Synergistic effect of F and triggered oxygen vacancies over F-TiO2 on enhancing NO ozonation.

Oxidation-absorption technology is a key step for NOx removal from low-temperature gas. Under the condition of low O3 concentration (O3/NO molar ratio = 0.6), F-TiO2 (F-TiO2), which is cheap and environmentally friendly, has been prepared as ozonation catalysts for NO oxidation. Catalytic activity tests performed at 120°C showed that the NO oxidation efficiency of F-TiO2 samples was higher than that of TiO2 (about 43.7%), and the NO oxidation efficiency of F-TiO2-0.15 was the highest, which was 65.3%. Combined with physicochemical characteristics of catalysts and the analysis of active species, it was found that there was a synergistic effect between F sites and oxygen vacancies on F-TiO2, which could accelerate the transformation of monomolecular O3 into multi-molecule singlet oxygen (1O2), thus promoting the selective oxidation of NO to NO2. The oxidation reaction of NO on F-TiO2-0.15 follows the Eley-Rideal mechanism, that is, gaseous NO reacts with adsorbed O3 and finally form NO2.

Enhancement of antitumor immunotherapy using mitochondria-targeted cancer cell membrane-biomimetic MOF-mediated sonodynamic therapy and checkpoint blockade immunotherapy.

Immunotherapeutic interventions represent a promising approach to treating cancer, with strategies such as immune checkpoint blockade (ICB), immunogenic sonodynamic therapy (SDT), and immune adjuvant T cell delivery having exhibited clinical promise. In this report, we describe the use of cancer cell membrane-coated triphenylphosphonium (TPP) decorated nano-metal-organic framework (nMOF) constructs [Zr-TCPP(TPP)/R837@M] that were used to generate homologous, mitochondria-targeted platforms with a high rate of sonosensitizer loading. This construct was utilized to simultaneously promote tumor antigen presentation via enhancing SDT while synergistically promoting dendritic cell (DC) maturation through the delivery of the Toll-like receptor agonist R837. In vitro, these functionalized nMOFs were readily internalized by homologous tumor cells in which they were efficiently targeted to the mitochondria, promoting DC activation through the induction of immunogenic cell death (ICD) following ultrasound exposure. Moreover, this nanoplatform was able to achieve in vivo synergy with anti-CTLA-4 ICB to reverse immunosuppression tumor microenvironment (TME), thus achieving more robust antitumor efficacy capable of suppressing metastatic disease progression and facilitating the development of durable antitumor memory responses. Together, these results highlight a promising approach to achieving enhanced SDT activity while overcoming an immunosuppressive TME, thereby achieving more robust antitumor immunity.

TiSe2-mediated sonodynamic and checkpoint blockade combined immunotherapy in hypoxic pancreatic cancer.

BACKGROUND: Pancreatic cancer remains among the most prevalent and aggressive forms of cancer. While immunotherapeutic treatment strategies have shown some promise in affected patients, the benefits of these interventions have been limited by insufficient tumor infiltration by activated T cells. RESULTS: Here, Titanium diselenide (TiSe2) nanosheets were synthesized with good stability. When exposed to ultrasound (US), the TiSe2 nanosheets served as a reliable nano-sensitizer capable of inducing large amounts of reactive oxygen species (ROS) mediating sonodynamic therapy (SDT) under hypoxic and normoxic conditions. The tumor-released TAAs induced by TiSe2 nanosheet-mediated SDT promoted immunogenic cell death (ICD) conducive to the maturation of dendritic cells (DCs), and cytokine secretion and the subsequent activation and infiltration of T cells into the tumor. Combining TiSe2-mediated SDT with anti-PD-1 immune checkpoint blockade treatment led to the efficient suppression of the growth of both primary tumor and distant tumor, while simultaneously preventing lung metastasis. These improved immunotherapeutic and anti-metastatic outcomes were associated with activated systematic antitumor immune responses, including the higher levels of DC maturation and cytokine secretion, the increased levels of CD8+ T cells and the decreased levels of Treg cells infiltrated in tumors. CONCLUSION: TiSe2 can be used as a sonosensitizer with good efficacy and high safety to mediate efficient SDT. The combination treatment strategy comprised of TiSe2-mediated SDT and PD-1 blockade activate anti-tumor immune responses effectively thorough inducing ICD, resulting in the inhibition the growth and metastasis of tumor. The combination therapy holds promise as a novel immunotherapy-based intervention strategy for pancreatic cancer patients.

Macrophage interactions with collecting duct epithelial cells are capable of driving tubulointerstitial inflammation and fibrosis in immunoglobulin A nephropathy.

BACKGROUND: Tubulointerstitial fibrosis is a powerful predictor of future progression inimmunoglobulin A (IgA) nephropathy (IgAN). Proximal tubular epithelial cells (PTECs), in concert with infiltrating macrophages, are regarded as the agents provocateurs for driving this fibrotic process. However, evidence is now emerging for a contributory role of the distal nephron. The aim of this study was to examine the potential influence of macrophages on collecting duct epithelial cells (CDECs) and their combined role in the progression of IgAN. METHODS: CDECs were cultured with macrophage-conditioned media (MCM) generated from human monocyte cell lines U937 and THP-1 stimulated with or without 100 µg/mL galactose-deficient IgA1. CDECs were analysed for evidence of inflammation and fibrosis. RESULTS: Staining of IgAN biopsies for CD68+ macrophages revealed the presence of macrophages juxtaposed to collecting ducts and within their lumina. CDEC exposed to MCM from IgA1-stimulated THP-1 cells (THP-1-IgA-MCM) exhibited markedly increased expression of neutrophil-associated gelatinase (NGAL) and proinflammatory cytokinesinterleukin (IL)-1ß, tumour necrosis factor-α, IL-6 and IL-8 compared with MCM from non-IgA-stimulated THP-1 cells (THP-1-MCM). U937-IgA-MCM increased fibronectin levels and reduced E-cadherinmRNA expression. THP-1-IgA-MCM-derived exosomes induced similar increases in NGAL and cytokine expression while in cross-over experiments exosomes extracted from IL-1ß-exposed CDEC induced IL-1ß and IL-6 mRNA expression in both sets of macrophages. MiRnome analysis revealed that microRNA (miR)-146a, -155 and -200b exhibited a >2-fold increase in expression in CDEC treated with THP-1-IgA-MCM compared with THP-1-MCM. Enforced miR-146a suppression further enhanced NGAL expression, while ectopic miR-146a over-expression downregulated it. NGAL mRNA and miR-146a were upregulated in the biopsies of patients with progressive IgAN compared with non-progressive IgAN. CONCLUSIONS: Taken together, these data suggest that CDEC-macrophage interactions potentially contribute to the tubulointerstitial fibrosis characteristic of progressive IgAN.

Single-shot T2 mapping using overlapping-echo detachment planar imaging and a deep convolutional neural network.

PURPOSE: An end-to-end deep convolutional neural network (CNN) based on deep residual network (ResNet) was proposed to efficiently reconstruct reliable T2 mapping from single-shot overlapping-echo detachment (OLED) planar imaging. METHODS: The training dataset was obtained from simulations that were carried out on SPROM (Simulation with PRoduct Operator Matrix) software developed by our group. The relationship between the original OLED image containing two echo signals and the corresponding T2 mapping was learned by ResNet training. After the ResNet was trained, it was applied to reconstruct the T2 mapping from simulation and in vivo human brain data. RESULTS: Although the ResNet was trained entirely on simulated data, the trained network was generalized well to real human brain data. The results from simulation and in vivo human brain experiments show that the proposed method significantly outperforms the echo-detachment-based method. Reliable T2 mapping with higher accuracy is achieved within 30 ms after the network has been trained, while the echo-detachment-based OLED reconstruction method took approximately 2 min. CONCLUSION: The proposed method will facilitate real-time dynamic and quantitative MR imaging via OLED sequence, and deep convolutional neural network has the potential to reconstruct maps from complex MRI sequences efficiently.

A study on the NH3-SCR performance and reaction mechanism of a cost-effective and environment-friendly black TiO2 catalyst.

In this paper, black TiO2 without adding active components was developed for NH3-SCR-DeNOx. The catalytic activity tests showed that the NO removal efficiency of black TiO2 was always greater than 90% at 330-390 °C, which almost reached that of the commercial NH3-SCR-DeNOx catalyst. XRD, UV-vis, TG, EPR, XPS, H2-TPR, DFT and NH3-TPD analyses were carried out to study the structure-effectiveness relationship. We found that a large number of oxygen vacancies were formed over the black TiO2 surface. It was not only promoted the adsorption of NH3via direct (oxygen vacancies as Lewis acid sites for NH3 adsorption) and indirect (oxygen vacancies promote the formation of surface hydroxyl groups, which are Brønsted acid sites for NH3 adsorption) forms, but also improved the redox properties by promoting the reduction of Ti4+ to Ti3+. These changes lead to the superior catalytic activity of black TiO2 for NH3-SCR-DeNOx. Additionally, an in situ DRIFT study demonstrated that the NH3-SCR-DeNOx reaction over black TiO2 occurred via the Eley-Rideal (E-R) mechanism. Finally, the catalytic stability and resistance to H2O and SO2 of the black TiO2 catalyst were studied, and it showed good performances. This study offered new and important insights into the understanding of the role of oxygen vacancies in determining the physical and chemical properties of catalysts.

Effects of synthesis methods on catalytic activities of CoOx-TiO2 for low-temperature NH3-SCR of NO.

A series of cobalt doped TiO2 (Co-TiO2) and CoOx loaded TiO2 (Co/TiO2) catalysts prepared by sol-gel and impregnation methods respectively were investigated on selective catalytic reduction with NH3 (NH3-SCR) of NO. It was found that Co-TiO2 catalyst showed more preferable catalytic activity at low temperature range. From characterization results of XRD, TEM, Raman and FT-IR, Co species were proved to be doped into TiO2 lattice by replaced Ti atoms. After being characterized and analyzed by NH3-TPD, PL, XPS, EPR and DRIFTS, it was found that the better NH3-SCR activities of Co-TiO2 catalysts, compared with Co/TiO2 catalyst, were ascribed to the formation of more oxygen vacancies which further promoted the production of more superoxide ions (O2-). The superoxide ions were crucial for the formation of low temperature SCR reaction intermediates (NO3-) by reacting with adsorbed NO molecule. Therefore, these aspects were responsible for the higher low temperature NH3-SCR activity of Co-TiO2 catalysts.

Highly Reversibly Stretchable and Elastically Wearable Textile Supercapacitor.

Rapid and full recovery is the major challenge for the commercialization and further growth of textile-based wearable supercapacitors. Herein, reversibly stretchable and rapidly reboundable textile supercapacitors (TSCs) are developed via the utilization of NiCu2Se3/Cu-Ni alloy-plated cotton cloth (CNAPCC) textile as the cathode and Fe2CuSe3/CNAPCC textile as the anode. Both NiCu2Se3/CNAPCC and Fe2CuSe3/CNAPCC are obtained by a simple in situ oxidation reaction, followed by an ion exchange strategy. Meanwhile, a stable double-network (DN) structure is constructed, covering the knitted cotton cloth (KCC) and Cu-Ni alloy-plated layer (CNAPL). The DN textile structure significantly endows the NiCu2Se3/CNAPCC stretchable electrode with superior mechanical properties, exhibiting high elongation at a break of 470% with a stress of 7.19 MPa and full recovery after 100% strain with almost no residual deformation left after merely 0.2 s. Moreover, the assembled TSC provides a large energy density of 82 Wh kg-1 at a power density of 750 W kg-1. Besides, 50,000 charge/discharge cycle tests under static stretching are performed. The supercapacitor exhibits rapid recovery and excellent cycling stability of 92.2% capacitance retention under different strains (from 0 to 200%).

Catalytically Active Metal-Organic Frameworks Elicit Robust Immune Response to Combination Chemodynamic and Checkpoint Blockade Immunotherapy.

Chemodynamic therapy (CDT) strategies rely on the generation of reactive oxygen species (ROS) to kill tumor cells, with hydroxyl radicals (•OH) serving as the key mediators of cytotoxicity in this setting. However, the efficacy of CDT approaches is often hampered by the properties of the tumor microenvironment (TME) and associated limitations to the Fenton reaction that constrains ROS generation. As such, there is a pressing need for the design of new nanoplatforms capable of improving CDT outcomes. In this study, an Fc-based metal-organic framework (MOF) vitamin k3 (Vk3)-loaded cascade catalytic nanoplatform (Vk3@Co-Fc) was developed. This platform was capable of undergoing TME-responsive degradation without impacting normal cells. After its release, Vk3 was processed by nicotinamide adenine dinucleotide hydrogen phosphate (NAD(P)H) quinone oxidoreductase-1 (NQO1), which is highly expressed in tumor cells, thereby yielding large quantities of H2O2 that in turn interact with Fe ions via the Fenton reaction to facilitate in situ cytotoxic •OH production. This process leads to immunogenic cell death (ICD) of the tumor, which then promotes dendritic cell maturation and ultimately increases T cell infiltration into the tumor site. When this nanoplatform was combined with programmed death 1 (PD-1) checkpoint blockade approaches, it was sufficient to enhance tumor-associated immune responses in breast cancer as evidenced by increases in the frequencies of CD45+ leukocytes and CD8+ cytotoxic T lymphocytes, thereby inhibiting tumor metastasis to the lungs and improving murine survival outcomes. Together, this Vk3@Co-Fc cascading catalytic nanoplatform enables potent cancer immunotherapy for breast cancer regression and metastasis prevention.

Self-Supporting Triphase Photocatalytic CO2 Reduction to CH3OH on Controllable Core-Shell Structure with Tunable Interfacial Wettability.

Enhancing the CO2 mass transfer and proton supply in the photocatalytic reduction of CO2 with H2O into CH3OH (PRC-M), while avoiding the hydrogen evolution reaction (HER), remains a challenge. Herein, we propose an approach to control the surface coverage of CO2 and H2O by modifying interfacial wettability, which is achieved by modulating the core-shell structure to expose either hydrophobic melamine-resorcinol-formaldehyde (MRF) or hydrophilic NiAl-layered double hydroxides (NAL). Characterizations reveal that an insufficient proton supply leads to the production of competing CO, while excessive coverage of H2O results in undesired HER. The NAL-MRF integrates hydrophobic and hydrophilic interfaces, contributing to the CO2 mass transfer and H2O adsorption, respectively. This combination forms a microreactor that facilitates the triphase photocatalysis of CO2, H2O, and catalyst, allowing for high local concentrations of both *CO and *H without competing binding sites. Importantly, the formation of covalent bonds and a Z-type heterojunction between hydrophilic NAL and hydrophobic MRF layers accelerates the charge separation. Furthermore, the density functional theory results indicate that the NAL linking promotes the continuous hydrogenation of *CO. As a result, an enhanced CH3OH yield of 31.41 µmol g-1 h-1, with selectivity of 93.62%, is achieved without hole scavengers or precious metals.

Ag and MOFs-derived hollow Co3O4 decorated in the 3D g-C3N4 for creating dual transferring channels of electrons and holes to boost CO2 photoreduction performance.

The rapid recombination of photoinduced charge carriers and low selectivity are still challenges for the CO2 photoreduction. Herein, we proposed that ZIF-67-derived Co3O4 hollow polyhedrons (CoHP) were embedded into NaCl-template-assisted synthesized 3D graphitic carbon nitride (NCN), subsequently, loading Ag by photo-deposition as efficient composites (CoHP@NCN@Ag) for CO2 photoreduction. This integration simultaneously constructs two heterojunctions: p-n junction between Co3O4 and g-C3N4 and metal-semiconductor junction between Ag and g-C3N4, in which Co3O4 and Ag serve as hole (h+) trapping sites and electron (e-) sinks, respectively, achieving spatial separation of charge carriers. The donor-acceptor structure design of NCN realize a good photogenerated e--h+ separation efficiency. The mesoporous structure of hollow Co3O4 facilitate gas-diffusion efficiency, light scattering and harvesting. And the introduction of plasmonic Ag further strengthens the light-harvesting and charge migration. Benefiting from the rational design, the optimized ternary heterostructures exhibit a high CO2-CO yield (562 µmol g-1), which is about 4-fold as high as that of the NCN (151 µmol g-1). Moreover, the conjectural mechanism was systematically summarized. We hope this study provides a promising strategy for designing efficient g-C3N4 systems for the CO2 photoreduction.

Effect of pre-oxidation process on V2O5/AC catalyst for the selective catalytic reduction of NOx with NH3.

Activated coke-based catalysts have attracted extensive attention in denitration by selective catalytic reduction by NH3 (NH3-SCR), due to their excellent catalytic performance at low temperature. In the paper, the V2O5/AC catalyst was prepared by the impregnation method to investigate the effect of pre-oxidation process on its NH3-SCR activity. Activity test results show that the V2O5/AC catalyst with 4-h pre-oxidation exhibits the best NOx removal efficiency, which reaches the NOx conversion is over 75% in the range of 200-240 °C and exhibits an excellent resistance to SO2 and H2O. Characterization results demonstrate that the V4+ was oxidized by oxygen molecule during pre-oxidation process, which contributes to the formation of V5+ ions and surface-active oxygen species. The surface-active oxygen species are conducive to promoting the "fast SCR" reaction; thus, the pre-oxidized process can contribute to the superior NH3-SCR performance for V2O5/AC catalyst at low temperature.

Snare-assisted flexible endoscope in trans-gastric endoscopic gallbladder-preserving surgery: A pilot animal study.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) gallbladder-preserving surgery by flexible endoscopy is an emerging technology. However, the gallbladder fails to obtain traction and positioning functions during the operation. AIM: To evaluate the feasibility and safety of a new surgical method, "snare-assisted pure NOTES gallbladder-preserving surgery". METHODS: Eight miniature pigs were randomly divided into the experimental group [NOTES gallbladder-preserving surgery using the snare device, snare assisted (SA)] and the control group (NOTES gallbladder-preserving surgery without using the snare device, NC), with four cases in each group. The differences between the two groups of animals in operating time, operating workload, complications, adverse events, white blood cells, and liver function were determined. RESULTS: No differences were found in the surgical success rate, gallbladder incision closure, white blood cell count, or liver function between the two groups. The total operating time, gallbladder incision blood loss, gallbladder disorientation time, gallbladder incision closure time, and workload scores on the National Aeronautics and Space Administration-Task Load Index were significantly reduced in the SA group (P < 0.05). CONCLUSION: These results indicated that snare-assisted pure NOTES gallbladder-preservation surgery using standard endoscopic instruments reduced the difficulty of operation, shortened operation time, and did not increase complications in pigs. A new method for pure NOTES gallbladder-preservation surgery was provided.

Ultrasound improved immune adjuvant delivery to induce DC maturation and T cell activation.

Tumor immunotherapy has emerged as a promising approach to tumor treatment. Currently, immune adjuvant-based therapeutic modalities are rarely curative in solid tumors owing to challenges including the low permeability and extremely poor water solubility of these adjuvants, limiting their ability to effectively promote dendritic cell (DC) maturation. Herein, we employed ultrasound-mediated cavitation (UMC) to promote the delivery of Toll-like receptor agonist (R837)-loaded pH-responsive liposomes (PEOz-Lip@R837) to tumors. The tumor-associated antigens (TAAs) produced by UMC treatment exhibited vaccinal activity, particularly in the presence of immune adjuvants, together promoting the maturation of DC and inducing cytokine production. Importantly, UMC can down-regulate immune checkpoint molecules, like Cd274, Foxp3 and Ctla4, synergistically stimulating the activation and proliferation of T cells in the body to facilitate tumor treatment. This UMC-enhanced PEOz-Lip@R837 approach was able to induce a robust antitumor immune response capable of arresting primary and distant tumor growth, while also developing immunological memory, protecting against tumor rechallenge following initial tumor clearance. Overall, these results highlight a promising UMC- and pH-sensitive immune adjuvant delivery-based treatment for tumors with the potential for clinical application.

Collagenase-Loaded H-TiO2 Nanoparticles Enhance Ultrasound Imaging-Guided Sonodynamic Therapy in a Pancreatic Carcinoma Xenograft Model via Digesting Stromal Barriers.

Sonodynamic therapy (SDT), a noninvasive therapy that relies on sonosensitizers and generates reactive oxygen species (ROS), has attracted considerable attention in the treatment of pancreatic cancer. However, being surrounded by dense stromal barriers, pancreatic cancer exhibits high interstitial fluid pressure (IFP) and hypoxia in the tumor microenvironment (TME), resulting in poor SDT efficacy. Collagenase-loaded hollow TiO2 (Col-H-TiO2) nanoparticles (NPs) capable of degrading stromal barriers and producing sufficient ROS production were synthesized in this study. After administration of NPs in the patient-derived xenograft (PDX) model, ultrasonic irradiation-released collagenase degraded tumor matrix fibers, decreased intratumoral IFP, and enhanced the penetration and retention of NPs within tumor tissues. Moreover, the NPs accumulated within the tumor not only generate abundant ROS under the influence of ultrasound irradiation but also improve intratumoral ultrasound signal, providing ultrasonic imaging-guided highly effective SDT for pancreatic cancer. In conclusion, this research improves the SDT technique and enhances the visualization of pancreatic cancer by remodeling the TME and is a promising strategy for further clinical applications.

Ultrasound-Based Radiomics Can Classify the Etiology of Cervical Lymphadenopathy: A Multi-Center Retrospective Study.

Medical diagnostic imaging is essential for the differential diagnosis of cervical lymphadenopathy. Here we develop an ultrasound radiomics method for accurately differentiating cervical lymph node tuberculosis (LNTB), cervical lymphoma, reactive lymph node hyperplasia, and metastatic lymph nodes especially in the multi-operator, cross-machine, multicenter context. The inter-observer and intra-observer consistency of radiomics parameters from the region of interest were 0.8245 and 0.9228, respectively. The radiomics model showed good and repeatable diagnostic performance for multiple classification diagnosis of cervical lymphadenopathy, especially in LNTB (area under the curve, AUC: 0.673, 0.662, and 0.626) and cervical lymphoma (AUC: 0.623, 0.644, and 0.602) in the whole set, training set, and test set, respectively. However, the diagnostic performance of lymphadenopathy among skilled radiologists was varied (Kappa coefficient: 0.108, *p < 0.001). The diagnostic performance of radiomics is comparable and more reproducible compared with those of skilled radiologists. Our study offers a more comprehensive method for differentiating LNTB, cervical lymphoma, reactive lymph node hyperplasia, and metastatic LN.

Metal-Organic Framework (MOF)-Based Ultrasound-Responsive Dual-Sonosensitizer Nanoplatform for Hypoxic Cancer Therapy.

Sonodynamic therapy (SDT), which uses reactive oxygen species to target tumors, has shown promise in the management of unresectable cancers. However, the hypoxic tumor environment limits SDT efficiency, making complete tumor destruction challenging. Here, a dual-sonosensitizer nanoplatform is developed by loading an alkyl radical generator (2,2-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH) onto a zirconium metal-organic framework (Zr-MOF). The Zr-MOF@AIPH nanoparticles (NPs) can produce singlet oxygen, which can kill tumor cells under normoxic conditions, as well as alkyl radicals, which can kill tumor cells under both normoxic and hypoxic conditions. The combination of these free radicals further enhances SDT efficiency. Meanwhile, the nitrogen generated owing to AIPH decomposition can reduce the cavitation threshold and enhance the acoustic cavitation effect, thereby promoting NP penetration at the tumor site. Moreover, Zr-MOF@AIPH NPs exhibit good photoacoustic, fluorescence, and ultrasound imaging abilities due to their porphyrin-based structure and the nitrogen generated, which can remotely control NP delivery and determine the optimal therapeutic time window, ensuring the maximization of SDT efficiency. In vitro and in vivo examinations prove the superior antitumor efficacy, excellent biocompatibility, and favorable imaging ability of Zr-MOF@AIPH. This study spearheads the charge toward improving SDT efficacy in hypoxic environments via a combination of complementary sonosensitizers.

Tablet-like TiO2/C nanocomposites for repeated type I sonodynamic therapy of pancreatic cancer.

Sonodynamic therapy (SDT) represents a viable approach to overcoming the limited ability of photodynamic therapy to penetrate biological barriers. However, pancreatic tumors contain a hypoxic microenvironment that limits the efficacy of oxygen-dependent type II SDT, complicating efforts to develop reliable, stable, and hypoxia-tolerant sonosensitizer. Herein, a tablet-like TiO2/C nanocomposite with a metal-organic-framework (MOF)-derived carbon structure was designed and found to be hypoxia-tolerant and stable in response to repeated ultrasound irradiation, enabling the TiO2/C-mediated generation of large quantities of reactive oxygen species (ROS) and thereby achieving efficacious type I SDT. Importantly, this nanocomposite continued to generate ROS in response to repeated ultrasound irradiation, and was able to induce tumor cell apoptosis via SDT-induced DNA damage in vitro and in vivo. This TiO2/C nanocomposite also exhibited good biocompatibility and did not induce any apparent toxicity in vitro and in vivo. Together, these data highlight TiO2/C as a valuable nanocomposite capable of facilitating repeated type I SDT, making it a promising tool for the treatment of hypoxic solid pancreatic tumors. STATEMENT OF SIGNIFICANCE: In this research, a tablet-like TiO2/C nanocomposite with a metal-organic-framework (MOF)-derived carbon structure was designed, which exhibited great stability upon repeated ultrasound irradiation, hypoxic-tolerant ability and good biocompatibility. After ultrasound irradiation, TiO2/C could efficiently generate reactive oxygen species in an oxygen-independent manner, which overcame the limitation of pure TiO2 nanoparticles. Therefore, it was applied to repeated type I sonodynamic therapy of hypoxic pancreatic tumor.

Double redox process to synthesize CuO-CeO2 catalysts with strong Cu-Ce interaction for efficient toluene oxidation.

In this study, a novel double redox (DR) method was developed to synthesize highly active CuO-CeO2 (CuCe-DR) catalyst for catalytic oxidative decomposition of toluene. Compare with CuCe-C catalyst prepared by co-precipitation method, CuCe-DR catalyst exhibits a higher Ce3+ ion and incorporated Cu2+ ion concentration, and has a stronger Cu-Ce interaction. Ce3+ and incorporated Cu2+ ions can induce the formation of oxygen vacancies, and thus increasing the amount of surface chemisorbed oxygen on CuCe-DR catalyst. The strong Cu-Ce interaction can promote the electron transfer between CuO and CeO2, which improves the redox properties of CuCe-DR catalyst. Although CuCe-DR catalyst has a lower toluene adsorption capacity, CuCe-DR exhibits much higher toluene oxidation performance than CuCe-C at the temperature below 300 °C. Moreover, CuCe-DR shows higher stability than CuCe-C during 100 h long-term test due to its high oxygen mobility which inhibits coking. Finally, the possible reaction pathways and promotional mechanism on CuCe-DR in toluene oxidation are proposed. We expect this study to shed more light on the nature of the surface active site(s) of CuCe catalyst for VOCs oxidation and the development of novel redox preparation method for the synthesis highly-active catalysts.

Hypoxia-Adapted Sono-chemodynamic Treatment of Orthotopic Pancreatic Carcinoma Using Copper Metal-Organic Frameworks Loaded with an Ultrasound-Induced Free Radical Initiator.

The efficacy of sonodynamic therapy (SDT) is largely dependent upon oxygen availability to generate deleterious reactive oxygen species, and as such, hypoxic microenvironments greatly constrain the efficacy of SDT. Development of free radical generators that are not dependent on oxygen and related combination treatment strategies thus have the potential to enhance the antitumor potential of SDT. Combined treatment strategies are expected to improve the efficacy of sonodynamic antitumor therapy. As metal-organic framework (MOF) platforms are highly amenable to integration with other therapeutic approaches, we herein report the development of tumor microenvironment (TME)-responsive nanoparticles constructed by embedding the azo initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (AIPH) into hypoxia-triggered copper metal-organic framework (Cu-MOF) nanovectors to achieve synergistic sono-chemodynamic therapy in an orthotopic murine pancreatic carcinoma model system. When exposed to hypoxic conditions within the TME, this Cu-MOF structure underwent degradation, leading to the release of Cu2+ and AIPH. Cu2+ was then able to deplete local glutathione stores, resulting in the reduction of Cu2+ to Cu+, which then reacts with endogenous H2O2 in a Fenton-like reaction to yield cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy. When exposed to ultrasound irradiation, AIPH further degraded in an oxygen-independent manner to yield nitrogen bubbles and alkyl radicals, the former of which enhanced the ability of these nanoparticles to penetrate deeply into the tumor. The resultant radicals induced substantial DNA damage and apoptotic cell death within target tumors under different levels of oxygen availability. As such, this hypoxic TME-responsive synergistic sono-chemodynamic approach offers an ideal means of achieving oxygen-independent free radical generation and enhanced treatment efficacy.