Oxygen‐Deficient Blue TiO2 for Ultrastable and Fast Lithium Storage

Developing a titanium dioxide (TiO₂)‐based anode with superior high‐rate capability and long‐term cycling stability is important for efficient energy storage. Herein, a simple one‐step approach for fabricating blue TiO₂ nanoparticles with oxygen vacancies is reported. Oxygen vacancies can enlarge lattice spaces, lower charge transfer resistance, and provide more active sites in TiO₂ lattices. As a result, this blue TiO₂ electrode exhibits a highly reversible capacity of 50 mAh g^?1 at 100 C (16 800 mA g^?1) even after 10 000 cycles, which is attributable to the combination of surface capacitive process and remarkable diffusion‐controlled insertion revealed by the kinetic analysis. The strategy of employing oxygen‐deficient nanoparticles may be extended to the design of other robust semiconductor materials as electrodes for energy storage.     

Combined effects of avasimibe immunotherapy,doxorubicin chemotherapy,and metal–organic frameworks nanoparticles on breast cancer

CD8⁺ T cells play a vital role in cancer immunotherapy and can be shaped by metabolism. Avasimibe is an acyl coenzyme A-cholesterol acyltransferase (ACAT) inhibitor, which has been clinically verified safe in other phase Ⅲ clinical trials. It can potentiate the killing function of CD8⁺ T cells by modulating cholesterol metabolism. Doxorubicin (DOX) is an anticancer drug widely used in many cancers to induce tumor cell apoptosis. Unfortunately, DOX also can induce toxic and side effects in many organs, compromising its usage and efficacy. Herein, we report the combinational usage of avasimibe and a safe pH sensitive nano-drug delivery system composing of DOX and metal–organic frameworks nanoparticles (MNPs). Our findings demonstrated that DOX–MNPs treatment inhibited tumor growth with good safety profile and avasimibe treatment combined DOX–MNPs treatment exhibited a better efficacy than monotherapies in 4T1 breast cancer therapy.     

Overexpression of polo-like kinase 1 and its clinical significance in human non-small cell lung cancer

Polo-like kinase 1 is a serine/threonine kinase which plays an essential role in mitosis and malignant transformation. The aim of this study was to investigate the prognostic significance of polo-like kinase 1 expression and determine its possibility as a therapeutic target in non-small cell lung cancer. Semi-quantitative RT-PCR assay was performed to detect polo-like kinase 1 mRNA expression in non-small cell lung cancer cells or tissues. Immunohistochemistry was performed to detect polo-like kinase 1 protein expression in 100 non-small cell lung cancer tissue samples, and the associations of polo-like kinase 1 expression with clinicopathological factors or prognosis of non-small cell lung cancer patients were evaluated. RNA interference was employed to inhibit endogenous polo-like kinase 1 expression and analyzed the effects of polo-like kinase 1 inhibition on the malignant phenotypes of non-small cell lung cancer cells including growth, apoptosis, radio- or chemoresistance. Also, the possible molecular mechanisms were also investigated. The levels of polo-like kinase 1 mRNA expression in non-small cell lung cancer cell lines or tissues were significantly higher than those in normal human bronchial epithelial cell line or corresponding non-tumor tissues. High polo-like kinase 1 expression was significantly correlated with advanced clinical stage, higher tumor classification and lymph node metastasis of non-small cell lung cancer patients (P = 0.001, 0.004 and 0.001, respectively). Meanwhile, high polo-like kinase 1 protein expression was also an independent prognostic molecular marker for non-small cell lung cancer patients (hazard ratio: 2.113; 95% confidence interval: 1.326-3.557; P = 0.017). Polo-like kinase 1 inhibition could significantly inhibit in vitro and in vivo proliferation, induce cell arrest of G₂/M phase and apoptosis enhancement in non-small cell lung cancer cells, which might be activation of the p53 pathway and the Cdc25C/cdc2/cyclin B1 feedback loop. Further, inhibition of polo-like kinase 1 could enhance the sensitivity of non-small cell lung cancer cells to taxanes or irradiation. Thus, polo-like kinase 1 might be a prognostic marker and a chemo- or radiotherapeutic target for non-small cell lung cancer.     

Laforin is required for the functional activation of malin in endoplasmic reticulum stress resistance in neuronal cells

Mutations in either EPM2A, the gene encoding a dual-specificity phosphatase named laforin, or NHLRC1, the gene encoding an E3 ubiquitin ligase named malin, cause Lafora disease in humans. Lafora disease is a fatal neurological disorder characterized by progressive myoclonus epilepsy, severe neurological deterioration and accumulation of poorly branched glycogen inclusions, called Lafora bodies or polyglucosan bodies, within the cell cytoplasm. The molecular mechanism underlying the neuropathogenesis of Lafora disease remains unknown. Here, we present data demonstrating that in the cells expressing low levels of laforin protein, overexpressed malin and its Lafora disease-causing missense mutants are stably polyubiquitinated. Malin and malin mutants form ubiquitin-positive aggregates in or around the nuclei of the cells in which they are expressed. Neither wild-type malin nor its mutants elicit endoplasmic reticulum stress, although the mutants exaggerate the response to endoplasmic reticulum stress. Overexpressed laforin impairs the polyubiquitination of malin while it recruits malin to polyglucosan bodies. The recruitment and activities of laforin and malin are both required for the polyglucosan body disruption. Consistently, targeted deletion of laforin in brain cells from Epm2a knockout mice increases polyubiquitinated proteins. Knockdown of Epm2a or Nhlrc1 in neuronal Neuro2a cells shows that they cooperate to allow cells to resist ER stress and apoptosis. These results reveal that a functional laforin-malin complex plays a critical role in disrupting Lafora bodies and relieving ER stress, implying that a causative pathogenic mechanism underlies their deficiency in Lafora disease.     

In vivo anti-osteoporotic activity of isotaxiresinol, a lignan from wood of Taxus yunnanensis

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.     

Prediction of the Mechanism of Action of Fusaricidin on Bacillus subtilis

Long-term use of antibiotics has engendered a large number of resistant pathogens, which pose a serious threat to human health. Here, we investigated the mechanism of fusaricidin antibacterial activity toward Bacillus subtilis and characterized the pathways responsible for drug resistance. We found that σ^w, an extracytoplasmic function sigma factor, plays an important role in the resistance to fusaricidins during the initial 5 minutes of drug addition. Approximately 18 genes were induced more than 3-fold, of which 66.7% are known to be regulated by σ^w. Over the following 3 h, fusaricidins induced 194 genes more than three-fold, and most were associated with classes of antibiotic-responsive stimulons. Moreover, the fusaricidin treatment increased the catabolism of fatty and amino acids but strongly repressed glucose decomposition and gluconeogenesis. In summary, our data provide insight into the mechanism of fusaricidin activity, on which we based our suggested strategies for the development of novel antibiotic agents.     

Community-based colorectal cancer intervention in underserved Korean Americans

Background: Despite evidence of a decline in both incidence and prevalence of colorectal cancer nationwide, it remains the second most commonly diagnosed cancer and the third highest cause of mortality among Asian Americans, including Korean Americans. This community-based and theoretically guided study evaluated a culturally appropriate intervention program that included a bilingual cancer educational program among Korean Americans including information on CRC risks, counseling to address psychosocial and access barriers, and patient navigation assistance. Methods: A two-group quasi-experimental design with baseline and post-intervention assessment and a 12-month follow-up on screening was used in the study. Korean Americans (N = 167) were enrolled from six Korean churches. The intervention group received culturally appropriate intervention program addressing accessibility and psychosocial barriers, and navigation assistance for screening. The control group received general health education that included cancer-related health issues and screening. Results: There was a significant difference (p < 0.05) between the post-intervention and control groups in awareness of CRC risk factors. There was also a significant improvement in the pre–post across HBM measures in the intervention group for perceived susceptibility (p < 0.05) and benefits and barriers to screening (p < 0.001). At baseline, 13% of participants in the intervention group and 10% in control group reported having had a CRC cancer screening test in the previous year. At the 12-month post-intervention follow-up, 77.4% of participants in the intervention group had obtained screening compared to 10.8% in the control group. Conclusion: While health disparities result from numerous factors, a culturally appropriate and church-based intervention can be highly effective in increasing knowledge of and access to, and in reducing barriers to CRC screening among underserved Koreans.