Enhancing Photoelectrochemical Water Oxidation on WO3 via Electrochromic Modulation: Universal Effects and Mechanistic Insights.

Although WO3 exhibits both electrochromic and photoelectrochemical (PEC) properties, there is no research conducted to investigate the correlation between them. The study herein reports the electrochromic enhancement of PEC activity on WO3. The electrochromic WO3 (e-WO3) exhibits a significantly enhanced activity for PEC water oxidation compared to raw WO3 (r-WO3), with a limiting photocurrent density three times that of r-WO3. The electrochromic enhancement of PEC activity is universal and independent of the type of cations inserted during electrochromism. Decoloring reduces the PEC activity but a simple re-coloring restores the activity to its maximum value. Electrochromism induces large amounts of oxygen vacancies and surface states, the former improving the electron density of WO3 and the latter facilitating the hole transfer across e-WO3/electrolyte interface. It is proved that the electrochromic enhancement effect is due to the significantly improved electron-hole separation efficiency and the charge transfer efficiency across the WO3/electrolyte interface.

Promoting the electrocatalytic oxygen evolution reaction on NiCo2O4 with infrared-thermal effect: A strategy to utilize the infrared solar energy to reduce activation energy during water splitting.

Utilization of the infrared (IR) solar energy remains a challenging task for traditional photo(electro)catalysis. Taking advantage of the IR-thermal effect to facilitate sluggish electrocatalytic reactions emerges as a promising way to utilize the IR band of the solar spectrum. In this work, nickel foam (NF) supported NiCo2O4 nanoneedles (NF/NiCo2O4 NNs) were prepared to promote the oxygen evolution reaction (OER) via the IR-thermal effect, with the NF/NiCo2O4 NNs acting as both the IR absorbing antennae and the OER active anode. The potential required to deliver a current density of 200 mA cm-2 is negatively shifted from 1.618 V in the dark to 1.578 V under IR irradiation, and the Tafel slope is also decreased from 106 to 89 mV dec-1. We demonstrate that the enhancement of OER activity is due to the localized temperature rise under IR irradiation. We measured the electrochemical activation energy of OER on NF/NiCo2O4 with and without IR irradiation, and the results reveal that IR irradiation reduces the kinetic energy barrier of the OER by IR-thermal effect and then facilitates OER kinetics. This work highlights a new approach to utilizing the IR portion of the sunlight to produce renewable hydrogen energy via water splitting.

Engineering Coupled NiSx -WO2.9 Heterostructure as pH-Universal Electrocatalyst for Hydrogen Evolution Reaction.

Exploiting highly active and low-cost materials as pH-universal electrocatalysts for the hydrogen evolution reaction (HER) and achieving high-purity hydrogen fuel is highly desirable but remains challenging. Herein, a novel type of coupled heterostructure was designed by simple electrodeposition followed by a sulfurization treatment. This hierarchical structure was composed of nickel sulfides (NiS, NiS2 , denoted as NiSx ) and oxygen-deficient tungsten oxide (WO2.9 ), which was directly grown on nickel foam (NF) as self-supporting electrodes (NiSx -WO2.9 /NF) for HER over a wide pH range. The systematic experimental characterizations confirmed that the material had abundant catalytic active sites, fast interfacial electron transfer ability, and strong electronic interaction, resulting in the optimized reaction kinetics for HER. Consequently, the NiSx -WO2.9 /NF catalyst required low overpotentials of 96 and 117 mV to reach current densities of 50 and 100 mA cm-2 in an alkaline medium, outperforming most of the reported non-noble metal-based materials. Moreover, this self-supported electrode exhibited impressive performance over a wide pH range, only requiring 220 and 304 mV overpotential at 100 mA cm-2 in 0.5 m H2 SO4 and 1 m phosphate-buffered saline electrolytes. This work may offer a new approach to the development of advanced pH-universal electrodes for hydrogen production.

Improving the clinical workflow of a MR-Linac by dosimetric evaluation of synthetic CT.

Adaptive radiotherapy performed on the daily magnetic resonance imaging (MRI) is an option to improve the treatment quality. In the adapt-to-shape workflow of 1.5-T MR-Linac, the contours of structures are adjusted on the basis of patient daily MRI, and the adapted plan is recalculated on the MRI-based synthetic computed tomography (syCT) generated by bulk density assignment. Because dosimetric accuracy of this strategy is a priority and requires evaluation, this study aims to explore the usefulness of adding an assessment of dosimetric errors associated with recalculation on syCT to the clinical workflow. Sixty-one patients, with various tumor sites, treated using a 1.5-T MR-Linac were included in this study. In Monaco V5.4, the target and organs at risk (OARs) were contoured, and a reference CT plan that contains information about the outlined contours, their average electron density (ED), and the priority of ED assignment was generated. To evaluate the dosimetric error of syCT caused by the inherent approximation within bulk density assignment, the reference CT plan was recalculated on the syCT obtained from the reference CT by forcing all contoured structures to their mean ED defined on the reference plan. The dose-volume histogram (DVH) and dose distribution of the CT and syCT plan were compared. The causes of dosimetric discrepancies were investigated, and the reference plan was reworked to minimize errors if needed. For 54 patients, gamma analysis of the dose distribution on syCT and CT show a median pass rate of 99.7% and 98.5% with the criteria of 3%/3 mm and 2%/2 mm, respectively. DVH difference of targets and OARs remained less than 1.5% or 1 Gy. For the remaining patients, factors (i.e., inappropriate ED assignments) influenced the dosimetric agreement of the syCT vs. CT reference DVH by up to 21%. The causes of the errors were promptly identified, and the DVH dosimetry was realigned except for two lung treatments for which a significant discrepancy remained. The recalculation on the syCT obtained from the planning CT is a powerful tool to assess and decrease the minimal error committed during the adaptive plan on the MRI-based syCT.

Local tuning of radiomics-based model for predicting pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

PURPOSE: This study aims to further enhance a validated radiomics-based model for predicting pathologic complete response (pCR) after chemo­radiotherapy in locally advanced rectal cancer (LARC) for use in clinical practice. METHODS: A generalized linear model (GLM) to predict pCR in LARC patients previously trained in Europe and validated with an external inter-continental cohort (59 patients), was first examined with further 88 intercontinental patient datasets to assess its reproducibility; then new radiomics and clinical features, and validation methods were investigated to build a new model for enhancing the pCR prediction for patients admitted to our department. The patients were divided into training group (75%) and validation group (25%) according to their demographic. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to reduce the dimensionality of the extracted features of the training group and select the optimal ones; the performance of the reference GLM and enhanced models was compared through the area under curve (AUC) of the receiver operating characteristics. RESULTS: The value of AUC of the reference model was 0.831 (95% CI, 0.701-0.961), and 0.828 (95% CI, 0.700-0.956) in the original and new validation cohorts, respectively, showing a reproducibility in the applicability of the GLM model. Eight features were found to be significant with LASSO and used to establish an enhanced model. The AUC of the enhanced model of 0.926 (95% CI, 0.859-0.993) for training, and 0.926 (95% CI, 0.767-1.00) for the validation group shows better performance than the reference model. CONCLUSIONS: The GLM model shows good reproducibility in predicting pCR in LARC; the enhanced model has the potential to improve prediction accuracy and may be a candidate in clinical practice.

Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors.

BACKGROUND: This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. METHODS: Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. RESULTS: Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p <0.001). Of the patients undergoing surgical treatment, 22.8% presented with significant complications that required a delay of systemic treatment. Grade 3-4 acute radiation therapy-related toxicities were observed in 6.1% of patients, mainly gastrointestinal toxicities (5.4%). CONCLUSION: Rectal surgery was a key predictive factor of increased progression-free survival and overall survival in patients receiving at least local radiotherapy. In our series of real-life patients, local surgery and radiation seemed as well tolerated as reported in selected phase III non-metastatic rectal cancer patients. These data suggested that local management could be beneficial for metastatic rectal cancer patients.

Identification of prognostic values defined by copy number variation, mRNA and protein expression of LANCL2 and EGFR in glioblastoma patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expression in glioblastoma remain unclear yet. METHODS: This study analyzed the prognostic values of the copy number variations (CNVs), mRNA and protein expression of LANCL2 and EGFR in 575 glioblastoma patients in TCGA database and 100 glioblastoma patients in tumor banks of the Shenzhen Second People's Hospital and the Sun Yat-sen University Cancer Center. RESULTS: The amplification of LANCL2 or EGFR, and their co-amplification were frequent in glioblastoma of TCGA database and our tumor banks. A significant correlation was found between the CNVs of LANCL2 and EGFR (p < 0.001). CNVs of LANCL2 or EGFR were significantly correlated with IDH1/2 mutation but not MGMT promoter methylation. Multivariate analysis showed that LANCL2 amplification was significantly correlated with reduced overall survival (OS) in younger (< 60 years) glioblastoma patients of TCGA database (p = 0.043, HR = 1.657) and our tumor banks (p = 0.018, HR = 2.199). However, LANCL2 or EGFR amplification, and their co-amplification had no significant impact on OS in older (≥ 60 years) or IDH1/2-wild-type glioblastoma patients. mRNA and protein overexpression of LANCL2 and EGFR was also frequently found in glioblastoma. The mRNA expression rather than the protein expression of LANCL2 and EGFR was positively correlated (p < 0.001). However, mRNA or protein expression of EGFR and LANCL2 was not significantly correlated with OS of glioblastoma patients. The protein expression level of LANCL2, rather than EGFR, was elevated in relapsing glioblastoma, compared with newly diagnosed glioblastoma. In addition, the intracellular localization of LanCL2, not EGFR, was associated with the grade of gliomas. CONCLUSIONS: Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients.

Synergism between the phosphatidylinositol 3-kinase p110ß isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation.

BACKGROUND: Glioblastoma multiforme, the most aggressive and malignant primary brain tumor, is characterized by rapid growth and extensive infiltration to neighboring normal brain parenchyma. Our previous studies delineated a crosstalk between PI3K/Akt and JNK signaling pathways, and a moderate anti-glioblastoma synergism caused by the combined inhibition of PI3K p110ß (PI3Kß) isoform and JNK. However, this combination strategy is not potent enough. MLK3, an upstream regulator of ERK and JNK, may replace JNK to exert stronger synergism with PI3Kß. METHODS: To develop a new combination strategy with stronger synergism, the expression pattern and roles of MLK3 in glioblastoma patient's specimens and cell lines were firstly investigated. Then glioblastoma cells and xenografts in nude mice were treated with the PI3Kß inhibitor AZD6482 and the MLK3 inhibitor URMC-099 alone or in combination to evaluate their combination effects on tumor cell growth and motility. The combination effects on cytoskeletal structures such as lamellipodia and focal adhesions were also evaluated. RESULTS: MLK3 protein was overexpressed in both newly diagnosed and relapsing glioblastoma patients' specimens. Silencing of MLK3 using siRNA duplexes significantly suppressed migration and invasion, but promoted attachment of glioblastoma cells. Combined inhibition of PI3Kß and MLK3 exhibited synergistic inhibitory effects on glioblastoma cell proliferation, migration and invasion, as well as the formation of lamellipodia and focal adhesions. Furthermore, combination of AZD6482 and URMC-099 effectively decreased glioblastoma xenograft growth in nude mice. Glioblastoma cells treated with this drug combination showed reduced phosphorylation of Akt and ERK, and decreased protein expression of ROCK2 and Zyxin. CONCLUSION: Taken together, combination of AZD6482 and URMC-099 showed strong synergistic anti-tumor effects on glioblastoma in vitro and in vivo. Our findings suggest that combined inhibition of PI3Kß and MLK3 may serve as an attractive therapeutic approach for glioblastoma multiforme.

Impact of Positioning Errors on the Dosimetry of Breath-Hold-Based Volumetric Arc Modulated and Tangential Field-in-Field Left-Sided Breast Treatments.

Heart diseases and cardiovascular events are well-known side effects in left-sided breast irradiation. Deep inspiration breath hold (BH) combined with fast delivery techniques such as volumetric modulated arc therapy (VMAT) or tangential field-in-field (TFiF) can serve as a valuable solution to reduce the dose to the heart. This study aims to compare the impact of positioning errors in VMAT and TFiF plans for BH left-sided breast treatments. Fifteen left-sided breast patients treated in BH with TFiF technique were included in this retrospective study. For each patient, a second plan with VMAT technique was optimized. Eighteen setup variations were introduced in each of these VMAT and TFiF reference plans, shifting the isocenter along six different directions by 3, 5, and 10 mm. A total of 540 perturbed plans, 270 for each technique, were recalculated and analyzed. The dose distributions on the target and organs at risk obtained in the different perturbed scenarios were compared with the reference scenarios, using as dosimetric endpoints the dose-volume histograms (DVH). The results were compared using the Wilcoxon test. Comparable plan quality was obtained for the reference VMAT and TFiF plans, except for low doses to organs at risk for which higher values (p < 0.05) were obtained for VMAT plans. For TFiF plans, perturbations of the isocenter position of 3, 5, or 10 mm produced mean deviations of the target DVH dosimetric parameters up to -0.5, -1.0, and -5.2%, respectively; VMAT plans were more sensitive to positioning errors resulting in mean deviations up to -0.5, -4.9, and -13.9%, respectively, for the same magnitude of the above mentioned perturbations. For organs at risk, only perturbations along the left, posterior, and inferior directions resulted in dose increase with a maximum deviation of +2% in the DVH dosimetric parameters. A notable exception were low doses to the left lung and heart for 10 mm isocenter shifts for which the mean differences ranged between +2.7 and +4.1%. Objective information on how external stresses affect the dosimetry of the treatment is the first step towards personalized radiotherapy.

Synthesis, and biological evaluation of 3,6-diaryl-[1,2,4]triazolo[4,3-a]pyridine analogues as new potent tubulin polymerization inhibitors.

On the basis of our previous work, twenty-nine novel [1,2,4]triazolo[4,3-a]pyridines possessing 3,4,5-trimethoxylphenyl groups were designed, synthesized, and evaluated as tubulin polymerization inhibitors. The bioassay results revealed that some of the compounds displayed excellent antiproliferative efficacies in the nanomolar range against HeLa cells, and the most promising derivative 7i demonstrated almost comparable activity to that of the reference CA-4 and sixty-two fold more potent than the parent compound 6 with an IC50 value of 12 nM. Importantly, 7i exhibited high selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 µM). Further mechanism studies revealed that 7i significantly arrested cell cycle at G2/M phase, induced apoptosis with a dose-dependent manner, and disrupted microtubule networks. Additionally, the most active compound 7i effectively inhibited tubulin polymerization with a value similar to that of CA-4 (3.4 and 4.2 µM, respectively). Furthermore, molecular docking analysis suggested that 7i well occupied the colchicine binding pocket of tubulin. The present study highlights that compound 7i is a novel potential tubulin polymerization inhibitor and deserves further investigation for the treatment of cancers.

Sulfur-Doped CoSe2 Porous Nanosheets as Efficient Electrocatalysts for the Hydrogen Evolution Reaction.

The electrochemical hydrogen evolution reaction (HER), as a promising route for hydrogen production, demands efficient and robust noble-metal-free catalysts. Doping foreign atoms into an efficient catalyst such as CoSe2 could further enhance its activity toward the HER. Herein, we developed a solvothermal ion exchange approach to doping S into CoSe2 nanosheets (NSs). We provide a combined experimental and theoretical investigation to establish the obtained S-doped CoSe2 (S-CoSe2) nanoporous NSs as highly efficient and Earth-abundant catalysts for the HER. The optimal S-CoSe2 catalyst delivers a catalytic current density of 10 mA·cm-2 for the HER at an overpotential of only 88 mV, demonstrating that S-CoSe2 is one of the most efficient CoSe- and CoS-based catalysts for the HER. We performed density functional theory (DFT) calculations to determine the stable structural configurations of S-CoSe2, and on the basis of which, we calculated the hydrogen adsorption Gibbs free energy (ΔGH) on CoSe2, CoS2, and the S-CoSe2 and the barrier energies of the rate-determining step of the HER on S-CoSe2. DFT calculations reveal that S-doping not only decreases the absolute value of ΔGH (move toward zero) but also significantly lowers the kinetic barrier energy of the rate-determining step of the HER on S-CoSe2, leading to a greatly improved HER performance.

Overexpression of EP300-interacting inhibitor of differentiation 3 predicts poor prognosis in patients with glioblastoma multiforme.

EP300-interacting inhibitor of differentiation 3 (EID3) is a member of the IED family and has been associated with tumorigenesis and tumor development in different cancer types. However, the role of EID3 in glioblastoma multiforme (GBM) prognosis is not clear. Whole transcriptome sequencing data of 249 and 149 GBM patients were collected from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) database respectively. The correlation between EID3 expression and overall survival (OS)/clinical pathologic features of GBM patients was investigated. Based on the Wilcoxon rank-sum test, EID3 expression in GBM tissues was significantly lower than in normal brain tissues (P < 0.001), and significantly higher than in LGG (low-grade glioma) (P < 0.001).There was a significant correlation between high EID3 expression with poor OS in CGGA (P = 0.049) and TCGA data (P = 0.024). Gene set enrichment analysis (GSEA) data analysis revealed a significant difference (FDR < 0.25, NOM p-value < 0.05) in the enrichment of MSigDB Collection (h.all.v6.2.symbols.gmt). A total of eight enriched pathways were identified in the high EID3 expression group, including Myc Targets V1, Kras signaling DN, and DNA repair pathways. Multivariate Cox regression analysis indicated that high expression of EID3 correlated with poor OS (P = 0.032, HR = 1.41, CI: 1.03-1.90). We conclude that EID3 could serve as an independent factor for predicting the prognosis of patients with GBM. Moreover, it is associated with GBM development through the regulation of the Myc Targets, Kras signaling DN, and DNA repair pathways.

Preoperative platelet-lymphocyte ratio is a superior prognostic biomarker to other systemic inflammatory response markers in non-small cell lung cancer.

Systemic inflammatory response markers are associated with poor survival in many types of malignances. This study aimed to evaluate the prognostic value of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein (CRP) in patients with non-small cell lung cancer (NSCLC).We retrospectively evaluated 254 NSCLC patients who underwent radical surgery between January 2012 and April 2014 in the Sichuan Provincial Cancer Hospital. The cut-off values of NLR, PLR, LMR, and CRP were determined according to the receiver operating characteristic curve, and the correlation of NLR, PLR, LMR, and CRP with prognosis was analyzed based on the cut-off value.The cut-off value for NLR, PLR, LMR, and CRP were 3.18, 122, 4.04, and 8.8, respectively. Univariate analysis showed that age (P = .022), tumor-node-metastasis (TNM) stage (P < .001), T stage (P = .001), and N stage (P < .001) were significantly correlated with disease-free survival (DFS), while age (P = .011), TNM stage (P < .001), T stage (P = .008), N stage (P < .001), and PLR (P = .001) were significantly correlated with overall survival (OS). In multivariate analysis, age (hazard ratio [HR]: 1.564, 95% confidence interval [CI]: 1.087-2.252, P = .016) and TNM stage (HR: 1.704, 95% CI: 1.061-2.735, P = .027) remained independent risk factors affecting DFS, while age (HR: 1.721, 95% CI: 1.153-2.567, P = .008), TNM stage (HR: 2.198, 95% CI: 1.263-3.824, P = .005), and PLR (HR: 1.850, 95% CI: 1.246-2.746, P = .002) were independent risk factors affecting OS.The preoperative PLR is superior to NLR, LMR, and CRP as a biomarker for evaluating the prognosis of patients undergoing curative surgery for NSCLC.

Design, synthesis and biological evaluation of novel indole-based oxalamide and aminoacetamide derivatives as tubulin polymerization inhibitors.

A series of novel indole-based oxalamide and aminoacetamide derivatives were designed, synthesized, and evaluated for antiproliferative activities. Preliminary results revealed that compound 8g exhibited significant antiproliferative effect against PC-3, HeLa and HCT-116 cell lines. Flow cytometric analysis of the cell cycle demonstrated the compound 8g induced the cell cycle arrest at G2/M phase in HeLa cell lines. Immunocytochemistry revealed loss of intact microtubule structure in cells treated with 8g andinhibition of tubulinpolymerization. Additionally, molecular docking analysis suggested that 8g formed stable interactions in the colchicine-binding site of tubulin. These preliminary results demonstrated that a new class of novel indole-based oxalamide and aminoacetamide derivatives described in the investigation could be developed as potential scaffolds to new anticancer agents.

Novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives as potent antitubulin agents: Design, multicomponent synthesis and antiproliferative activities.

As restricted CA-4 analogues, a novel series of [1,2,4]triazolo[1,5-a]pyrimidines possessing 3,4,5-trimethoxylphenyl groups has been achieved successfully via an efficient one-pot three-component reaction of 3-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazol-5-amine, 1,3-dicarbonyl compounds and aldehydes. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against three cancer cell lines. Among them, the most highly active analogue 26 inhibited the growth of HeLa, and A549 cell lines with IC50 values at 0.75, and 1.02 µM, respectively, indicating excellent selectivity over non-tumoural cell line HEK-293 (IC50 = 29.94 µM) which suggested that the target compounds might possess a high safety index. Moreover, cell cycle analysis illustrated that the analogue 26 significantly induced HeLa cells arrest in G2/M phase, meanwhile the compound could dramatically affect cell morphology and microtubule networks. In addition, compound 28 exhibited potent anti-tubulin activity with IC50 values of 9.90 µM, and molecular docking studies revealed the analogue occupied the colchicine-binding site of tubulin. These observations suggest that [1,2,4]triazolo[1,5-a]pyrimidines represent a new class of tubulin polymerization inhibitors and well worth further investigation aiming to generate potential anticancer agents.

Discovery of novel pyrimidine-based benzothiazole derivatives as potent cyclin-dependent kinase 2 inhibitors with anticancer activity.

To develop novel CDK2 inhibitors as anticancer agents, a series of novel pyrimidine-based benzothiazole derivatives were designed and synthesized. Initial biological evaluation demonstrated some of target compounds displayed potent antitumor activity in vitro against five cancer cell lines. Especially, the analogue 10s exhibited approximately potency with AZD5438 toward four cells including HeLa, HCT116, PC-3, and MDA-MB-231 with IC50 values of 0.45, 0.70, 0.92, 1.80 µM, respectively. More interestingly, the most highly active compound 10s in this study also possessed promising CDK2/cyclin A2 inhibitory activities with IC50 values of 15.4 nM, which was almost 3-fold potent than positive control AZD5438, and molecular docking studies revealed that the analogue bound efficiently with the CDK2 binding site. Further studies indicated that compound 10s could induce cell cycle arrest and apoptosis in a concentration-dependent manner. These observations suggest that pyrimidine-benzothiazole hybrids represent a new class of CDK2 inhibitors and well worth further investigation aiming to generate potential anticancer agents.

Facile one-pot synthesis, antiproliferative evaluation and structure-activity relationships of 3-amino-1H-indoles and 3-amino-1H-7-azaindoles.

A highly efficient method has been developed for the one-pot synthesis of substituted 3-amino-1H-indole and 3-amino-1H-7-azaindole derivatives starting from ethyl 2-cyanophenylcarbamate/ethyl 3-cyanopyridin-2-ylcarbamate, and α-bromoketones in good to excellent yields. All newly synthesized analogues were screened for their antiproliferative activities against four cancer cell lines. The most promising compound 8v demonstrated 13-, 5-, and 1.4-fold improvement compared to fluorouracil in inhibiting HeLa, HepG2, and MCF-7 cell proliferation with IC50 values of 3.7, 8.0, and 19.9 µM, respectively. Furthermore, 8v induced significant cell cycle arrest at the G2/M phase in HeLa cell lines via a concentration-dependent manner. These encouraging findings indicate that the common 3-amino-1H-7-azaindole is a very favorable scaffold for the design of novel anticancer small-molecule drugs.

Is breast-conserving therapy adequate in BRCA 1/2 mutation carriers? The radiation oncologist's point of view.

Breast conserving therapy (BCT) is currently a recognized alternative to mastectomy for early BC patients. However, the therapeutic index of BCT was considered controversial for decades in BRCA1/2 mutation carriers. The aim of the present review was to investigate the outcome of mutation carriers undergoing BCT regarding local and distant endpoints. A short review was performed from the point of view of the radiation oncologist. Only retrospective data were available regarding local outcome assessment. They generated conflicting results. In studies with limited follow-up, BCT did not increase the risk of local recurrence in BRCA1/2 mutation carriers versus non-carriers. Conversely, some studies with longer follow-up supported that local relapse was increased in mutation carriers. Yet, according to some publications, their long-term risk of ipsilateral recurrence post-BCT was not different from general population cohorts. Besides, overall and metastasis-free survivals were the same after BCT regardless of the BRCA1/2 mutation status. Similar survival rates were also reported when BCT and mastectomy were compared in mutation carriers. Regarding acute or late toxicity, normal rates were reported in BRCA mutation carriers after breast radiotherapy. The BRCA1/2 mutation does not seem to widely alter the therapeutic index (efficacy/toxicity ratio) of modern adjuvant breast irradiation. Although the long term equivalence of BCT/mastectomy on local control is still not clearly recognised, BCT can be considered an adequate option for BRCA1/2 mutation carriers. This review highlights that BCT is a reasonable option for BRCA1/2 mutation carriers however litterature is controversial concerning long-term local outcome and results of a large prospective cohort are needed.

Hybrids of iridium-cobalt phosphates as a highly efficient electrocatalyst for the oxygen evolution reaction in neutral solution.

Hybrids of iridium-cobalt phosphates (IrCo-Pi) were prepared via a facile co-electrodeposition approach and employed as an electrocatalyst for the oxygen evolution reaction (OER). IrCo-Pi with an optimized Ir-to-Co ratio (RIr-to-Co) exhibited an intrinsic activity toward the OER superior to the two well-known catalysts: cobalt phosphate (Co-Pi) and iridium phosphate (Ir-Pi).