Synthesizing Chiral Hydrocarbazoles with a Tetrasubstituted Carbon Using Holmium-Catalyzed Enantioselective [4 + 2] Cycloaddition: Mechanistic Insights from Luminescence and DFT Studies.

This study analyzes the feasibility of utilizing the catalytic and enantioselective [4 + 2] cycloaddition of sterically demanding heterocycle-incorporated siloxydienes to yield polycyclic skeletons with a tetrasubstituted carbon. A catalyst derived from lanthanide triflimide enabled the reaction. The mechanistic investigations and transformations of the adducts are also discussed. The proposed approach facilitates the synthesis of intricate polysubstituted skeletons, each with multiple contiguous chiral centers, thereby aiding in the production of diverse hydrocarbazoles for drug discovery purposes.

Aspects of lanthanide complexes for selectivity, intensity and sharpness in luminescence bands from twenty-four praseodymium, europium and gadolinium complexes with differently distorted-hexadentate ligands.

We structurally and spectroscopically investigated a series of praseodymium (Pr) complexes with eight ligands that form helicate molecular structures. The mother ligand skeleton (L) has two bipyridine moieties bridged with ethylenediamine. The bridged skeleton of PrL was changed to diamines 1-methyl-ethylenediamine, trimethylenediamine and 2,2'-dimethyl-trimethylenediamine, and the corresponding ligands were designated as Lme, Lpr and Ldmpr, for each Pr in these complexes upon UV-excitation. The luminescence quantum yields of PrL and PrLpr in the visible and near infrared (NIR) regions indicate that PrL is excited by both the electronic state of the ligand and the ff absorption band, whereas PrLpr is excited through the ligand. The addition of a methyl group to PrL and PrLpr has a different effect on the Pr emission intensity with the intensity of PrLme decreasing more than that of PrL and PrLdmpr and increasing more than that of PrLpr. Thus, the coordination of Pr and the increased rigidity of the ligand upon methylation enhance luminescence. The azomethine moieties on Lme, Lpr and Ldmpr were reduced and formed the corresponding PrLH, PrLmeH, PrLprH and PrLdmprH complexes. The luminescence of the non-methylated series is due to transitions related to the 1D2 level and thus the methylated series luminesces due to high energy levels such as 3PJ arising from the shortened π electronic systems. We also discuss the strong red emission of a series of Eu complexes with eight ligands from the viewpoint of their molecular structures and luminescence efficiencies and evaluate the Judd-Ofelt parameters from the luminescence spectra of Eu complexes.

Soft Crystals: Flexible Response Systems with High Structural Order.

A new material concept of soft crystals is proposed. Soft crystals respond to gentle stimuli such as vapor exposure and rubbing but maintain their structural order and exhibit remarkable visual changes in their shape, color, and luminescence. Various interesting examples of soft crystals are introduced in the article. By exploring the interesting formation and phase-transition phenomena of soft crystals through interdisciplinary collaboration, new materials having both the characteristics of ordered hard crystals and those of flexible soft matter are expected.

Multicolor upconversion luminescence of dye-coordinated Er3+ at the interface of Er2O3 and CaF2 nanoparticles.

Multicolor upconversion luminescence of Er3+ was successfully enhanced by optimizing the interface in dye-coordinated nanoparticles with a core/shell structure. Red and green upconversion emissions of Er3+ were obtained at the interface of oxide nanoparticles via the intramolecular energy transfer from the coordinating squaraine dye with high light-absorption ability, which was more efficient than emissions through the energy transfer from metal ions such as Yb3+. Additionally, CaF2 nanoparticles as a core material minimized the energy loss with nonradiative downward relaxations in Er3+, resulting in the observation of unusual blue upconversion emissions from the upper energy level of Er3+ by nonlaser excitation using a continuous-wave (CW) Xe lamp at an excitation power of 1.2 mW/cm2.

Slow Magnetic Relaxation in a Palladium-Gadolinium Complex Induced by Electron Density Donation from the Palladium Ion.

Incorporating palladium in the first coordination sphere of acetato-bridged lanthanoid complexes, [Pd2 Ln2 (H2 O)2 (AcO)10 ]⋅2 AcOH (Ln=Gd (1), Y (2), Gd0.4 Y1.6 (3), Eu (4)), led to significant bonding interactions between the palladium and the lanthanoid ions, which were demonstrated by experimental and theoretical methods. We found that electron density was donated from the d8 Pd2+ ion to Gd3+ ion in 1 and 3, leading to the observed slow magnetic relaxation by using local orbital locator (LOL) and X-ray absorption near-edge structure (XANES) analysis. Field-induced dual slow magnetic relaxation was observed for 1 up to 20 K. Complex 3 and frozen aqueous and acetonitrile solutions of 1 showed only one relaxation peak, which confirms the role of intermolecular dipolar interactions in slowing the magnetic relaxation of 1. The slow magnetic relaxation occurred through a combination of Orbach and Direct processes with the highest pre-exponential factor (τo =0.06 s) reported so far for a gadolinium complex exhibiting slow magnetic relaxation. The results revealed that transition metal-lanthanoid (TM-Ln) axial interactions indeed could lead to new physical properties by affecting both the electronic and magnetic states of the compounds.

Computational study on the luminescence quantum yields of terbium complexes with 2,2'-bipyridine derivative ligands.

Terbium complexes are widely used as luminescent materials because of their bright green emission and sharp emission spectra and the independence of their emission wavelengths from the surrounding environment. The luminescence quantum yield (LQY), however, heavily depends on the surroundings, and an appropriate ligand design is indispensable. In this study, we focus on a Tb3+ complex coordinated by a 2,2'-bipyridine derivative ligand (L1), whose LQY is almost zero at room temperature [M. Hasegawa et al., New. J. Chem. 2014, 38, 1225] and compare it with a Tb3+ complex with a bipyridine ligand, which is widely used as a photo-antenna ligand. To discuss the LQYs of the complexes, we computed their energy profiles, i.e. the energetic and structural changes during the emission and quenching processes. The low LQY of the TbL1(NO3)2 complex was explained by the stability of the minimum energy crossing point between the potential energy surfaces of the ligand-centered lowest triplet state and the ground state, which was induced by the out-of-plane bending of the azomethine moiety. The most efficient way to improve the LQY by modification of the ligand is to replace the azomethine moieties by other functional groups, such as ether or reduced azomethine groups, whose minimum energy crossing points are unstable enough to reduce the rate of the quenching processes.

The first high frequency of recombination-like conjugal transfer from an integrated origin of transfer sequence in Bacillus subtilis 168.

Bacillus subtilis 168 was developed as a genome vector to manipulate large DNA fragments. The system is based on the inherent natural transformation (TF) activity. However, DNA size transferred by TF is limited up to approximately 100 kb. A conjugal transfer system capable of transferring DNA fragments considerably larger than those transferred by TF was developed. A well-defined oriT110 sequence and a cognate relaxase gene from the pUB110 plasmid were inserted into the xkdE gene of the B. subtilis genome. Transfer of antibiotic resistance markers distant from the oriT110 locus to the recipient B. subtilis occurred only in the presence of pLS20, a helper plasmid that provides a type IV secretion system. Marker transmission was consistent with the orientation of oriT110 and required a recA-proficient recipient. The first conjugal transfer system of genomic DNA should provide a valuable alternative genetic tool for editing the B. subtilis genome.

Impact of pectoral nerve block on postoperative pain and quality of recovery in patients undergoing breast cancer surgery: A randomised controlled trial.

BACKGROUND: In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery. The effect of PECS block on quality of recovery (QoR) after breast cancer surgery has not been evaluated. OBJECTIVES: To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery. DESIGN: Randomised controlled study. SETTING: A tertiary hospital. PATIENTS: Sixty women undergoing breast cancer surgery between April 2014 and February 2015. INTERVENTIONS: The patients were randomised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a saline mock block (control group). The patients answered a 40-item QoR questionnaire (QoR-40) before and 1 day after breast cancer surgery. MAIN OUTCOME MEASURES: Numeric Rating Scale score for postoperative pain, requirement for intra-operative propofol and remifentanil, and QoR-40 score on postoperative day 1. RESULTS: PECS block combined with propofol-remifentanil anaesthesia significantly improved the median [interquartile range] pain score at 6 h postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P = 0.018]. PECS block also reduced propofol mean (± SD) estimated target blood concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group 2.65 (± 0.52) vs. Control group 3.08 (± 0.41) µg ml; P < 0.001) but not remifentanil consumption (PECS group 10.5 (± 4.28) vs. Control group 10.4 (± 4.68) µg kg h; P = 0.95). PECS block did not improve the QoR-40 score on postoperative day 1 (PECS group 182 [176 to 189] vs. Control group 174.5 [157.75 to 175]). CONCLUSION: In patients undergoing breast cancer surgery, PECS block combined with general anaesthesia reduced the requirement for propofol but not that for remifentanil, due to the inability of the PECS block to reach the internal mammary area. Further, PECS block improved postoperative pain but not the postoperative QoR-40 score due to the factors that cannot be measured by analgesia immediately after surgery, such as rebound pain. TRIAL REGISTRATION: This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013435).

The Enhanced Intramolecular Energy Transfer and Strengthened ff Luminescence of a Stable Helical Eu Complex in Ionic Liquids.

The luminescence of a Eu complex (EuL) is enhanced by stabilization of the coordination structure in highly viscous ionic liquids. The EuL was found to maintain a stable single helical structure both in organic solvents and in the ionic liquids [BMIM][PF6] and [EMIM][PF6]. A colorless solution of EuL dissolved in [BMIM][PF6] exhibits bright red luminescence with a quantum yield of 32.3%, a value that is much higher than that in acetonitrile (12%). Estimated rate constants for the energy relaxation pathway indicate that the energy transfer efficiency is enhanced in [BMIM][PF6] as a result of the suppression of molecular fluctuations in the ligands. Additionally, a highly luminescent helical structure is preserved in [EMIM][PF6] up to 120 °C.

[A Case of Metachronal Phyllodes Tumors That Presented Bilaterally in the Breast].

A 33-year-old woman underwent resection of a right breast mass, which was diagnosed as a fibroadenoma 15 years ago. Ten years later, a right breast mass appeared again, and it was diagnosed as a fibroadenoma based on core needle biopsy. After observation for a while, the mass increased in size, and she underwent resection of the tumor, which was diagnosed as a borderline-malignant phyllodes tumor. A mass appeared again in the right breast and rapidly expanded. A malignant phyllodes tumor was suspected, and right mastectomy was performed. The pathological diagnosis revealed a benign phyllodes tumor. Four years ago, a left breast mass was also detected. Because the mass was suspected to be a fibroadenoma, it has been observed for a few years. The mass has increased in size since 1 year ago, and another mass emerged 2 months ago. Core needle biopsy of the 2 masses revealed that both were phyllodes tumors. She underwent left mastectomy, and the pathological examination revealed that both masses were benign phyllodes tumors. We report this rare case of metachronal phyllodes tumors that presented bilaterally.

[A Case of Breast Cancer with Metastatic Nodules in Additionally Resected Specimens].

A 68-year-old woman who had leftbreastcancer (cT2N0M0, cStage ⅡA)underwentbreast -conserving therapy and sentinel lymph node biopsy. Pathological diagnosis of the resected specimen revealed a 60mm cancer lesion including a 50 mm invasive ductal carcinoma with surrounding ductal carcinoma in situ, although the pre-operative MRI suggested a 30mm invasive cancer. The surgical margin was positive with the exposure of ductal carcinoma in situ. Additional resection was performed with a resection margin of 20mm from the head-side stump of the previous surgery. Pathological diagnosis of the additionally resected specimen revealed a 6mm invasive carcinoma with its exposure on the surface of the specimen around the new surgical stump distant from the initial surgical margin, where no remnant cancer was noted. She underwent left mastectomy. Pathological diagnosis further revealed 7mm and 2mm invasive carcinomas in the remnant breast. The preoperative imaging was reviewed retrospectively, and it was found that identifying the nodules in the remnant breast was quite difficult based on the images, including MRI. We report a case of breast cancer with metastatic nodules in additionally resected specimens.

Multiple Magnetic Relaxation Pathways and Dual-Emission Modulated by a Heterometallic Tb-Pt Bonding Environment.

A heterometallic Tb-Pt complex, [Tb2 Pt3 (SAc)12 (H2 O)2 ] (SAc=thioacetate), was synthesized. Dual emission was modulated by the presence of a heterometallic Tb-Pt bonding environment. The heterometallic Tb-Pt bond lowers the symmetry of the Tb ion and enhanced the emission efficiency. In addition, the Tb-Pt complex shows field-induced multiple magnetic relaxation pathways. Furthermore, it served as an antenna for the observed dual emission. In other words, the heterometallic Tb-Pt bond has a significant effect on the luminescence and magnetic properties of the complex.

[Clinical Experience of a Primary Accessory Breast Cancer Patient].

A 59-year-old woman attended a previous hospital complaining of a nodule of the right axilla. Although ultrasonography had shown no evidenceof malignancy, a growth of thenodulewas found on follow-up. Excisional biopsy revealed a primary accessory breast cancer. Because the resected margins were involved, she was referred to our hospital for additional treatment. Based on imaging, both bilateral mammary glands and axillary lymph nodes were reported normal, and distant metastasis was not observed. We performed additional resection of the right axillary tissue around the biopsy site and the right axillary lymph nodedisse ction. Histo-pathological examination revealed the residual invasive ductal carcinoma in the resected specimen. Both the new surgical margins and the lymph nodes were free of disease. Accessory breast cancer is relatively rare, with the incidence being less than 1% of all breast cancers. It is most frequent in the axillary region. Local extensive resection with sufficient surgical margin and axillary lymph node dissection are generally required. This case report presents our clinical experience of accessory breast cancer with some discussion of the literature.

High levels of sphingolipids in human breast cancer.

BACKGROUND: Sphingolipids, including sphingosine-1-phosphate (S1P) and ceramide, have emerged as key regulatory molecules that control various aspects of cell growth and proliferation in cancer. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients have yet to be determined. The aims of this study were to determine the levels of sphingolipids including S1P, ceramides, and other sphingolipids, in breast cancer and normal breast tissue and to compare the difference in levels of each sphingolipid between the two tissues. MATERIALS AND METHODS: Tumor and noncancerous breast tissue were obtained from 12 patients with breast cancer. Sphingolipids including S1P, ceramides, and their metabolites of sphingosine, sphingomyelin, and monohexosylceramide were measured by liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: The levels of S1P, ceramides, and other sphingolipids in the tumor were significantly higher than those in normal breast tissue. There was a relatively strong correlation in the levels of S1P between the tumor and those of normal breast tissue from the same person. On the other hand, there was no correlation in the levels of most of the ceramide species between the tumor and those of normal breast tissue from the same person. CONCLUSIONS: To our knowledge, this is the first study to reveal that levels of sphingolipids in cancer tissue are generally higher than those of normal breast tissue in patients with breast cancer. The correlation of S1P levels in these tissues implicates the role of S1P in interaction between cancer and the tumor microenvironment.

[A Case of Minimally Invasive Apocrine Carcinoma Derived from Ductal Adenoma].

A 63-year-old woman was found to have a mass in her right breast and visited our hospital to undergo a detailed examination. A histopathological examination by using ultrasound-guided core needle biopsy revealed ductal carcinoma in situ. A partial mastectomy with sentinel lymph node biopsy was performed for the cancer of the right breast. The postoperative histopathological examination indicated apocrine carcinoma with a predominantly intraductal component without lymph node metastasis. The discrimination between ductal adenoma and apocrine carcinoma sometimes becomes a problem in making decisions about treatment. We need to take care when making a diagnosis.

[Study of Breast Cancer Patients Diagnosed Preoperatively with Ductal Carcinoma In Situ].

Although ductal carcinoma in situ(DCIS)is generally cured by surgical resection, it has been suggested that resection is over-treatment for some patients with DCIS. The aim of this study was to reconsider operative indications for patients with DCIS by examining clinicopathological features of 23 patients who underwent surgical resection for DCIS in our institute over a single year. Postoperative histological examination revealed that there were Luminal and HER2-positive subtypes, but no triple negative cancers. We found coincidental invasive ductal carcinoma(IDC)in 5 patients, and in all 5 the tumor size exceeded 60 mm. There was no coincidence of IDC in patients with a Ki-67 index ≤5%. Positive surgical margins were observed in 7 patients, all of which were histologically diagnosed as DCIS. Only 1 of the 7 patients underwent additional surgical resection; the 6 remaining patients, including 2 patients who received no treatment, did not undergo additional resection. All patients including those with positive surgical margins have had a 5-year relapse-free survival. Our findings imply that the subgroup of DCIS patients without IDC could be followed up without surgery.

Unrestricted modification search reveals lysine methylation as major modification induced by tissue formalin fixation and paraffin embedding.

Formalin-fixed paraffin-embedded (FFPE) tissue is considered as an appropriate alternative to frozen/fresh tissue for proteomic analysis. Here we study formalin-induced alternations on a proteome-wide level. We compared LC-MS/MS data of FFPE and frozen human kidney tissues by two methods. First, clustering analysis revealed that the biological variation is higher than the variation introduced by the two sample processing techniques and clusters formed in accordance with the biological tissue origin and not with the sample preservation method. Second, we combined open modification search and spectral counting to find modifications that are more abundant in FFPE samples compared to frozen samples. This analysis revealed lysine methylation (+14 Da) as the most frequent modification induced by FFPE preservation. We also detected a slight increase in methylene (+12 Da) and methylol (+30 Da) adducts as well as a putative modification of +58 Da, but they contribute less to the overall modification count. Subsequent SEQUEST analysis and X!Tandem searches of different datasets confirmed these trends. However, the modifications due to FFPE sample processing are a minor disturbance affecting 2-6% of all peptide-spectrum matches and the peptides lists identified in FFPE and frozen tissues are still highly similar.

[Locally Advanced Breast Cancer Treated with Halsted's Operation Because of Drug-Induced Lung Injury Caused by Neoadjuvant Chemotherapy--A Case Report].

A 64-year-old woman discovered a mass in her left breast and visited our hospital. A thorough examination resulted in a diagnosis of left, locally advanced breast cancer (cT4bN3, M0, cStage Ⅲc) with muscle invasion and Level Ⅲ lymph node metastases. Because of drug-induced lung disease following 4 courses of adriamycin and cyclophosphamide, the chemotherapy had to be stopped. Halsted's operation and postoperative radiotherapy (50 Gy) were performed. The patient was alive with no evidence of recurrence 9 months after surgery. Although multidisciplinary therapy is recommended in locally advanced breast cancer, chemotherapy sometimes cannot be performed due to factors such as age and physical status. Halsted's operation could be considered as a treatment of choice in patients with locally advanced breast cancer. It is important to choose the treatment strategy based on the condition of the patient.

Control of the single-molecule magnet behavior of lanthanide-diarylethene photochromic assemblies by irradiation with light.

Lanthanide-based extended coordination frameworks showing photocontrolled single-molecule magnet (SMM) behavior were prepared by combining highly anisotropic Dy(III) and Ho(III) ions with the carboxylato-functionalized photochromic molecule 1,2-bis(5-carboxyl-2-methyl-3-thienyl)perfluorocyclopentene (H2 dae), which acts as a bridging ligand. As a result, two new compounds of the general formula [{Ln(III) 2 (dae)3 (DMSO)3 (MeOH)}⋅10 MeOH]n (M=Dy for 1 a and Ho for 2) and two additional pseudo-polymorphs [{Dy(III) 2 (dae)3 (DMSO)3 (H2 O)}⋅x MeOH]n (1 b) and [{Dy(III) 2 (dae)3 (DMSO)3 (DMSO)}⋅x MeOH]n (1 c) were obtained. All four compounds have 2D coordination-layer topologies, in which carboxylate-bridged Ln2 units are linked together by dae(2-) anions into grid-like frameworks. All four compounds exhibited a strong reversible photochromic response to UV/Vis light. Moreover, both 1 a and 2 show field-induced SMM behavior. The slow magnetic relaxation of 1 a is influenced by the photoisomerization reaction leading to the observation of the cross-effect: photocontrolled SMM behavior.

[A case of a large liposarcoma of the chest].

A49 -year-old woman with a growing tumor of the left anterior chest wall was admitted to our hospital. This patient was diagnosed with a malignant well-differentiated tumor by needle biopsy and underwent surgery involving wide resection of the tumor, associated excision of the major pectoralis muscle, and part of the mammary tissue and skin. The tumor measured 14.2×17.8 cm and weighed 1,220 g. Histopathologically, the tumor was confirmed to be a dedifferentiated liposarcoma, and local recurrence and metastasis often occurs in spite of complete surgical resection. However, no local recurrence or metastasis has been detected 2 months post-surgery. The main anatomic sites of liposarcomas are the retroperitoneum and lower extremities; only 19 liposarcoma cases of the anterior chest wall have been reported in Japan.