Additional file 1 of Breast cancer risk in papilloma patients: Osteopontin splice variants indicate prognosis

Additional file 1. Table S1: Relative risk based on pathology scores. Figure S1: Breast cancer risk scores

DataSheet_1_Cost-effectiveness of active surveillance versus early surgery for thyroid micropapillary carcinoma based on diagnostic and treatment norms in China.pdf

ObjectivesIn this study, we compared the cost-effectiveness comparison of the active surveillance (AS) and early surgery (ES) approaches for papillary thyroid microcarcinoma (PTMC) from the perspective of the Chinese healthcare system.MethodsWe performed a cost-effectiveness analysis using a Markov model of PTMC we developed to evaluate the incremental cost-effectiveness ratio of AS and ES. Our reference case was of a 40-year-old woman diagnosed with unifocal (ResultsES exhibited an effectiveness of 5.2 QALYs, whereas AS showed an effectiveness of 25.8 QALYs. Furthermore, the incremental cost-effectiveness ratio for ES versus AS was ¥1,009/QALY. The findings of all sensitivity analyses were robust. Compared with ES, AS was found to be the cost-effective strategy at initial monitoring ages of 20 and 60 years, with an incremental cost-effectiveness ratio of ¥3,431/QALY and −¥1,316/QALY at 20 and 60 years, respectively. AS was a more cost-effective strategy in patients with PTMC aged more than 60.ConclusionsWith respect to the norms of the Chinese healthcare system, AS was more cost-effective for PTMC over lifetime surveillance than ES. Furthermore, it was cost-effective even when the initial monitoring ages were different. In addition, if AS is incorporated into the management plan for PTMC in China at the earliest possible stage, a predicted savings of ¥10 × 108/year could be enabled for every 50,000 cases of PTMC, which indicates a good economic return for future management programs. The identification of such nuances can help physicians and patients determine the best and most individualized long-term management strategy for low-risk PTMC.</p

Additional file 1 of BSA modification of bacterial surface: a promising anti-cancer therapeutic strategy

Additional file 1

AZA decreased AQP1protein content by promoting AQP1 degradation.

<p><b>A</b>, The time-course effect of AZA on ubiquitinated AQP1 protein expression. HK-2 cells were treated with 3×10⁻⁶ mol/L AZA for 5min, 6 h and 24 h. Control cells were treated with vehicle. Cell membrane and cytoplasm were separated. After immunoprecipitation with AQP1 antibody, cell lysates was determined with ubiquitin antibodies. Each lane was loaded with 60 μg of total protein. The representative blotting image of ubiquitin is shown (up panel). IP and IB are short for immunoprecipitation and immunoblot, respectively. Statistical data is shown (down panel). Results are expressed as a percentage of the control. Values are presented as means±S.E.M. *<i>p</i><0.05, **<i>p</i><0.01 compared to control. <b>B</b>, Effect of AZA on AQP1 expression in the presence of MG132. HK-2 cells were pretreated with MG132 (10 μM) or vehicle for 8 h, then incubated with AZA for 24 hours. A representative blotting image and summary data are shown. Values are the means±S.E.M. *<i>p</i><0.05, **<i>p</i><0.01 compared to control. <b>C</b>, Effects of AZA on AQP1 mRNA in HK-2 cells. Cells were incubated with 3×10⁻⁶ mol/L AZA for a series of times. RT-PCR analysis was performed for the detection of AQP1 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs. Values are presented as means±S.E.M.</p

AZA promoted the interaction between AQP1 and MHC.

<p><b>A</b>, The confocal laser scanning microscopy images of MHC and AQP1 immunofluorescence in HK-2 cells. HK-2 cells were grown with 3×10⁻⁶mol/L AZA, 1×10⁻²mol/L BDM or both of them (BDM+AZA) for 6 h. Control cells were treated with vehicle (Control). Blue fluorescent indicates nuclear stained by Hoechst 33342 and the green fluorescent shows the AQP1 staining and the red fluorescent shows the MHC staining. <b>B</b>, The yellow stain in merged pictures from Fig. 5A was analyzed by IPP (Image-Pro Plus) software. Results are expressed as a percentage of the control. Values are shown as means±S.E.M. *<i>p</i><0.05 compared to Control. <b>C</b>, The time-course effect of AZA on AQP1 and MHC interaction. HK-2 cells were incubated with 3×10⁻⁶mol/L AZA for 5min to 24 h. Total extracts were immunoprecipitated with 2 µg/ml of anti-AQP1 antibody. The samples were then loaded onto SDS-PAGE gel and immunoblotted on PVDF sheet. The latter was incubated with anti- MHC (1∶1000) overnight. The representative blotting image of MHC is shown (up panel) and summary data is shown (down panel). Results are expressed as a percentage of the control. Values are presented as the means±S.E.M. *<i>p</i><0.05, **<i>p</i><0.01 compared to Control. <b>D</b>, The effect of AZA on AQP1 and MHC expression in the presence of myosin inhibitor BDM. HK-2 cells were treated with vehicle, 3×10⁻⁶mol/L AZA, 1×10⁻²mol/L BDM or both of them for 6 h. Cell membrane was separated and determined by western blot analysis with AQP1 and MHC antibodies. The representative blot of AQP1 and MHC is shown. <b>E and F</b>, Summary data from immunoblotting results. Results are expressed as a percentage of the control. Values are shown as means±S.E.M. <b>*</b><i>p</i><0.05, **<i>p</i><0.01 compared to Control. <b>G</b>, BDM reversed AQP1 reduction induced by AZA. HK-2 cells were treated with vehicle, 3×10⁻⁶mol/L AZA, 1×10⁻²mol/L BDM or both of them for 24 h. Cell lysates were detected with AQP1 antibodies. The representative blotting image of AQP1 is shown. Statistical data is shown. Results are expressed as a percentage of the control. Values are shown as means±S.E.M. <b>*</b><i>p</i><0.05 compared to Control. Ns, non-significant.</p

Diuretic effect of AZA on rats and knock out mice.

<p><b>A</b>, The effect of oral administration of AZA (40 mg/kg/day) with or without NaHCO₃ (30 mg/kg/day) on urine volume in rats. Urine outcomes were determined in three separate groups (n = 6 each) of rats (vehicle, AZA, AZA+NaHCO₃). Urine was collected after different administration times (8 hours, 1 day, 3 days, 7 days and 14 days). Values are presented as means±S.E.M. <b>*</b><i>p</i><0.05, <b>**</b><i>p</i><0.01, <b>***</b><i>p</i><0.001 compared to the control group. <b>B</b>, The effect of oral administration of AZA (40 mg/kg/day) on urine volume in AQP1^−/− mice. Urine outcomes were determined in 2 separate groups (n = 6 each) of mice (wild mice treated with AZA, AQP1^−/− mice treated with AZA). Urine was collected after different administration times (before dosing, 8 hours and 14 days after dosing). Values are shown as means±S.E.M. <b>***</b><i>p</i><0.001 compared to the wild type controls. ††<i>p</i><0.01 compared with counterparts. ##<i>p</i><0.01 compared to the AQP1^−/− controls. Ns, non-significant.</p

Isocyanide-Based Multicomponent Bicyclization with Substituted Allenoate and Isatin: Synthesis of Unusual Spirooxindole Containing [5.5]-Fused Heterocycle

A three-component bicyclization reaction of isocyanide, substituted allenoate, and isatin has been disclosed. This protocol is proposed to proceed through Michael addition, double cyclization, and [1,5]-hydride shift sequence, thus leading to the formation of two new rings and five new chemical bonds, including C–C, C–O, and C–N bonds

AZA induced CAs activity recovery and AQP1 reduction.

<p><b>A</b>, The time course of total CAs activity in rat kidney cortex. The carbonic anhydrase activity was assayed by endpoint colorimetric microtechnique after the treatment with AZA (40 mg/kg/day) or AZA (40 mg/kg/day) and NaHCO₃ (30 mg/kg/day) at the indicated time. Results are expressed as a percentage of the control. Values are the means±S.E.M. <b>*</b><i>p</i><0.05, <b>**</b><i>p</i><0.01, <b>***</b><i>p</i><0.001 compared to control. <b>B and C</b>, CAs and AQP1 extracted from rat kidney cortex were examined by immunoblotting in B and C. Each lane was loaded with 60 μg of total protein from rats at various times after AZA (40 mg/kg/day) (B) or combination with NaHCO₃ (30 mg/kg/day) (C) treatment. The representative blotting images of CA II, CA IV and AQP1 are shown with β-actin as an internal control. Summary data is shown in down panels. Results are expressed as a percentage of the control. Values are the means±S.E.M. <b>*</b><i>p</i><0.05, <b>**</b><i>p</i><0.01 compared to control.</p

Signaling pathway participated in the AQP1translocation and degradation induced by AZA.

<p><b>A</b>, The effects of AZA on the activation of MAPK signaling pathway in HK-2 cells. For the MAPK immunoblotting, cells were incubated with 3×10⁻⁶ mol/L AZA for a series of times. Cells were harvested. Immunoblot analysis was performed by using antibodies to p-ERK, ERK, p-p38 kinase, p38 kinase, p-JNK, JNK, respectively. Representative blots and summary data are shown. Data is expressed as means±S.E.M. **<i>p</i><0.01 compared to Control. <b>B</b>, The effect of AZA on AQP1 expression in the presence of ERK inhibitor U0126. After pretreated with U0126 (2 mol/L) or vehicle for 30 min, cells were incubated with AZA for 24 hours. Values are as means±S.E.M. <b>*</b><i>p</i><0.05 compared to Control. <b>C</b>, The effect of AZA on the activation of MLC in HK-2 cells. For p-MLC immunoblotting, cells were incubated with 3×10⁻⁶ mol/L AZA for a series of times. Cells were harvested. Immunoblot analysis was performed by using antibodies to p-MLC and summary data is shown here. Values are presented as means±S.E.M. <b>*</b><i>p</i><0.05, **<i>p</i><0.01 compared to Control. <b>D</b>, The effect of AZA on MLCK activity. Cells were incubated with 3×10⁻⁶ mol/L AZA for a series of times. Cells were harvested and MLCK activity was analyzed by ELISA assay. Summary data is shown. Values are expressed as means±S.E.M. <b>*</b><i>p</i><0.05, **<i>p</i><0.01 compared to Control.</p

Synthesis and Antimicrobial Evaluation of Fire Ant Venom Alkaloid Based 2‑Methyl-6-alkyl‑Δ^1,6-piperideines

The first synthesis of 2-methyl-6-pentadecyl-Δ^1,6-piperideine (<b>1</b>), a major alkaloid of the piperideine chemotype in fire ant venoms, and its analogues, 2-methyl-6-tetradecyl-Δ^1,6-piperideine (<b>2</b>) and 2-methyl-6-hexadecyl-Δ^1,6-piperideine (<b>3</b>), was achieved by a facile synthetic method starting with glutaric acid (<b>4</b>) and urea (<b>5</b>). Compound <b>1</b> showed in vitro antifungal activity against <i>Cryptococcus neoformans</i> and <i>Candida albicans</i> with IC₅₀ values of 6.6 and 12.4 μg/mL, respectively, and antibacterial activity against vancomycin-resistant <i>Enterococcus faecium</i> with an IC₅₀ value of 19.4 μg/mL, while compounds <b>2</b> and <b>3</b> were less active against these pathogens. All three compounds strongly inhibited the parasites <i>Leishmania donovani</i> promastigotes and <i>Trypanosoma brucei</i> with IC₅₀ values in the range of 5.0–6.7 and 2.7–4.0 μg/mL, respectively