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An imbalance in oxidative and inflammatory regulation is the main contributor to intervertebral disc degeneration (IDD). Hydrogen (H2) therapy is a promising antioxidation and anti-inflammatory approach. However, the key to the treatment is how to maintain the long-term effective H2 concentration in the intervertebral disc (IVD). Therefore, we developed a pH-responsive delivery of H2 through ammonia borane-loaded hollow polydopamine (AB@HPDA) for IDD therapy, which has sufficient capacity to control long-term H2 release in an acid-dependent manner in degenerative IVD. The characterization, toxicity, and pH-responsive H2 release of AB@HPDA was detected in vitro. The metabolization of AB@HPDA in the degenerated IVD was tested by in vivo imaging. The therapeutic effect of AB@HPDA on IDD was tested in vivo by X-ray, MRI, water content of the disc, and histological changes. Nuclear extracellular matrix (ECM) components, oxidative stress, and inflammation were also tested to explore potential therapeutic mechanisms. AB@HPDA has good biocompatibility at concentrations less than 500 μg/mL. The H2 release of AB@HPDA was pH responsive. Therefore, AB@HPDAs can provide efficient hydrogen therapy with controlled H2 release in response to the acidic degenerated IVD microenvironment. The metabolization of AB@HPDA in IVD was slow and lasted up to 11 days. HPDA and AB@HPDA significantly inhibited IDD, as tested by X-ray, MRI, disc water content, and histology ( P < 0.05 ). pH-responsive H2 delivery through AB@HPDAs has the potential to efficiently treat IDD by inhibiting ECM degradation and rebalancing oxidative stress and inflammation in degenerative IVDs.

Background Divergence time analysis can provide a reference for the evolution process of species and is also the basis for other further studies. In this study, a complete mitochondrial genome of the Strix aluco was reported for the first time, with a total length of 18,632 bp. There were 37 genes, including 22 tRNAs, 2 rRNAs, 13 protein-coding genes (PCGs), and 2 non-coding control regions (D-loop). This study provides a reference for the evolution history of the S. aluco. New information The second-generation sequencing of the complete mitochondrial genome of the S. aluco was conducted using the Illumina platform, and then Tytoninae was used as the out-group, PhyloSuite software was applied to build the ML-tree and BI-tree of the Strigiformes, and finally, the divergence time tree was constructed using Beast2.6.7 software, the age of Miosurnia diurna fossil-bearing sediments (6.0~9.5 Ma) was set as the internal correction point. The common ancestor of the Strix was confirmed to have diverged during the Pleistocene(2.58~0.01Ma). The dramatic uplift of the Qinling Mountains in the Middle Pleistocene and the climate oscillation of the Pleistocene together caused Strix divergence between the northern and southern parts of mainland China. The isolation of glacial-interglacial rotation and glacier refuge was the main reason for the divergence of the common ancestor of the Strix uralensis and the S. aluco during this period.

Gut micriobiota have important roles in the immune, nutrition, and physiology of animals. To study the cause of gut microbiota change in black-necked cranes, we collected 9fresh Black-necked cranes’ fecal samples from Dashanbao Reserve. High throughput Illumina sequencing technology was used to analyze the microbial community structure of the collected samples for the V4 region of the 16S rRNA gene. Proteobacteria (44.14%) followed by Firmicutes (17.95%) and Bacteroidetes (9.97%) were the core dominant groups, and all of them play a role in the degradation of cellulose in Black-necked cranes. Bacteroidetes and Firmicutes contain glycan degrading enzymes, play a vital role in polysaccharide fermentation, and could help the host obtain more energy and materials. Higher Proteobacteria were unusual in birds. To explain this phenomenon, we analyzed the genus abundance of Proteobacteria in detail, found that Psychrobacter has the highest abundance and can grow at sub-zero temperatures. Through comparison, it was show that there were certain differences in the abundance of gut microbiota in different period The significance of this study was to provide a reference for understanding the function of intestinal microbiota and factors of gut microbiota structure change of Black-necked cranes and other migratory waterbirds.

In this study, a complete mitochondrial genome of theStrix alucowas reported for the first time, with a total length of 18,632 bp. There were 37 genes, including 22 tRNAs, 2 rRNAs, 13 protein-coding genes (PCGs), and 2 non-coding control regions (D-loop). The second-generation sequencing of the complete mitochondrial genome of theS. alucowas conducted using the Illumina platform, and then Tytoninae was used as the out-group, PhyloSuite software was applied to build the ML-tree and BI-tree of the Strigiformes, and finally, the divergence time tree was constructed using Beast2.6.7 software, the age ofMiosurnia diurnafossil-bearing sediments (6.0-9.5 Ma) was set as the internal correction point. The common ancestor of theStrixwas confirmed to have diverged during the Pleistocene(2.59~0.01Ma). The dramatic uplift of the Qinling Mountains in the Middle Pleistocene and the climate oscillation of the Pleistocene together causedStrixdivergence between the northern and southern parts of mainland China. The isolation of glacial-interglacial rotation and glacier refuge was the main reason for the divergence of the common ancestor of theStrix uralensisand theS. alucoduring this period. This study provides a reference for the evolution history of theStrix.Summary statementThis study was the first time to assemble the complete mitochondrial genome ofStrix aluco, and report the divergence time ofStrix. A full discussion was made, and it was inferred that the uplift of the Qinling Mountains and the glacial refuge led to the differentiation of this genus.

Wild boars (Sus scrofa) are extremely common in southern of China, but little study has reported dietary habits of wild boars using high-throughput sequencing technology. Due to the difficulty in obtaining samples of the stomach contents of wild boars, there are few reports on the diet of wild boars especially in karst areas. In our study, the stomach contents of 14 south China wild boars were analyzed by 16S rRNA high-throughput sequencing technology. The results showed that there were 153 genera, 93 families, and 48 orders, of which 78% were plants. Main plants food component of wild boar were Cissus, Dioscorea, Quercus, Actinidia and Houttuynia. The remaining 21% was animal food sources. It is noteworthy that Elaphodus cephalophus were detected in most of stomach samples, accounted for a large part of animal food sources. Predation of Elaphodus cephalophus by wild boars could cause a series of unforeseen problems, especially if this ongoing issue continues in the future. Our study revealed the dietary preference of wild boars under the special forest vegetation conditions in the mountainous area of southwest China, and the relationship between the diet habits of wild boars and their habitats from the perspective of resource utilization, thus providing a key scientific basis for the prevention and control of wild boars and resource protection.

PD-1/PD-L1 pathway caused immunosuppression accounts, at least partly, for the poor therapeutic effect of Chimeric Antigen Receptor T (CAR-T) on solid tumors. In this study, we designed and prepared CAR-T cells that could secrete PD-L1 blocking antibody and target Mesothelin antigen (Sec-MesoCAR-T), to remove the immunosuppressive effect of tumor on CAR-T cells, thereby increasing the therapeutic effect of CAR-T cells on pancreatic cancer. The CAR-T cells that could not secret PD-L1 blocking antibodies (MesoCAR-T) were used as a control. Sec-MesoCAR-T cells showed an enhanced inhibitory effect on BxPC-3 tumor than MesoCAR-T cells in vitro and in vivo. Besides, Sec-MesoCAR-T cells secreted higher level of cytokines including IL-2, IL-6 and IFN-γ in vitro than MesoCAR-T cells. Following injection, there were significantly more CAR-T cells in the peripheral blood of Sec-MesoCAR-T group than that of MesoCAR-T group. This work demonstrated that the PD-L1 antibody secreted by Sec-MesoCAR-T cells relieved the immunosuppressive effect of pancreatic cancer on CAR-T cells and improved the anti-tumor activity of CAR-T cells, which has a good guiding significance for the clinical application of CAR-T cells in treating solid tumors.

To address the issue of local drug delivery in tumor treatment, a novel nanoparticle-hydrogel superstructure, namely semi-interpenetrating polymer networks (semi-IPNs) hydrogel composed of poly (ethylene glycol) diacrylate (PEGDA) and hyaluronic acid (HA) and incorporated with paclitaxel (PTX) loaded PLGA nanoparticles (PEGDA-HA/PLGA-PTX), was prepared by in situ UV photopolymerization for the use of local drug delivery.Using the gelation time, swelling rate and degradation rate as indicators, the optimal proportion of Irgacure 2959 initiator and the concentration of HA was screened and obtained for preparing hydrogels. Next, paclitaxel (PTX) loaded PLGA nanoparticles (PLGA-PTX NPs) were prepared by the emulsion solvent evaporation method.The mass ratio of the initiator was 1%, and the best concentration of HA was 5 mg/mL in PEGDA-HA hydrogel. In vitro experiments showed that PLGA-PTX NPs had similar cytotoxicity to free PTX, and the cell uptake ratio on NCI-H460 cells was up to 96% by laser confocal microscopy and flow cytometry. The drug release of the PEGDA-HA/PLGA-PTX hydrogel local drug delivery system could last for 13 days. In vivo experiments proved that PEGDAHA/PLGA-PTX hydrogel could effectively inhibit the tumor growth without causing toxic effects in mice.This study demonstrated that the PEGDA-HA/PLGA-PTX hydrogel is a promising local drug delivery system in future clinical applications for tumor therapy. A photopolymerized semi-interpenetrating polymer networks-based hydrogel incorporated with paclitaxel-loaded nanoparticles was fabricated by in situ UV photopolymerization, providing a promised nanoplatform for local chemotherapy of tumors.

Animal gut is a dynamic ecosystem, and there are many factors affecting the structure of intestinal flora and the diversity of intestinal microbes, among which food differences are the direct causes. To investigate the effect of food composition on the intestinal flora structure of mandarin duck during the reproductive period, 9 feces were collected from 2 foraging sites of Shiqian Mandarin Duck Lake National Wetland Park, Guizhou, China. We analyzed the chloroplast rbcL gene, mitochondrial COI gene and 16S rRNA gene from the total DNA of the feces in detail to know the plants and animals in food compositions and intestinal bacteria of mandarin duck by high-throughput sequencing technology. We found that the gut microbiota composition were significantly correlated with the number of feeding species, the mandarin duck with a wide variety of feeding food had the more complex gut flora with more probiotics and less pathogenic bacterium. This study provides further theoretical support for food difference to affect the changes of intestinal bacterial structure of host, and provides scientific basis for understanding the feeding preference of mandarin duck at breeding area.

The animal gut is a dynamic ecosystem. Many factors affect the structure and diversity of the gut microbiota, among which the composition of the diet is a direct determinant. To investigate the effect of dietary components on the gut microbiota of mandarin duck, nine fecal samples were collected from two foraging sites at Shiqian Mandarin Duck Lake National Wetland Park, Guizhou, China. We analyzed the chloroplast rbcL gene, mitochondrial COI gene, and 16S rRNA gene from the total DNA of the fecal samples by high-throughput sequencing to identify plant and animal components of the diet and the composition of the gut microbiota of mandarin duck. We found that the gut microbiota composition was significantly correlated with the number of species in the diet. Mandarin ducks with more diverse diets had a more complex gut microbiota with fewer pathogenic bacteria. This study provides further theoretical support for the effect of dietary differences on the structure of the host gut microbiota and clarifies the feeding preferences of mandarin duck in breeding areas.

The rapid evolution of cell-based theranostics has attracted extensive attention due to their unique advantages in biomedical applications. However, the inherent functions of cells alone cannot meet the needs of malignant tumor treatment. Thus endowing original cells with new characteristics to generate multifunctional living cells may hold a tremendous promise. Here, the nanoengineering method is used to combine customized liposomes with neutrophils, generating oxygen-carrying sonosensitizer cells with acoustic functions, which are called Acouscyte/O

The Trigonidiidae, a family of crickets, comprises 981 valid species with only one mitochondrial genome (mitogenome) sequenced to date. To explore mitogenome features of Trigonidiidae, six mitogenomes from its two subfamilies (Nemobiinae and Trigonidiinae) were determined. Two types of gene rearrangements involving a trnN-trnS1-trnE inversion and a trnV shuffling were shared by Trigonidiidae. A long intergenic spacer was observed between trnQ and trnM in Trigonidiinae (210−369 bp) and Nemobiinae (80–216 bp), which was capable of forming extensive stem-loop secondary structures in Trigonidiinae but not in Nemobiinae. The anticodon of trnS1 was TCT in Trigonidiinae, rather than GCT in Nemobiinae and other related subfamilies. There was no overlap between nad4 and nad4l in Dianemobius, as opposed to a conserved 7-bp overlap commonly found in insects. Furthermore, combined comparative analysis and transcript verification revealed that nad1 transcripts ended with a U, corresponding to the T immediately preceding a conserved motif GAGAC in the superfamily Grylloidea, plus poly-A tails. The resultant UAA served as a stop codon for species lacking full stop codons upstream of the motif. Our findings gain novel understanding of mitogenome structural diversity and provide insight into accurate mitogenome annotation.

Imbalance of oxidative and inflammatory regulation is the main contributor to neurofunctional deterioration and failure of rebuilding spared neural networks after spinal cord injury (SCI). As an emerging biosafe strategy for protecting against oxidative and inflammatory damage, hydrogen (H2) therapy is a promising approach for improving the microenvironment to allow neural regeneration. However, achieving release of H2 at sufficient concentrations specifically into the injured area is critical for the therapeutic effect of H2. Thus, we assembled SiO2@mSiO2 mesoporous silica nanoparticles and loaded them with ammonia borane (AB), which has abundant capacity and allows controllable release of H2 in an acid-dependent manner. The release of H2 from AB/SiO2@mSiO2 was satisfactory at pH 6.6, which is approximately equal to the microenvironmental acidity after SCI. After AB/SiO2@mSiO2 were intrathecally administered to rat models of SCI, continuous release of H2 from these nanoparticles synergistically enhanced neurofunctional recovery, reduced fibrotic scar formation and promoted neural regeneration by suppressing oxidative stress reaction. Furthermore, in the subacute phase of SCI, microglia were markedly polarized toward the M2 phenotype by H2 via inhibition of TLR9 expression in astrocytes. In conclusion, H2 delivery through AB/SiO2@mSiO2 has the potential to efficiently treat SCI through comprehensive modulation of the oxidative and inflammatory imbalance in the microenvironment.

Background: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is closely associated with pulmonary diseases. N6-methyladenosine (m6A) is involved in the process of intermittent hypoxia-reoxygenation (IR) promoting lung injury. However, it is unclear whether m6A regulates the progression of lung injury under IR.Methods: Pathological examination by using Hematoxylin and eosin and Masson staining. Protein and mRNA were determined by Western blot and RT-qPCR, respectively. The m6A levels and concentrations of inflammatory cytokines were measured using ELISA. Cell apoptosis was measured by Annexin V-FITC/PI staining. m6A methylation modification of pre-miR-21 detected by gene-specific m6A assay.Results: Toll-like receptors 4 (TLR4) was elevated in IR-induced rat lung tissues and pulmonary microvascular endothelial cells (PMVEC). Knockdown of TLR4 alleviated IR-induced PMVEC cell inflammation and apoptosis via inhibiting MyD88/NF-kB signaling pathway. Next, we found the miR-21-5p expression downregulated and targeted TLR4 expression. Overexpression miR-21-5p alleviated IR-induced PMVEC cells inflammation and apoptosis, and inhibited MyD88/NF-kB signaling pathway by targeting TLR4. Interestingly, we found the m6A demethylase AlkB homolog 5 (ALKHB5) was increased in IR-induced rat lung tissues and PMVEC cells, which was associated with decreased m6A levels. ALKBH5 overexpression decreased m6A methylations of pre-miR-21 and reduced the levels of both pre-miR-21 and miR-21-5p. In addition, suppression of ALKBH5 alleviates IR-induced lung injury by reducing the activity of TLR4/MyD88/NF-kB signaling pathway in a miR-21-5p-dependent manner.Conclusion: Our findings demonstrated that ALKBH5 promotes OSA-induced lung injury through activation of TLR4/MyD88/NF-kB signaling pathway by reducing m6A methylations of pre-miR-21 to decrease the expression levels of both pre-miR-21 and miR-21-5p.

Objective Suicide ideation (SI) and suicide plan (SP) can be seen as immediate precursors of suicide. The major aim of this study is to estimate the severity of SI and SP among LBC, and explore their associated factors. Method A population-based random sampling survey of 2898 LBC was performed. Self-developed structured questionnaire was used to collect relevant information. The prevalence of one-week and lifetime SI and SP was estimated, univariate and multivariate logistic regression model were used to analyze the associated factors of SI in LBC, as well as the associated factors of SP in LBC who reported SI. Results For surveyed LBC, the one-week prevalence rates of SI and SP were 6.76% (95%CI: 5.30–8.00%) and 2.31% (95%CI: 1.80–2.93%), the lifetime prevalence rates of SI and SP were 20.8% (95%CI: 17.2–25.0%) and 7.69% (95%CI: 4.84–11.0%). Girls reported higher prevalence of SI, while SP severity showed insignificant gender difference. Sex, grade, SH behaviors, depression and psychological resilience were consistently associated with both one-week and lifetime SI. Age and depression were prominent influencing factors of SP in one-week suicide ideators, grade, self-harm history, depression, mother's education level were associated factors of SP in lifetime suicide ideators. Conclusions The prevalence of SI and SA in Chinese LBC is high. Girls, junior high school students, self-harmed, depressed, less psychologically resilient individuals were observed increased prevalence of SI, depression may play a significant role in facilitating the transition from SI to SP.

In this work, multifunctional polystyrene@chitosan@gold nanoparticles-Fe

Jinghua Liu,1 Zhen Yu,2 Yuanyuan Xiao,2 Qiong Meng,2 Yeying Wang,2 Wei Chang2 1Department of Gastroenterology and Hepatology, The 4th Affiliated Hospital of Kunming Medical University, 2School of Public Health, Kunming Medical University, Kunming, China Background: The Forkhead transcription family member FOXA2 plays a fundamental role in hepatocellular carcinoma (HCC) progression, but the precise interaction factor and molecular regulation of FOXA2 are not fully understood. Objective: In this study, we found that FOXA2 could interact with sirtuin 6 (SIRT6) directly in vivo and in vitro. We explored that the expressions of FOXA2 and SIRT6 were significantly downregulated in human HCC and HCC cell lines. Methods: Functionally, cell counting kit-8 assay and Transwell® assay were performed; we demonstrated that the knockdown of FOXA2 and SIRT6 promoted HepG2 cells and Huh7 cells proliferation and invasion in vitro. Results: Mechanically, using luciferase reporter assay and fast chromatin immunoprecipitation assay, we showed that FOXA2 and SIRT6 regulated the expression of ZEB2 from transcription level. ZEB2 suppression was involved in the anti-oncogenesis effect of FOXA2 and SIRT6. The negative correlation between the expressions of ZEB2 and FOXA2 or SIRT6 was observed in the tissues of HCC patients.Conclusion: Our findings indicated that the coordination function of FOXA2 and SIRT6 played a critical role in HCC progression and may serve as potential drug candidates for HCC. Keywords: FOXA2, SIRT6, ZEB2, proliferation, invasion

In this study, a versatile tumor-targeted and multi-stimuli-responsive drug delivery vehicle (Se particle@porous silica-folic acid-copper sulfide/doxorubicin (Se@SiO2-FA-CuS/DOX)) was fabricated for combined photothermal therapy with chemotherapy in cancer treatment. Due to excellent targeting ability, the Se@SiO2-FA-CuS/DOX nanocomposites actively accumulated in tumor tissues and thus provided photothermal therapy under NIR irradiation and chemotherapy through the release of DOX and Se. Owing to the synergistic effect of chemotherapy (Se and DOX) and photothermal therapy, the Se@SiO2-FA-CuS/DOX nanocomposites could efficiently inhibit cancer cells both in vitro and in vivo and even completely eliminate tumors. Moreover, as the toxicity of DOX could be reduced by Se, the treatment using Se@SiO2-FA-CuS/DOX nanocomposites exhibited no appreciable adverse reactions. Thus, the Se@SiO2-FA-CuS/DOX nanocomposites have great potential as a multifunctional nanoplatform in future clinical applications.

In this study, we elucidated the complete mitochondrial genome (mitogenome) of Tachycines (Gymnaeta) zorzini (accession number MW322826). The circular mitogenome is 15,369-bp-long, including 13 pro...

Gas-assisted therapy and diagnosis of tumors have attracted extensive interest due to their low toxicity and convenience, but are severely limited by the uncontrollable gas release. In this work, we proposed a kind of ammonia borane (AB) and doxorubicin (DOX) co-loaded and PEGylated Hollow Mesoporous Polydopamine (AB/DOX@HMPDA-PEG) nanoparticles for acid-sensitive hydrogen (H2)-assisted ultrasonic (US) imaging and chemotherapy of drug-resistant tumors. The in vitro experiment showed that as a high H2-storage molecule, AB can controllably release massive H2 in an acidic environment. For one thing, the H2 release in the acidic tumor environment and lysosomes of tumor cells in vivo helped to improve the US imaging performance; for another, it facilitated the lysosomal escape of nanoparticles, DOX release from nanoparticles, and blockage of mitochondrial respiratory chain. Furtherly, the blockage of mitochondrial respiratory chain reduced the production of triphosadenine (ATP), thereby decreasing the expression of heat shock protein 90 (HSP90) and promoting the therapeutic effect of DOX on drug-resistant tumors. Therefore, the nanoparticles provided an effective platform for controllable H2-assisted chemotherapy and US imaging of the drug-resistant tumors.

Chimeric antigen receptor T cells (CAR-T) immunotherapy has shown promising clinical results in the treatment of leukemia and lymphoma, but the effectiveness is limited for solid tumors. The PD-1/PD-L1 pathway is a key immunosuppressive mechanism for cancer cells to avoid eradication by CAR-T cells. In this study, the shRNA (short hair RNA) gene-silencing technique was used to construct the third-generation of CAR-T cells with PD-1 silencing which targeted CD19 antigen (CD19/△PD-1 CAR-T) and prostate stem cell antigen (PSCA/△PD-1 CAR-T), thereby blocking the PD-1/PD-L1 pathway in treatment of lymphoma and prostate subcutaneous xenograft and enhancing the anti-tumor effect of CAR-T cells. The cell experiments showed that PD-1 silencing in CAR-T cells effectively blocked the PD-1 / PD-L1 pathway. When the ratio of effector to target cell is 8:1, △PD-1 CAR-T cells exhibited higher killing ability and cytokine releasing ability than normal CAR-T cells did. The subcutaneous tumor models were constructed using human chronic myelogenous leukemia cells expressing CD19 (K562-CD19) and human prostate cancer cells expressing PSCA (PC3-PSCA), and treated with CD19/△PD-1 CAR-T and PSCA/△PD-1 CAR-T cells, respectively. The tumor volumes significantly reduced within one week, indicating the good tumor growth inhibitory effect of △PD-1 CAR-T cells. Mice injected with △PD-1 CAR-T cells showed a significantly prolonged survival time compared to those with normal CAR-T cells. This study proved that shRNA-mediated PD-1 silencing technology is an effective strategy for blocking the PD-1/PD-L1 immunosuppression pathway and enhancing the therapeutic effect of CAR-T cells on subcutaneous xenograft. Summary: The effect of CAR-T in treating solid tumors has not been as successful as that in hematological malignancies. The key immunosuppressive mechanism is the expression of PD-1/PD-L1. We used gene silencing technique mediated by shRNA (short hair RNA) to block the PD-1/PD-L1 pathway in lymphoma and prostate tumors, thus enhancing the anti-tumor effect of CAR-T cells on subcutaneous xenograft.

The graphene oxide (GO) functionalized by Fe 3 O 4 @SiO 2 @CS-TETA nanoparticles, Fe 3 O 4 @SiO 2 @CS-TETA-GO, was firstly fabricated in a mild way as a novel adsorbent for the removal of Cu(II) ions and methylene blue (MB) from aqueous solutions. The magnetic composites showed a good dispersity in water and can be conveniently collected for reuse through magnetic separation due to its excellent magnetism. When the Fe 3 O 4 @SiO 2 @CS- TETA-GO was used as an absorbent for the absorption of MB and Cu(II), the adsorption kinetics and isotherms data well fitted the pseudo-second-order model and the Langmuir model, respectively. Under the optimized pH and initial concentration, the maximum adsorption capacity was about 529.1 mg g −1 for MB in 20 min and 324.7 mg g −1 for Cu(II) in 16 min, respectively, exhibiting a better adsorption performance than other GO-based adsorbents reported recently. More importantly, the synthesized adsorbent could be effectively regenerated and repeatedly utilized without significant capacity loss after six times cycles. All the results demonstrated that Fe 3 O 4 @SiO 2 @CS-TETA-GO could be used as an excellent adsorbent for the adsorption of Cu(II) and MB in many fields.

Obstructive sleep apnea (OSA) is a disorder with high morbidity in adults. OSA damages multiple organs and tissues, including the cardiovascular and cerebrovascular systems, the metabolism system, the lungs, liver and heart. OSA-induced damage is earliest and greatest to the pulmonary tissue. The present study established a rat OSA model of differing severity by inducing intermittent hypoxia with different concentrations of O2 and it was determined that OSA caused a severe oxidative stress response and pulmonary inflammation in a dose-dependent manner. OSA increased serum levels of C-reactive protein and 8-isoprostane and elevated the expression of malondialdehyde, tumor necrosis factor α, interleukin (IL)-1β and IL-6 in the pulmonary tissue. Furthermore, the expression of two important antioxidants, superoxide dismutase and glutathione, was downregulated following intermittent hypoxia. By contrast, levels of cylooxygenase 2 and inducible nitric oxide synthase, which are crucial in the antioxidative response, increased. In addition, OSA activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (OH)-1 antioxidative signaling pathway. Finally, all increases and decreases in levels of inflammatory and antioxidative substances were dependent on oxygen concentrations. Therefore, the present study demonstrated that OSA, simulated by intermittent hypoxia, caused an oxidative stress response and pulmonary inflammation, and activated the canonical antioxidative Nrf2/HO-1 signaling pathway in a dose-dependent manner. These results may facilitate the development of clinical therapies to treat pulmonary diseases caused by OSA.

Yeying Wang,1,2 Li Ai,1 Jiahong Luo,2 Ran Li,1 Yanlin Chai,1 Xiaojie He,1 Yu Cao,1 Yongxia Li1 1Department of Respiratory Medicine, The Second Affiliated Hospital of Kunming Medical University, 2Department of Epidemiology and Biostatistics, School of Public Health, Kunming Medical University, Chenggong New City, Kunming, Yunnan Province, People’s Republic of China Objectives: The aims of this study were to describe changes in day- and nighttime symptoms and the adherence to nasal continuous positive airway pressure (nCPAP) during the first 3-month nCPAP therapy among newly diagnosed patients with obstructive sleep apnea/hypopnea syndrome (OSAS) and to identify the effect of adherence on the changes in day- and nighttime symptoms during the first 3months.Methods: Newly diagnosed OSAS patients were consecutively recruited from March to August 2013. Baseline clinical information and measures of the Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Zung’s Self-Rating Depression Scale (SDS) and the Pittsburgh Sleep Quality Index (PSQI) at baseline and the end of 3rd, 6th, 9th and 12th week of therapy were collected. Twelve weeks’ adherence was calculated as the average of each 3-week period. Mixed model was used to explore the effect of adherence to nCPAP therapy on ESS, FSS, SDS and PSQI in each 3-week phase.Results: Seventy-six patients completed the 12-week follow-up. The mixed-effects models showed that under the control of therapy phase adherence in the range of

In this work, multifunctional polystyrene@chitosan@gold nanoparticles-Fe3O4 nanoparticles-folic acid/indocyanine green (PS@CS@Au-Fe3O4-FA/ICG) nanocomposites that can integrate diagnosis and therapy into one nanoplatform was fabricated. The constructed PS@CS@Au-Fe3O4-FA/ICG nanocomposites possessed excellent computed tomography, magnetic resonance and fluorescence imaging performances which could be used to diagnose tumor and monitor the nanocomposites' localization in vivo. Moreover, PS@CS@Au-Fe3O4-FA/ICG nanocomposites can be delivered in a targeted manner to cancer cells by folic acid in a receptor-mediated way, and tumor growth could be efficiently inhibited, even completely ablated, under NIR irradiation. That is, the constructed PS@CS@Au-Fe3O4-FA/ICG nanocomposites had great potential for computed tomography, magnetic resonance and fluorescence imaging performances, which could be used to diagnose tumors and to monitor local therapy and fluorescence imaging-guided targeted therapy of cancer cells using nanocomposites.

Existing literature supports the association between depression and deliberate self-harm (DSH), a prominent risk factor of suicide. Our major aim was to evaluate the possible moderation and mediation of resilience in depression-DSH association, an issue which has never been extensively discussed among Chinese left-behind children (LBC). We implemented a population-based cross-sectional study of 2,619 LBC aged from 10 to 17. Multivariate logistic regression model which incorporated the cross-product term of resilience and depression was used to determine the moderation effect of resilience in depression-DSH association, whereas the mediating role of resilience was measured by path analysis. We found that depression was positively associated with DSH whereas resilience was negatively associated with DSH. Resilience in general was a prominent effect moderator in depression-DSH association, meanwhile, resilience also played as a significant mediator in this association, accounted for 26.8 % of the total effect. Our findings indicated that resilience was important moderator and mediator in the association between depression and DSH among Chinese LBC. Building up resilience of LBC may be an ideal choice in preventing depression related DSH.

Psychological resilience of Chinese left-behind children (LBC) remains under-studied. In this cross-sectional survey, we intended to analyze factors associated with resilience in a large group of LBC. One-stage random cluster sampling was used to select 2898 LBC aged between 10 and 17 years in Yunnan province of southwestern China. Face-to-face interview was used to collect relevant information from the participants. Resilience was measured by the Resilience Scale for Chinese Adolescents (RSCA). Multivariate logistic regression models revealed that having a better educated mother, feeling closer to people living in the same residence, and having more close friends were associated with higher psychological resilience in LBC. LBC who felt less close to people living in the same residence were consistently lower in all five dimensions of resilience. Compared with LBC with 2 or less close friends, LBC with more close friends had significantly greater resilience in goal concentration, family support, and interpersonal assistance. Higher mother's education level was related to higher resilience in emotion regulation, family support, and interpersonal assistance. Our findings suggest that dimension-specific intervention measures should be developed and implemented to improve psychological resilience of LBC.

Obstructive sleep apnea (OSA) has been demonstrated to be implicated in disorder of insulin secretion and diabetes mellitus. In this study, we aimed to evaluate the protective role of tempol, a powerful antioxidant, in chronic intermittent hypoxia (IH)-induced pancreatic injury. The rat model of OSA was established by IH exposure. The pathological changes, increased blood-glucose level, and raised proinsulin/insulin ratio in pancreatic tissues of rats received IH were effectively relieved by tempol delivery. In addition, the enhanced levels of pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and inflammatory mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible nitric oxide synthase (iNOS) in pancreatic tissue were suppressed by tempol. Moreover, tempol inhibited IH-induced apoptosis in pancreatic tissue as evidenced by upregulated Bcl-2 level, and downregulated Bax and cleaved caspase-3 levels. Finally, the abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways induced by IH was restrained by tempol administration. In summary, our study demonstrates that tempol relieves IH-induced pancreatic injury by inhibiting inflammatory response and apoptosis, which provides theoretical basis for tempol as an effective treatment for OSA-induced pancreatic injury.