Radical C-Glycosylation Using Photoexcitable Unprotected Glycosyl Borate.

We have developed radical C-glycosylation using photoexcitable unprotected glycosyl borate. The direct excitation of glycosyl borate under visible light irradiation enabled the generation of anomeric radical without any photoredox catalysts. The in situ generated anomeric radical was applicable to the radical addition such as Giese-type addition and Minisci-type reaction to introduce alkyl and heteroaryl groups at the anomeric position. In addition, the radical-radical coupling between the glycosyl borate and acyl imidazolide provided unprotected acyl C-glycosides.

Exploring predictive molecules of acute adverse events in response to volumetric­modulated arc therapy for prostate cancer using urinary metabolites.

Volumetric-modulated arc therapy (VMAT) is a radiotherapy technique used to treat patients with localized prostate cancer, which is frequently associated with acute adverse events (AEs) that can affect subsequent treatment. Notably, the radiation dose of VMAT can be tailored to each patient. In the present study, a retrospective analysis was performed to predict acute AEs in response to a therapeutic high radiation dose rate based on urinary metabolomic molecules, which are easily collected as noninvasive biosamples. Urine samples from 11 patients with prostate cancer who were treated with VMAT (76 Gy/38 fractions) were collected. The study found that seven patients (~64%) exhibited genitourinary toxicity (Grade 1) and four patients had no AEs. A total of 630 urinary metabolites were then analyzed using a mass spectrometer (QTRAP6500+; AB SCIEX), and 234 relevant molecules for biological and clinical applications were extracted from the absolute quantified metabolite values using the MetaboINDICATOR tool. In the Grade 1 acute AE group, there was a significant negative correlation (rs=-0.297, P<0.05) between the number of VMAT fractions and total phospholipase A2 activity in the urine. Additionally, patients with Grade 1 AEs exhibited a decrease in PC aa C40:1, a phospholipid. These findings suggested that specific lipids found in urinary metabolites may serve as predictive biomarkers for acute AEs in response to external radiotherapy.

Case Reports of TFE3-Rearranged Renal Cell Carcinoma: FDG-PET Uptake Might Help Diagnosis.

Translocation and transcription factor E3 (TFE3)-rearranged renal cell carcinoma (RCC) is a rare subtype of RCCs characterised by the fusion of the TFE3 transcription factor genes on chromosome Xp11.2 with one of the multiple genes. TFE3-rearranged RCC occurs mainly in children and adolescents, although middle-aged cases are also observed. As computed tomography (CT)/magnetic resonance imaging (MRI) findings of TFE3-rearranged RCC overlap with those of other RCCs, differential diagnosis is often challenging. In the present case reports, we highlighted the features of the fluorine-18-labelled fluorodeoxyglucose positron emission tomography with CT (FDG PET-CT) in TFE3-rearranged RCCs. Due to the rarity of the disease, FDG PET-CT features of TFE3-rearranged RCC have not yet been reported. In our cases, FDG PET-CT showed high standardised uptake values (SUVmax) of 7.14 and 6.25 for primary tumours. This might imply that TFE3-rearranged RCC has high malignant potential. This is conceivable when the molecular background of the disease is considered in terms of glucose metabolism. Our cases suggest that a high SUVmax of the primary tumour is a clinical characteristic of TFE3-rearranged RCCs.

Generation of germ cell-deficient pigs by NANOS3 knockout.

NANOS3 is an evolutionarily conserved gene expressed in primordial germ cells that is important for germ cell development. Germ cell deletion by NANOS3 knockout has been reported in several mammalian species, but its function in pigs is unclear. In the present study, we investigated the germline effects of NANOS3 knockout in pigs using CRISPR/Cas9. Embryo transfer of CRISPR/Cas9-modified embryos produced ten offspring, of which one showed wild-type NANOS3 alleles, eight had two mutant NANOS3 alleles, and the other exhibited mosaicism (four mutant alleles). Histological analysis revealed no germ cells in the testes or ovaries of any of the nine mutant pigs. These results demonstrated that NANOS3 is crucial for porcine germ cell production.

Diagnostic utility of a conventional MRI-based analysis and texture analysis for discriminating between ovarian thecoma-fibroma groups and ovarian granulosa cell tumors.

OBJECTIVE: To evaluate the diagnostic utility of conventional magnetic resonance imaging (MRI)-based characteristics and a texture analysis (TA) for discriminating between ovarian thecoma-fibroma groups (OTFGs) and ovarian granulosa cell tumors (OGCTs). METHODS: This retrospective multicenter study enrolled 52 patients with 32 OGCTs and 21 OTFGs, which were dissected and pathologically diagnosed between January 2008 and December 2019. MRI-based features (MBFs) and texture features (TFs) were evaluated and compared between OTFGs and OGCTs. A least absolute shrinkage and selection operator (LASSO) regression analysis was performed to select features and construct the discriminating model. ROC analyses were conducted on MBFs, TFs, and their combination to discriminate between the two diseases. RESULTS: We selected 3 features with the highest absolute value of the LASSO regression coefficient for each model: the apparent diffusion coefficient (ADC), peripheral cystic area, and contrast enhancement in the venous phase (VCE) for the MRI-based model; the 10th percentile, difference variance, and maximal correlation coefficient for the TA-based model; and ADC, VCE, and the difference variance for the combination model. The areas under the curves of the constructed models were 0.938, 0.817, and 0.941, respectively. The diagnostic performance of the MRI-based and combination models was similar (p = 0.38), but significantly better than that of the TA-based model (p < 0.05). CONCLUSIONS: The conventional MRI-based analysis has potential as a method to differentiate OTFGs from OGCTs. TA did not appear to be of any additional benefit. Further studies are needed on the use of these methods for a preoperative differential diagnosis of these two diseases.

Binaphthyl-Bridged Pyrenophanes: Intense Circularly Polarized Luminescence Based on a D2 Symmetry Strategy.

A series of D2 -symmetric macrocycles composed of alternately linked pyrene and binaphthyl moieties (binaphthyl-bridged pyrenophanes) have been synthesized. Among them, a pyrenophane possessing ether linkers at the 2,7-positions of the pyrenes exhibited intense circularly polarized luminescence (CPL) with a |glum | value of 0.053. This value is by far the highest for excimers and was not sensitive to temperature, solvent, or concentration. The CPL originated from a twisting pyrene excimer, with the (R)-binaphthyl moieties producing a left-handed twist excimer, which exhibited (-)-CPL. The electric and magnetic transition dipole moments are perfectly parallel, which is the best relationship for strong CPL.

Chiral exciplex dyes showing circularly polarized luminescence: extension of the excimer chirality rule.

A series of axially chiral binaphthyls and quaternaphthyls possessing two kinds of aromatic fluorophores, such as pyrenyl, perylenyl, and 4-(dimethylamino)phenyl groups, arranged alternately were synthesized by a divergent method. In the excited state, the fluorophores selectively formed a unidirectionally twisted exciplex (excited heterodimer) by a cumulative steric effect and exhibited circularly polarized luminescence (CPL). They are the first examples of a monomolecular exciplex CPL dye. This versatile method for producing exciplex CPL dyes also improved fluorescence intensity, and the CPL properties were not very sensitive to the solvent or to the temperature owing to the conformationally rigid exciplex. This systematic study allowed us to confirm that the excimer chirality rule can be applied to the exciplex dyes: left- and right-handed exciplexes with a twist angle of less than 90° exhibit (-)- and (+)-CPL, respectively.

Photocatalytic Activation of Elemental Sulfur Enables a Chemoselective Three-Component Thioesterification.

A mild and chemoselective three-component thioesterification using olefins, α-ketoacids, and elemental sulfur has been developed. The photocatalytic activation of elemental sulfur, a cheap and abundant sulfur source, enables the rapid installation of a sulfur atom into molecules, reactions that ordinarily would require the use of reactive and malodorous sulfur-containing compounds such as thiols and thioacids. This novel reaction is characterized by high yields and a broad substrate scope, which enables the introduction of thioester moieties into complex molecules including a steroid, a peptide, and a nonprotected glycoside. Mechanistic studies indicated that the success of this transformation depends on the multiple roles played by the elemental sulfur, including those of a sulfurizing agent, a terminal oxidant, and a HAT mediator.

Mild and Chemoselective Thioacylation of Amines Enabled by the Nucleophilic Activation of Elemental Sulfur.

A mild and chemoselective method for the thioacylation of amines using α-keto acids and elemental sulfur has been developed. The key to the success of this transformation is the nucleophilic activation of elemental sulfur by thiols such as 1-dodecanethiol. A variety of functional groups, including unprotected hydroxyl, carboxyl, amide, sulfide, and tertiary amine moieties, are tolerated under the applied reaction conditions. To demonstrate the advantages of this method compared with conventional O-S exchange reactions using Lawesson's reagent or P2S5, thioamide moieties were introduced site-specifically into biologically active compounds.

The thrombopoietin mimetic romiplostim leads to the complete rescue of mice exposed to lethal ionizing radiation.

For the primary treatment of emergency exposure to high-dose radiation, such as in the event of a radiation accident, the top priority is the reconstitution and restoration of haematopoiesis. In most radiation accidents, drug therapy is chosen as the most suitable treatment; the chosen drug should already be approved domestically, stably supplied and regularly stockpiled. In the present study, a single administration of romiplostim (RP), an approved thrombopoietin receptor agonist, produced a 100% survival rate in C57BL/6 J mice exposed to a lethal dose (7 Gy) of 137Cs γ-rays, and all irradiated mice survived for more than 30 days with both 3- and 5-day consecutive administrations. By day 30, the peripheral blood cells, bone marrow cells and haematopoietic progenitor cells of the RP-administered irradiated mice had all recovered to a level that was not significantly different from that in non-irradiated mice. In contrast to myelosuppression, which did not fully recover until day 30, the expression of several bone marrow cell surface antigens recovered sooner, and DNA repair concurrently increased in haematopoietic cells, speeding the resolution of double strand breaks and reducing the rates of apoptosis. These findings suggest that RP may be a clinic-ready countermeasure to treat victims of radiation accidents.

Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells.

Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E-mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell-related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E-mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells.