Construction of atom co-sharing Bi/Bi4O5Br2 nanosheet heterojunction for plasmonic-enhanced visible-light-driven photocatalytic antibacterial activity.

The rapid advancement of photodynamic therapy (PDT) antibacterial materials has led to promising alternatives to antibiotics for treating bacterial infections. However, antibacterial drugs have poor light absorption and utilization rates, which limits their practical application. Constructing two-dimensional (2D) heterojunctions from materials with matching photophysical properties has emerged as a highly effective strategy for achieving high-efficiency photo-antibacterial performance. Here, we designed and prepared an atom co-sharing Bi/Bi4O5Br2 nanosheet heterojunction by a simple in situ reduction. This heterojunction material combines outstanding biocompatibility with excellent bactericidal efficiency, which exceeded 90 % against Escherichia coli (a Gram-negative bacterium) and Staphylococcus aureus (a Gram-positive bacterium) under visible light irradiation, around nine-fold higher than that with pure Bi4O5Br2 nanosheets. The results suggest that localized surface plasmon resonance (LSPR) of shared Bi atoms on the Bi4O5Br2 nanosheets promotes light utilization and the separation and transfer of photo-generated charges, thus producing more abundant reactive oxygen species (ROS), which can partake in the PDT antibacterial effect. Our study underscores the potential utility of LSPR-enhanced Bi-based nanosheet heterojunctions for safe and efficient PDT to combat bacterial infections.

Rapid Reassembly, Biomass-Derived Adhesive Based on Soybean Oil and Diels-Alder Bonds.

Synthetic adhesives play a crucial role in holding together solid materials through interfacial interactions. Thermoplastic and thermosetting adhesives are important types of synthetic adhesives, with thermoplastic adhesives being reassemblable and thermosetting adhesives exhibiting high adhesive strength and creep resistance. However, there is a need to combine the advantages of both types and develop high bonding strength, reassemblable adhesives. Here, epoxidized soybean oil (ESO) was used to prepare adhesive networks and Diels-Alder bonds were incorporated to enhance reassembly ability. The ESO was functionalized with furyl groups and cross-linked via the reaction between furyl and imide groups to involve the Diels-Alder bonds. The resulting adhesive exhibited good solvent resistance and mechanical properties, which could be regulated by adjusting the quantity of cross-linker. The prepared adhesives also demonstrated self-healing capabilities, as the scratch on the surface gradually diminished with heating. Additionally, the adhesives showed the ability to undergo recycling without significant changes in properties. The prepared adhesives exhibited hydrophilicity and the flow characteristics during reassembly were characterized by a decrease in torque. This study provides a promising approach for the development of synthetic adhesives with reassembly ability, which has important implications for the field of bonding.

Potential diagnostic value of multiple indicators combined with total prostate-specific antigen in prostate cancer.

OBJECTIVE: We aimed to investigate the diagnostic value of different laboratory indicators in combination with total prostate-specific antigen (TPSA) for prostate cancer (PCa). METHODS: In this retrospective study, we selected 291 patients who underwent prostate biopsy. Patients were divided into the benign prostatic hyperplasia group and the PCa group. In both groups, patients were again divided into a group with TPSA 4.0-10.0 ng/mL and a group with TPSA >10.0 ng/mL. Clinical data including age, pre-puncture TPSA, free prostate-specific antigen (FPSA), and prostate volume (PV) were collected from all patients. We calculated the metrics PSA/PV (prostate-specific antigen density, PSAD), age/PV (AVR), age × PV/TPSA (PSA-AV), and (FPSA/TPSA)/PSAD [(F/T)/PSAD]). We plotted receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). RESULTS: We found statistically significant differences in PV, PSAD, AVR, PSA-AV, and (F/T) PSAD for patients with TPSA 4.0-10.0 ng/mL and TPSA >10 ng/mL. We further plotted the ROC of individual or combined indices in different subgroups and calculated the AUC. We found that the diagnostic efficacy of the combined indices was higher with TPSA >10 ng/mL. CONCLUSION: The combination of TPSA with multiple indicators may improve diagnostic accuracy for PCa.

A Unified Strategy to Fluorinated Nucleoside Analogues Via an Electrophilic Manifold.

Herein, we present a strategy for the preparation of 3'-fluorinated nucleoside analogues via the aminocatalytic, electrophilic fluorination of readily accessible and bench-stable 2'-ketonucleosides. Initially developed to facilitate the manufacture of 3'-fluoroguanosine (3'-FG)─a substructure of anticancer therapeutic MK-1454─this strategy has been extended to the synthesis of a variety of 3'-fluoronucleosides. Finally, we demonstrate the utility of the 2'-ketonucleoside synthon as a platform for further diversification and suggest that this methodology should be broadly applicable to the discovery of novel nucleoside analogues.

Space-Confined Synthesis of Thin Polypyrrole Nanosheets in Layered Bismuth Oxychloride for a Photoresponse Antibacterial within the Near-Infrared Window and Accelerated Wound Healing.

Bacterial infection greatly affects the rate of wound healing. Both photothermal and photodynamic antibacterial therapies activated by near-infrared (NIR) light with semiconductor nanomedicine are two effective approaches to address bacterial infections, but they cannot coexist synergistically to kill bacteria more efficiently because of the limitation of the band structure. Here, inspired by the natural core-shell structure and photosynthesis simultaneously, polypyrrole (PPy) is synthesized in the two-dimensional restricted area of the layered bismuth oxychloride (BiOCl) nanosheets through the in situ ultrasonic recombination method. The atomic-level interface contact and bonding formed in the PPy-BiOCl intercalated nanosheets not only improve the light-to-heat conversion capabilities of PPy but also promote the transmission of PPy photogenerated charge carriers to the BiOCl semiconductor. The nanocomposites take advantage of the deeper tissue penetration under NIR light irradiation and exhibit excellent photothermal and photodynamic synergistic antibacterial activity. In addition, PPy-BiOCl intercalated nanosheets have good biocompatibility and accelerate wound healing through their antimicrobial activity and skin repair function. The space-confined synthesis of thin PPy nanosheets in layered structures offers an efficient NIR photoresponsive nanomedicine for the treatment of pathogen infection, with promising applications in infected wound healing.

[Retracted] The Fanconi anemia pathway sensitizes to DNA alkylating agents by inducing JNK­p53­dependent mitochondrial apoptosis in breast cancer cells.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that one of the fluorescence microscopic images featured in Fig. 4A had previously appeared in a different form (a portion of data in a different orientation) in another article published by the same authors [Yu J, Zhao L, Li Y, Li N, He M, Bai H, Yu Z, Zheng Z, Mi X, Wang E and We M: Silencing of Fanconi anemia complementation group F exhibits potent chemosensitization of mitomycin C activity in breast cancer cells. J Breast Cancer 16: 291­299, 2013]. Furthermore, the data panel shown for the 'MDA­MB­231/untreated' experiment in Fig. 4A in the above paper appeared to be duplicated as the 'MDA­MB­231/MMC + control shRNA' experiment, albeit stained differently. After having received a request from the authors to publish a corrigendum in view of the errors identified in Fig. 4 of the above paper, the Editor of International Journal of Oncology has conducted an independent investigation of the matter and determined that this article should be retracted from the Journal on account of a lack of confidence in the presented data. Upon receiving this decision, the authors were not in agreement that the paper should be retracted. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in International Journal of Oncology 45: 129­138, 2014; DOI: 10.3892/ijo.2014.2400].

Oxetane Promise Delivered: Discovery of Long-Acting IDO1 Inhibitors Suitable for Q3W Oral or Parenteral Dosing.

3,3-Disubstituted oxetanes have been utilized as bioisosteres for gem-dimethyl and cyclobutane functionalities. We report the discovery of a novel class of oxetane indole-amine 2,3-dioxygenase (IDO1) inhibitors suitable for Q3W (once every 3 weeks) oral and parenteral dosing. A diamide class of IDO inhibitors was discovered through an automated ligand identification system (ALIS). Installation of an oxetane and fluorophenyl dramatically improved the potency. Identification of a biaryl moiety as an unconventional amide isostere addressed the metabolic liability of amide hydrolysis. Metabolism identification (Met-ID)-guided target design and the introduction of polarity resulted in the discovery of potent IDO inhibitors with excellent pharmacokinetic (PK) profiles in multiple species. To enable rapid synthesis of the key oxetane intermediate, a novel oxetane ring cyclization was also developed, as well as optimization of a literature route on kg scale. These IDO inhibitors may enable unambiguous proof-of-concept testing for the IDO1 inhibition mechanism for oncology.

Poly(ADP-ribose) polymerase-3 overexpression is associated with poor prognosis in patients with breast cancer following chemotherapy.

Double strand breaks induced by genotoxic agents, if inappropriately repaired, will cause cell death or induce cancer. Poly(ADP-ribose) polymerase-3 (PARP-3) serves a role in double strand break repair, and may be involved in tumorigenesis. To the best of our knowledge, the role of PARP-3 in breast cancer has not yet been examined. In the present study, the expression of PARP-3 was investigated in 493 breast cancer samples and 54 tumor-adjacent control samples using tissue-microarray-based immunohistochemistry. PARP-3 expression was higher in breast cancer samples compared with control samples. PARP-3 overexpression was significantly associated with histological grade II-III (P=0.012). In addition, PARP-3 overexpression was significantly associated with shorter disease-free survival (DFS; P=0.027) time and exhibited a tendency toward shorter overall survival (OS; P=0.183) time in patients with breast cancer compared with patients with lower PARP-3 expression, particularly in BRCA1-positive patients (P=0.004 for disease-free survival and P=0.095 for OS). Multivariate Cox regression analysis indicated that PARP-3 was an independent prognostic factor in patients with breast cancer. Furthermore, it was revealed that PARP-3 overexpression was associated with shorter survival time in patients with cyclophosphamide/doxorubicin or epirubicin/5-fluorouracil (CAF/CEF) chemotherapy compared with low PARP-3 expression, but not in patients with CAF/CEF + docetaxel chemotherapy. The present study suggested that PARP-3 may be used as a biomarker for predicting the clinical outcome of patients receiving chemotherapy, and targeting PARP-3 may be a potential therapeutic strategy for the treatment of breast cancer.

Combined expression of aldehyde dehydrogenase 1A1 and ß-catenin is associated with lymph node metastasis and poor survival in breast cancer patients following cyclophosphamide treatment.

This study investigated the expression of ALDH1A1 and ß-catenin in breast cancer patients, and analyzed the correlation of their combined expression with clinicopathological features, chemotherapeutic responses, and prognosis of breast cancer patients. In total 276 human breast cancer tissues and 80 benign hyperplasia tissues were included. The expression of ALDH1A1 and ß-catenin was examined using tissue microarray-based immunohistochemistry. ROC curve analysis was performed to determine an optimal cut-off score for the expression of ALDH1A1 and ß-catenin, based on the survival status of breast cancer patients. Survival probabilities were estimated by the Kaplan-Meier method. ALDH1A1 expression was higher, but ß-catenin showed no significant difference in breast cancer samples compared to controls. Compared with the membrane expression of ß-catenin [ß-catenin(m)], the cytoplasmic expression of ß-catenin [ß-catenin(c)] occurred significantly more frequently in breast cancer with the high expression of ALDH1A1 [ALDH1A1(high)] than in breast cancer with the low expression of ALDH1A1 [ALDH1A1(low)] (P=0.014). The expression level of ALDH1A was significantly higher in ß-catenin(c) breast cancer than in ß-catenin(m) breast cancer (P=0.020). ALDH1A1(high) expression or ß-catenin(c) expression alone was associated with lymph node metastasis, and worse clinical outcome in breast cancer patients, especially in patients receiving cyclophosphamide treatment. Combined expression of ALDH1A1(high) and ß-catenin(c) was associated with lymph node metastasis, poor outcome, and resistance to cyclophosphamide treatment. ß-catenin may regulate ALDH1A1 expression in a subtype of breast cancer with ALDH1A1(high) and ß-catenin(c) expression. ALDH1A1(high) and ß-catenin

Docetaxel modulates the delayed rectifier potassium current (IK) and ATP-sensitive potassium current (IKATP) in human breast cancer cells.

Ion channel expression and activity may be affected during tumor development and cancer growth. Activation of potassium (K(+)) channels in human breast cancer cells is reported to be involved in cell cycle progression. In this study, we investigated the effects of docetaxel on the delayed rectifier potassium current (I K) and the ATP-sensitive potassium current (I KATP) in two human breast cancer cell lines, MCF-7 and MDA-MB-435S, using the whole-cell patch-clamp technique. Our results show that docetaxel inhibited the I K and I KATP in both cell lines in a dose-dependent manner. Compared with the control at a potential of +60 mV, treatment with docetaxel at doses of 0.1, 1, 5, and 10 µM significantly decreased the I K in MCF-7 cells by 16.1 ± 3.5, 30.2 ± 5.2, 42.5 ± 4.3, and 46.4 ± 9% (n = 5, P < 0.05), respectively and also decreased the I KATP at +50 mV. Similar results were observed in MDA-MB-435S cells. The G-V curves showed no significant changes after treatment of either MCF-7 or MDA-MB-435S cells with 10 µM docetaxel. The datas indicate that the possible mechanisms of I K and I KATP inhibition by docetaxel may be responsible for its effect on the proliferation of human breast cancer cells.

DNA methyltransferase 1/3a overexpression in sporadic breast cancer is associated with reduced expression of estrogen receptor-alpha/breast cancer susceptibility gene 1 and poor prognosis.

DNA methyltransferases (DNMTs), including DNMT1, 3a, and 3b, play an important role in the progression of many malignant tumors. However, it remains unclear whether expression of DNMTs is associated with the development of breast cancer. This study aimed to explore the clinical significance of DNMT proteins in sporadic breast cancer. We investigated the expression of DNMT1, 3a, and 3b in 256 breast cancer and 36 breast fibroadenoma, using immunohistochemistry. The expression of DNMT1 and 3a was significantly higher in breast cancer than in fibroadenoma. In breast cancer, the expression of DNMT1 was significantly correlated with lymph node metastasis (P = 0.020), and the expression of DNMT3a and 3b was significantly correlated with advanced clinical stages (P = 0.046 and 0.012, respectively). Overexpression of DNMT1/3a was correlated with promoter hypermethylation and reduced expression of ERα and BRCA1. The expression levels of DNMT1 or DNMT3a were associated with a significantly shorter DFS or OS in a subgroup of breast cancer patients (patients with the age ≤50 years old, ERα-negative status, or HER2-postive status). The expression of DNMT1 or a combined expression of DNMT1 and 3a was associated with poor prognosis in patients who received chemotherapy and endocrine therapy, but not in patients who received chemotherapy alone. These findings suggest that DNMT1 and 3a may be involved in the progression and prognosis of sporadic breast cancer.

BRCA1 promoter hypermethylation in sporadic epithelial ovarian carcinoma: Association with low expression of BRCA1, improved survival and co-expression of DNA methyltransferases.

The breast cancer susceptibility gene 1 (BRCA1) inactivation in sporadic epithelial ovarian carcinoma (EOC) is common and low BRCA1 expression is associated with promoter hypermethylation. The clinical validation of BRCA1 methylation as a prognostic marker in EOC remains unresolved. The aim of the present study was to determine the aberrant promoter methylation of BRCA1 in benign and malignant ovarian tumor tissues, to establish the association with the clinicopathological significance and the prognostic value. Additionally, the contribution of DNA methyltransferase (DNMT) expression to BRCA1 promoter hypermethylation was determined. The rate of BRCA1 methylation was observed to be 35.2% (50/142) in the EOCs; however, no methylation (0/32) was observed in the benign tumors. BRCA1 methylation was significantly associated with the downregulation of BRCA1 expression (P<0.001) and the frequency of BRCA1 methylation was greater in the carcinomas of patients whose tumor was bilateral than that of patients with a unilateral carcinoma (P=0.015). BRCA1 methylation was significantly associated with the preoperative serum carbohydrate antigen-125 level (P=0.013), improved overall survival (P=0.005) and disease-free survival (P=0.007). In addition, a significant correlation was observed between the co-expression of DNMTs and the methylation status of BRCA1. Thus, the present study provided support for BRCA1 promoter hypermethylation as a prognostic marker for survival in sporadic EOC, and co-expression of DNMTs was observed to contribute to BRCA1 promoter hypermethylation.

The Fanconi anemia pathway sensitizes to DNA alkylating agents by inducing JNK-p53-dependent mitochondrial apoptosis in breast cancer cells.

The Fanconi anemia/BRCA (FA/BRCA) DNA damage repair pathway plays a pivotal role in the cellular response to DNA alkylating agents and greatly influences drug response in cancer treatment. However, the molecular mechanisms underlying the FA/BRCA pathway reversed resistance have received limited attention. In the present study, we investigated the effect of Fanconi anemia complementation group F protein (FANCF), a critical factor of the FA/BRCA pathway, on cancer cell apoptosis induced by DNA alkylating agents such as mitomycin c (MMC). We found that FANCF shRNA potentiated MMC-induced cytotoxicity and apoptosis in MCF-7 and MDA-MB-231 breast cancer cells. At a mechanistic level, FANCF shRNA downregulated the anti-apoptotic protein Bcl-2 and upregulated the pro-apoptotic protein Bax, accompanied by release of cyt-c and smac into the cytosol in MMC-treated cells. Furthermore, activation of caspase-3 and -9, other than caspase-8, cleavage of poly(ADP ribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated that involvement of the mitochondrial apoptotic pathway in FANCF silencing of MMC-treated breast cancer cells. A decrease in IAP family proteins XIAP and survivin were also observed following FANCF silencing in MMC-treated breast cancer cells. Notably, FANCF shRNA was able to increase p53 levels through activation of the JNK pathway in MMC-treated breast cancer cells. Furthermore, p53 inhibition using pifithrin-α abolished the induction of caspase-3 and PARP by FANCF shRNA and MMC, indicating that MMC-induced apoptosis is substantially enhanced by FANCF shRNA via p53-dependent mechanisms. To our knowledge, we provide new evidence for the potential application of FANCF as a chemosensitizer in breast cancer therapy.

MiR-487a resensitizes mitoxantrone (MX)-resistant breast cancer cells (MCF-7/MX) to MX by targeting breast cancer resistance protein (BCRP/ABCG2).

Breast cancer resistance protein (BCRP/ABCG2) specifically transports various chemotherapeutic agents and is involved in the development of multidrug resistance (MDR) in cancer cells. MicroRNAs (miRNAs) can play an important role in modulating the sensitivity of cancer cells to chemotherapeutic agents. Therefore, after confirming that BCRP was increased in the mitoxantrone (MX)-resistant MCF-7 breast cancer cell line MCF-7/MX compared with its parental sensitive MCF-7 cell line, we aimed to explore the miRNAs that regulate BCRP expression and sensitize breast cancer cells to chemotherapeutic agents. In the present study, bioinformatic analysis indicated that miR-487a was one of the miRNAs that could bind to the 3' untranslated region (3'UTR) of BCRP. Quantitative RT-PCR (qRT-PCR) analysis demonstrated that the expression of miR-487a was reduced in MCF-7/MX cells, and a luciferase reporter assay demonstrated that miR-487a directly bound to the 3'UTR of BCRP. Moreover, ectopic miR-487a down-regulated BCRP expression at the mRNA and protein levels, increasing the intracellular accumulation and cytotoxicity of MX in resistant MCF-7/MX breast cancer cells. Meanwhile, inhibition of miR-487a increased BCRP expression at the mRNA and protein levels and induced MX resistance in sensitive MCF-7 breast cancer cells. Furthermore, the reduced expression of BCRP and increased antitumor effects of MX were also detected in MCF-7/MX xenograft tumors treated with the miR-487a agmir. Thus, our results suggested that miR-487a can directly regulate BCRP expression and reverse chemotherapeutic drug resistance in a subset of breast cancers.

Clinicopathological significance and prognostic value of DNA methyltransferase 1, 3a, and 3b expressions in sporadic epithelial ovarian cancer.

Altered DNA methylation of tumor suppressor gene promoters plays a role in human carcinogenesis and DNA methyltransferases (DNMTs) are responsible for it. This study aimed to determine aberrant expression of DNMT1, DNMT3a, and DNMT3b in benign and malignant ovarian tumor tissues for their association with clinicopathological significance and prognostic value. A total of 142 ovarian cancers and 44 benign ovarian tumors were recruited for immunohistochemical analysis of their expression. The data showed that expression of DNMT1, DNMT3a, and DNMT3b was observed in 76 (53.5%), 92 (64.8%) and 79 (55.6%) of 142 cases of ovarian cancer tissues, respectively. Of the serious tumors, DNMT3a protein expression was significantly higher than that in benign tumor samples (P = 0.001); DNMT3b was marginally significant down regulated in ovarian cancers compared to that of the benign tumors (P = 0.054); DNMT1 expression has no statistical difference between ovarian cancers and benign tumor tissues (P = 0.837). Of the mucious tumors, the expression of DNMT3a, DNMT3b, and DNMT1 was not different between malignant and benign tumors. Moreover, DNMT1 expression was associated with DNMT3b expression (P = 0.020, r = 0.195). DNMT1 expression was associated with age of the patients, menopause status, and tumor localization, while DNMT3a expression was associated with histological types and serum CA125 levels and DNMT3b expression was associated with lymph node metastasis. In addition, patients with DNMT1 or DNMT3b expression had a trend of better survival than those with negative expression. Co-expression of DNMT1 and DNMT3b was significantly associated with better overall survival (P = 0.014). The data from this study provided the first evidence for differential expression of DNMTs proteins in ovarian cancer tissues and their associations with clinicopathological and survival data in sporadic ovarian cancer patients.

An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction.

An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an alpha,beta-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported. Highly efficient Cu(I)-mediated ether formation was used to install the ether side chain, and selective debenzylation conditions were developed to remove the benzyl protecting groups on the phenols.

[The clinical significance of thymosin ß4 expression in human non-small cell lung cancer].

BACKGROUND: To study the relationship between human thymosin ß4 (Tß4 )expression and biological factors regarding invasion, metastasis and prognosis of human non-small cell lung cancer (NSCLC). METHODS: Tß4 expression was detected in samples of 76 paraffin-embedded specimens with the neighboring noncancerous tissue using anti-Tß4 IgY antibody (primary antibody) by immunohistochemical staining. The relationship between Tß4 expression and the clinicopthological factors was analyzed by Chi-square test, multivariate analysis and Kaplan-Meier method. RESULTS: In immunoreactive cells, staining was mainly located in cytoplasma. Human Tß4 expression was high positive in lung cancer tissues (76.3%, 58/76) while low positive in normal lung tissues. Tß4 expression was positively associated with TNM stage (r=0.239, P=0.032), lymphatic metastasis (r=0.243, P=0.029) and venous metastasis (r=0.224, P=0.045).A negative correlation was found between Tß4 expression and cell differentiation (r=-0.368, P=0.002). Patients with high Tß4 expression had a worse prognosis than those with low Tß4 expression (P < 0.05) CONCLUSIONS: Lung cancer has overexpression of Tß4, which is closely related to TNM stages, cell differentiation, metastasis of the cancer and prognosis of the patients with lung cancer. Detection of Tß4 expression in lung cancer tissues might be helpful to predict prognosis of patients with lung cancer.

Ullmann diaryl ether synthesis: rate acceleration by 2,2,6,6-tetramethylheptane-3,5-dione.

[reaction: see text]. In the copper salt catalyzed ether formation from aryl bromides or iodides and phenols, 2,2,6,6-tetramethylheptane-3,5-dione (TMHD) was found to greatly accelerate the ordinarily difficult reaction, making it occur under more moderate temperatures and reaction times. A series of aryl halides and phenols were shown to form ethers in NMP as the solvent, cesium carbonate as the base, and CuCl and TMHD as the catalysts. The reaction was shown to tolerate electron-rich aryl bromides and electron-neutral phenols.