Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress.

BACKGROUND: Cell division cyclin 25C (CDC25C) is a protein that plays a critical role in the cell cycle, specifically in the transition from the G2 phase to the M phase. Recent research has shown that CDC25C could be a potential therapeutic target for cancers, particularly for hepatocellular carcinoma (HCC). However, the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood. AIM: To explore the impact of CDC25C on cell proliferation and apoptosis, as well as its regulatory mechanisms in HCC development. METHODS: Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences (LV-CDC25C shRNA) to knock down CDC25C. Subsequently, a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo. Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays, respectively. The expression of endoplasmic reticulum (ER) stress-related molecules (glucose-regulated protein 78, X-box binding protein-1, and C/EBP homologous protein) was measured in both cells and subcutaneous xenografts using quantitative real-time PCR (qRT-PCR) and western blotting. Additionally, apoptosis was investigated using flow cytometry, qRT-PCR, and western blotting. RESULTS: CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction. A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice. CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response, ultimately promoting ER stress-induced apoptosis in HCC cells. CONCLUSION: The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

The Research of Antagonistic Endophytic Bacterium Bacillus velezensis CSUFT-BV4 for Growth Promotion and Induction of Resistance to Anthracnose in Camellia oleifera.

Camellia oleifera (C. oleifera) is one of the four main, woody, edible oil tree species in the world, while C. oleifera anthracnose is mainly caused by the fungus Colletotrichum fructicola (C. fructicola), which severely affects the yield of C. oleifera and the quality of tea oil. Bacillus velezensis (B. velezensis) CSUFT-BV4 is an antagonistic endophytic bacterium isolated from healthy C. oleifera leaves. This study aimed to investigate the biocontrol potential of strain CSUFT-BV4 against C. oleifera anthracnose and its possible functional mechanism, and to determine its growth-promoting characteristics in host plants. In vitro, CSUFT-BV4 was shown to have efficient biofilm formation ability, as well as significant functions in the synthesis of metabolic substances and the secretion of probiotic substances. In addition, the CSUFT-BV4 fermentation broth also presented efficient antagonistic activities against five major C. oleifera anthracnose pathogens, including C. fructicola, C. gloeosporioides, C. siamense, C. camelliae, and C. kahawae, and the inhibition rate was up to 73.2%. In vivo, it demonstrated that the growth of C. oleifera treated with CSUFT-BV4 fermentation broth was increased in terms of stem width, plant height, and maximum leaf area, while the activities of various defense enzymes, e.g., superoxide dismutase (SOD), phenylalanine aminotransferase (PAL), and polyphenol oxidase (PPO), were effectively increased. The remarkable antagonistic activities against C. oleifera anthracnose, the growth-promoting characteristics, and the induction of host defense responses indicate that endophytic bacterium CSUFT-BV4 can be effectively used in the biological control of C. oleifera anthracnose in the future, which will have a positive impact on the development of the C. oleifera industry.

Astragalus polysaccharides attenuate rat aortic endothelial senescence via regulation of the SIRT-1/p53 signaling pathway.

BACKGROUND: Astragalus polysaccharides (APS) have been verified to have antioxidative and antiaging activities in the mouse liver and brain. However, the effect of APS on aortic endothelial senescence in old rats and its underlying mechanism are currently unclear. Here, we aimed to elucidate the effects of APS on rat aortic endothelial oxidative stress and senescence in vitro and in vivo and investigate the potential molecular targets. METHODS: Twenty-month-old natural aging male rats were treated with APS (200 mg/kg, 400 mg/kg, 800 mg/kg daily) for 3 months. Serum parameters were tested using corresponding assay kits. Aortic morphology was observed by staining with hematoxylin and eosin (H&E) and Verhoeff Van Gieson (VVG). Aging-related protein levels were evaluated using immunofluorescence and western blot analysis. Primary rat aortic endothelial cells (RAECs) were isolated by tissue explant method. RAEC mitochondrial function was evaluated by the mitochondrial membrane potential (MMP) measured with the fluorescent lipophilic cationic dye JC­1. Intracellular total antioxidant capacity (T-AOC) was detected by a commercial kit. Cellular senescence was assessed using senescence-associated-ß-galactosidase (SA-ß-Gal) staining. RESULTS: Treatment of APS for three months was found to lessen aortic wall thickness, renovate vascular elastic tissue, improve vascular endothelial function, and reduce oxidative stress levels in 20-month-old rats. Primary mechanism analysis showed that APS treatment enhanced Sirtuin 1 (SIRT-1) protein expression and decreased the levels of the aging marker proteins p53, p21 and p16 in rat aortic tissue. Furthermore, APS abated hydrogen peroxide (H2O2)-induced cell senescence and restored H2O2-induced impairment of the MMP and T-AOC in RAECs. Similarly, APS increased SIRT-1 and decreased p53, p21 and p16 protein levels in senescent RAECs isolated from old rats. Knockdown of SIRT-1 diminished the protective effect of APS against H2O2-induced RAEC senescence and T-AOC loss, increased the levels of the downstream proteins p53 and p21, and abolished the inhibitory effect of APS on the expression of these proteins in RAECs. CONCLUSION: APS may reduce rat aortic endothelial oxidative stress and senescence via the SIRT-1/p53 signaling pathway.

Primary pulmonary myxoid sarcoma with EWSR1::CREB1 fusion: a literature review.

PURPOSE: This review primarily aims to review the epidemiology, clinical characteristics, imaging, pathology, immunohistochemistry, diagnosis, differential diagnosis, treatment, and prognosis of Primary pulmonary myxoid sarcoma (PPMS) with EWS RNA binding protein 1::cAMP response element binding protein 1 (EWSR1::CREB1) fusion. It provides reference for the diagnosis and treatment of this disease. METHODS: Retrospectively collected the literature about PPMS with EWSR1::CREB1 fusion, its clinical, radiology, histology, molecular characteristics and current treatment strategies were collated and analyzed. This review provides a detailed differential diagnosis of the disease. RESULTS: PPMS is an exceptionally rare, low-grade malignant tumor of the lung. This tumor commonly infiltrates lung tissue and develops within bronchial passages. It is identified by a genetic rearrangement involving the EWSR1 gene and a distinct chromosomal translocation t(2; 22)(q33; q12). Variants include EWSR1::CREB1 fusion and EWS RNA binding protein 1::activating transcription factors (EWSR1::ATF1) fusion. PPMS with EWSR1::CREB1 fusion is more prevalent among middle-aged individuals and affects both sexes almost equally. Clinical symptoms are relatively non-specific, primarily including cough, hemoptysis, and weight loss. Most patients undergo surgery and experience a favorable prognosis. Further research is required to validate the effectiveness of alternative treatments for PPMS with EWSR1::CREB1 fusion. CONCLUSION: EWSR1 rearrangement and EWSR1::CREB1 fusion are crucial genetic features of PPMS and serve as important diagnostic markers. Immunohistochemically, PPMS tests positive for EMA. In terms of treatment, surgery has been the primary approach in recent years. Therefore, the efficacy of other treatments still requires further investigation.

Low-Temperature Adaptive Single-Atom Iron Nanozymes against Viruses in the Cold Chain.

Outbreaks of viral infectious diseases, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV), pose a great threat to human health. Viral spread is accelerated worldwide by the development of cold chain logistics; Therefore, an effective antiviral approach is required. In this study, it is aimed to develop a distinct antiviral strategy using nanozymes with low-temperature adaptability, suitable for cold chain logistics. Phosphorus (P) atoms are added to the remote counter position of Fe-N-C center to prepare FeN4P2-single-atom nanozymes (SAzymes), exhibiting lipid oxidase (OXD)-like activity at cold chain temperatures (-20, and 4 °C). This feature enables FeN4P2-SAzymes to disrupt multiple enveloped viruses (human, swine, and avian coronaviruses, and H1-H11 subtypes of IAV) by catalyzing lipid peroxidation of the viral lipid envelope. Under the simulated conditions of cold chain logistics, FeN4P2-SAzymes are successfully applied as antiviral coatings on outer packaging and personal protective equipment; Therefore, FeN4P2-SAzymes with low-temperature adaptability and broad-spectrum antiviral properties may serve as key materials for developing specific antiviral approaches to interrupt viral transmission through the cold chain.

Bidirectionally Regulating Viral and Cellular Ferroptosis with Metastable Iron Sulfide Against Influenza Virus.

Influenza virus with numerous subtypes and frequent variation limits the development of high-efficacy and broad-spectrum antiviral strategy. Here, a novel multi-antiviral metastable iron sulfides (mFeS) against various influenza A/B subtype viruses is developed. This work finds that mFeS induces high levels of lipid peroxidation and •OH free radicals in the conservative viral envelope, which depends on Fe2+ . This phenomenon, termed as a viral ferroptosis, results in the loss of viral infectibility and pathogenicity in vitro and in vivo, respectively. Furthermore, the decoction of mFeS (Dc(mFeS)) inhibits cellular ferroptosis-dependent intracellular viral replication by correcting the virus-induced reprogrammed sulfur metabolism, a conserved cellular metabolism. Notably, personal protective equipment (PPE) that is loaded with mFeS provides good antiviral protection. Aerosol administration of mFeS combined with the decoction (mFeS&Dc) has a potential therapeutic effect against H1N1 lethal infection in mice. Collectively, mFeS represents an antiviral alternative with broad-spectrum activity against intracellular and extracellular influenza virus.

PA-X protein of H9N2 subtype avian influenza virus suppresses the innate immunity of chicken bone marrow-derived dendritic cells.

H9N2 subtype avian influenza (AI) is an infectious disease associated with immunosuppression in poultry. Here, the regulation function of PA-X protein was determined on the host innate immune response of H9N2-infected chicken bone marrow-derived DCs (chBM-DCs). Based on 2 mutated viruses expressing PA-X protein (rTX) or deficient PA-X protein (rTX-FS), and the established culture system of chBM-DCs, results showed PA-X protein inhibited viral replication in chBM-DCs but not in non-immune chicken cells (DF-1). Moreover, PA-X protein downregulated the expression of phenotypic markers (CD40, CD86, and MHCII) and proinflammatory cytokine (IL-12 and IL-1ß) of chBM-DCs. The mixed lymphocyte reaction between chBM-DCs and chicken T cells showed PA-X protein significantly decreased H9N2-infected chBM-DCs to induce T cell proliferation, implying a suppression of the DC-induced downstream T cell response. Taken together, these findings indicated that PA-X protein is a key viral protein to help H9N2 subtype AIVs escape the innate immunity of chBM-DCs.

Parathyroid carcinoma: Report of 10 patients and literature review.

OBJECTIVE: Parathyroid carcinoma (PC) is a rare disease with high rates of misdiagnosis and recurrence. This report summarized the clinical and pathological characteristics of 10 patients with PC at our hospital, to improve the early recognition and prognosis of PC. METHODS: The clinical manifestations, imaging findings, pathological features, treatments, and prognostic data of 10 patients diagnosed with PC at the First Medical Center, Chinese PLA General Hospital from 2003 to 2021 were analyzed. RESULTS: There were 7 male and 3 female patients with PC whose average age was 41.4 ± 9.4 years. All patients had bone involvement (bone pain and/or osteoporosis), meanwhile 6 patients had kidney stones and 7 patients had palpable neck masses. Five patients presented with tumor metastasis, invading lymph nodes, lung, liver, or bone. Laboratory examinations revealed elevated serum total calcium (4.15 ± 0.81 mmol/L), parathyroid hormone (PTH, 1236.1 ± 519.9 pg/mL) and alkaline phosphatase (405.8 ± 219.0 IU/L) levels. Especially, hypercalcemic crisis occurred in 9 patients. The diagnosis of PC depended on histopathological features of the parathyroid tumor, including capsular and/or vascular invasion. All patients underwent at least en bloc resection. In the follow-up, six patients with relatively high preoperative PTH levels (1519.5 ± 436.8 pg/mL) relapsed postoperatively. Two patients with the Ki-67 index ≥ 10% in parathyroid tumor tissue and distant metastasis died within 2 years after the operation. CONCLUSION: Severe bone pain, kidney stones, hypercalcemic crisis, and markedly elevated PTH usually indicate PC. A markedly elevated PTH level, tumor metastasis, and the Ki-67 index ≥ 10% may be indicators of poor prognosis.

The p190 RhoGAPs, ARHGAP35, and ARHGAP5 are implicated in GnRH neuronal development: Evidence from patients with idiopathic hypogonadotropic hypogonadism, zebrafish, and in vitro GAP activity assay.

PURPOSE: The study aimed to identify novel genes for idiopathic hypogonadotropic hypogonadism (IHH). METHODS: A cohort of 1387 probands with IHH underwent exome sequencing and de novo, familial, and cohort-wide investigations. Functional studies were performed on 2 p190 Rho GTPase-activating proteins (p190 RhoGAP), ARHGAP35 and ARHGAP5, which involved in vivo modeling in larval zebrafish and an in vitro p190A-GAP activity assay. RESULTS: Rare protein-truncating variants (PTVs; n = 5) and missense variants in the RhoGAP domain (n = 7) in ARHGAP35 were identified in IHH cases (rare variant enrichment: PTV [unadjusted P = 3.1E-06] and missense [adjusted P = 4.9E-03] vs controls). Zebrafish modeling using gnrh3:egfp phenotype assessment showed that mutant larvae with deficient arhgap35a, the predominant ARHGAP35 paralog in the zebrafish brain, display decreased GnRH3-GFP+ neuronal area, a readout for IHH. In vitro GAP activity studies showed that 1 rare missense variant [ARHGAP35 p.(Arg1284Trp)] had decreased GAP activity. Rare PTVs (n = 2) also were discovered in ARHGAP5, a paralog of ARHGAP35; however, arhgap5 zebrafish mutants did not display significant GnRH3-GFP+ abnormalities. CONCLUSION: This study identified ARHGAP35 as a new autosomal dominant genetic driver for IHH and ARHGAP5 as a candidate gene for IHH. These observations suggest a novel role for the p190 RhoGAP proteins in GnRH neuronal development and integrity.

PA-X protein assists H9N2 subtype avian influenza virus in escaping immune response of mucosal dendritic cells.

H9N2 subtype low pathogenicity avian influenza virus (AIV) poses a potential zoonotic risk. PA-X, a novel protein generated by PA gene ribosomal frameshift, is considered to be the virulence factor of H9N2 subtype AIVs. Our study found that rTX possessing PA-X protein enhanced the mammalian pathogenicity of H9N2 subtype AIVs compared with PA-X-deficient virus (rTX-FS). Furthermore, PA-X protein inhibited H9N2 subtype AIVs to infect dendritic cells (DCs), but not nonimmune cells (MDCK cells). Meanwhile, PA-X protein suppressed the phenotypic expression (CD80, CD86, CD40 and MHCII), early activation marker (CD69) and pro-inflammatory cytokines (IL-6 and TNF-α), whereas increased anti-inflammatory cytokine (IL-10) in DCs. After intranasally viral infection in mice, we found that PA-X protein of H9N2 subtype AIVs reduced CD11b+ and CD103+ subtype mucosal DCs recruitment to the nasal submucosa by inhibiting CCL20 expression. Moreover, PA-X protein abolished the migratory ability of CD11b+ and CD103+ DCs into draining cervical lymph nodes by down-regulating CCR7 expression. The rTX-infected DCs significantly impaired the allogeneic CD4+ T cell proliferation, suggesting PA-X protein suppressed the immune functions of DCs for hindering the downstream immune activation. These findings indicated that PA-X protein assisted H9N2 subtype AIVs in escaping immune response of mucosal DCs for enhancing the pathogenicity.

Biochar-Stimulated Pumpkin Performance Under Cadmium Stress Is Strongly Linked to Metabolite Pattern.

In this study, pumpkin seedlings were subjected to cadmium stress (100 mg/L cadmium ion solution, 10 days) without or with wheat straw biochar at different concentrations (0%, 0.5%, 1%, and 2% w/v). As the biochar concentration increased, the amount of cadmium accumulated in the root and stem of pumpkin seedlings decreased and the fresh weight of root, stem and leaf increased. The highest cadmium concentration was in the root, followed by the stem and then the leaf. 1% and 2% biochar treatments reduced the oxidative stress of cadmium to seedlings, and added the contents of fatty acid, carbohydrate, amino acid and indoleacetic acid in the root. With the increase of biochar concentration, the metabolites promoting root growth increased. These results provide new information about how biochar alleviates cadmium stress by affecting the metabolic response.

Bacillus natto ameliorates obesity by regulating PI3K/AKT pathways in rats.

Obesity has become the second leading cause of death globally after smoking. Probiotic Bacillus has noticeable weight-loss effects. This study aimed to investigate the mechanism of Bacillus natto (B. natto) on insulin resistance in obese rats. The obese rat model was established with a HFD for 8 weeks, and then, B. natto was orally administered at different dosed for 8 weeks. The results showed that B. natto significantly reduced the body weight, epididymis fat weight, total cholesterol, triglyceride, low-density lipoprotein while increasing the level of high-density lipoprotein in HFD rats. B. natto intervention improved liver injury by reducing alanine aminotransferase and aspartate transaminase levels. B. natto intervention was also beneficial for the inhibition of hepatic steatosis and inflammation factors in HFD rats by inhibiting the mRNA expression level of SREBP-1 gene. Moreover, B. natto improved insulin resistance homeostasis by activating PI3K/AKT signaling pathway. Therefore, B. natto could be used as a potential probiotic supplement to provided new strategy for the prevention and treatment of metabolic diseases such as obesity.

Phytoremediation for Co-contaminated Soils of Cadmium and Polychlorinated Biphenyls Using the Ornamental Plant Tagetes patula L.

In this study, pot-culture experiments were conducted to investigate the single effect of Cd, PCBs, and the combined effect of Cd-PCBs with Tagetes patula L. The study highlights that the minimum concentration of PCBs (100 µg kg-1) could enable the growth of the plant with an increase in biomass by 27.76% when compared with the control. In all the experiments performed, the Cd concentrations over the surface parts were found to be above 100 mg kg-1. Significant positive correlations were observed between the Cd and PCBs concentrations accumulated in tissues of the soil and plants (p < 0.05). T. patula exhibited high tolerance to Cd and PCBs, and the plant promoted the removal rate of PCBs. The removal rates of PCB18 and PCB28 were up to 42.72 and 42.29%, respectively. The study highlights the potential and suitability of T. patula for phytoremediation of Cd and PCBs in contaminated soils.

Is there a relationship between neural EGFL like 1 (NELL1) promoter hypermethylation and prognosis of gastric cancer?

We hypothesized that neural EGFL like 1 (NELL1) promoter hypermethylation might be associated with the prognosis of gastric cancer. Some studies considered NELL1 as a tumor suppressor gene and our research confirmed for the first time the hypermethylation in the promoter region of NELL1 by the application of mass spectrometry. Promoter hypermethylation can cause the silencing of tumor suppressor genes and promote tumor progression. Based on present studies and research results, we proposed that NELL1 promoter hypermethylation might be associated with cancer staging and the survival of gastric cancer patients and had prognostic value. We hoped that NELL1 promoter hypermethylation would be applied not only for early detection but also prognosis prediction of gastric cancer and would become a new prognostic biomarker.

Paget's disease of bone: Report of 11 cases.

BACKGROUND: Paget's disease of bone (PDB) is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation. The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability. The disease has high missed diagnosis and misdiagnosis rates. This report summarizes the clinical manifestations, imaging and pathological features, and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB. CASE SUMMARY: There were eight male and three female patients whose average age was 48.7 ± 11.0 years with a PDB course of 1-16 years. Nine patients had bone pain and bone deformities in different parts of the body, the majority of which involved the long bones. Laboratory examinations revealed elevated serum alkaline phosphatase (ALP) in all patients with an average of 618 ± 460 IU/L (normal range 0-130 IU/L), and serum calcium and phosphorus levels were in the normal range. Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones. 99mTc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions. Six patients underwent bone tissue biopsy, and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts. Ten of the 11 patients were effectively treated with bisphosphonates. CONCLUSION: Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

Ciprofloxacin-Resistant Staphylococcus aureus Displays Enhanced Resistance and Virulence in Iron-Restricted Conditions.

The unreasonable misuse of antibiotics has led to the emergence of large-scale drug-resistant bacteria, seriously threatening human health. Compared with drug-sensitive bacteria, resistant bacteria are difficult to clear by host immunity. To fully explore the adaptive mechanism of resistant bacteria to the iron-restricted environment, we performed data-independent acquisition-based quantitative proteomics on ciprofloxacin (CIP)-resistant (CIP-R) Staphylococcus aureus in the presence or absence of iron. On bioinformatics analysis, CIP-R bacteria showed stronger amino acid synthesis and energy storage ability. Notably, CIP-R bacteria increased virulence by upregulating the expression of many virulence-related proteins and enhancing the synthesis of virulence-related amino acids under iron-restricted stress. This study will help us to further explain the adaptive mechanisms that lead to bacterial resistance to antibiotics depending on the host environment and provide insights into the development of novel drugs for the treatment of drug-resistant bacterial infections.

The chemokine CCL7 regulates invadopodia maturation and MMP-9 mediated collagen degradation in liver-metastatic carcinoma cells.

Liver metastases remain a major cause of death from gastrointestinal tract cancers and other malignancies, such as breast and lung carcinomas. Understanding the underlying biology is essential for the design of effective therapies. We previously identified the chemokine CCL7 and its receptor CCR3 as critical mediators of invasion and metastasis in lung and colon carcinoma cells. Here we show that the CCL7/CCR3 axis regulates a late stage in invadopodia genesis namely, the targeting of MMP-9 to the invadopodia complex, thereby promoting invadopodia maturation and collagen degradation. We show that this process could be blocked by overexpression of a dominant negative RhoA in highly invasive cells, while a constitutively active RhoA upregulated invadopodia maturation in CCL7-silenced and poorly invasive and metastatic cells and also enhanced their metastatic potential in vivo, collectively, implicating RhoA activation in signaling downstream of CCL7. Blockade of the ERK or PI3K pathways by chemical inhibitors also inhibited invadopodia formation, but affected the initiation stage of invadopodia genesis. Our data implicate CCL7/CCR3 signaling in invadopodia maturation and suggest that chemokine signaling acts in concert with extracellular matrix-initiated signals to promote invasion and liver metastasis.

Catalytic inactivation of influenza virus by iron oxide nanozyme.

Influenza poses a severe threat to human health in the world. However, developing a universal anti-viral strategy has remained challenging due to the presence of diverse subtypes as well as its high mutation rate, resulting in antigenic shift and drift. Here we developed an antiviral strategy using iron oxide nanozymes (IONzymes) to target the lipid envelope of the influenza virus. Methods: We evaluated the antiviral activities of our IONzymes using a hemagglutination assay, together with a 50% tissue culture infectious doses (TCID50) method. Lipid peroxidation of the viral envelope was analyzed using a maleic dialdehyde (MDA) assay and transmission electron microscopy (TEM). The neighboring viral proteins were detected by western blotting. Results: We show that IONzymes induce envelope lipid peroxidation and destroy the integrity of neighboring proteins, including hemagglutinin, neuraminidase, and matrix protein 1, causing the inactivation of influenza A viruses (IAVs). Furthermore, we show that our IONzymes possess a broad-spectrum antiviral activity on 12 subtypes of IAVs (H1~H12). Lastly, we demonstrate that applying IONzymes to a facemask improves the ability of virus protection against 3 important subtypes that pose a threat to human, including H1N1, H5N1, and H7N9 subtype. Conclusion: Together, our results clearly demonstrate that IONzymes can catalyze lipid peroxidation of the viral lipid envelope to inactivate enveloped viruses and provide protection from viral transmission and infection.

[Establishment of senescent cell model in primary rat aortic endothelial cells].

Objective To establish senescent models in rat aortic endothelial cells (RAECs) induced by high glucose (HG), angiotensin II (AngII), hydrogen peroxide and palmitic acid (PA), and compare the senescence-induced effects of these factors. Methods Primary RAECs were extracted from two-month-old male Wistar rats by issue explant method and identified by CD31 immunofluorescence cytochemistry. RAECs were treated separately by 30 mmol/L (HG), 10 µmol/L AngII, 100 umol/L hydrogen peroxide (H2O2) and 0.5 mmol/L PA. Twenty-four hours later, senescence-associated ß-galactosidase (SA-ß-gal) staining was used to evaluate the senescent state. Real-time quantitative PCR was used to investigate mRNA expression level of senescence-related gene P16. Western blot analysis was performed to determine protein expression levels of P16, P21 and P53. Immunofluorescence cytochemistry was used to detect the expression of P16 protein in cells. The cell viability of RAECs was tested via CCK-8 assay. Results Compared with the control group, positive rate of SA-ß-gal staining in each treatment group increased, especially in H2O2 and PA groups. And mRNA expression level of P16 increased in all four groups. P16 and P21 proteins had high expression in AngII, H2O2 and PA groups, most obviously in H2O2 group. P16 immunofluorescence expression level was enhanced in all groups. The cell viability in HG and AngII groups was similar with the control group, while H2O2 and PA groups had low cell viability. Conclusion The aging mode of RAECs is successfully established by HG, AngII, H2O2 or PA treatment, and H2O2 treatment shows the strongest effect.

Relationship between abnormal glucose metabolism and osteoporosis in Han Chinese men over the age of 50 years.

AIM: The aim of this study was to determine the relationship between abnormal glucose metabolism and osteoporosis (OP) in Han Chinese men over the age of 50 years. PATIENTS AND METHODS: A cross-sectional study of 775 male patients aged over 50 years was performed at our hospital in 2011. The patients were divided into a normal glucose metabolism group, an impaired glucose regulation (IGR) group, and a type 2 diabetes mellitus (T2DM) group. Differences in their bone mineral densities (BMDs), OP detection rates, and indices of bone metabolism were assessed. RESULTS: After adjusting for age and body mass index (BMI), there were no significant differences in lumbar spine, femoral neck, and total hip BMD values in the three groups (P>0.05) nor in OP detection rates (P=0.19). However, there were some significant differences in bone metabolism markers between the groups after adjusting for age, BMI, and serum creatinine (Cr): 25-hydroxyvitamin D (25(OH)D) was positively correlated with the presence of abnormal glycometabolism (r=0.08; P<0.01), while ß-carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTX), bone gamma-carboxyglutamic acid protein (BGP; osteocalcin [OC]), and procollagen type 1 intact N-terminal propeptide (P1NP) were negatively correlated (r=-0.13, -0.21, -0.14, respectively; P<0.01). Logistic regression analysis of the data indicated that BGP was the only bone metabolism marker significantly influenced by abnormal glucose metabolism (OR =0.96). CONCLUSION: There were no significant differences in BMD or OP detection rates between the three glycometabolism groups after adjusting for age and BMI. However, the bone metabolism marker, BGP, was significantly negatively correlated with abnormal glucose metabolism.