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Introduction: There is evidence for the anticancer effects of l-arginine (arginine); however, the direct effects on cancer cells and mechanism of action are unclear. Methods: Various upper gastrointestinal cancer cells (OE19, OE33, MKN1, MKN45, MKN74, and AGS) were divided into arginine-treated and -untreated groups and cultured using two-dimensional and three-dimensional culture systems. Proliferation was evaluated using the MTT assay to identify arginine-sensitive (OE33) and arginine-insensitive (OE19) strains. Furthermore, the effects of arginine were evaluated using a mitochondrial stress test, cell cycle assay, comprehensive metabolic analysis, and tracer study using (13C6) l-arginine. Results: In OE33 (but not in OE19), the maximal respiratory capacity of mitochondria was lower in the treated group than in the control group. In OE33, S phase cells (determined using BrdU) were significantly reduced. In a comprehensive metabolic analysis of OE33, citrulline/ornithine levels were significantly lower in arginine-treated than in untreated cells. Using OE33, carbamoyl aspartic acid (CAA) levels were significantly lower in arginine-treated than in untreated cells. A tracer study suggested that arginine promotes the urea cycle. Conclusion: Arginine affected urea cycle metabolism, thereby decreasing CAA, which is required for pyrimidine nucleotide synthesis. These findings provide insight into the mechanism underlying the anticancer effects of arginine. [ABSTRACT FROM AUTHOR]

Oleanolic acid is the main component of wine pomace and has anti-caries properties, antitumor effects, anti-obesity effects, and protects hepatic function. However, the majority of pomace has only been used for compost despite the production of thousands of tons per year of wine pomace in Japan. The present study describes the use of low-toxicity solvents called betaine-based deep eutectic solvents (DESs) for efficient extraction of oleanolic acid. H2O and 1,3-butanediol were used as control solvents to evaluate the extraction. Quantitative analysis using reversed phase high-performance liquid chromatography (RP-HPLC) indicated that extraction of pomace using betaine/xylitol (molar ratio 3:2) afforded the highest yield of oleanolic acid among the deep eutectic solvents. Scanning electron microscope observations and antioxidant assays of extracted samples were also conducted. The results demonstrated effective extraction of pomace under milder conditions than those needed for conventional methods. The less toxic and environmentally benign DESs for extraction would be applicable to the food and cosmetic industries. [ABSTRACT FROM AUTHOR]

Vigna nakashimae is a wild species closely related to the azuki bean (V. angularis), with salt-tolerance abilities. The present study aimed to explore the genetic and salt tolerance diversity within the species, by evaluating the phylogenetic relationships of 55 accessions of V. nakashimae including 25 newly collected from the Gotō Islands and Iki in Nagasaki Prefecture, Japan. We conducted salt-tolerance analysis for 48 of the accessions, including 18 of the newly collected accessions. Phylogenetic analysis based on single-nucleotide polymorphisms obtained from MIGseq and RADseq analyses revealed the genetic diversity of V. nakashimae to reflect the geographic arrangement of the habitat islands. Korean accessions formed one clade, while Japanese accessions predominantly grouped into Uku Island and Fukue Island subclades. Within this population, we identified "G4-2" (JP248291) as the most salt tolerant, surpassing even the previously reported Ukushima" accession. Both accessions collected from Uku Island, with accessions belonging to the Uku Island subclade exhibiting a strong trend of salt tolerance. Our results strongly suggest the occurrence of genetic mutations conferring enhanced salt tolerance in specific clade and region. This study highlights the potential of genetic analyses for identifying regions suitable for collecting valuable genetic resources for stress tolerance. [ABSTRACT FROM AUTHOR]

DNA metabarcoding (DNA-MB) targeting the whole plankton community is a promising approach in studies of sediment samples from water bodies, but its effectiveness in ancient material is not well demonstrated. We applied DNA-MB of plankton in a sediment core to reconstruct the paleo-environment of Lake Shinji, Japan, through a marine lagoon/freshwater lake transition during the past 2300 years. We interpreted core-sample plankton taxonomy and habitat by reference to the modern plankton community in water samples. OTUs (operational taxonomic units) belonging to Dictyochophyceae were 81.05% of the total reads in sediments. However, Ciliophora, Copepoda and Labyrinthulea formed the majority of plankton taxa in the water samples, suggesting that they are under-represented in sediment. A drastic change in plankton composition correlated with a large decrease in sediment sulfur concentration, implying the change of aquatic environment from marine lagoon to freshwater lake. This event took place ca. 1200 CE in Lake Shinji. A 250 year-long transitional period followed, during which the total DNA sequence reads were very low. This suggests that salinity fluctuations created a hostile environment for both marine and freshwater plankton species. Our results show that DNA-MB of the whole plankton community is effective in reconstructing paleo-environments. [ABSTRACT FROM AUTHOR]

Background: Common buckwheat (2n = 2x = 16) is an outcrossing pseudocereal whose seeds contain abundant nutrients and potential antioxidants. As these beneficial compounds are damaged by preharvest sprouting (PHS) and PHS is likely to increase with global warming, it is important to find efficient ways to develop new PHS-tolerant lines. However, genetic loci and selection markers associated with PHS in buckwheat have not been reported. Results: By next-generation sequencing (NGS) of whole-genome of parental lines, we developed a genome-wide set of 300 markers. By NGS- based bulked segregant analysis (NGS-BSA), we developed 100 markers linked to PHS tolerance. To confirm the effectiveness of marker development from NGS-BSA data, we developed 100 markers linked to the self-compatibility (SC) trait from previous NGS-BSA data. Using these markers, we developed genetic maps with AmpliSeq technology, which can quickly detect polymorphisms by amplicon-based multiplex targeted NGS, and performed quantitative trait locus (QTL) analysis for PHS tolerance in combination with NGS-BSA. QTL analysis detected two major and two minor QTLs for PHS tolerance in a segregating population developed from a cross between the PHS-tolerant 'Kyukei 29' and the self-compatible susceptible 'Kyukei SC7'. We found different major and minor QTLs in other segregating populations developed from the PHS-tolerant lines 'Kyukei 28' and 'NARO-FE-1'. Candidate markers linked to PHS developed by NGS-BSA were located near these QTL regions. We also investigated the effectiveness of markers linked to these QTLs for selection of PHS-tolerant lines among other segregating populations. Conclusions: We efficiently developed genetic maps using a method combined with AmpliSeq technology and NGS-BSA, and detected QTLs associated with preharvest sprouting tolerance in common buckwheat. This is the first report to identify QTLs for PHS tolerance in buckwheat. Our marker development system will accelerate genetic research and breeding in common buckwheat. [ABSTRACT FROM AUTHOR]

Mycosis fungoides is a low‐grade lymphoma, but on reaching the tumor stage, it can cause cardiac tamponade owing to epicardial infiltration. Myocardial infiltration, even in the absence of abnormal imaging findings, requires attention because it can lead to arrhythmia and cardiac arrest. [ABSTRACT FROM AUTHOR]

Vigna vexillata (L.) A. Rich. (tuber cowpea) is an underutilized crop for consuming its tuber and mature seeds. Wild form of V. vexillata is a pan-tropical perennial herbaceous plant which has been used by local people as a food. Wild V. vexillata has also been considered as useful gene(s) source for V. unguiculata (cowpea), since it was reported to have various resistance gene(s) for insects and diseases of cowpea. To exploit the potential of V. vexillata, an SSR-based linkage map of V. vexillata was developed. A total of 874 SSR markers successfully amplified single DNA fragment in V. vexillata among 1,336 SSR markers developed from Vigna angularis (azuki bean), V. unguiculata and Phaseolus vulgaris (common bean). An F2 population of 300 plants derived from a cross between salt resistant (V1) and susceptible (V5) accessions was used for mapping. A genetic linkage map was constructed using 82 polymorphic SSR markers loci, which could be assigned to 11 linkage groups spanning 511.5 cM in length with a mean distance of 7.2 cM between adjacent markers. To develop higher density molecular linkage map and to confirm SSR markers position in a linkage map, RAD markers were developed and a combined SSR and RAD markers linkage map of V. vexillata was constructed. A total of 559 (84 SSR and 475 RAD) markers loci could be assigned to 11 linkage groups spanning 973.9 cM in length with a mean distance of 1.8 cM between adjacent markers. Linkage and genetic position of all SSR markers in an SSR linkage map were confirmed. When an SSR genetic linkage map of V. vexillata was compared with those of V. radiata and V. unguiculata, it was suggested that the structure of V. vexillata chromosome was considerably differentiated. This map is the first SSR and RAD marker-based V. vexillata linkage map which can be used for the mapping of useful traits. [ABSTRACT FROM AUTHOR]

The alteration of photoperiod sensitivity has let breeders diversify flowering time in Oryza sativa (rice) and develop cultivars adjusted to a range of growing season periods. Map-based cloning revealed that the rice flowering-time quantitative trait locus ( QTL) Heading date 16 ( Hd16) encodes a casein kinase- I protein. One non-synonymous substitution in Hd16 resulted in decreased photoperiod sensitivity in rice, and this substitution occurred naturally in an old rice cultivar. By using near-isogenic lines with functional or deficient alleles of several rice flowering-time genes, we observed significant digenetic interactions between Hd16 and four other flowering-time genes ( Ghd7, Hd1, DTH8 and Hd2). In a near-isogenic line with the weak-photoperiod-sensitivity allele of Hd16, transcription levels of Ehd1, Hd3a, and RFT1 increased under long-day conditions, and transcription levels of Hd3a and RFT1 decreased under short-day conditions. Expression analysis under continuous light and dark conditions showed that Hd16 was not likely to be associated with circadian clock regulation. Biochemical characterization indicated that the functional Hd16 recombinant protein specifically phosphorylated Ghd7. These results demonstrate that Hd16 acts as an inhibitor in the rice flowering pathway by enhancing the photoperiod response as a result of the phosphorylation of Ghd7. [ABSTRACT FROM AUTHOR]

When penetrating the soil during germination, dicotyledonous plants protect their shoot apical meristem through the formation of an apical hook. Apical hook formation is a dynamic process that can be subdivided into hook formation, maintenance and opening. It has previously been established that these processes require the transport and signaling of the phytohormone auxin, as well as the biosynthesis and signaling of the phytohormones ethylene and gibberellin (GA). Here, we identify a molecular mechanism for an auxin-GA crosstalk by demonstrating that the auxin transport-regulatory protein kinase WAG2 is a crucial transcription target during apical hook opening downstream from GA signaling. We further show that WAG2 is directly activated by PHYTOCHROME INTERACTING FACTOR 5 (PIF5), a light-labile interactor of the DELLA repressors of the GA pathway. We find that wag2 mutants are impaired in the repression of apical hook opening in dark-grown seedlings and that this phenotype correlates with GA-regulated WAG2 expression in the concave (inner) side of the apical hook. Furthermore, wag2 mutants are also impaired in the maintenance or formation of a local auxin maximum at the site of WAG2 expression in the hook. WAG2 is a regulator of PIN auxin efflux facilitators and, in line with previous data, we show that this kinase can phosphorylate the central intracellular loop of all PINFORMED (PIN) proteins regulating apical hook opening. We therefore propose that apical hook opening is controlled by the differential GA-regulated accumulation of WAG2 and subsequent local changes in PIN-mediated auxin transport. [ABSTRACT FROM AUTHOR]

Flowering time of rice depends strongly on photoperiodic responses. We previously identified a quantitative trait locus, Heading date 17 (Hd17), that is associated with a difference in flowering time between Japanese rice (Oryza sativa L.) cultivars. Here, we show that the difference may result from a single nucleotide polymorphism within a putative gene that encodes a homolog of the Arabidopsis EARLY FLOWERING 3 protein, which plays important roles in maintaining circadian rhythms. Our results demonstrate that natural variation in Hd17 may change the transcription level of a flowering repressor, Grain number, plant height and heading date 7 (Ghd7), suggesting that Hd17 is part of rice’s photoperiodic flowering pathway. [ABSTRACT FROM AUTHOR]

Much progress has been made in our understanding of photoperiodic flowering of rice and the mechanisms underlying short-day (SD) promotion and long-day (LD) repression of floral induction. In this study, we identified and characterized the Ef7 gene, one of the rice orthologs of Arabidopsis EARLY FLOWERING 3 (ELF3). The ef7 mutant HS276, which was induced by γ-irradiation of the japonica rice cultivar ‘Gimbozu’, flowers late under both SD and LD conditions. Expression analyses of flowering time-related genes demonstrated that Ef7 negatively regulates the expression of Ghd7, which is a repressor of the photoperiodic control of rice flowering, and consequently up-regulates the expression of the downstream Ehd1 and FT-like genes under both SD and LD conditions. Genetic analyses with a non-functional Ghd7 allele provided further evidence that the delayed flowering of ef7 is mediated through the Ghd7 pathway. The analysis of light-induced expression of Ghd7 revealed that the ef7 mutant was more sensitive to red light than the wild-type plant, but the gate of Ghd7 expression was unchanged. Thus, our results show that Ef7 functions as a floral promoter by repressing Ghd7 expression under both SD and LD conditions. [ABSTRACT FROM AUTHOR]

Green stem disorder (GSD) of soybean is characterized by delayed leaf and stem maturation despite normal pod maturation. Previous studies have suggested that GSD occurrence is promoted by a high source–sink ratio, which is produced by thinning or shade removal at the R5 growth stage (the beginning of seed filling). Here the effects of different times and durations of shade removal after the R5 stage on GSD severity were analyzed. First, shade removal for more than 28 days after R5 increased GSD severity by more than 0.4 point in GSD score. Thinning treatment at R5 increased specific leaf weight by 23%, suppressed stem dry weight reduction, and upregulated 19 genes including those encoding vegetative storage proteins at R5 + 28d, indicating excess source ability relative to sink size. On the contrary, shade removal for 14 days after R5 decreased GSD severity by 0.5 point in GSD score. In this treatment, seed size was smaller, while seed number was significantly larger than control, suggesting that shortage of source ability relative to sink size. These results implied that soybean plants regulate GSD occurrences either positively or negatively according to a source-sink ratio during the R5 to R5 + 28d growth stages. [ABSTRACT FROM AUTHOR]

DNA metabarcoding on a single organism is a promising approach to clarify the biological interactions (e.g., predator–prey relationships and symbiosis, including parasitism) of difficult‐to‐culture protists. To evaluate the effectiveness of this method, Radiolaria and Phaeodaria, which are ecologically important protistan groups, were chosen as target taxa. DNA metabarcoding on a single organism focused on the V9 region of the 18S rRNA gene revealed potential symbionts, parasites and food sources of Radiolaria and Phaeodaria. Previously reported hosts and symbionts (parasites) were detected, and newly recognized combinations were also identified. The contained organisms largely differed between Radiolaria and Phaeodaria. In Radiolaria, members of the same order tended to contain similar organisms, and the taxonomic composition of possible symbionts, parasites, and food sources was fixed at the species level. Members of the same phaeodarian family, however, did not contain similar organisms, and body part (i.e., the central capsule or the phaeodium) was the most important factor that divided the taxonomic composition of detected organisms, implying that the selection of appropriate body part is important when trying to ascertain contained organisms, even for unicellular zooplankton. Our results show that DNA metabarcoding on a single organism is effective in revealing the biological interactions of difficult‐to‐culture protists. [ABSTRACT FROM AUTHOR]

In rice (Oryza sativa L.), there is a diversity in flowering time that is strictly genetically regulated. Some indica cultivars show extremely late flowering under long-day conditions, but little is known about the gene(s) involved. Here, we demonstrate that functional defects in the florigen gene RFT1 are the main cause of late flowering in an indica cultivar, Nona Bokra. Mapping and complementation studies revealed that sequence polymorphisms in the RFT1 regulatory and coding regions are likely to cause late flowering under long-day conditions. We detected polymorphisms in the promoter region that lead to reduced expression levels of RFT1. We also identified an amino acid substitution (E105K) that leads to a functional defect in Nona Bokra RFT1. Sequencing of the RFT1 region in rice accessions from a global collection showed that the E105K mutation is found only in indica, and indicated a strong association between the RFT1 haplotype and extremely late flowering in a functional Hd1 background. Furthermore, SNPs in the regulatory region of RFT1 and the E105K substitution in 1,397 accessions show strong linkage disequilibrium with a flowering time–associated SNP. Although the defective E105K allele of RFT1 (but not of another florigen gene, Hd3a) is found in many cultivars, relative rate tests revealed no evidence for differential rate of evolution of these genes. The ratios of nonsynonymous to synonymous substitutions suggest that the E105K mutation resulting in the defect in RFT1 occurred relatively recently. These findings indicate that natural mutations in RFT1 provide flowering time divergence under long-day conditions. [ABSTRACT FROM AUTHOR]

In the presence of Ru(bpy) 3 Cl 2 ·6H 2 O and ( i -Pr) 2 NEt, the photo-induced cascade radical addition–cyclization–trapping reaction proceeded in aqueous media. When i -C 3 F 7 I was employed as a radical precursor, the iodine atom-transfer radical cyclization proceeded even in the absence of ( i -Pr) 2 NEt. Under the photo-induced conditions, ICH 2 CN and ICH 2 CF 3 also worked well as carbon radical precursors. The photo-induced reductive electron-transfer to CF 3 SO 2 Cl promoted the chlorine atom-transfer radical cyclization. [ABSTRACT FROM AUTHOR]

The unprecedented novel coronavirus disease 2019 (COVID‐19) pandemic is a threat to global health and the economy. Since the outbreak of COVID‐19, great effort has been made to reposition existing drugs to shorten development timelines, in addition to vaccine development and drug discovery campaigns. Umifenovir is a broad‐spectrum antiviral agent used to treat influenza in China and Russia and is currently undergoing clinical trials for the treatment of COVID‐19. In this article, the synthesis of umifenovir analogues and their biological evaluation are reported. The inhibitory activities of analogues against the binding of the spike glycoprotein (S‐protein) of the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) to the ACE2 receptor, which is a possible mode of action for umifenovir to inhibit viral infection, were investigated. [ABSTRACT FROM AUTHOR]

Flavonoid 3ʹ‐hydroxylase (F3ʹH) catalyzes hydroxylation at the 3ʹ position of the B ring of flavonoids. F3ʹH is associated with the seed coat and pubescence color, antioxidant properties, and chilling stress tolerance of soybean [Glycine max (L.) Merr.]. In this study, we found that soybean F3ʹH increases the calcium (Ca) and magnesium (Mg) contents in pods and reduces the levels of these elements in seeds. Inductively coupled plasma mass spectrometry (ICP‐MS) analysis using a near‐isogenic line (NIL) derived from Japanese cultivars 'Natto‐shoryu' and 'Hyoukei‐kuro 3' for F3ʹH (Glyma.06g202300), also known as the T gene, indicated that the contents of Ca and Mg were higher in the pods but lower in the seed coats and cotyledons from soybean with active F3ʹH than from soybean with inactive F3ʹH. No such clear tendency was observed for other inorganic ions measured in this study. These data suggested that the transport of Ca and Mg from the pod to the seed was inhibited by flavonoid produced through F3ʹH activity. The hardness of cooked beans from soybean with active F3ʹH was lower than that from soybean with inactive F3ʹH, which was likely related to the increase in heat‐labile pectin caused by fewer cross‐linked divalent ions. These results were supported by ICP‐MS analysis and the hardness of cooked beans of other NILs for the T gene. Our findings demonstrate a novel and unexpected effect of flavonoids on the processing quality of soybean. Core Ideas: Soybean flavonoid 3ʹ‐hydroxylase (F3ʹH) reduces seed Ca and Mg contents.F3ʹH likely inhibits Ca and Mg transport from the pod to the seed.F3ʹH softens the cooked bean, partly due to the increase in heat‐labile pectin.Soybean F3ʹH affects seed quality, which is an unexpected effect. [ABSTRACT FROM AUTHOR]

Survival rates of both early and middle instar larvae of the nymphalid butterfly, Sasakia charonda, were estimated to be lowest on test trees planted in a meadow (site A), intermediate in a small, narrow secondary deciduous broadleaf forest (small patch, site B) and highest in a large secondary deciduous broadleaf forest (large forest, site C). The larval mortality rates due to predation by tree-climbing predators from the ground (tree climbing predator) such as ants and the larvae of carabids were estimated to be greater at sites A and B than those at site C. The number of predatory ants climbing test trees was significantly greater at sites A and B than at site C, and the ants harvested honeydew from aphids living on tree leaves at those two sites. Aphid densities were significantly higher on trees at sites A and B than at site C, and aphid densities and numbers of predatory ants were significantly and positively correlated at sites A and B. In an experiment controlling aphid density per branch on test trees, the numbers of ants and the mortality rates of S. charonda larvae were greater on branches with high aphid densities than on those with low aphid densities at both sites A and B. These results suggest that the aphid density per host tree was higher in the meadow and the small patch than in the large forest; at both sites these higher aphid densities attracted higher numbers of predatory ants to test trees, and as a result, mortality rates of S. charonda larvae were increased. [ABSTRACT FROM AUTHOR]

An autopsy case of diffuse axonopathic leukoencephalopathy induced by drug treatment is reported. A 70-year-old woman with multiple myeloma developed encephalopathy several days after completing a course of intravenous human immunoglobulin (IVIg) and granulocyte-colony stimulating factor (G-CSF), and died within I month. T2-weighted MRI demonstrated multifocal high-signal areas in the bilateral cerebral white matter, especially in the right frontal lobe. Neuropathologically, multifocal hydropic axonal swelling with a poor glial reaction was recognized diffusely in the bilateral deep cerebral white matter, being especially marked in the frontal lobe. The cortex, subcortical U-fibers, corpus callosum, and anterior commissure were spared. The cerebellar white matter also showed similar changes, albeit less marked, but the brainstem was spared. Microscopically, the myeloma involvement of the CNS was limited to the dura, and the cerebral arteries showed slight atherosclerosis, but neither thrombi nor angitis. This case, although ultimately fatal, neurologically and neuroradiologically resembled reversible posterior leukoencephalopathy syndrome (RPLS) induced by IVIg and/or G-CSF, and the nature and selective distribution of the neuropathological changes suggested that the pathogenesis involved vasospasm of the bilateral internal carotid artery and the main trunks of the cerebral arteries, due to unknown cause, inducing ischemia in the deep white matter, which is supplied by long nutrient arteries. [ABSTRACT FROM AUTHOR]

HBV causes hepatocellular carcinoma (HCC). While it was recently shown that the ability of HBV X protein (HBx) to impair the Smc5/6 (structural maintenance of chromosome 5/6) complex is important for viral transcription, HBx is also a potent driver of HCC. However, the mechanism by which HBx expression induces hepatocarcinogenesis is unclear. Degradation of the Smc5/6 complex and accumulation of DNA damage were observed in both in vivo and in vitro HBV infection models. Rescue experiments were performed using nitazoxanide (NTZ), which inhibits degradation of the Smc5/6 complex by HBx. HBx-triggered degradation of the Smc5/6 complex causes impaired homologous recombination (HR) repair of DNA double-strand breaks (DSBs), leading to cellular transformation. We found that DNA damage accumulated in the liver tissue of HBV-infected humanized chimeric mice, HBx-transgenic mice, and human tissues. HBx suppressed the HR repair of DSBs, including that induced by the CRISPR-Cas9 system, in an Smc5/6-dependent manner, which was rescued by restoring the Smc5/6 complex. NTZ restored HR repair in, and colony formation by, HBx-expressing cells. Degradation of the Smc5/6 complex by HBx increases viral transcription and promotes cellular transformation by impairing HR repair of DSBs. The hepatitis B virus expresses a regulatory protein called HBV X protein (or HBx). This protein degrades the Smc5/6 complex in human hepatocytes, which is essential for viral replication. We found that this process also plays a key role in the accumulation of DNA damage, which contributes to HBx-mediated tumorigenesis. [Display omitted] • DNA damage accumulated in HBV-infected and HBx-expressing liver tissues. • Smc5/6 degradation by HBx impaired homologous recombination repair, driving tumorigenesis. • Restoration of Smc5/6 by nitazoxanide rescued homologous recombination repair and inhibited tumorigenesis. [ABSTRACT FROM AUTHOR]

The Vulnerable Elders Survey-13 (VES-13) is a well-studied simplified frailty screening tool for elderly patients in the oncology setting. We conducted a prospective clinical trial to evaluate the efficacy and safety of dose-adjusted treatment based on the VES-13 in transplant-ineligible patients with newly diagnosed multiple myeloma (MM). In the Fit group (VES-13 <3), patients were treated with 4 cycles of standard-dose VCD (bortezomib, cyclophosphamide, and dexamethasone) followed by 4 cycles of standard-dose VTD (bortezomib, thalidomide, and dexamethasone). In the Frail group (VES-13 ≥3), patients were treated with 4 cycles of reduced-dose VCD followed by 4 cycles of reduced-dose VTD. The median age was 75 years (66–86 years), and 34% of the cases were classified as PS 3. Among the Fit group (n=16), the overall response rate (ORR) was 87.5%. Among the Frail group (n=31), the ORR was 87.1%. There were no significant differences in progression-free survival (PFS) and overall survival (OS) between the Fit and Frail groups (3-year PFS: 68.8% vs 53.3%, P = 0.658; 3-year OS: 70.0% vs 77.6%, P = 0.919). Personalized VCD-VTD sequential therapy based on the VES-13 was associated with high response rates and showed acceptable safety in elderly frail patients with MM. The study is registered as UMIN000011235. [ABSTRACT FROM AUTHOR]

Enterocolic lymphocytic phlebitis (ELP) is a phlebitis that occurs predominantly in the right colon to ileum without systemic vasculitis and is mainly seen in older persons.1 Segmental and circumferential enterocolic stenosis with erosions and ulcers is seen with intestinal involvement of ELP. Since the coexistence of ELP and LC is unusual, the first case of ELP in association with LC in Japan is described. [Extracted from the article]

Although the detection of circulating tumor cells (CTCs) should be crucial for future personalized medicine, no efficient and flexible methods have been established. The current study established a polymeric custom-made chip for capturing CTCs with a high efficiency and flexibility. As an example of clinical application, the effects of self-expandable metallic stent (SEMS) placement on the release of cancer cells into the blood of patients with colorectal cancer and bowel obstruction were analyzed. This was assessed as the placement of SEMS may cause mechanical damage and physical force to malignant tissue, increasing the risk of cancer cell release into the bloodstream. The present study examined the number of CTCs using a custom-made chip, before, at 24 h after and at 4 days after SEMS placement in patients with colorectal cancer. The results revealed that, among the 13 patients examined, the number of CTCs was increased in three cases at 24 h after SEMS placement. However, this increase was temporary. The number of CTCs also decreased at 4 days after stent placement in most cases. The CTC chip of the current study detected the number of CD133-positive cancer stem-like cells, which did not change, even in the patient whose total number of CTCs temporarily increased. The results indicated that this custom-made microfluid system can efficiently and flexibly detect CTCs, demonstrating its potential for obtaining information during the management of patients with cancer. [ABSTRACT FROM AUTHOR]

A fundic gland polyp (FGP) is a common gastric polyp. Intraepithelial neoplasia in FGPs, referred to as FGP with dysplasia, is often seen in patients with familial adenomatous polyposis (FAP). In sporadic FGPs, low‐grade dysplasia (LGD) is rare, and high‐grade dysplasia (HGD) or carcinoma arising from sporadic FGPs is extremely rare. Because of this rarity, the prognosis and appropriate management of these lesions have not been clarified. In the present case, a sporadic FGP with LGD did not develop into invasive carcinoma, but contained foci of HGD 14 years after diagnosis. The biopsy specimen of the polyp taken at the first esophagogastroduodenoscopy 15 years earlier was diagnosed as FGP without dysplasia. At the second histological examination, LGD was found. Because the polyp increased in size during proton pump inhibitor therapy for 14 years, endoscopic mucosal resection was performed. The pathological diagnosis of the resected specimen was FGP with HGD mixed in LGD, with no invasive carcinoma. Dysplasia in FGPs might have less malignant potential regardless of dysplasia or size. [ABSTRACT FROM AUTHOR]

Abstract Asian soybean rust (ASR), caused by the obligate biotrophic fungus Phakopsora pachyrhizi , is responsible for severe yield losses of up to 90% in all soybean producing countries. Till today, eight resistance to Phakopsora pachyrhizi (Rpp) loci have been mapped in soybean. Their resistance mechanism is race specific but largely unknown. The transcriptomes of susceptible BRS184 and Rpp3 with ASR isolates T1-2 at 24 h after inoculation (hai) and without ASR inoculation (mock) were annotated by similarity searching with different databases. A total of 4518 differentially expressed genes were identified. We found 70.89%, 56.61%, 32.13%, and 56.04% genes in the protein family databases (PFAM), Gene Ontology (GO), Eukaryotic clusters of Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG), respectively. KEGG disclosed that 52% of the phenylpropanoid pathway related genes were up-regulated. The relative gene expression study for selected genes of that pathway was conducted by RT-qPCR using Rpp1-Rpp4 carrying lines with T1-2 infection. The RT-qPCR results revealed that the Rpp lines utilized these genes in a rate limiting manner as a defence response. With the exception of glycinol 4-dimethylallyltransferase (G4DT) and chalcone reductase (CHR), all the genes showed the greatest expression at 12 hai, but the gene expressions which occur between 24 and 96 hai make these Rpp lines unique to their respective ASR isolates. Moreover, functional coordination of arogenate dehydratase 6 (ADT6) and 4-hydroxy-3-methylbut-2-enyl diphosphate synthase (ispG), chalcone synthase (CHS) and CHR, and G4DT and phytyltransferase 3 (PT3) may have a great impact on soybean resistance against ASR. Highlights • Transcriptomic analysis identified 4518 differentially expressed genes during Rpp3 -mediated resistance in soybean. • The genes related to phenylpropanoid pathway were up-regulated in soybean R -genes mediated resistance against Phakopsora pachyrhizi. • Rpp gene mediated resistance tends to be steady state metabolite flux output. [ABSTRACT FROM AUTHOR]

Purpose: Transbrachial carotid artery stenting (TB-CAS) is performed as an alternative procedure for patients with hostile vascular anatomy of the aortic arch and aortic or peripheral artery disease. Proximal protection during TB-CAS is not generally feasible because a small size of the brachial artery may preclude using a large-diameter sheath introducer. We, herein present a novel method that enables proximal protection during TB-CAS by sheathless navigation of a 9-F balloon-guiding catheter equivalent to a 7-F sheath.Methods: We analyzed eight consecutive patients who underwent TB-CAS with proximal protection using the sheathless method from April 2016 to June 2017. Relevant demographic, radiographic, and procedural features were retrospectively reviewed.Results: We performed TB-CAS using our method for five patients with a bovine or type 3 aortic arch, for one patient with combined peripheral artery disease, and for two patients with a type 1 or 2 aortic arch. We successfully navigated the balloon-guiding catheter via the brachial artery and performed CAS under proximal flow control in all patients. However, we experienced kinking and exchange of the balloon-guiding catheter in one patient and a periprocedural thromboembolic event occurred. A pseudoaneurysm at the access site developed in one patient.Conclusion: TB-CAS with proximal embolic protection using the sheathless method is feasible and may provide an alternative approach in carefully selected patients who have difficult anatomy in the transfemoral approach and plaques with a high risk of distal embolization. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Invasive pulmonary aspergillosis (IPA) often occurs during the treatment of malignant lymphoma. However, invasive tracheobronchial aspergillosis (ITBA) is a rare form of IPA. Particularly, due to the decrease in immunity associated with chemotherapy, it is difficult to diagnose ITBA only by CT imaging and serological findings. Pathologic diagnosis by bronchoscopy is important. [ABSTRACT FROM AUTHOR]

[Display omitted] Elastic fibers consist of an insoluble inner core of elastin, which confers elasticity and resilience to vertebral organs and tissues. Desmosine (DES) and isodesmosine (IDES) are potential biomarkers of pathologies that lead to decreased elastin turnover. Mice are commonly used in research to mimic humans because of their similar genetics, physiology, and organ systems. The present study thus used senescent accelerated prone (SAMP10) and senescent accelerated resistant (SAMR1) mice to examine the connection between aging and histological or biomolecular changes. Mice were divided into three groups: SAMP10 fed a control diet (CD), SAMP10 fed a high-fat diet (HFD), and SAMR1 fed a CD. The percent liver to total body weight ratio (%LW/BW), desmosines (DESs or DES/IDES) content, and histological alterations in skin samples were evaluated. DESs were quantified using an isotope-dilution liquid chromatography–tandem mass spectrometry method with isodesmosine-13C 3 ,15N 1 as the internal standard (ISTD). The assays were repeatable, reproducible, and accurate, with %CV values ≤ (1.90, 1.77, and 3.03), ISTD area %RSD of (1.54, 0.92, and 1.13), and %AC of (99.02 ± 1.86, 101.00 ± 2.30, and 101.30 ± 2.90) for the calibrations (equimolar DES/IDES, DES, and IDES, respectively). The average DESs content per dry-weight abdominal skin and %LW/BW were similar between the three groups. Histological analyses revealed elastin fibers in five randomly selected samples. The epidermis and dermal white adipose tissue layers were thicker in SAMP10 mice than SAMR1 mice. Thus, characteristic signs of aging in SAMP10 and SAMR1 mice could not be differentiated based on measurement of DESs content of the skin or %LW/BW, but aging could be differentiated based on microscopic analysis of histological changes in the skin components of SAMP10 and SAMR1 mice. [ABSTRACT FROM AUTHOR]

[Display omitted] Ligamentum flavum (LF) pathologies often lead to severe myelopathy or radiculopathy characterized by reduced elasticity, obvious thickening, or worsened ossification. Elastin endows critical mechanical properties to tissues and organs such as vertebrae and ligaments. Desmosine (DES) and isodesmosine (IDES) are crosslinkers of elastin monomers called tropoelastin. These crosslinkers are potential biomarkers of chronic obstructive pulmonary disease. As a biological diagnostic tool that supplements existing symptomatic, magnetic resonance imaging scanning or radiological imaging diagnostic measures for LF hypertrophy and associated pathologies, an isotope-dilution liquid chromatography-tandem mass spectrometry method with selected reaction monitoring mode for the quantitation of DESs in human plasma, urine, cerebrospinal fluid (CSF), and yellow ligamentum was investigated. Isotopically labeled IDES-13C 3 ,15N 1 was used as an internal standard (ISTD) for DES quantitation for the first time. The samples plus ISTD were hydrolyzed with 6 N hydrochloric acid. Analytes and ISTD were extracted using a solid phase extraction cellulose cartridge column. The assays were repeatable, reproducible, and accurate with % CV ≤ 7.7, ISTD area % RSD of 7.6, and % AC ≤ (101.2 ± 3.90) of the calibrations. The ligamentum samples gave the highest average DES/IDES content (2.38 μg/mg) on a dry-weight basis. A high percentage of the CSF samples showed almost no DESs. Urine and plasma samples of patients showed no significant difference from the control (p -value = 0.0519 and 0.5707, respectively). Microscopy of the yellow ligamentum samples revealed dark or blue-colored zones of elastin fibers that retained the hematoxylin dye and highly red-colored zones of collagen after counterstaining with van Gieson solution. Thus, we successfully developed a method for DES/IDES quantitation in clinical samples. [ABSTRACT FROM AUTHOR]

• Cold air drainage causes minimum temperature variation at fine spatial scales. • A new algorithm for flow accumulation was determined. • The algorithm was combined with inversion strength. • These approaches improved spatiotemporal estimation of daily minimum temperature. • The proposed model can be used to investigate frost risk in complex terrains. In complex terrains, the minimum temperature varies at fine spatial scales owing to cold air drainage. This leads to large spatial variabilities in phenological events and frost risk in plants. Various topographic variables have been used to model cold air drainage and its influence on temperature. In this study, we modified a conventional approach using flow accumulation (FA). First, we developed a new algorithm for FA by reconsidering effective areas of cold air drainage. This allowed us to increase the model's applicability. The FA model was then combined with the vertical gradient of potential temperature, which represents the inversion strength during stable, nighttime conditions. This process facilitated minimum temperature estimation at a given date and point. The model was developed using temperature observations in tea fields with complex terrains, where frost risk is increasing due to climate change. The maximum difference in daily minimum temperature across 15 observation points was 6.7°C, despite only a 73-m elevation difference. Compared with models using spatial interpolation alone, the proposed model produced a better estimate of the spatiotemporal variability of daily minimum temperature and improved the average residuals between estimated and measured temperatures in valley areas from 1.9 to 0.03°C. Moreover, compared to the conventional algorithm, the proposed algorithm improved temperature estimations in ridge areas and clarified the boundaries between ridges and valleys. Our approach could contribute to the spatiotemporal analysis of temperature variations and concomitant changes in phenological events and frost risk in complex terrains. [ABSTRACT FROM AUTHOR]

Visual dysfunctions are common in Alzheimer's disease (AD). Our aim was to establish a neurophysiological biomarker for amnestic mild cognitive impairment (aMCI). Visual evoked potentials (VEPs) were recorded in aMCI patients who later developed AD (n = 15) and in healthy older (n = 15) and younger controls (n = 15). Visual stimuli were optimized to separately activate lower and higher levels of the ventral and dorsal streams. We compared VEP parameters across the three groups of participants and conducted a linear correlation analysis between VEPs and data from neuropsychological tests. We then used a receiver operating characteristic (ROC) analysis to discriminate those with aMCI from those who were healthy older adults. The latency and phase of VEPs to lower-level stimuli (chromatic and achromatic gratings) were significantly affected by age but not by cognitive decline. Conversely, VEP latencies for higher-ventral (faces and kanji-words) and dorsal (kana-words and optic flow motion) stimuli were not affected by age, but they were significantly prolonged in aMCI patients. Interestingly, VEPs for higher-dorsal stimuli were related to outcomes of neuropsychological tests. Furthermore, the ROC analysis showed that the highest areas under the curve were obtained for VEP latencies in response to higher-dorsal stimuli. These results suggest aMCI-related functional impairment specific to higher-level visual processing. Further, dysfunction in the higher-level of the dorsal stream could be an early indicator of cognitive decline. Therefore, we conclude that VEPs associated with higher-level dorsal stream activity can be a sensitive biomarker for early detection of aMCI. [ABSTRACT FROM AUTHOR]

Key message: QTL mapping in F population [ V. luteola × V. marina subsp. oblonga ] revealed that the salt tolerance in V. marina subsp. oblonga is controlled by a single major QTL. Abstract: The habitats of beach cowpea ( Vigna marina) are sandy beaches in tropical and subtropical regions. As a species that grows closest to the sea, it has potential to be a gene source for breeding salt-tolerant crops. We reported here for the first time, quantitative trait loci (QTLs) mapping for salt tolerance in V. marina. A genetic linkage map was constructed from an F population of 120 plants derived from an interspecific cross between V. luteola and V. marina subsp. oblonga. The map comprised 150 SSR markers. The markers were clustered into 11 linkage groups spanning 777.6 cM in length with a mean distance between the adjacent markers of 5.59 cM. The F population was evaluated for salt tolerance under hydroponic conditions at the seedling and developmental stages. Segregation analysis indicated that salt tolerance in V. marina is controlled by a few genes. Multiple interval mapping consistently identified one major QTL which can explain about 50 % of phenotypic variance. The flanking markers may facilitate transfer of the salt tolerance allele from V. marina subsp. oblonga into related Vigna crops. The QTL for domestication-related traits from V. marina are also discussed. [ABSTRACT FROM AUTHOR]

A Ru-catalyzed photolytic cascade radical reaction of dienic derivatives of O-benzyl hydroxylamine with perhalogenated aliphatic halides is developed leading to functionalized pyrrolidinones as mixtures of diastereomers, also for compounds (III), or as mixtures of E/Z isomers. [ABSTRACT FROM AUTHOR]

The polarity-mismatched perfluoroalkyl radical addition to electron-deficient alkenes was studied. For this study, several substrates having two polarity-different radical acceptors were employed to investigate the regiochemical courses of cascade reaction. In the case of substrate 1 having a methacryloyl moiety, we found polarity-mismatched perfluoroalkylation giving 15a-e as a major course over the polarity-matched perfluoroalkylation giving 16a-e. Moreover, in the case of substrates 2-7, perfluoroalkyl radicals selectively added to an electron-deficient alkene moiety of 2-7, to give polarity-mismatched perfluoroalkylation products without the formation of regioisomers. Next, the control of enantioselectivity was studied. In the case of substrates 1 and 3, the reaction proceeded with good enantioselectivities by employing a chiral Lewis acid, prepared from chiral box ligand 24 and Zn(OTf)2. For direct comparison, we also studied the reaction with other carbon radicals, derived from ICH2CO2Et, ICH2CN, BrC(CO2Et)2Me, and CCl3Br, which have electrophilic character. [ABSTRACT FROM AUTHOR]

Abstract: The Li3AlB2O6 ceramic were prepared by using the conventional solid-state reaction method; these pellets were sintered at the temperature range of 650–775°C for 2h in air. The X-ray powder diffraction pattern of the Li3AlB2O6 ceramic sintered at 650°C showed a single phase which corresponded to the triclinic phase with a space group of ; the crystallization of the ceramics was observed with increasing the sintering temperatures from 650 to 775°C. The dielectric constant of the Li3AlB2O6 ceramic increased slightly from 4.2 to 5.4 as the sintering temperatures were increased from 650 to 775°C, whereas the Q × f value of the ceramic ranged from 12,460 to 20,448GHz. The improvement in the Q × f value is substantially related to the crystallization of the Li3AlB2O6 ceramic. The temperature coefficient of resonant frequency of the ceramic showed the large negative values, ranging from −290 to −201ppm/°C. However, by the addition of 5wt% TiB compound, the τ f value of the Li3AlB2O6 ceramic was improved (τ f ≒10ppm/°C); a dielectric constant of 4.2 and Q × f value of 13,027GHz were obtained at the sintering temperature of 675°C. [Copyright &y& Elsevier]

Abstract: The influence of Sr substitution for Ba on the microwave dielectric properties and crystal structure of the Sm2(Ba1−x Sr x )(Cu0.5Zn0.5)O5 ceramics was studied. However, it was found that the limit of the solid solution was approximately x =0.4 from the XRPD patterns. In the single phase region, the sintering temperature dependence of the microwave dielectric properties of the solid solutions was investigated. The dielectric constants of the solid solutions were approximately 18 in the sintering temperature range of 1150–1250°C, whereas the Qf values of the solid solutions strongly depended on the composition x. The Qf values of the solid solution decreased with an increase in composition x; the differences in the Qf values were attributed to the morphological changes in the samples which arose from the Sr substitution for Ba. However, the Qf value of approximately 65,000GHz was obtained at x =0 in the sintering temperatures ranging from 1150 to 1250°C. The temperature coefficient of resonant frequency (τ f ) of the solid solutions varied from negative to positive values, ranging from −6 to 7ppm/°C with the Sr substitution for Ba; a near zero τ f value was obtained at x =0.05; a small amount of Sr substitution for Ba was substantially effective in improving the τ f values of the solid solutions. [Copyright &y& Elsevier]

MICA/B proteins are expressed on the surface of various types of stressed cells, including cancer cells. Cytotoxic lymphocytes expressing natural killer group 2D (NKG2D) receptor recognize MICA/B and eliminate the cells. However, cancer cells evade such immune recognition by inducing proteolytic shedding of MICA/B proteins. Therefore, preventing the shedding of MICA/B proteins could enhance antitumor immunity. Here, by screening a protease inhibitor library, we found that the fatty-acid amide hydrolase (FAAH) inhibitor, URB597, suppresses the shedding of MICA/B. URB597 significantly reduced the soluble MICA level in culture medium and increased the MICA level on the surface of cancer cells. The effect was indirect, being mediated by increased expression of tissue inhibitor of metalloproteinases 3 (TIMP3). Knockdown of TIMP3 expression reversed the effect of URB597, confirming that TIMP3 is required for the MICA shedding inhibition by URB597. In contrast, FAAH overexpression reduced TIMP3 expression and the cell-surface MICA level and increased the soluble MICA level. These results suggest that inhibition of FAAH could prevent human cancer cell evasion of immune-mediated clearance. [ABSTRACT FROM AUTHOR]

In this paper, we discuss stress-adapted wild Vigna plants and several important Vigna crops. Seeds, young shoots and/or tubers of many wild Vigna species are edible and are eaten by people in some locations where they grow. We propose the concept of ‘neo-domestication’ of stress-adapted wild edible Vigna species. As the causative change of the mutation resulting in a domestication gene is usually ‘loss-of-function’ type, ‘neo-domestication’ could be achieved by conventional mutation breeding together with screening by TILLING. The ‘neo-crops’ could play an important role in areas unsuitable for growing other crops to increase world food production. We also propose that wild Vigna species can be ‘new model plant species’ for the genetic study of natural adaptation to stresses (e.g. salt, acid, alkali, drought, flood, pests and diseases). To facilitate this, the Vigna Genome Project has been initiated. In addition, sustainable cropping systems may be enhanced by analysis of the nitrogen-fixing systems of stress-adapted Vigna species. Stress-adapted symbiotic bacteria produce nodules on stress-adapted Vigna species. Therefore, analyses of the genetic diversity of symbiotic bacteria and the process of symbiosis under stress environments should be conducted. [ABSTRACT FROM AUTHOR]