiation enteritis. The finding suggests a new application of clinically approved carbon nanoparticles, which not only promotes the development of new intestinal radioprotector, but also has a great potential for clinical transformation.

BiO2-x Nanosheets as Radiosensitizers with Catalase-Like Activity for Hypoxia Alleviation and Enhancement of the Radiotherapy of Tumors.

Tumor hypoxia is known to be one of the vital factors that aggravate tumor resistance to radiation therapy (RT) in which oxygen plays a critical role in tumor destruction. Herein, we synthesize a simple nanoradiosensitizer based on ultrathin BiO2-x nanosheets (NSs) modified with Tween 20 (T-BiO2-x NSs) to overcome the hypoxia-induced radioresistance as well as increase the efficacy of RT. On the one hand, bismuth as a high-Z element can effectively enhance the sensitivity of RT by depositing a higher radiation dose in tumors. The semiconductor property also endows its photocatalytic ability to produce extra reactive oxygen species (ROS) by reaction with the surrounding water. On the other hand, the defect-abundant BiO2-x NSs are also found to decompose the highly expressed hydrogen peroxide (H2O2) at the tumor site into oxygen (O2) for combating hypoxia. Both in vitro and in vivo experiments indicate that the as-prepared T-BiO2-x NSs could effectively inhibit tumor growth with X-ray irradiation. Our work thus provides a simple nanoradiosensitizer with multifunctionalities for increasing the RT efficacy while alleviating tumor hypoxia at the same time.

A Bi2S3@mSiO2@Ag nanocomposite for enhanced CT visualization and antibacterial response in the gastrointestinal tract.

The non-invasive imaging of the gastrointestinal (GI) tract is highly desired for clinical research due to the various GI tract bacterial infection-induced diseases. To treat GI tract infections, various antibiotics have been used in the clinic. The growing problem of multidrug-resistant bacteria calls for effective antibiotic alternatives. Here, we construct a dual-functional Bi2S3@mSiO2@Ag nanocomposite for simultaneous enhanced X-ray computed tomography (CT) imaging and efficient antibacterial activity in the GI tract. The nanocomposite also has good stability, low cytotoxicity, and negligible hemolysis. Moreover, the investigation of the long-term toxicity and biodistribution of the Bi2S3@mSiO2@Ag nanocomposite after oral administration confirms its safety at the tested dosage. In particular, Ag nanoparticles (NPs) well dispersed on a silica substrate can reduce the antibacterial dosage and enhance the antibacterial activity of the Bi2S3@mSiO2@Ag nanocomposite. Furthermore, we have established bacterially infected enteritis animal models to confirm the antibacterial ability of the nanocomposite. This work opens up a new avenue for the design of a nanotheranostic agent that acts as both a contrast agent for the enhanced visualization of the GI tract and an antibacterial agent as an alternative to antibiotics.

Enhanced Generation of Non-Oxygen Dependent Free Radicals by Schottky-type Heterostructures of Au-Bi2S3 Nanoparticles via X-ray-Induced Catalytic Reaction for Radiosensitization.

Despite the development of nanomaterials with high-Z elements for radiosensitizers, most of them suffer from their oxygen-dependent behavior in hypoxic tumor, nonideal selectivity to tumor, or inevasible damages to normal tissue, greatly limiting their further applications. Herein, we develop a Schottky-type heterostructure of Au-Bi2S3 with promising ability of reactive free radicals generation under X-ray irradiation for selectively enhancing radiotherapeutic efficacy by catalyzing intracellular H2O2 in tumor. On the one hand, like many other nanomaterials with rich high-Z elements, Au-Bi2S3 can deposit higher radiation dose within tumors in the form of high energy electrons. On the other hand, Au-Bi2S3 can remarkably improve the utilization of a large number of X-ray-induced low energy electrons during radiotherapy for nonoxygen dependent free radicals generation even in hypoxic condition. This feature of Schottky-type heterostructures Au-Bi2S3 attributes to the generated Schottky barrier between metal Au and semiconductor Bi2S3, which can trap the X-ray-generated electrons and transfer them to Au, resulting in efficient separation of the electron-hole pairs. Then, because of the matched potential between the conduction band of Bi2S3 and overexpressed H2O2 within tumor, the Au-Bi2S3 HNSCs can decompose the intracellular H2O2 into highly toxic •OH for selective radiosensitization in tumor. As a consequence, this kind of nanoparticle provides an idea to develop rational designed Schottky-type heterostructures as efficient radiosensitizers for enhanced radiotherapy of cancer.

Mass production of poly(ethylene glycol) monooleate-modified core-shell structured upconversion nanoparticles for bio-imaging and photodynamic therapy.

Developing robust and high-efficient synthesis approaches has significant importance for the expanded applications of upconversion nanoparticles (UCNPs). Here, we report a high-throughput synthesis strategy to fabricate water-dispersible core-shell structured UCNPs. Firstly, we successfully obtain more than 10 grams core UCNPs with high quality from one-pot reaction using liquid rare-earth precursors. Afterwards, different core-shell structured UCNPs are fabricated by successive layer-by-layer strategy to get enhanced fluorescence property. Finally, the hydrophobic UCNPs are modified with poly(ethylene glycol) monooleate (PEG-OA) though a novel physical grinding method. On the basis of mass-production, we use the as-prepared PEG-UCNPs to construct an 808-nm stimuli photodynamic therapy agent, and apply them in cancer therapy and bio-imaging.

Enhanced radiosensitization of ternary Cu3BiSe3 nanoparticles by photo-induced hyperthermia in the second near-infrared biological window.

The development of a new multifunctional nanomedicine capable of enhancing radiosensitization by photo-induced hyperthermia for the inhibition of cancer growth and metastasis is highly required for efficient treatment of cancer cells. Compared to the first near-infrared (NIR) window, the second NIR window light could provide a maximum penetration depth as well as minimizing autofluorescence due to its low scattering and energy absorption. Here, we report a new versatile theranostic agent based on ternary Cu3BiSe3 nanoparticles (NPs) modified by poly(vinylpyrollidone) (PVP-Cu3BiSe3). Benefiting from their preferable X-ray attenuation ability and strong NIR absorbance in the second NIR biological window, PVP-Cu3BiSe3 NPs can not only deposit more radiation doses to destroy the cancer cells, but also conduct the optical energy into hyperthermia for thermal eradication of tumor tissues and the improvement of the tumor oxygenation to overcome the hypoxia-associated radio-resistance of tumors. According to both in vitro and in vivo results, exposure to an X-ray plus 1064 nm laser completely kills cancer cells and even inhibits tumor metastasis, displaying no warning signs of a relapse. On the other hand, PVP-Cu3BiSe3 NPs can be used as a multi-model imaging agent for X-ray computer tomography (CT) and photoacoustic tomography (PAT) imaging. These demonstrate the potential of PVP-Cu3BiSe3 NPs in multimodal imaging-guided synergetic radiophotothermal therapy of deep-seated tumors and effective inhibition of their metastasis.

Translocation, biotransformation-related degradation, and toxicity assessment of polyvinylpyrrolidone-modified 2H-phase nano-MoS2.

Nano-MoS2 has been extensively investigated in materials science and biomedicine. However, the effects of different methods of exposure on their translocation, biosafety, and biotransformation-related degradability remain unclear. In this study, we combined the advantages of synchrotron radiation (SR) X-ray absorption near-edge structure (XANES) and high-resolution single-cell SR transmission X-ray microscopy (SR-TXM) with traditional analytical techniques to investigate translocation, precise degraded species/ratio, and correlation between the degradation and toxicity levels of polyvinylpyrrolidone-modified 2H-phase MoS2 nanosheets (MoS2-PVP NSs). These NSs demonstrated different biodegradability levels in biomicroenvironments with H2O2, catalase, and human myeloperoxidase (hMPO) (H2O2 < catalase < hMPO). The effects of NSs and their biodegraded byproducts on cell viability and 3D translocation at the single-cell level were also assessed. Toxicity and translocation in mice via intravenous (i.v.), intraperitoneal (i.p.), and intragastric (i.g.) administration routes guided by fluorescence (FL) imaging were investigated within the tested dosage. After i.g. administration, NSs accumulated in the gastrointestinal organs and were excreted from feces within 48 h. After i.v. injection, NSs showed noticeable clearance due to their decreased accumulation in the liver and spleen within 30 days when compared with that in the i.p. group, which exhibited slight accumulation in the spleen. This work paves the way for understanding the biological behaviors of nano-MoS2 using SR techniques that provide more opportunities for future applications.

Tumor Microenvironment-Responsive Cu2(OH)PO4 Nanocrystals for Selective and Controllable Radiosentization via the X-ray-Triggered Fenton-like Reaction.

Traditional radiotherapy can induce injury to the normal tissue around the tumor, so the development of novel radiosensitizer with high selectivity and controllability that can lead to more effective and reliable radiotherapy is highly desirable. Herein, a new smart radiosensitizer based on Cu2(OH)PO4 nanocrystals that can simultaneously respond to endogenous stimulus (H2O2) and exogenous stimulus (X-ray) is reported. First, Cu2(OH)PO4 nanocrystals can generate CuI sites under X-ray irradiation through X-ray-induced photoelectron transfer process. Then, X-ray-triggered CuI sites serve as a catalyst for efficiently decomposing overexpressed H2O2 in the tumor microenvironment into highly toxic hydroxyl radical through the Fenton-like reaction, finally inducing apoptosis and necrosis of cancer cells. Meanwhile, this nonspontaneous Fenton-like reaction is greatly limited within normal tissues because of its oxygen-rich condition and insufficient H2O2 relative to tumor tissues. Thus, this strategy can ensure that the process of radiosentization can only be executed within hypoxic tumors but not in normal cells, resulting in the minimum damages to surrounding healthy tissues. As a result, the X-ray-triggered Fenton-like reaction via introducing nontoxic Cu2(OH)PO4 nanocrystals under the dual stimuli provides a more controllable and reliable activation approach to simultaneously enhance the radiotherapeutic efficacy and reduce side effects.

Graphdiyne Nanoparticles with High Free Radical Scavenging Activity for Radiation Protection.

Numerous carbon networks materials comprised of benzene moieties, such as graphene and fullerene, have held great fascination for radioprotection because of their acknowledged good biocompatibility and strong free radical scavenging activity derived from their delocalized π-conjugated structure. Recently, graphdiyne, a new emerging carbon network material consisting of a unique chemical structure of benzene and acetylenic moieties, has gradually attracted attention in many research fields. Encouraged by its unique structure with strong conjugated π-system and highly reactive diacetylenic linkages, graphdiyne might have free radical activity and can thus be used as a radioprotector, which has not been investigated so far. Herein, for the first time, we synthesized bovine serum albumin (BSA)-modified graphdiyne nanoparticles (graphdiyne-BSA NPs) to evaluate their free radical scavenging ability and investigate their application for radioprotection both in cell and animal models. In vitro studies indicated that the graphdiyne-BSA NPs could effectively eliminate the free-radicals, decrease radiation-induced DNA damage in cells, and improve the viability of cells under ionizing radiation. In vivo experiments showed that the graphdiyne-BSA NPs could protect the bone marrow DNA of mice from radiation-induced damage and make the superoxide dismutase (SOD) and malondialdehyde (MDA) (two kinds of vital indicators of radiation-induced injury) recover back to normal levels. Furthermore, the good biocompatibility and negligible systemically toxicity responses of the graphdiyne-BSA NPs to mice were verified. All these results manifest the good biosafety and radioprotection activity of graphdiyne-BSA NPs to normal tissues. Therefore, our studies not only provide a new radiation protection platform based on graphdiyne for protecting normal tissues from radiation-caused injury but also provide a promising direction for the application of graphdiyne in the biomedicine field.