No abstract

We report a facile method toward preparation of conducting polymer-supported Pd nanoparticles by in situ reducing the palladium salt [Pd(NO3)2] on the surface of polyaniline (PANI) film/membrane. The palladium(0) particles distribute evenly on the PANI surfaces. The size and morphology of Pd particles are dependent on the nature of the substrate surfaces. The palladium (Pd) particles on the PANI membrane surfaces have a rough surface morphology with a size distribution of ∼200 nm, and the Pd particles on the PANI film have a smooth surface with a size distribution of ∼500 nm. These Pd particles are in fact conglomerates of much smaller nanoparticles with an average size distribution of 13 nm. Pd nanoparticles exhibit efficient catalytic activity toward hydrogenation of alkynes and cinnamaldehyde with high selectivities dominated by a kinetic mechanism. Moreover, our results suggest that the variation in particle morphology resulting from substrates leads to differences in their catalytic efficiency presumably due to the difference in surface area. The PANI-supported Pd nanoparticles are robust and can be reused at least seven times without the significant loss of its catalytic activity and selectivity.

Background: Both hypokalemia (hypoK) and hyperkalemia (hyperK) are life-threatening to hemodialysis (HD) patients. This study was conducted to compare their clinical characteristics and long-term survival. Methods: Patients were divided into three groups according to the last mid-week predialysis serum potassium concentrations: hypoK (<3.5 mEq/l), normoK (between 3.5 and 5.5 mEq/l), and hyperK (>5.5 mEq/l). The maximal duration of the follow-up period was 54 months. Results: Compared with the hyperK group,patients in the hypoK group were older (p <0.05), had a higher incidence of comorbidity factors, less body weight gain prior to HD (p < 0.05), lower body mass index (BMI, p < 0.05), and higher BUN to creatinine ratio and hs-CRP (p < 0.05). The serum albumin and prealbumin concentrations were also lowest in the hypoK group, compared with the normoK and hyperK groups, respectively (all p < 0.001). A similar finding was also obtained for the normalized protein catabolism rate (nPCR, p < 0.001) among the three groups. Positive linear correlations between serum albumin and potassium concentration were only found in the hypoK and normoK groups (p < 0.001). Multiple logistic regression analysis showed that hypoalbuminemia, low BUN, and phosphate concentrations were significantly correlated with hypoK. HypoK patients also had a lower cumulative survival rate than hyperK patients. Conclusion: HypoK HD patients, with lower serum levels of albumin, prealbumin, nPCR, and BMI, but higher level of hs-CRP, showed a malnutritional and inflammatory status, and caused increased mortality rate.

Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for autologous hematopoietic cell transplantation (HSCT). Total marrow irradiation (TMI) tomotherapy planned with melphalan 140 mg/m2 as a preconditioning regimen of HSCT. Two image sets of computed tomography (CT) were scanned with 2.5 mm and 5 mm for the upper and lower part of the plan, respectively. The junction was determined and marked at 15 cm above knee on both thighs for upper and lower part of the plan. The clinical target volume (CTV) included the entire skeletal system. The planning target volume (PTV) was generated with with 0.8 cm for CTV(extremities) and with 0.5 cm margin for all other bones of CTV. A total dose of 800 cGy (200 cGy/fraction) was delivered to the PTV. Update to presentation, all of three patients post transplant without evidence of active disease were noted. During TMI treatment, one with grade 1 vomiting, two with grade 1 nausea, one with grade 1 mucositis, and three with grade 1 anorexia were noted. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The average for upper part versus lower part of PTV (Bone marrow) of CI and H-index were 1.5 and 1.4 versus 1.2 and 1.2, respectively. The dose reduction of TMI tomotherapy to various OARs of head, chest, and abdomen relative to TBI varied from 31% to 74%, 21% to 51%, and 46% to 63%, respectively. The maximum average value of registration for upper torso versus lower extremities in different translation directions were 5.1 mm versus 4.1 mm for pretreatment and 1.5 mm versus 0.7 mm for post-treatment, respectively. The average treatment time for the upper versus lower part in beam-on time, setup time, and MVCT registration time took roughly 49.9, 23.3, and 11.7 min versus 11.5, 10.0, and 7.3 min, respectively. The margin of PTV could be less than 1 cm under good fixation and close position confirmation with MVCT. Antiemetics should be prescribed in the whole course of TMI for emesis prevention. TMI technique replaced TBI technique with 8 Gy as conditioning regiment for multiple myeloma could be acceptable for the Asian and the outcomes were feasible for the Asian.

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Herein, we report the discovery and optimization of a series of orally bioavailable acyl sulfonamide NaV1.7 inhibitors that are selective for NaV1.7 over NaV1.5 and highly efficacious in in vivo models of pain and hNaV1.7 target engagement. An analysis of the physicochemical properties of literature NaV1.7 inhibitors suggested that acyl sulfonamides with high fsp3 could overcome some of the pharmacokinetic (PK) and efficacy challenges seen with existing series. Parallel library syntheses lead to the identification of analogue 7, which exhibited moderate potency against NaV1.7 and an acceptable PK profile in rodents, but relatively poor stability in human liver microsomes. Further, design strategy then focused on the optimization of potency against hNaV1.7 and improvement of human metabolic stability, utilizing induced fit docking in our previously disclosed X-ray cocrystal of the NaV1.7 voltage sensing domain. These investigations culminated in the discovery of tool compound 33, one of the most potent and efficacious NaV1.7 inhibitors reported to date.

Endoplasmic reticulum stress occurs in a variety of patho-physiological mechanisms and there has been great interest in managing this pathway for the treatment of clinical diseases. Autophagy is closely interconnected with endoplasmic reticulum stress to counteract the possible injurious effects related with the impairment of protein folding. Studies have shown that glomerular podocytes exhibit high rate of autophagy to maintain as terminally differentiated cells. In this study, podocytes were exposed to tunicamycin and thapsigargin to induce endoplasmic reticulum stress. Thapsigargin/tunicamycin treatment induced a significant increase in endoplasmic reticulum stress and of cell death, represented by higher GADD153 and GRP78 expression and propidium iodide flow cytometry, respectively. However, thapsigargin/tunicamycin stimulation also enhanced autophagy development, demonstrated by monodansylcadaverine assay and LC3 conversion. To evaluate the regulatory effects of autophagy on endoplasmic reticulum stress-induced cell death, rapamycin (Rap) or 3-methyladenine (3-MA) was added to enhance or inhibit autophagosome formation. Endoplasmic reticulum stress-induced cell death was decreased at 6 h, but was not reduced at 24 h after Rap+TG or Rap+TM treatment. In contrast, endoplasmic reticulum stress-induced cell death increased at 6 and 24 h after 3-MA+TG or 3-MA+TM treatment. Our study demonstrated that thapsigargin/tunicamycin treatment induced endoplasmic reticulum stress which resulted in podocytes death. Autophagy, which counteracted the induced endoplasmic reticulum stress, was simultaneously enhanced. The salvational role of autophagy was supported by adding Rap/3-MA to mechanistically regulate the expression of autophagy and autophagosome formation. In summary, autophagy helps the podocytes from cell death and may contribute to sustain the longevity as a highly differentiated cell lineage.

Conducting polymer (polyaniline) sheets are shown to be active substrates to promote the growth of nanostructured silver thin films with highly tunable morphologies. Using the spontaneous electroless deposition of silver, we show that a range of nanostructured metallic features can be controllably and reproducibly formed over large surface areas. The structural morphology of the resulting metal-polymer nanocomposite is demonstrated to be sensitive to experimental parameters such as ion concentration, temperature, and polymer processing and can range from densely packed oblate nanosheets to bulk crystalline metals. The deposition mechanisms are explained using a diffusion-limited aggregation (DLA) model to describe the semi-fractal-like growth of the metal nanostructures. We find these composite films to exhibit strong surface-enhanced Raman (SERS) activity, and the nanostructured features are optimized with respect to SERS activity using a self-assembled monolayer of mercapto-benzoic acid as a model Raman reporter. SERS enhancements are estimated to be on the order of 10(7). Through micro-Raman SERS mapping, these materials are shown to exhibit uniform SERS responses over macroscopic areas. These metal-polymer nanocomposites benefit from the underlying polymer's processability to yield SERS-active materials of almost limitless shape and size and show significant promise for future SERS-based sensing and detection schemes.