Fabrication of continuous mesoporous carbon films with face-centered orthorhombic symmetry through a soft templating pathway

Preparation of well-ordered continuous mesoporous carbon films without the use of an intermediate inorganic template was achieved by spin coating of a thermosetting phenolic resin, resorcinol/phloroglucinol/formaldehyde, and a thermally-decomposable organic template, Pluronic F127 (PEO106–PPO70–PEO106). The carbon films were deposited onto silicon, platinum/silicon, copper, glass, and quartz substrates. Afterwards, decomposition of the organic template and solidification of the carbon precursors are simultaneously performed through a carbonization process. The resulting films referred to as CKU-F69, are (010)-oriented, and possess a face-centered orthorhombic Fmmm symmetry. Film periodicity is maintained even after a 68% uniaxial contraction perpendicular to the substrate brought on by carbonization at 800 °C. This method could facilitate the mass-production and creation of new carbon and carbon–polymer porous films that find broad potential applications in catalysis, separation, hydrogen storage, bioengineering, nanodevices, and nanotemplates

Retinol Supplements Antiviral Action of Interferon in Patients with Chronic Hepatitis C: A Prospective Pilot Study

Sustained virologic response with peg-interferon and ribavirin combination therapy for 48 weeks is still inadequate. Our study examined whether short-term administration of retinol clinically influences the anti-viral activity of interferon early during interferon and ribavirin combination therapy. The control group received 6 MIU of interferon α-2b every day for two weeks and then 3 times a week for 22 weeks intramuscularly plus 600 mg or 800 mg per day of ribavirin orally for 24 weeks. The retinol group, in addition to above treatment, received retinol 30,000 units per day orally for 3 weeks from one week before the start of interferon α-2b plus ribavirin combination therapy. The hepatitis C virus (HCV) RNA negativity rate at 1 week after the end of interferon α-2b and ribavirin combination therapy was 46.7% (28/60) for the retinol group and 31.7% (19/60) for the control group, which was significantly higher for the retinol group. The level of serum HCV RNA in the retinol group was significantly lower at 1 week after beginning treatment as compared to the control group (p<0.01). Furthermore, serum 2,5'AS protein at 1 week after beginning treatment was significantly higher in the retinol group (p = 0.0002). The results suggest that retinol supplement increases the antiviral effect of interferon α-2b plus ribavirin only during the administration of IFN α-2b, ribavirin and retinol in patients with chronic hepatitis C

Adsorption and Diffusion Phenomena in Crystal Size Engineered ZIF‑8 MOF

ZIF-8 is a flexible zeolitic imidazole-based metal−organic framework whose narrow pore apertures swing open by reorientation of imidazolate linkers and expand when probed with guest molecules. This work reports on the crystal size dependency of both structural transitions induced by N2 and Ar adsorption and dynamic adsorption behavior of n-butanol using well-engineered ZIF-8 crystals with identical surface area and micropore volume. It is found that the crystal downsizing of ZIF-8 regulates the structural flexibility in equilibrium adsorption and desorption of N2 and Ar. Adsorption kinetics of n-butanol in ZIF-8 are strongly affected by the crystal size, however, not according to a classical intracrystalline diffusion mechanism. Our results suggest that structural transitions and transport properties are dominated by crystal surface effects. Crystal downsizing increases the importance of such surface barriers

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

精索静脈瘤根治術の体外授精, 胚移植における受精および妊娠におよぼす影響

精索静脈瘤根治術が精液所見あるいはハムスター卵貫通試験の成績を改善させることはひろく知られている。しかしこれらは, 体外授精の成功率とは相関しない。そこで, 精索静脈瘤根治術の体外授精におよぼす影響を調べる目的で, 高度の乏精子症を呈する夫が精索静脈瘤を有し, かつ体外授精に失敗した13組の夫婦を追跡した。この13組は, 夫の精索静脈瘤根治術終了後再び体外授精を試みた。その結果, 術前は妊娠例が認められなかったが, 術後4例に妊娠が確認された。この4例においては, 精子濃度および運動率は上昇したAlthough varicocelectomy is generally believed to improve semen quality and the hamster egg penetration assay, these parameters do not correlate well with in vitro fertilization (IVF) success. The effect of varicocelectomy on IVF of human oocytes was examined on thirteen couples with normal female fertility, but severe oligozoospermia and the presence varicocele in the males with failure of fertilization preoperatively in in vitro fertilization-embryo of transfer (IVF-ET) attempts. The couples were readmitted for the IVF-ET procedure following varicocelectomy. A 31% pregnancy rate was achieved after the operation, while no pregnancies occurred before surgery. Sperm density and motility improved significantly after operation, resulting in a coinciding improved fertilization and pregnancy rates

鶏卵尿漿膜上に異種移植されたヒト腫瘍の増殖動態

腎細胞癌の78.6%, 尿路上皮癌の77.8%, 精巣腫瘍の66.7%, 結腸腺癌, 及び卵巣腺癌は移植に成功したが, 前立腺癌は全て失敗した。組織学的に膜上で生存している細胞は, 構造が良く保たれている類器官を形成していた。しかし, 癌巣の生存力は壊死組織周囲の炎症性変化の影響を受けなかった。腎細胞癌は生存し, 瀰漫性に顕著に血管を形成していた。膜上の癌細胞の%BrdU(ブロモデオキシウリジン)標識指数と元の腫瘍の%Ki-67指数との間には強い相関が認められた。癌巣の大小によっては%BrdU指数に差異がなかった。接種後8日間成長状態は一定に留まっていた。生存している癌巣の成長能力はインキュベーション中不変We evaluated the success rates of transplantation and growth conditions of 33 human tumor xenografts transplanted on the chorioallantoic membrane of chick embryos. Eleven out of 14 renal cell carcinomas (78.6%), 7 out of 9 urothelial carcinomas (77.8%), 2 out of 3 testicular tumors (66.7%), an adenocarcinoma of the colon and an adenocarcinoma of the ovary but none of the 5 prostatic carcinomas were transplanted successfully. Histologically, carcinoma cells survived on the chorioallantoic membrane forming organoids the structure of which was well preserved. Several regions of the grafts frequently became necrotized. However, the viability of carcinoma nests was not influenced by the inflammatory changes surrounding necrotic tissues. Renal cell carcinomas survived diffusely with prominent angiogenesis. Immunostaining with anti-bromodeoxyuridine (BrdU) and Ki-67 monoclonal antibodies demonstrated a strong correlation between the %BrdU labeling index of the cancer cells on the chorioallantoic membrane and %Ki-67 index of the original tumors. No difference in %BrdU indexes was found between small and large cancer nests. Growth conditions remained constant for 8 days after inoculation. The growth potential of cancer nests surviving on the chorioallantoic membrane, which was identical to that of the original carcinomas, appeared to be unchanged during incubation. However, it might be difficult to exploit the chorioallantoic membrane for anticancer chemosensitivity tests except for renal cell carcinoma since few cancer cell nests were produced in spite of the high transplantation success rates