eIF2α signaling regulates ischemic osteonecrosis through endoplasmic reticulum stress

Osteonecrosis of the femoral head (ONFH) primarily results from ischemia/hypoxia to the femoral head, and one of the cellular manifestations is the endoplasmic reticulum (ER) stress. To understand possible linkage of ischemic osteonecrosis to the ER stress, a surgery-induced animal model was employed and salubrinal was administered to evaluate the role of ER stress. Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eIF2α, and it can suppress cell death from the ER stress at a proper dose. The results indicated that the ER stress was associated with ONFH and salubrinal significantly improved ONFH-induced symptoms such as osteonecrosis, bone loss, reduction in vessel perfusion, and excessive osteoclastogenesis in the femoral head. Salubrinal also protected osteoblast development by upregulating the levels of ATF4, ALP and RUNX2, and it stimulated angiogenesis of endothelial cells through elevating ATF4 and VEGF. Collectively, the results support the notion that the ER stress is an important pathological outcome in the surgery-induced ONFH model, and salubrinal improves ONFH symptoms by enhancing angiogenesis and bone healing via suppressing the ER stress

Simple transanal total mesorectal resection versus laparoscopic transabdominal total mesorectal resection for the treatment of low rectal cancer: a single-center retrospective case-control study

AimTo evaluate the efficacy and safety of simple TaTNE in the treatment of low rectal cancer compared with laparoscopic transabdominal TME.MethodsWe collected patients with low rectal cancer admitted to our hospital between January 2019 and November 2021 who received simple TaTME or laparoscopic transabdominal TME. The main outcome was the integrity of the TME specimen. Secondary outcomes were the number of lymph nodes dissected, intraoperative blood loss, operative time, surgical conversion rate, Specimen resection length, circumferential margin (CRM), and distal resection margin (DRM), complication rate. In addition, the Wexner score and LARS score of fecal incontinence were performed in postoperative follow-up.ResultsPathological tissues were successfully resected in all patients. all circumferential margins of the specimen were negative. Specimen resection length was not statistically significant (9.94 ± 2.85 vs. 8.90 ± 2.49, P > 0.05). The incidence of postoperative complications in group A (n = 0) was significantly lower than that in group B (n = 3) (P > 0.05). There was no significant difference in operation time between group A and group B (296 ± 60.36 vs. 305 ± 58.28, P > 0.05). Among the patients with follow-up time less than 1 year, there was no significant difference in Wexner score and LARS score between group A and group B (P > 0.05). However, in patients who were followed up for more than 1 year, the Wexner score in group A (9.25 ± 2.73) was significantly lower than that in group B (17.36 ± 10.95) and was statistically significant (P < 0.05).ConclusionFor radical resection of low rectal cancer, Simple TaTME resection may be as safe and effective as laparoscopic transabdominal TME, and the long-term prognosis may be better

スマホで古辞書 : 『篆隷万象名義』のIDS検索を例に

会議名: 言語資源活用ワークショップ2016, 開催地: 国立国語研究所, 会期: 2017年3月7日-8日, 主催: 国立国語研究所 コーパス開発センター近年,スマートフォンやタブレットのようなモバイル端末が普及し,日常生活を変えつつあり,日本語教育・日本語研究にも使えるようになると予想される。しかしながら,構築・公開が盛んである古典籍・古文書のデータベースはPC 向けが多く,PC以外の端末で利用する際は表示サイズのずれや機能障害がしばしば発生する。そこで,モバイル端末でデータベースを利用しているユーザを想定した利便性が高い言語資源データベースのWeb インターフェイスを開発したい。漢字字形の構造情報を用いて古辞書のテキスト・画像を検索することによって文字の同定に利用できるWeb アプリはまだないので,篆隷万象名義の掲出字についてIDS 検索と画像表示を可能にするツールを試作した。本アプリによって,漢字のパーツで篆隷万象名義に掲載している文字の画像をスマートフォンなどの携帯端末で検索でき,写本の解読・翻刻する際に役立つと期待している

Synthesis, photophysical properties and two-photon absorption study of tetraazachrysene-based N-heteroacenes

Three novel N‐heteroacene molecules (SDNU‐1, SDNU‐2 and SDNU‐3) based on tetraazachrysene units as cores have been designed, synthesized and fully characterized. Their photophysical, electrochemical and fluorescence properties were investigated, and they exhibited blue to green emission in the solid state. Interestingly, SDNU‐2 exhibited high solid photoluminescence quantum efficiencies (75.3 %), which is the highest value of N‐heteroacenes derivatives to date. Two‐photon absorption studies have been conducted by using the open and close aperture Z‐san technique. SDNU‐3 showed a significant enhancement in the two‐photon absorption cross‐section with magnitudes as high as about 700 GM (1 GM=1×10−50 cm4 s/photon) when excited with 800 nm light, which is the largest value based on a heteroacene system measured by using a Z‐scan experiment so far. We attribute the outcome to sufficient electronic coupling between the strong charge transfer of quadrupolar substituents and the tetraazachrysene core. Our result would provide a new guideline to design novel efficient two‐photon materials based on N‐heteroacene cores

夢梅本『倭玉篇』全文テキストデータベースの構築

会議名: 言語資源活用ワークショップ2016, 開催地: 国立国語研究所, 会期: 2017年3月7日-8日, 主催: 国立国語研究所 コーパス開発センター本発表は,夢梅本『倭玉篇』の全文テキストデータベースの構築と,その利用について述べるものである。『倭玉篇』は中世に生まれ近世まで広く用いられた漢和字書である。多種の写刊本が現存し,それらについて研究が行われてきたが,その多くは部首配列や特定の部を対象にした部分的なものであった。そこで『倭玉篇』の,特に和訓に関する全体的な研究を目的として,慶長10 年（1605)刊行の夢梅本『倭玉篇』の全文テキストデータベースを構築した。この字書は『大広益会玉篇』を中心とした中国辞書を編纂基盤としており,すでに構築されているデータを用いて効率的に入力作業を進めることができる。構築したデータベースは約22,000 字を収録する掲出字テーブルと,約24,000 の和訓を収録する和訓テーブルからなり,中世末期の字訓対応の資料としても価値がある。また,このデータは「平安時代漢字字書総合データベース」の和訓データの整備にも使用される予定である

MoS2 Nanosheets Assembled on Three-Way Nitrogen-Doped Carbon Tubes for Photocatalytic Water Splitting

In this work, a micron-sized three-way nitrogen-doped carbon tube covered with MoS2 nanosheets (TNCT@MoS2) was synthesized and applied in photocatalytic water splitting without any sacrificial agents for the first time. The micron-sized three-way nitrogen-doped carbon tube (TNCT) was facilely synthesized by the calcination of commercial sponge. The MoS2 nanosheets were assembled on the carbon tubes by a hydrothermal method. Compared with MoS2, the TNCT@MoS2 heterostructures showed higher H2 evolution rate, which was ascribed to the improved charge separation efficiency and the increased active sites afforded by the TNCT

Programmable Base Editing of the Sheep Genome Revealed No Genome-Wide Off-Target Mutations

Since its emergence, CRISPR/Cas9-mediated base editors (BEs) with cytosine deaminase activity have been used to precisely and efficiently introduce single-base mutations in genomes, including those of human cells, mice, and crop species. Most production traits in livestock are induced by point mutations, and genome editing using BEs without homology-directed repair of double-strand breaks can directly alter single nucleotides. The p.96R > C variant of Suppressor cytokine signaling 2 (SOCS2) has profound effects on body weight, body size, and milk production in sheep. In the present study, we successfully obtained lambs with defined point mutations resulting in a p.96R > C substitution in SOCS2 by the co-injection of BE3 mRNA and a single guide RNA (sgRNA) into sheep zygotes. The observed efficiency of the single nucleotide exchange in newborn animals was as high as 25%. Observations of body size and body weight in the edited group showed that gene modification contributes to enhanced growth traits in sheep. Moreover, targeted deep sequencing and unbiased family trio-based whole genome sequencing revealed undetectable off-target mutations in the edited animals. This study demonstrates the potential for the application of BE-mediated point mutations in large animals for the improvement of production traits in livestock species

Trio-Based Deep Sequencing Reveals a Low Incidence of Off-Target Mutations in the Offspring of Genetically Edited Goats

Unintended off-target mutations induced by CRISPR/Cas9 nucleases may result in unwanted consequences, which will impede the efficient applicability of this technology for genetic improvement. We have recently edited the goat genome through CRISPR/Cas9 by targeting MSTN and FGF5, which increased muscle fiber diameter and hair fiber length, respectively. Using family trio-based sequencing that allow better discrimination of variant origins, we herein generated offspring from edited goats, and sequenced the members of four family trios (gene-edited goats and their offspring) to an average of ∼36.8× coverage. This data was to systematically examined for mutation profiles using a stringent pipeline that comprehensively analyzed the sequence data for de novo single nucleotide variants, indels, and structural variants from the genome. Our results revealed that the incidence of de novo mutations in the offspring was equivalent to normal populations. We further conducted RNA sequencing using muscle and skin tissues from the offspring and control animals, the differentially expressed genes (DEGs) were related to muscle fiber development in muscles, skin development, and immune responses in skin tissues. Furthermore, in contrast to recently reports of Cas9 triggered p53 expression alterations in cultured cells, we provide primary evidence to show that Cas9-mediated genetic modification does not induce apparent p53 expression changes in animal tissues. This work provides adequate molecular evidence to support the reliability of conducting Cas9-mediated genome editing in large animal models for biomedicine and agriculture

Functionalizing tetraphenylpyrazine with perylene diimides (PDIs) as high-performance nonfullerene acceptors

Perylene diimide (PDI)-based small molecular acceptors with a three-dimensional structure are thought to be essential for efficient photocurrent generation and high power conversion efficiencies (PCEs). Herein, a couple of new perylene diimide acceptors (PPDI-O and PPDI-Se) have been designed and successfully synthesized using pyrazine as the core-flanking pyran and selenophene-fused PDIs, respectively. Compared to PPDI-O, PPDI-Se exhibits a blue-shifted absorption in the 400–600 nm range, a comparable LUMO level, and a more distorted molecular geometry. The PPDI-Se-based organic solar cell device with PDBT-T1 as the donor achieved the highest PCE of 7.47% and a high open-circuit voltage (Voc) of up to 1.05 V. The high photovoltaic performance of PPDI-Se-based devices can be attributed to its high LUMO energy level, complementary absorption spectra with donor materials, favorable morphology and balanced carrier transport. The results demonstrate the potential of this type of fullerene-free acceptor for high efficiency organic solar cells