H2O2 self-sufficient nanoplatform based on CeO2 QDs decorated MgO2 nanosheet for amplified chemodynamic therapy.

Chemodynamic therapy (CDT), which employs Fenton/Fenton-like agents to decompose hydrogen peroxide (H2O2) into toxic hydroxyl radical (•OH) to induce cancer cell apoptosis and necrosis, holds great promise in tumor therapy due to its high selectivity. Nevertheless, its efficiency is impaired by the insufficient intracellular H2O2 concentration and/or the insensitive response of Fenton/Fenton-like agents to the slightly acid tumor microenvironment (pH∼7.0-6.5). Herein, we develop a novel CDT reagent based on CeO2 quantum dot (QD) decorated MgO2 nanosheets engineered with cascade reactions to boost the intracellular H2O2 level and high pH-activated (pH = 6.5) characteristic for an enhanced CDT. Under the tumor microenvironment (pH = 6.5), MgO2 nanosheets that are highly reactive can react with H2O to produce nontoxic Mg2+ and abundant H2O2, boosting the intracellular H2O2 level. The self-generated H2O2 is subsequently converted into •OH by CeO2 QD, which is served as a relatively high pH-activated (pH = 6.5) Fenton-like agent. The sufficient intracellular H2O2 supply and sensitive response to the slightly acid tumor sites significantly improve the Fenton reaction, leading to the excellent in vivo CDT results with tumor growth inhibition effect. Our work presents a distinctive paradigm for self-boosting CDT efficacy.

CeO2 QDs anchored on MnO2 nanoflowers with multiple synergistic effects for amplified tumour therapy.

Chemodynamic therapy (CDT) is an emerging tumour-specific therapeutic technology. However, the relatively insufficient catalytic activity of CDT agents in the tumour microenvironment (TME) limits their biomedical application. In addition, severe hypoxia and glutathione (GSH) overexpression in the TME greatly limit the antitumour efficiency of monotherapy. Herein, a cancer cell membrane-camouflaged and ultrasmall CeO2-decorated MnO2 (mMC) composite is developed for amplified CDT, photodynamic therapy (PDT) and photothermal therapy (PTT). Due to the homotypic targeting ability of cancer cell membranes, mMC nanoparticles preferentially accumulate in tumour tissue. In the TME, CeO2 acts as a highly efficient CDT agent to convert endogenous H2O2 to toxic reactive oxygen species (ROS) for killing cancer cells. Meanwhile, MnO2 irradiated with near-infrared (NIR) light displays prominent hyperthermia and ROS generation performance to perform PTT and PDT. Moreover, MnO2 can produce oxygen to ameliorate hypoxia and deplete GSH to relieve the antioxidant capability of tumours, which is beneficial to the simultaneous augmentation of PDT and CDT. Most importantly, the catalytic activity of CeO2 was greatly improved by hyperthermia. Consequently, a significantly enhanced therapeutic efficiency was obtained by the above multiple synergistic effects. This work provides a proof of concept for amplified tumour therapy by synchronously self-supplying oxygen, consuming GSH, and enhancing catalytic activity.

Bowl-like mesoporous polydopamine with size exclusion for highly selective recognition of endogenous glycopeptides.

It has been confirmed that endogenous glycopeptide plays an important role in a variety of pathological and physiological processes. However, direct analysis of endogenous glycopeptide is still a great challenge owing to the low abundance of endogenous glycopeptides and the presence of a large number of interfering substances such as large-sized proteins and heteropeptides in complex biological sample. Herein, we reported a novel bowl-like mesoporous polydopamine nanoparticle modified by carrageenan (denoted as MPDA@PEI@CA) with strong hydrophilicity and size-exclusion effect for high specificity enrichment of endogenous glycopeptides. Thanks to the suitable pore channel structure as well as strong hydrophilic surface, the as-prepared MPDA@PEI@CA nanoparticles exhibited prominent performance in enrichment of N-linked glycopeptide with ultrahigh selectivity (1:5000 M ratio of horseradish peroxidase (HRP) digests/bovine serum albumin (BSA) digests), low detection limit (5 fmol µL-1), outstanding size-exclusion ability (1:1000 mass of HRP/BSA), and unique reusability (five times). 125 N-glycosylation sites of 134 glycopeptides from 65 glycoproteins were identified from 2 µL sample of human serum treated with the MPDA@PEI@CA nanoparticles, which manifested the ability to enrich endogenous N-linked glycopeptides from complex biological samples. These results indicated that the bowl-like MPDA@PEI@CA nanoparticles with novel structure prepared in this work had great potential for glycopeptidome analysis.

Biodegradable flower-like manganese for synergistic photothermal and photodynamic therapy applications.

A flower-like nanostructured MnO2 with near-infrared (NIR) light-triggered high photothermal conversion capability of 30% and reactive oxygen species (ROS) generation ability was successfully developed. Different from the reported MnO2 nanomaterials those were used in the nanomedicine field for only relieving tumor hypoxia and/or imaging, the flower-like MnO2 inherently acts as a competent agent for simultaneously enhanced photothermal and photodynamic therapy. A flower-like nanostructured MnO2 with near-infrared (NIR) light triggered high photothermal conversion capability of 30% and reactive oxygen species (ROS) generation ability was successfully developed.

Monitoring land surface thermal environments under the background of landscape patterns in arid regions: A case study in Aksu river basin.

Land surface temperature (LST) is defined as an important indicator in the formation and evolution of climate. In some cases, changes in landscape patterns affect LST, even more than the contribution of greenhouse gases. Although much work has been done with respect to the correlations between urban development and thermal environment dynamics, the related questions regarding relationships between LST and landscape patterns in arid regions are not thoroughly considered. Understanding these questions is important in climate change and land planning. The objective of this study was to explore the spatiotemporal variations of LST by distribution index (DI) and Mann-Kendall mutation analysis method and to quantify the relationships between landscape patterns, climatic factors, topographic factors, and the land surface thermal environment (LSTE) by the ordinary linear regressions (OLS) model. The landscape patterns dataset, which was validated by a field trip, was extracted from the Land satellite (Landsat) TM/OLI images by the Random Forest methodology in ArcGIS software. The MODIS/LST product was validated by the "Monthly dataset of China's surface climate" and a field trip. Annual LST increased by 0.54 °C (23.15 °C in 2000 and 23.79 °C in 2015). In different landscape patterns, the percentage of areas with a high level of LST showed a significant difference. In barren land, the highest area proportion for the high LST level was larger than in other landscape patterns. Meanwhile, the area of low LST was mainly concentrated in water bodies. Considerable changes have occurred in landscape patterns, in which the most noteworthy was cultivated land encroaching on grass land (3708.44 km2). The composition of landscape patterns was more important than distribution in determining the region's LST. These findings provide valuable information for land planners dealing with climate change and ecosystem conservation in arid regions.

Early Stage Impacts of Adenoidectomy With/Without Tonsillectomy on Immune Functions of Children Aged Less Than Three Years.

Objective: To evaluate the early stage effects of adenoidectomy with/without tonsillectomy on immune functions in children aged <3 years. Methods: Twenty-four children aged <3 years underwent adenoidectomy with/without tonsillectomy were included. The levels of IgG, IgA, IgM, C3, and C4 were measured for humoral immunity, and the levels of CD3+, CD4+, CD8+, CD19+, CD56+, CD3+CD4-CD8-, and CD3+CD4+CD8+ T cells were measured for cellular immunity before and 2 weeks after the operation. Results: The postoperative levels of IgA, IgG, IgM, C3, and C4 were significantly increased compared with the preoperative levels (P < 0.05). The levels of CD3+, CD4+, CD8+, CD56+, CD3+CD4-CD8-, and CD3+CD4+CD8+ T cells were increased, while the level of CD19+ was decreased in postoperative period compared with preoperative period. Compared with those in the control group, the preoperative levels of IgA, IgG, and CD3+CD4+CD8+ T cells were significantly increased (P < 0.05), while the levels of IgM, C3, C4 and CD3+, CD4+, CD8+, CD56+, and CD3+CD4-CD8- T cells were not significantly changed. The postoperative levels of IgA, IgG, C3, C4, CD3+CD4-CD8-, and CD3+CD4+CD8+ T cells were significantly increased (P < 0.05), while the levels of IgM, CD3+, CD4+, CD8+, and CD56+ T cells were not significantly changed compared with those in the control group. Conclusion: Adenoidectomy with/without tonsillectomy could stimulate the immune responses, which could avoid significant immune deficiency in a short period of time in children aged <3 years.

Short- and long-term impacts of adenoidectomy with/without tonsillectomy on immune function of young children <3 years of age: A cohort study.

To investigate the short- and long-term impacts of adenoidectomy with/without tonsillectomy on the immune functions of young children < 3 years of age.This longitudinal prospective study included 40 pediatric patients (age <3 y) undergoing adenoidectomy with/without tonsillectomy for snoring and sleep apnea. Serum immunoglobulin IgA, IgG, IgM, complement C3, and C4 levels were measured for the status of humoral immunity; CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD56+, CD3+CD4-CD8-, and CD3+CD4+CD8+ T cells were measured for the status of cellular immunity. Blood samples were taken at 3 time points: before surgery, 1 month after surgery (short-term), and 3 months after surgery (long-term). All patients were assessed for short-term outcome at 1-month postoperation, but only 30 patients were followed at 3 months after surgery. The incidence of recurrent respiratory tract infections and other immune-related conditions were recorded at each follow-up.The levels of IgA significantly decreased from the preoperative level at 1-month follow-up (P < .05), but still within normal range. No significant changes were found in the levels of IgA, IgG, IgM, C3, C4, CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD56+, CD3+CD4-CD8-, and CD3+CD4+CD8+ T cell at 3-month follow-up in comparison with preoperative levels. There was also no episode of recurrent respiratory tract infection and other immune-deficiency conditions.Adenoidectomy with/without tonsillectomy may result in a reduction in individual antibodies in children <3 years of age, but did not show negative impacts on their immune functions. Also, the surgery does not lead to the increased risk of upper respiratory tract infection in these children.

Using IFN-γ antibodies to identify the pathogens of fungal rhinosinusitis: A novel immunohistochemical approach.

Fungal rhinosinusitis (FRS) is commonly caused by various Aspergillus species (spp) and Mucorales fungi, and the treatment and prognosis of cases differ depending on the causative fungus. The present study describes a novel immunohistochemical method that has high sensitivity and specificity for distinguishing between these two types of fungi in patients with FRS. Three groups were included in the study. Group A included formalin­fixed paraffin­embedded blocks of 51 nasal tissue specimens of patients with FRS (27 Aspergillus spp and 24 Mucorales) that were continuously obtained from the Department of Pathology of Tongren Hospital in Beijing as the experimental group and 34 cultures (26 Aspergillus spp and 8 Mucorales) of FRS that were randomly selected from the bacterial laboratory of Tongren Hospital in Beijing to verify the staining results of the paraffin­embedded blocks. Formalin­fixed paraffin­embedded blocks of 10 esophageal cancer specimens were included in Group B as the positive control group. All specimens in Groups A and B were stained with interferon­Î³ (IFN­Î³) antibody. Group C consisted of the same specimens as described in Group A, however, when performing the immunohistochemical assay, IFN­Î³ antibody was replaced by PBS and this served as the negative control group. The differences in IFN­Î³ immunohistochemical staining between Aspergillus spp and Mucorales were analyzed. Staining of IFN­Î³ in paraffin­embedded samples was positive in 92.6% (25/27) of specimens in which Aspergillus spp were the causative pathogen, which was significantly higher compared with specimens in which Mucorales was causative (P<0.001), with only 4.2% (1/24) of specimens staining positive for IFN­Î³. Immunohistochemical staining of cell cultures was 100% positive for Aspergillus spp, whereas all Mucorales were negative. Thus, the results of the current study indicated that IFN­Î³ antibody immunohistochemical staining may be used as a novel diagnostic tool to distinguish between Aspergillus spp and Mucorales when identifying the causative agent in FRS, providing a useful supplementary test to the current immunohistochemical methods in the clinical diagnosis of FRS.

[Clinical efficacy analysis of adult sinonasal rhabdomyosarcoma].

OBJECTIVE: To investigate the clinical prognostic impact factors of adult sinonasal rhabdomyosarcoma (SNRMS). METHOD: The clinical features, treatment methods, and disease outcome were reviewed retrospectively for twenty-three adult SNRMS between 2006 January and 2014 December. The survival analysis was performed by Kaplan-Meier estimate and the comparison between groups by Log-rank test. Multivariate analysis was carried out by Cox proportional hazard model. RESULT: Patients' ages ranged from 18 to 59 years (median, 23.2 years). With a median follow-up of 20 moths (3-47 moths), 14 cases dead and 9 cases alive, the 1-year and 2-year overall survival (OS) rates were 77.1% and 35.0%, respectively. Within the 1-year and 2-year OS rates,early stage group had a higher overall survival rates than advanced diease group (100.0%, 66.7% and 83.3%, 10.5%, P < 0.05); combined therapy group had a higher overall survival rates than single treatment group (86.7%, 50.0% and 50.8%, 0, P < 0.05). In the non-metastasis group (21 cases), 1-year and 2-year distant metastasis rates were 38.1% and 70.5%, respectively. Multivariate analysis showed that radiotherapy, chemotherapy and tumor diameter less than 5 cm were good prognostic factors (P < 0.05), while the lymph node metastasis, meningeal involvement and orbital involvement were poor prognostic factors (P < 0 05). In the 14 cases of dead patients, 92 8% (13/14) died of distant metastasis. CONCLUSION: Adult RMS had a high advanced rate with poor prognosis. Distant metastasis is the leading cause of death. Controlling distant metastasis is a key to improve the survival rate.

Endoscopic Resection for Benign Parotid Tumor Through a Cosmetic Retroauricular Incision with Water Sac Establishing Operative Space: A New Approach.

PURPOSE: To develop a new approach of endoscopic resection for benign parotid tumor through a cosmetic retroauricular incision with a water sac establishing the operative space. MATERIALS AND METHODS: Fifty-eight patients with benign parotid superficial lobe tumor were randomly assigned to an endoscopic (29 patients) or a conventional (29 patients) surgery group. The maximum diameter of the tumors was 6 cm. The subjective satisfaction scores with the incision scar, incision length, operative bleeding volume, postoperative complications, and recurrence rate were compared between the groups. RESULTS: All operations were successfully performed. The endoscopic incision length (4.3±0.5 cm), bleeding volume (26.6±10.4 mL), and incidence of temporary facial paresis (6.9%) differed from the conventional surgery group (P<.05). The scars were almost invisible behind the ear. The mean patient satisfaction score was 8.9±0.7 in the endoscopic surgery group and 6.7±1.8 in the conventional surgery group (P<.05). Otherwise, Frey's syndrome and salivary fistula incidences were 3.4% (1/29) and 3.4% (1/29), respectively, in the endoscopic surgery group, which was not significantly different from the conventional surgery group (P>.05). No tumor recurrence was found during the 3-72 months of follow-up. CONCLUSIONS: Endoscopic resection through a cosmetic retroauricular incision with a water sac establishing operative space is a feasible method for treatment of benign parotid superficial lobe tumor. Its main advantages are that the small and concealed operative scars improved the cosmetic results, and it provided a novel method for establishing the operation working space that could reduce the operative trauma.

A novel fungus concentration-dependent rat model for acute invasive fungal rhinosinusitis: an experimental study.

BACKGROUND: Acute invasive fungal rhinosinusitis is a lethal infectious process afflicting immunocompromised individuals. Knowledge about this disease is still limited due to the scarcity of animal models designed to study the pathogenesis of this infection. Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast cells in acute invasive fungal rhinosinusitis. Therefore, the objectives of this study were to create a rat model of acute invasive fungal rhinosinusitis based on analyzing the impact of different fungal concentrations on establishing infection, and to observe the changes of mast cells in rats with this disease. METHODS: Sprague-Dawley rats were divided randomly into four groups, three of which were experimental and received different concentrations of Aspergillus fumigatus inoculations, and one was a control group (D). The inoculated Aspergillus fumigatus concentrations were 5 × 10(7) conidia/ml in group A, 10(7) conidia/ml in group B, and 10(6) conidia/ml in group C. Before fungal inoculation, rats were immunosuppressed using cyclophosphamide and cortisone acetate, and had Merocel sponges inserted into the right nares. Hematology and histopathology investigations were then performed. RESULTS: An acute invasive fungal rhinosinusitis rat model was established successfully with an incidence rate of 90% in group A, 50% in group B and 10% in group C. Aspergillus fumigatus invasion was observed in 20% of the lungs in group A, but was not seen in the remaining groups. In addition, no fungi invaded the orbital tissue, brains, livers, spleens or kidneys of any rat. Compared with the control set, the total number of mast cells in the experimental groups was not significantly increased, but mast cell degranulation, on the other hand, was only found in infected nasal cavities. CONCLUSIONS: This investigation illustrates that various fungal concentrations have different effects on the incidence of acute invasive fungal rhinosinusitis, and it also demonstrates the feasibility of using this model to study the process of fungal rhinosinusoidal invasion. In addition, the results suggest that mast cells may play a role in the protection of sinuses against acute Aspergillus fumigatus infection and in the clearance of established hyphal masses.