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A functional linkage between light-harvesting and photocatalytic components is a pivotal issue for using solar energy in chemical conversions; however, this concept is far from being practically re...

Photosynthetic light-harvesting (LH) systems consist of photosynthetic pigments, which are non-covalently self-assembled with protein scaffolds in many phototrophs and attain highly efficient excitation energy transfer via ultrafast dynamics. In this study, we constructed a biohybrid LH system composed of an LH complex (LH2) from Rhodoblastus acidophilus strain 10050 and a hydrophobic fluorophore ATTO647N (ATTO) as an extrinsic antenna in the lipid bilayer. Through the addition of ATTOs into a solution of LH2-reconstituted lipid vesicles, ATTOs were incorporated into the hydrophobic interior of the lipid bilayer to configure the non-covalently self-assembled biohybrid LH. Steady-state fluorescence spectroscopy clearly showed efficient energy transfer from ATTO to B850 bacteriochlorophylls in LH2. Femtosecond transient absorption spectroscopy revealed that the energy transfer took place in the time range of 3–13 ps, comparable to that of the covalently linked LH2-ATTO that we previously reported. In addition, the biohybrid LH system exhibited a much higher antenna effect than the LH2-ATTO system because of the higher loading level of ATTO in the membrane. These findings suggest that the facile self-assembled biohybrid LH system is a promising system for constructing LH for solar-energy conversion.

Recently, a new erythroid regulator, erythroferrone (ERFE), which downregulates hepatic hepcidin production, has been identified. However, the relationship between ERFE and abnormal iron metabolism in MDS is unclear. In this study, we examined the level of ERFE mRNA during ex vivo erythroid differentiation using cord blood CD34+ cells and we further analyzed whether ERFE could be produced by MDS cells using a public database (GSE58831). ERFE mRNA was increased during normal erythroid differentiation. An analysis of GSE58831 indicated that ERFE expression in bone marrow (BM) MDS cells was higher than that in healthy volunteer (HV)-derived BM cells. ERFE expression significantly and positively correlated with the expression of erythropoietin (EPO) receptors (EPO-R), ALAS2 (5'-Aminolevulinate Synthase 2), STEAP3 (STEAP family member 3) and the presence of ring sideroblasts or the SF3B1 mutation. These results suggest that EPO-R+ MDS cells with ring sideroblasts or an SF3B1 mutation produce high levels of ERFE that may be associated with a reduction in hepcidin.

BACKGROUND AND AIM In Japan, screening colonoscopy for colorectal cancer is expected to reduce colorectal cancer mortality, although its complication rate has not been sufficiently examined. The aim of this study is to analyze severe complications due to colonoscopy. METHODS As a study population, we retrospectively used commercially anonymized health insurance claims data covering 5.71 million patients from January 2005 to August 2018. We extracted patients who received colonoscopy with lesions resection or without treatment. Main outcomes were rates of hemorrhage, perforation, fatal events, and their risk factors. RESULTS Among 341 852 colonoscopy without treatment in 260 128 patients (mean age: 49.6 ± 11.7 years), the rates of hemorrhage, perforation, and fatal events were 0.0059% (95% confidence interval [CI] 0.0031-0.0085), 0.0032% (95% CI 0.0011-0.0052), and 0.00029% (95% CI 0-0.0012), respectively. Regarding hemorrhage, compared with the rate for patients

Patients with HIV are at higher risk of developing thrombosis than the general population. We present a rare case of a 57-year-old Japanese man with HIV infection and a malignant lymphoma. He had fever with unknown origin and cervical lymph node swelling 2 months before his hospital visit. Because he was positive for the HIV antibody, he was referred to our HIV special outpatient section. HIV RNA level was found to be 846,680 copies/ml. Therefore, antiretroviral therapy of DTG/ABC/3TC was initiated. However, the high fever continued for 7 days after treatment initiation; moreover, renal dysfunction was progressive. After admission, antibiotic therapy was initiated, due to which the fever subsided. However, renal dysfunction continued to progress. Fourteen days later, he died due to acute renal failure with hyperkalemia. An autopsy revealed a large mass in the spleen, and histological findings revealed a diffuse large B cell lymphoma (DLBCL). Furthermore, thrombi were detected in the right and left ventricles, right atrium, iliac artery, and renal artery. Pathological findings revealed that the thrombus induced the renal failure. These thrombi contained fibrin with inflammatory cell infiltration but not tumor cells. Patients with HIV and malignant lymphoma are at a higher risk of thrombosis. It is important to consider thrombosis during the treatment of patients with HIV.

Objectives Intensive nutritional support during allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields improved clinical outcomes. However, the clinical implications of early enteral nutrition (EN) in allo-HSCT remain unclear. This retrospective study was conducted to determine the significance of early EN in individuals who underwent allo-HSCT, and the association between early nutritional intervention and clinical outcomes, including the status of the intestinal microbiome. Methods Thirty-one participants received EN before conditioning. The intestinal microbiota was examined by meta 16S rRNA gene sequencing of fecal samples. Results The median body mass variation was only −0.35 kg on day 60. The probability of 2-y overall survival was 61.1%. The cumulative incidence of treatment-related mortality was 17.4%, and those of acute graft-versus-host disease were 32.3% (grades II–IV) and 3.2% (grades III–IV). Chronic graft-versus-host disease was observed in four participants. Dysbiosis of the intestines and acute graft-versus-host disease occurred simultaneously, and Enterococcus species were abundant. Conclusions Our results suggest that early nutritional support can improve the outcomes for individuals who have undergone allo-HSCT and can maintain homeostasis of their intestinal microbiome. Future prospective clinical trials are required to elucidate the role of EN in allo-HSCT and the association between the intestinal microbiome and EN.

Background. Iron absorption from gastrointestinal tract was enhanced in a subset of patients with myelodysplastic syndrome (MDS) exhibiting ineffective erythropoiesis. Duodenal iron absorption was achieved via an iron transporter divalent metal transporter (DMT)-1 and ferroportin which was downregulated by hepatic hepcidin. Recently, three erythroid regulators such as growth differentiation factor 15 (GDF15), twisted gastrulation protein homolog 1 (TWSG1) and erythroferrone (ERFE) which down regulated hepatic hepcidin production has been identified. However, it has been not yet clarified which molecules could contribute to the increased iron absorption in patients with MDS. Materials and Methods. In the present study, we examined the expression level of GDF15, TWSG1 and ERFE mRNA during ex vivo erythroid differentiation from sodium butyrate (SB)-treated K562 and CD34+ bone marrow (BM) cells in the presence of 4 U/mL erythropoietin (EPO), 100 U/mL interleukin-3, 10 ng/mL stem cell factor, 20 ng/mL insulin-like growth factor (IGF)-1 and 500 micro g/mL iron-saturated transferrin. We further analyzed the expression level of GDF15 and ERFE by using a GEO dataset (GSE58831). GEO dataset was downloaded as a matrix by GEOquery package (Bioconductor). The numerical data of the matrix were normalized by quantile normalization using limma package. Clinical and sequencing data were downloaded from supplementary materials. Those were combined with a GEO dataset (GSE58831) before analysis. Results. The levels of ERFE and GDF15 mRNA were dramatically increased during erythroid differentiation from SB-treated K562 and normal CD34+ cells in response to EPO in vitro. Using GEO data sets (GSE58831), the levels of ERFE and GDF15 mRNA in CD34+ cells derived from MDS patients were significantly elevated as compared with that from healthy volunteers. Importantly, the levels of ERFE and GDF15 mRNA in CD34+ cells in a subset of MDS with ring sideroblasts (RS) or SF3B1 mutation were significantly and highly elevated as compared with other subsets of MDS (GSE58831). Additionally, the supernatant derived from SB-treated K562 reduced hepcidin level in HepG2 in the presence of EPO. Conclusion. These results suggested that productions of ERFE and GDF15 in CD34+ MDS cells with RS or SF3B1 mutation may be associated with abnormal iron metabolism via hepcidin reduction. These findings may be useful to understanding the high ferritin level in a subset of MDS patients. Figure 1 Disclosures Kobune: Takeda Pharmaceutical Company: Research Funding; Alexion Pharmaceuticals Inc: Research Funding; Novartis Pharma K.K.: Research Funding; ONO PHARMACEUTICAL CO., LTD: Research Funding. Ikeda:Alexion Pharmaceuticals Inc: Research Funding; Takeda Pharmaceutical Company Limited: Research Funding; Novartis Pharma K.K.: Research Funding; Sanofi K.K.: Research Funding; ONO PHARMACEUTICAL CO., LTD: Research Funding.

A 62-year-old man was referred to our hospital due to pancytopenia and abnormal leukocyte fraction in December 2016. Bone marrow aspiration showed a massive proliferation of blast cells (96%) with rich myeloperoxidase-negative basophilic granules. He was diagnosed with acute basophilic leukemia, and an appropriate treatment for acute myelogenous leukemia was initiated. Blast cells were positive for minor BCR-ABL mutations, and chemotherapy using imatinib was initiated on day 7. The treatment was effective and complete remission was achieved on day 30. The ultrastructural features of blast cells showed typical basophilic granules with high electron density structure on electron microscopy. However, immunohistochemical analysis were positive for CD79a, PAX5, and TdT expression. Rearrangements of immunoglobulin heavy chain and T-cell receptor genes were detected, prompting the diagnosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph

We report three cases of POEMS syndrome treated with lenalidomide and dexamethasone who presented with peripheral neuropathy. All of them had markedly elevated serum vascular endothelial growth factor (VEGF) levels treated with lenalidomide and dexamethasone for severe peripheral neuropathy, which normalized serum VEGF levels and improved peripheral neuropathy. The standard treatment of POEMS syndrome has not been established, but has been effectively treated with high-dose chemotherapy with autologous stem cell transplantation. Newer agents currently used for plasma cell dyscrasias include bortezomib and immunomodulatory drugs, such as thalidomide and lenalidomide. A randomized controlled trial on thalidomide plus dexamethasone for POEMS syndrome showed reduced serum VEGF levels after therapy; however, the incidence of peripheral neuropathy, a well-known side effect of both thalidomide and bortezomib, increased. Lenalidomide is associated with lower incidence of peripheral neuropathy compared to thalidomide and bortezomib, making it a reasonable treatment option for POEMS syndrome.

We and others have demonstrated that various abnormalities of the bone marrow (BM) mesenchymal stromal cells (MSCs) such as aberrant cytokine expression, abnormal hedgehog signaling, and impaired miRNA biogenesis are observed in patients with acute myeloid leukemia (AML). However, underlying mechanisms to induce the dysfunction of BM MSCs have not yet been clarified. We previously showed that AML cells release abundant exosomal miR-7977, which, in turn, enters BM mesenchymal stromal cells (MSCs). However, the precise function of miR-7977 is not known. In this study, we performed transduction of a miR-7977 mimic into MSCs, compared transcriptomes between control-transduced (n = 3) and miR-7977-transduced MSCs (n = 3), and conducted pathway analysis. The array data revealed that the expression of 0.05% of genes was reduced 2-fold and the expression of 0.01% of genes was increased 2-fold. Interestingly, approximately half of these genes possessed a miR-7977 target site, while the other genes did not, suggesting that miR-7977 regulates the gene expression level directly and indirectly. Gene set enrichment analysis showed that the gene sets of Yes-associated protein 1 (YAP1) _up were significantly enriched (p

[Background] We and others have revealed that various abnormalities of the bone marrow (BM) environment such as aberrant cytokine expression and impaired microRNA (miRNA) biogenesis are observed in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, underlying mechanisms to induce BM stromal dysfunction have not yet been clarified. Recently, we have found that abundant extracellular vesicles including exosomes, were detected in the BM interstitial fluid. Furthermore, we have shown that exosomal miR-7977 was highly released from AML cells (GSE64029) and was taken up by BM mesenchymal stem cells (MSCs). Based on these findings, we hypothesized that exosomal miR-7977 could be involved in the alteration of BM stromal function of MDS/AML. [Materials and Methods] To gain an insight into the function of exosomal miR-7977 in BM, we firstly performed transduction of a miR-7977 mimic into BM MSCs and compared transcriptomes between control-transduced and miR-7977-transduced MSCs (GSE108186). Subsequently, we selected the differentially expressed genes (DEGs) and conduced gene set enrichment analysis (GSEA). [Results] Regarding DEGs, we focused on poly(rC) binding protein 1 (PCBP1), since PCBP1 was predicted to be a target gene of miR-7977 by an online database for miRNA target prediction using miRDB. The reductions in PCBP1 mRNA and protein were confirmed in MSCs after miR-7977 transfer by real time PCR. Because PCBP1 is known to be involved in splicing, and the expression levels of several genes, we analyzed the expression of several hematopoietic factors and found that expression level of stem cell factor (SCF), angiopoietin-1 (ANGPT1) and Jagged-1 (JAG1) were remarkably decreased. Regarding the pathway analysis, GSEA showed that the gene sets of Yes-associated protein 1 (YAP1)_up were significantly enriched (p [Conclusion] Collectively, these results indicated that miR-7977 is an important factor that inhibits normal hematopoiesis via PCBP1 reduction and up-regulate the growth of functionally-disturbed MSCs via inactivation of Hippo-YAP signaling pathway in MDS/AML. Disclosures No relevant conflicts of interest to declare.