98 research outputs found

    Enhancing thermoelectric performance of Cu3SnS4-based solid solutions through coordination of the Seebeck coefficient and carrier concentration

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    Improving the thermoelectric (TE) performance of Cu3SnS4 is challenging because it exhibits a metallic behavior, therefore, a strategy should be envisaged to coordinate the carrier concentration (nH) and Seebeck coefficient (α). The coordination in this work has been realized through the Fermi level (Ef) unpinning and shifting towards the conduction band (CB) via addition of excess Sn in Cu3SnS4. As a result, the solid solution Cu3Sn1+xS4 (x = 0.2) has a moderate α (178.0 μV K−1) at 790 K and a high nH (1.54 × 1021 cm−3) value. Along with the lowest lattice thermal conductivity κL (0.39 W K−1 m−1) caused by the increased phonon scattering by carriers, the highest ZT value of 0.75 is attained at ∼790 K. This value is 2.8 times that of the stoichiometric Cu3SnS4, and stands among the highest for ternary Cu–Sn–S sulfide thermoelectrics at the corresponding temperatures. More importantly, this approach used in the case of ternary Cu3SnS4 provides a guidance or reference to improve the TE performance of other materials

    Intestinal epithelial cell-derived IL-15 determines local maintenance and maturation of intraepithelial lymphocytes in the intestine

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    Interleukin-15 (IL-15) is a cytokine critical for maintenance of intestinal intraepithelial lymphocytes (IELs), especially CD8αα+ IELs (CD8αα IELs). In the intestine, IL-15 is produced by intestinal epithelial cells (IECs), blood vascular endothelial cells (BECs) and hematopoietic cells. However, the precise role of intestinal IL-15 on IELs is still unknown. To address the question, we generated two kinds of IL-15 conditional knockout (IL-15cKO) mice: villin-Cre (Vil-Cre) and Tie2-Cre IL-15cKO mice. IEC-derived IL-15 was specifically deleted in Vil-Cre IL-15cKO mice, whereas IL-15 produced by BECs and hematopoietic cells is deleted in Tie2-Cre IL-15cKO mice. The cell number and frequency of CD8αα IELs and NK IELs were significantly reduced in Vil-Cre IL-15cKO mice. By contrast, CD8αα IELs were unchanged in Tie2-Cre IL-15cKO mice, indicating that IL-15 produced by BECs and hematopoietic cells is dispensable for CD8αα IELs. Expression of an anti-apoptotic factor, Bcl-2, was decreased, whereas Fas expression was increased in CD8αα IELs of Vil-Cre IL-15cKO mice. Forced expression of Bcl-2 by a Bcl-2 transgene partially restored CD8αα IELs in Vil-Cre IL-15cKO mice, suggesting that some IL-15 signal other than Bcl-2 is required for maintenance of CD8αα IELs. Furthermore, granzyme B production was reduced, whereas PD-1 expression was increased in CD8αα IELs of Vil-Cre IL-15cKO mice. These results collectively suggested that IEC-derived IL-15 is essential for homeostasis of IELs by promoting their survival and functional maturation

    Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database

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    Introduction: Linezolid is an oxazolidinone antibiotic that is active against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups.Results: A total of 11,176 reports of linezolid as the “primary suspected” drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia (n = 1,139, ROR 21.98), anaemia (n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis (n = 90, ROR 4.33), and electrocardiogram QT prolonged (n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs (n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment (n = 46).Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings

    A circulating subset of iNKT cells mediates antitumor and antiviral immunity

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    新規の循環型iNKT細胞を発見 --抗腫瘍・抗ウイルス感染効果の高い免疫細胞療法の開発への貢献に期待--. 京都大学プレスリリース. 2022-10-24.Invariant natural killer T (iNKT) cells are a group of innate-like T lymphocytes that recognize lipid antigens. They are supposed to be tissue resident and important for systemic and local immune regulation. To investigate the heterogeneity of iNKT cells, we recharacterized iNKT cells in the thymus and peripheral tissues. iNKT cells in the thymus were divided into three subpopulations by the expression of the natural killer cell receptor CD244 and the chemokine receptor CXCR6 and designated as C0 (CD244⁻CXCR6⁻), C1 (CD244⁻CXCR6⁺), or C2 (CD244⁺CXCR6⁺) iNKT cells. The development and maturation of C2 iNKT cells from C0 iNKT cells strictly depended on IL-15 produced by thymic epithelial cells. C2 iNKT cells expressed high levels of IFN-γ and granzymes and exhibited more NK cell–like features, whereas C1 iNKT cells showed more T cell–like characteristics. C2 iNKT cells were influenced by the microbiome and aging and suppressed the expression of the autoimmune regulator AIRE in the thymus. In peripheral tissues, C2 iNKT cells were circulating that were distinct from conventional tissue-resident C1 iNKT cells. Functionally, C2 iNKT cells protected mice from the tumor metastasis of melanoma cells by enhancing antitumor immunity and promoted antiviral immune responses against influenza virus infection. Furthermore, we identified human CD244⁺CXCR6⁺ iNKT cells with high cytotoxic properties as a counterpart of mouse C2 iNKT cells. Thus, this study reveals a circulating subset of iNKT cells with NK cell–like properties distinct from conventional tissue-resident iNKT cells

    Potential metabolism of pharmaceuticals in radish : Comparison of in vivo and in vitro exposure

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    Metabolism of pharmaceuticals in plants is important to evaluate their fate and accumulation in vegetables, and subsequently the risks to human health. However, limited knowledge is available to evaluate metabolism of pharmaceuticals in plants due to the lack of appropriate research approaches. In this study, radish was selected as a model plant to investigate metabolism of pharmaceuticals in intact plants (in vivo) growing in hydroponic solution and in plant tissue enzyme extracts (in vitro). For caffeine, six phase-I demethylation metabolites identified in the intact radish plant were also found in the plant enzyme extracts. After 7 days of in vivo exposure, the amount of the identified metabolites was about 5.4 times greater than the parent compound caffeine in radish roots. Furthermore, the metabolism potential of fifteen pharmaceuticals in radish was evaluated on the basis of mass balance. After 7 days of hydroponic exposure, oxytetracycline, trimethoprim, carbamazepine, lincomycin, monensin and tylosin manifested relatively less extent of metabolism with the mass recoveries ranging from 52.3 to 78.2%. In contrast, 17 β-estradiol, sulfamethoxazole, sulfadiazine, estrone, triclosan, acetaminophen, caffeine, carbadox and lamotrigine underwent extensive metabolism with only 3.0 to 32.1% of the parent compound recovered. In the in vitro system, 17 β-estradiol, estrone, triclosan, oxytetracycline, acetaminophen, sulfadiazine and sulfamethoxazole were readily metabolized in radish root enzyme extracts with 1.8 to 34.0% remaining after 96-h exposure. While in the leaf enzyme extracts, only triclosan was rapidly metabolized with 49.2% remaining, and others pharmaceuticals were ≥60%, indicating that the varying extents of metabolism occurred in different plant parts. This study highlights the importance of pharmaceutical metabolism in plants, and suggests that plant tissue enzyme extracts could serve as an alternative tool to assess pharmaceutical metabolism in plants. Similar metabolism patterns were observed for rapidly metabolized pharmaceuticals in both in vivo (radish tissue enzyme extracts) and in vivo (the intact plant) exposure

    Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus

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    Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis

    Highly efficient firewood-fuelled cooking stoves

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    1 Comment an Anonymous Multi-receiver Identity-based Encryption Scheme

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    Abstract—Anonymous receiver encryption is an important cryptographic primitive. It can protect the privacy of the receiver. In 2010, Fan et al proposed an anonymous multireceiver ID-based encryption by using Lagrange interpolating polynomial. Recently, Wang et al showed that Fan et al’s scheme satisfied anonymity of the receivers. Then they provided an improved scheme to fix it and showed that the improved scheme was secure. Unfortunately, we pointed out that Wang et al’s improved scheme did’t satisfy the receiver’s anonymity by analyzing the security of the scheme yet. After analyzing the reason to produce such flaw, we give an improved method to repair it and show that our improved scheme satisfies the receiver’s anonymity, and the improved scheme has advantage over Wang et al’s scheme in terms of computational cost. Keywords: Anonymity, multi-receiver ID-based encryption, attack, the improved metho
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