Asymmetric three-component 1,2-oxytrifluoromethylations of styrenes were explored by using N-oxyphthalimide (NOPI) as the resulting benzylic radical anchor after cross-coupling by a CF3 radical under ...the catalyses of chiral N-salicylidene-derived oxovanadium(V) complexes. Among the 15 different solvents and 15 different catalysts examined, the best scenarios were in i-PrOH with C3-tert-butyl or C3-fluoro-/2,5-dimethylphenyl-substituted vanadyl catalysts that led to the corresponding complementary S and R products in up to 88% yields and 87/86% ees, respectively, with further enrichment to at least 94% ee after a single recrystallization. The ccontrol α-(2-phenylcyclopropyl)styrene was tested to prove the asymmetric event involving the benzylic radical species. DFT computations showed that the SOMO of the benzylic radical is placed in a way to orient the CF3CH2 group away from the tert-butyl group in the salicylidene-l-tert-butylglycinate template by interacting with the N-oxygen atom of NOPI bound to the vanadium center with a bimolecular homolytic substitution (SH2) type mechanism. The enantioselectivity profile was dominated by several noncovalent interactions between the intermediary vanadium(NOPI) complex and the resulting benzylic radical.
Considering a device structure consisting of multi-stacked layers with different refractive indices, we proposed a composite electrode to diminish total internal reflection, thereby improving the ...out-coupling efficiency of organic light-emitting diodes (OLEDs). The selected transparent conducting oxide materials for the composite electrode were composed of the same main material, gallium-doped zinc oxide (GZO), to avoid lattice mismatch and reduce interfacial strain. Herein, silicon-doped GZO (SGZO) with a relatively low refractive index was used in combination with molybdenum-doped GZO (MGZO) with a high work function to form a multifunctional transparent composite electrode. High transmittance of 94.5% and adequate sheet resistance of 52.3 Ohm/sq were realized through the design of SGZO/MGZO films on a glass substrate. The tested blue phosphorescent OLEDs with SGZO/MGZO composite anode outperformed devices with other selected single-layer electrodes, achieving a high peak efficiency of 29.0% (57.6 cd/A and 47.6 lm/W). These results demonstrate clear advantages of using this composite-electrode concept for realizing high efficiency OLEDs or other flexible optoelectronics.
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•SGZO with a relatively low refractive index was used in combination with MGZO with a high work function to form a multifunctional transparent composite electrode.•High transmittance and adequate sheet resistance were realized through the design of SGZO/MGZO films on a glass substrate.•An alternative SGZO/MGZO composite electrode presents a remarkable potential for realizing OLEDs with outstanding EL performance.
Mitochondria are key organelles in mammary cells in responsible for a number of cellular functions including cell survival and energy metabolism. Moreover, mitochondria are one of the major targets ...under doxorubicin treatment. In this study, low‐abundant mitochondrial proteins were enriched for proteomic analysis with the state‐of‐the‐art two‐dimensional differential gel electrophoresis (2D‐DIGE) and matrix‐assistant laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) strategy to compare and identify the mitochondrial protein profiling changes in response to the development of doxorubicin resistance in human uterine cancer cells. The mitochondrial proteomic results demonstrate more than fifteen hundred protein features were resolved from the equal amount pooled of three purified mitochondrial proteins and 101 differentially expressed spots were identified. In which, 39 out of these 101 identified proteins belong to mitochondrial proteins. Mitochondrial proteins such as acetyl‐CoA acetyltransferase (ACAT1) and malate dehydrogenase (MDH2) have not been reported with the roles on the formation of doxorubicin resistance in our knowledge. Further studies have used RNA interference and cell viability analysis to evidence the essential roles of ACAT1 and MDH2 on their potency in the formation of doxorubicin resistance through increased cell viability and decreased cell apoptosis during doxorubicin treatment. To sum up, our current mitochondrial proteomic approaches allowed us to identify numerous proteins, including ACAT1 and MDH2, involved in various drug‐resistance‐forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for the treatment of doxorubicin‐resistant uterine cancer.
The most frequent cancers among women worldwide. The mortality of cervical cancer has declined significantly primarily due to the widespread use of Pap smear tests as a screening test and therapeutic ...vaccination. However, cervical cancer still remains a severe disease among the female population, as the prognosis of metastatic cervical cancer is very poor.
In this study, we performed 2D-DIGE and MALDI-TOF/TOF MS to analyze differentially expressed proteins between HeLa and invasive HeLa-I5 cells..
According to our proteomics data, 68 differentially expressed proteins between the HeLa and HeLa-I5 cells were identified. One of these differentially expressed proteins, Progesterone receptor membrane component 1 (PGRMC1), was selected as a candidate for further studies. To correlate the role of PGRMC1 with cellular migration and cancer progression, small interfering RNA (siRNA) was used to knockdown the expression of PGRMC1. Similar function of PGRMC1 was also observed in two other cervical cancer lines, CaSki and ME-180.
PGRMC1 plays an essential role in regulating cancer progression and metastasis of cervical cancer cells, thus serving as a potential therapeutic target for cervical cancer.
Ankle brachial index (ABI) is a diagnostic tool for peripheral artery disease (PAD), which is an important issue in hemodialysis (HD) patients. We enrolled 198 maintenance HD patients in this study. ...PAD is defined as ABI ≤ 0.90. Only PAD patients received far-infrared (FIR) therapy using the WS TY101 FIR emitter for 40 min during each HD session, three times weekly for 6 months. The ABI was measured at the bilateral lower extremities for 4 times pre-dialytic timing (0 min) and 40 min after the initiation of HD session at both day 0 and 6 months after the FIR therapy. The primary outcome is the change in ABI. There were 51 out of 198 patients with PAD. In comparison with the period without FIR therapy in the 51 PAD patients, 6 months of FIR therapy significantly improved the ABI of the right/left side for 0 min (from 0.77 ± 0.19 to 0.81 ± 0.20,
p
= 0.027/0.79 ± 0.20 to 0.81 ± 0.17,
p
= 0.049), 40 min during HD (from 0.73 ± 0.23 to 0.83 ± 0.19,
p
< 0.001/from 0.77 ± 0.21 to 0.83 ± 0.18,
p
< 0.001), and the incremental change between 0 and 40 min (from − 0.04 ± 0.14 to 0.05 ± 0.13,
p
= 0.007/from − 0.05 ± 0.13 to 0.03 ± 0.11,
p
= 0.012), respectively. In conclusion, the application of FIR therapy for 40 min, three times weekly for 6 months, has improved the ABI of both lower extremities, thus providing a new strategy of PAD treatment in HD patients.
Vascular diseases are commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD). We aim to investigate the differences in the risk for arteriovenous fistula or graft ...(AVF/AVG) dysfunction in haemodialysis (HD) patients with and without ADPKD. 557 ADPKD and 1671 non-ADPKD patients were enrolled in the study after propensity score matching. The primary outcome measure is the incidence rate of AVF/AVG dysfunction. The incidence rates and risks of AVF/AVG dysfunction (per 100 person-years) for ADPKD and non-ADPKD patients were (1) 38.83 and 48.99 SHR = 0.79, P = 0.137, respectively, for within 90 days, (2) 45.85 and 51.31 SHR = 0.90, P = 0.300, respectively, for within 180 days, (3) 44.42 and 41.40 SHR = 1.08, P = 0.361, respectively, for within the first year, (4) 27.38 and 24.69 SHR = 1.09, P = 0.168, respectively, for within 5 years, (5) 17.35 and 13.80 SHR = 1.19, P = 0.045, respectively, for between the 1st and 10th year, and (6) 25.40 and 21.22 SHR = 1.14, P = 0.031, respectively, for all periods. ADPKD patients had lower incidence rates of AVF/AVG dysfunction within the first 180 days than non-ADPKD patients, but presented a higher incidence rate after 1 year of AVF/AVG creation and onwards.
Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD ...patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001), lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025), right-sided (31.8% vs. 18.4%, p = 0.002) and upper arm AVF (26.6% vs. 9.7%, p < 0.001), and higher mean dynamic venous pressure (DVP) (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021). In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs), rs275653 (Odds ratio 1.90, p = 0.038) and rs1492099 (Odds ratio 2.29, p = 0.017) of angiotensin II receptor 1 (AGTR1), were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA) of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005). In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could be a potential genetic risk factor of AVF malfunction in male HD patients.
OBJECTIVE—Defects in angiogenesis/vasculogenesis or vessel repair are major complications of coronary artery disease (CAD). Endothelial progenitor cells (EPCs) play a fundamental role in postnatal ...vascular repair and CAD. The role of microRNAs in CAD pathogenesis and their potential as biomarkers remain to be elucidated.
APPROACH AND RESULTS—MicroRNA-31 (miR-31) level in both the plasma and EPCs of patients with CAD is found lower. miR-31 regulates EPC activities by targeting FAT atypical cadherin 4 and thromboxane A2 receptor, which show increased expression in CAD EPCs. Overexpressing miR-31 in CAD EPCs rescued their angiogenic and vasculogenic abilities both in vitro and in vivo. When exploring approaches to restore endogenous miR-31, we found that far-infrared treatment enhanced the expression of not only miR-31, but also miR-720 in CAD EPCs. miR-720, which was also decreased in EPCs and the plasma of patients with CAD, stimulated EPC activity by targeting vasohibin 1. The miR720–vasohibin 1 pair was shown to be downstream of FAT atypical cadherin 4, but not of thromboxane A2 receptor. FAT atypical cadherin 4 inhibited miR-720 expression via repression of the planar cell polarity signaling gene four-jointed box 1 (FJX1), which was required for miR-720 expression through a hypoxia-inducible factor 1, α subunit–dependent mechanism. Restoring miR-720 level strengthened activity of CAD EPCs. The miR-31–miR-720 pathway is shown critical to EPC activation and that downregulation of this pathway contributes to CAD pathogenesis. Circulating levels of miR-31, miR-720, and vasohibin 1 have the potential to allow early diagnosis of CAD and to act as prognosis biomarkers for CAD and other EPC-related diseases.
CONCLUSIONS—Manipulating the expression of the miR-31–miR-720 pathway in malfunction EPCs should help develop novel therapeutic modalities.
Radical hysterectomy (RH) is the standard treatment for early stage cervical cancer, but the surgical approach for locally bulky-size cervical cancer (LBS-CC) is still unclear. We retrospectively ...compared the outcomes of women with LBS-CC treated with neoadjuvant chemotherapy (NACT) and subsequent RH between the robotic (R-RH) and abdominal approaches (A-RH). Between 2012 and 2014, 39 women with LBS-CC FIGO (International Federation of Gynecology and Obstetrics) stage IB2-IIB were treated with NACT-R-RH (
= 18) or NACT-A-RH (
= 21). Surgical parameters and prognosis were compared. Patient characteristics were not significantly different between the groups, but the NACT-R-RH group had significantly more patients with FIGO stage IIB disease, received multi-agent-based NACT, and had a lower percentage of deep stromal invasion than the NACT-A-RH group. After NACT-R-RH, surgical parameters were better, but survival outcomes, such as disease-free survival (DFS) and overall survival (OS), were significantly worse. On multivariate analysis, FIGO stage IIB contributed to worse DFS (
= 0.003) and worse OS (
= 0.012) in the NACT-A-RH group. Women with LBS-CC treated with NACT-R-RH have better perioperative outcomes but poorer survival outcomes compared with those treated with NACT-A-RH. Thus, patients with FIGO stage IIB LBS-CC disease might not be suitable for surgery after multi-agent-based NACT.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and plays a significant role in the pathogenesis of arteriovenous fistula (AVF) dysfunction. The aim of this ...study is to evaluate the effect of far-infrared (FIR) therapy on the maturation and patency of newly-created AVFs in patients with advanced diabetic kidney disease (DKD) as well as the concurrent change in plasma ADMA. The study enrolled 144 participants with advanced DKD where 101 patients were randomly allocated to the FIR therapy group (N = 50) and control group (N = 51). Patients receiving FIR therapy had a decreased AVF failure rate within 12 months (16% versus 35.3%; p = 0.027); decreased incremental change of ADMA concentration at the 3rd and 12th month; increased AVF blood flow at the 1st, 3rd, and 12th month; increased 3-month physiologic maturation rate (88% versus 68.6%; p = 0.034); increased 1-year unassisted AVF patency rate (84% versus 64.7%; p = 0.017); and increased clinical AVF maturation rate within 12 months (84% versus 62.7%; p = 0.029) compared to the control group. The study demonstrates that FIR therapy can reduce the incremental changes in plasma ADMA concentration, which may be associated with the improvement of AVF prognosis in patients with advanced DKD.
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