Progress of Angiogenesis Signal Pathway and Antiangiogenic Drugs in Nasopharyngeal Carcinoma.

Nasopharyngeal cancer is a rare cancer with unique ethnic and geographic distribution. Since nasopharyngeal cancer often originates from the pharyngeal crypt, early symptoms are not obvious. They are difficult to detect in time, and the disease is usually diagnosed and treated only when it has progressed to an advanced-stage. Since angiogenesis is essential for the growth and invasion of solid tumors, antiangiogenic therapy has become a common treatment strategy for many solid tumors, and it has also achieved remarkable results in the treatment of nasopharyngeal carcinoma, which is prone to recurrence and distant metastasis. In this paper, we review the latest research progress of antiangiogenic drugs for nasopharyngeal carcinoma and their antiangiogenic mechanism of action and further propose some promising antiangiogenic therapeutic targets.

Homolytic H2 dissociation for enhanced hydrogenation catalysis on oxides.

The limited surface coverage and activity of active hydrides on oxide surfaces pose challenges for efficient hydrogenation reactions. Herein, we quantitatively distinguish the long-puzzling homolytic dissociation of hydrogen from the heterolytic pathway on Ga2O3, that is useful for enhancing hydrogenation ability of oxides. By combining transient kinetic analysis with infrared and mass spectroscopies, we identify the catalytic role of coordinatively unsaturated Ga3+ in homolytic H2 dissociation, which is formed in-situ during the initial heterolytic dissociation. This site facilitates easy hydrogen dissociation at low temperatures, resulting in a high hydride coverage on Ga2O3 (H/surface Ga3+ ratio of 1.6 and H/OH ratio of 5.6). The effectiveness of homolytic dissociation is governed by the Ga-Ga distance, which is strongly influenced by the initial coordination of Ga3+. Consequently, by tuning the coordination of active Ga3+ species as well as the coverage and activity of hydrides, we achieve enhanced hydrogenation of CO2 to CO, methanol or light olefins by 4-6 times.

Fast-Response Nickel-Promoted Indium Oxide Catalysts for Carbon Dioxide Hydrogenation from Intermittent Solar Hydrogen.

Construction of a "net-zero-emission" system through CO2 hydrogenation to methanol with solar energy is an eco-friendly way to mitigate the greenhouse effect. Traditional CO2 hydrogenation demands centralized mass production for cost reduction with mass water electrolysis for hydrogen supply. To achieve continuous reaction with intermittent and fluctuating flow of H2 on a small-scale for distributed application scenarios, modulating the catalyst interface environment and chemical adsorption capacity to adapt fluctuating reaction conditions is highly desired. This paper describes a distributed clean CO2 utilization system in which the surface structure of catalysts is carefully regulated. The Ni catalyst with unsaturated electrons loaded on In2 O3 can reduce the dissociation energy of H2 to overcome the slow response of intermittent H2 supply, exhibiting a faster response (12 min) than bare oxide catalysts (42 min). Moreover, the introduction of Ni enhances the sensitivity of the catalyst to hydrogen, yielding a Ni/In2 O3 catalyst with a good performance at lower H2 concentrations with a 15 times adaptability for wider hydrogen fluctuation range than In2 O3 , greatly reducing the negative impact of unstable H2 supplies derived from renewable energies.

Nature of Catalytic Behavior of Cobalt Oxides for CO2 Hydrogenation.

Cobalt oxide (CoO x ) catalysts are widely applied in CO2 hydrogenation but suffer from structural evolution during the reaction. This paper describes the complicated structure-performance relationship under reaction conditions. An iterative approach was employed to simulate the reduction process with the help of neural network potential-accelerated molecular dynamics. Based on the reduced models of catalysts, a combined theoretical and experimental study has discovered that CoO(111) provides active sites to break C-O bonds for CH4 production. The analysis of the reaction mechanism indicated that the C-O bond scission of *CH2O species plays a key role in producing CH4. The nature of dissociating C-O bonds is attributed to the stabilization of *O atoms after C-O bond cleavage and the weakening of C-O bond strength by surface-transferred electrons. This work may offer a paradigm to explore the origin of performance over metal oxides in heterogeneous catalysis.

Identification of Pseudomonas aeruginosa From the Skin Ulcer Disease of Crocodile Lizards (Shinisaurus crocodilurus) and Probiotics as the Control Measure.

The crocodile lizard (Shinisaurus crocodilurus) is an endangered ancient reptile species. Captive breeding is an important conservation measure for the potential restoration and recovery of their wild populations. However, a skin ulcer disease caused by an unknown pathogen has become a serious threat to captive breeding individuals. In the current study, based on microbial isolation, we identified Pseudomonas aeruginosa as the dominant pathogen in skin ulcer disease. Chinese skinks (Plestiodon chinensis) were used to verify the pathogenicity of P. aeruginosa in skin ulcer disease in vivo. As expected, subcutaneous inoculation of P. aeruginosa induced skin disease in healthy skinks and P. aeruginosa was re-isolated from the induced skin ulcers. Therefore, P. aeruginosa, an opportunistic and ubiquitous pathogen that causes a wide range of infections, appears to be the main pathogen of the skin disease affecting crocodile lizards. In the aquaculture industry, probiotics are widely used in the prevention and control of animal diseases caused by such pathogens. Here, we administered probiotics to the breeding crocodile lizards for 6 months. The three experiment groups treated with different kinds of probiotics showed significance at controlling case incidence. Three of the four groups treated with probiotics showed significant disease prevention (Effective Microorganisms mixed probiotics P = 0.0374; Double-dose Effective Microorganisms, P = 0.0299; Bacillus subtilis, P = 0.0140, T-test), and CFUs in the water of the breeding enclosures were also inhibited after probiotics usage (P < 0.001, T-test). Our study demonstrated the role of Pseudomonas aeruginosa in development of skin ulcer disease of crocodile lizards in a local zoo and offered the probiotic-based method for control measurements, which would be of benefit for the conservation of endangered reptiles.

Moderate Surface Segregation Promotes Selective Ethanol Production in CO2 Hydrogenation Reaction over CoCu Catalysts.

Cobalt-copper (CoCu) catalysts have industrial potential in CO/CO2 hydrogenation reactions, and CoCu alloy has been elucidated as a major active phase during reactions. However, due to elemental surface segregation and dealloying phenomena, the actual surface morphology of CoCu alloy is still unclear. Combining theory and experiment, the dual effect of surface segregation and varied CO coverage over the CoCu(111) surface on the reactivity in CO2 hydrogenation reactions is explored. The relationship between C-O bond scission and further hydrogenation of intermediate *CH2 O was discovered to be a key step to promote ethanol production. The theoretical investigation suggests that moderate Co segregation provides a suitable surface Co ensemble with lateral interactions of co-adsorbed *CO, leading to promoted selectivity to ethanol, in agreement with theory-inspired experiments.

Correlation study of cytokine levels in alveolar lavage fluid with exhaled nitric oxide and lung function in children with bronchial asthma.

BACKGROUND: The associations between cytokines in the bronchoalveolar lavage fluid (BALF), lung cytokine expression, fractional exhaled nitric oxide (FeNO) and pulmonary function test results in pediatric asthmatics have not been extensively characterized. This study sought to explore correlations between cytokines BALF, FeNO, and pulmonary function test results. METHODS: From October 2018 to October 2020, a prospective study was conducted on 42 children with asthma and 17 children with pulmonary foreign bodies that required bronchoscopy. Pulmonary function tests and FeNO tests were performed on all patients. Patients were divided into a high FeNO group or low FeNO group based on their FeNO results. Interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, and IL-17 in the BALF were measured by enzyme-linked immunosorbent assays. Pearson correlations were used to assess the correlations between the cytokines in BALF, the pulmonary function test results, and the FeNO results. Pearson correlation was used to calculate the correlation coefficient "r" among alveolar lavage fluid cytokines, lung function, and FeNO. Receiver operating characteristic (ROC) curves were used to determine the area under the curve (AUC), sensitivity, and specificity of BALF cytokines for the high and low FeNO groups. RESULTS: IL-4, IL-5, IL-6, IL-8, IL-13, and IL-17 in BALF were significantly correlated with FeNO, but were not significantly correlated with the pulmonary function test results. Cytokine IL-4, IL-5, IL-6, IL-8, IL-13, and IL-17 in BALF were significantly different in the high FeNO, low FeNO, and control groups (all P<0.05). The AUCs for differentiating between low and high FeNO based on BALF cytokines ranged from 0.72 to 0.95. The sensitivity and specificity for discriminating between low and high FeNO based on IL-5 and IL-13 reached 95.7% and 100%, respectively. CONCLUSIONS: The cytokine levels of the BALF of children with asthma were significantly elevated, correlated with FeNO, and can be used evaluate airway inflammation in children with asthma.

Strong Electronic Oxide-Support Interaction over In2O3/ZrO2 for Highly Selective CO2 Hydrogenation to Methanol.

Metal oxides are widely employed in heterogeneous catalysis, but it remains challenging to determine their exact structure and understand the reaction mechanisms at the molecular level due to their structural complexity, in particular for binary oxides. This paper describes the observation of the strong electronic interaction between In2O3 and monoclinic ZrO2 (m-ZrO2) by quasi-in-situ XPS experiments combined with theoretical studies, which leads to support-dependent methanol selectivity. In2O3/m-ZrO2 exhibits methanol selectivity up to 84.6% with a CO2 conversion of 12.1%. Moreover, at a wide range of temperatures, the methanol yield of In2O3/m-ZrO2 is much higher than that of In2O3/t-ZrO2 (t-: tetragonal), which is due to the high dispersion of the In-O-In structure over m-ZrO2 as determined by in situ Raman spectra. The electron transfer from m-ZrO2 to In2O3 is confirmed by XPS and DFT calculations and improves the electron density of In2O3, which promotes H2 dissociation and hydrogenation of formate intermediates to methanol. The concept of the electronic interaction between an oxide and a support provides guidelines to develop hydrogenation catalysts.

The Interplay between Structure and Product Selectivity of CO2 Hydrogenation.

Identification of the active structure under reaction conditions is of great importance for the rational design of heterogeneous catalysts. However, this is often hampered by their structural complexity. The interplay between the surface structure of Co3 O4 and the CO2 hydrogenation is described. Co3 O4 with morphology-dependent crystallographic surfaces presents different reducibility and formation energy of oxygen vacancies, thus resulting in distinct steady-state composition and product selectivity. Co3 O4 -0 h rhombic dodecahedra were completely reduced to Co0 and CoO, which presents circa 85 % CH4 selectivity. In contrast, Co3 O4 -2 h nanorods were partially reduced to CoO, which exhibits a circa 95 % CO selectivity. The crucial role of the Co3 O4 structure in determining the catalytic performance for higher alcohol synthesis over CuCo-based catalysts is demonstrated. As expected, Cu/Co3 O4 -2 h shows nine-fold higher ethanol yield than Cu/Co3 O4 -0 h owing to the inhibition for methanation.

Activation and Spillover of Hydrogen on Sub-1†nm Palladium Nanoclusters Confined within Sodalite Zeolite for the Semi-Hydrogenation of Alkynes.

The search for efficient nontoxic catalysts able to perform industrial hydrogenations is a topic of interest, with relevance to many catalytic processes. Herein, we describe a mechanistic phenomenon for the activation and spillover of hydrogen for remarkable selectivity in the semi-hydrogenation of acetylene over sub-1 nm Pd nanoclusters confined within sodalite (SOD) zeolite (Pd@SOD). Specifically, hydrogen is dissociated on the Pd nanoclusters to form hydrogen species (i.e., hydrogen atoms and hydroxyl groups) that spill over the SOD surfaces. The design and utilization of the small-pore zeolite SOD (six-membered rings with 0.28×0.28 nm channels) is crucial as it only allows H2 diffusion into the channels to reach the encapsulated Pd nanoclusters and thus avoids over-hydrogenation to form ethane. Pd@SOD exhibits an ethylene selectivity of over 94.5 %, while that of conventional Pd/SOD is approximately 21.5 %.

Hydroxyl-mediated ethanol selectivity of CO2 hydrogenation.

Oxide-supported Rh nanoparticles have been widely used for CO2 hydrogenation, especially for ethanol synthesis. However, this reaction operates under high pressure, up to 8 MPa, and suffers from low CO2 conversion and alcohol selectivity. This paper describes the crucial role of hydroxyl groups bound on Rh-based catalysts supported on TiO2 nanorods (NRs). The RhFeLi/TiO2 NR catalyst shows superior reactivity (≈15% conversion) and ethanol selectivity (32%) for CO2 hydrogenation. The promoting effect can be attributed to the synergism of high Rh dispersion and high-density hydroxyl groups on TiO2 NRs. Hydroxyls are proven to stabilize formate species and protonate methanol, which is easily dissociated into *CH x , and then CO obtained from the reverse water-gas shift reaction (RWGS) is inserted into *CH x to form CH3CO*, followed by CH3CO* hydrogenation to ethanol.

pH- and GSH-Sensitive Hyaluronic Acid-MP Conjugate Micelles for Intracellular Delivery of Doxorubicin to Colon Cancer Cells and Cancer Stem Cells.

A dual-sensitive polymeric drug conjugate (HA-SS-MP) was synthesized by conjugating hydrophobic 6-mercaptopurine (MP) to thiolated hyaluronic acid (HA) as the carrier and ligand to deliver doxorubicin (Dox) to parental colon cancer and colon cancer stem cells. Because of the amphiphilic nature of HA-SS-MP, it was self-assembled in the aqueous media, and Dox was physically encapsulated in the core of the micelles. The particle size and the zeta potential of the micelle were analyzed by dynamic light scattering (DLS), and the morphology of the micelle was investigated using transmission electron microscopy (TEM). Drug release study results revealed more drug release at pH 5.0 in the presence of GSH than that at the physiological pH value. The cytotoxicity of free Dox was slightly greater than that of Dox-loaded HA-SS-MP micelles. In vitro cytotoxicity of HA-SS-MP and Dox-loaded HA-SS-MP micelles was greater for cancer stem cells (HCT116-CSCs) than for parental HCT116 colon cancer cells and L929 normal fibroblast cells. The MTT and flow cytometry results confirmed that free HA competitively inhibited Dox-loaded HA-SS-MP uptake. Similarly, flow cytometry results revealed anti-CD44 antibody competitively inhibited cellular uptake of Rhodamine B isothiocyanate conjugated micelles, which confirms that the synthesized micelle is uptaken via CD44 receptor. Cell cycle analysis revealed that free drugs and Dox-loaded HA-SS-MP arrested parental HCT116 colon cancer cells at the S phase, while cell arrest was observed at the G0G1 phase in HCT116-CSCs. In addition, ex vivo biodistribution study showed that Dox-loaded HA-SS-MP micelles were accumulated more in the tumor region than in any other organ. Furthermore, the in vivo results revealed that Dox-loaded HA-SS-MP micelles exhibited more therapeutic efficacy than the free drugs in inhibiting tumor growth in BALB/C nude mice. Overall, the results suggested that the synthesized micelles could be promising as a stimuli carrier and ligand for delivering Dox to colon cancer cells and also to eradicate colon cancer stem cells.