A tumor microenvironment-responsive micelle co-delivered radiosensitizer Dbait and doxorubicin for the collaborative chemo-radiotherapy of glioblastoma

Glioblastoma is rather recalcitrant to existing therapies and effective interventions are needed. Here we report a novel microenvironment-responsive micellar system (ch-K5(s-s)R8-An) for the co-delivery of the radiosensitizer Dbait and the chemotherapeutic doxorubicin (DOX) to glioblastoma. Accordingly, the ch-K5(s-s)R8-An/(Dbait-DOX) micelles plus radiotherapy (RT) treatment resulted in a high degree of apoptosis and DNA damage, which significantly reduced cell viability and proliferation capacity of U251 cells to 64.0% and 16.3%, respectively. The angiopep-2-modified micelles exhibited substantial accumulation in brain-localized U251 glioblastoma xenografts in mice compared to angiopep-2-lacking micelles. The ch-K5(s-s)R8-An/(Dbait-DOX) + RT treatment group exhibited the smallest tumor size and most profound tumor tissue injury in orthotopic U251 tumors, leading to an increase in median survival time of U251 tumor-bearing mice from 26 days to 56 days. The ch-K5(s-s)R8-An/(Dbait-DOX) micelles can be targeted to brain-localized U251 tumor xenografts and sensitize the tumor to chemotherapy and radiotherapy, thereby overcoming the inherent therapeutic challenges associated with malignant glioblastoma

Pre-Treatment with Melatonin Enhances Therapeutic Efficacy of Cardiac Progenitor Cells for Myocardial Infarction

Background/Aims: Melatonin possesses many biological activities such as antioxidant and anti-aging. Cardiac progenitor cells (CPCs) have emerged as a promising therapeutic strategy for myocardial infarction (MI). However, the low survival of transplanted CPCs in infarcted myocardium limits the successful use in treating MI. In the present study, we aimed to investigate if melatonin protects against oxidative stress-induced CPCs damage and enhances its therapeutic efficacy for MI. Methods: TUNEL assay and EdU assay were used to detect the effects of melatonin and miR-98 on H2O2-induced apoptosis and proliferation. MI model was used to evaluate the potential cardioprotective effects of melatonin and miR-98. Results: Melatonin attenuated H2O2-induced the proliferation reduction and apoptosis of c-kit+ CPCs in vitro, and CPCs which pretreated with melatonin significantly improved the functions of post-infarct hearts compared with CPCs alone in vivo. Melatonin was capable to inhibit the increase of miR-98 level by H2O2 in CPCs. The proliferation reduction and apoptosis of CPCs induced by H2O2 was aggravated by miR-98. In vivo, transplantation of CPCs with miR-98 silencing caused the more significant improvement of cardiac functions in MI than CPCs. MiR-98 targets at the signal transducer and activator of the transcription 3 (STAT3), and thus aggravated H2O2-induced the reduction of Bcl-2 protein. Conclusions: Pre-treatment with melatonin protects c-kit+ CPCs against oxidative stress-induced damage via downregulation of miR-98 and thereby increasing STAT3, representing a potentially new strategy to improve CPC-based therapy for MI

Bilateral Two-Dimensional Neighborhood Preserving Discriminant Embedding For Face Recognition

In this paper, we propose a novel bilateral 2-D neighborhood preserving discriminant embedding for supervised linear dimensionality reduction for face recognition. It directly extracts discriminative face features from images based on graph embedding and Fisher\u27s criterion. The proposed method is a manifold learning algorithm based on graph embedding criterion, which can effectively discover the underlying nonlinear face data structure. Both within-neighboring and between-neighboring information are taken into account to seek an optimal projection matrix by minimizing the intra-class scatter and maximizing the inter-class scatter based on Fisher\u27s criterion. The performance of the proposed method is evaluated and compared with other face recognition schemes on the Yale, PICS, AR, and LFW databases. The experiment results demonstrate the effectiveness and superiority of the proposed method as compared with the state-of-the-art dimensionality reduction algorithms

Bilateral Two-Dimensional Neighborhood Preserving Discriminant Embedding for Face Recognition

In this paper, we propose a novel bilateral 2-D neighborhood preserving discriminant embedding for supervised linear dimensionality reduction for face recognition. It directly extracts discriminative face features from images based on graph embedding and Fisher\u27s criterion. The proposed method is a manifold learning algorithm based on graph embedding criterion, which can effectively discover the underlying nonlinear face data structure. Both within-neighboring and between-neighboring information are taken into account to seek an optimal projection matrix by minimizing the intra-class scatter and maximizing the inter-class scatter based on Fisher\u27s criterion. The performance of the proposed method is evaluated and compared with other face recognition schemes on the Yale, PICS, AR, and LFW databases. The experiment results demonstrate the effectiveness and superiority of the proposed method as compared with the state-of-the-art dimensionality reduction algorithms

Shapes Control of Bi2WO6 Nano-Structures as Photo-Fenton Catalysts for Pulping Wastewater Treatment

Bi2WO6 assembled by flower-like microspheres and nanosheets were controllably synthesized through a one-step hydrothermal approach. Multiple technologies, including X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and UV–Vis diffuse reflectance spectrum (UV–Vis), were carried out to characterize the as-synthesized samples. The photocatalytic efficiency of Bi2WO6 synthesized with a series of temperature and pH values shows different morphologies and photocatalytic properties. The photocatalyst (Bi2WO6) synthesized at 220 °C and pH of 7 exhibited the best photocatalytic performance, with the methylene blue (MB) degradation approaching 91.6% after reaction time of 60 min. Free radical capture experiments indicate that •OH is the primary reactive species in the methylene blue (MB) degradation reaction, h+ and •O2− contribute negligible influence, while the addition of H2O2 significantly improves the photocatalytic activity of Bi2WO6. Biodegraded poplar preconditioning refiner chemical alkaline peroxide mechanical pulp wastewater (PPW) was treated over Bi2WO6 under UV light (Bi2WO6/UV/H2O2); chemical oxygen demand (CODCr) and color degradation rate were 85.8% and 92.0%, respectively. These results show that Bi2WO6 semiconductors can be introduced as an efficient and stable photocatalyst for industry wastewater treatment

Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report

Hypervirulent Klebsiella pneumoniae (hvKp) causes increasing infections in healthy individuals from the community. In severe cases, it can cause multiple organ infection with invasive metastasis of blood sources, seriously threatening the patients’ life. Rapid and accurate diagnosis of the pathogen becomes the key to timely antibiotic treatment to improve the prognosis. This article reports a case of liver abscess complicated with multiple organ invasive infection caused by hematogenous-disseminated hvKp. K. pneumoniae was identified by culture and metagenomic next-generation sequencing (mNGS) using blood and liver abscess drainage fluid. The isolates from the two samples were subsequently identified with high homology (99.999%) by whole genome sequencing. In addition, multiple virulence genes were detected in the two isolates and the string test was positive, indicating hvKp with hypermucoviscosity phenotype. Multiple antibiotic treatments were given. The conditions of the patient were stable but the temperature remained high. Surgical drainage treatment was performed, and the patient’s body temperature immediately dropped to normal. He finally recovered after 6 months of follow-up. mNGS using body fluids can facilitate the rapid diagnosis of pathogens. For hvKp infection, choosing a better antibiotic therapy and receiving surgical drainage can significantly improve the prognosis of the patient

Porcine Circovirus Type 3 in Pig Farms Experiencing Diarrhea in Jiangxi, China: Prevalence, Genome Sequence and Pathogenicity

Porcine circovirus 3 (PCV3) infections have been reported in different clinical presentations. However, the prevalence and pathogenicity of PCV3 associated with diarrhea in piglets have been limited. Herein, we present an investigation and genome analyses of PCV3 in piglets experiencing diarrhea, and observed clinical signs, gross lesions, and histological changes in pigs negative for all known pathogens associated with diarrhea but positive for PCV3 alone. Among the feces (n = 141) tested, 16.31% (23/141) were positive for PCV3. Of which, 27.28% (15/55) and 14.29% (5/35) were present in diarrheal samples from suckling and weaned piglets, respectively. Moderate to severe atrophic villi was confined in duodenum, jejunum, and ileum, and significantly decreased average heights of villi, and the depths of crypt were observed in PCV3-infected piglets. The complete genome of a representative strain of PCV3, designated as JX/CH/2018, was determined. Multialignment analysis indicated that JX/CH/2018 had 97.7–99.7% nucleotide identity at the complete genome level, and 97.2–100% at the amino acid level of the capsid protein when compared with reference PCV3 strains. Phylogenetic analysis showed that the PCV3 strain identified in this study belonged to PCV3a lineage. The present study demonstrated that PCV3 is a common virus in diarrheal suckling and weaned piglets

Risk factors for poor treatment outcomes in patients with MDR-TB and XDR-TB in China: retrospective multi-center investigation.

BACKGROUND: The treatment of patients with MDR- and XDR-TB is usually more complex, toxic and costly and less effective than treatment of other forms of TB. However, there is little information available on risk factors for poor outcomes in patients with MDR- and XDR-TB in China. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyzed the clinical records of HIV-negative TB Patients with culture-proven MDR- or XDR-TB who were registered from July 2006 to June 2011 at five large-scale Tuberculosis Specialized Hospitals in China. Among 1662 HIV-seronegative TB cases which were culture-positive for M. tuberculosis complex and had positive sputum-smear microscopy results, 965 cases (58.1%) were DR-TB, and 586 cases (35.3%) were classified as having MDR-TB, accounting for 60.7% of DR-TB. 169 cases (10.2%) were XDR-TB, accounting for 17.5% of DR-TB, 28.8% of MDR-TB. The MDR-TB patients were divided into XDR-TB group (n=169) and other MDR-TB group (non-XDR MDR-TB) (n=417). In total, 240 patients (40.95%) had treatment success, and 346 (59.05%) had poor treatment outcomes. The treatment success rate in other MDR-TB group was 52.2%, significantly higher than that in the XDR-TB group (13%, P<0.001). In multivariate logistic regression analysis, poor outcomes were associated with duration of previous anti-TB treatment of more than one year (OR, 0.077; 95% CI, 0.011-0.499, P<0.001), a BMI less than 18.5 kg/m(2) (OR, 2.185; 95% CI, 1.372-3.478, P<0.001), XDR (OR, 13.368; 95% CI, 6.745-26.497, P<0.001), retreatment (OR, 0.171; 95% CI, 0.093-0.314, P<0.001), diabetes (OR, 0.305; 95% CI, 0.140-0.663, P=0.003), tumor (OR, 0.095; 95% CI, 0.011-0.795, P=0.03), decreased albumin (OR, 0.181; 95% CI, 0.118-0.295, P<0.001), cavitation (OR, 0.175; 95% CI, 0.108-0.286, P<0.001). CONCLUSIONS/SIGNIFICANCE: The patients with MDR-TB and XDR-TB have poor treatment outcomes in China.The presence of extensive drug resistance, low BMI, hypoalbuminemia, comorbidity, cavitary disease and previous anti-TB treatment are independent prognostic factors for poor outcome in patients with MDR-TB