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1.
惊鸿 (2024-06-30 17:55):
#paper No CRISPR: oddball ‘jumping gene’ enzyme edits genomes without breaking DNA Pub Date : 2024-06-27 DOI : 10.1038/d41586-024-02141-x 阅读了关于利用跳跃基因进行基因编辑的研究论文,我对其科学创新和潜在应用产生了兴趣。这项技术通过利用细菌中的跳跃基因,提供了一种新的基因编辑手段,能够在不破坏DNA的情况下进行大规模的基因序列操作。与传统的CRISPR-Cas9技术相比,它在理论上能够进行更精确和更少副作用的基因编辑。 论文中提到的IS110和IS1111家族的转座元件,以及它们使用的RNA引导系统,展示了基因编辑领域的新方向。这项技术在细菌中的成功应用,为未来可能的人类细胞应用提供了初步证据,尽管在实际应用于人类之前,还需要进一步的研究和优化。 此外,这项技术在医学上的应用前景,尤其是在治疗遗传性疾病和癌症方面,是值得关注的。尽管目前还存在一些技术挑战,但科研人员的努力和创新思维为解决这些问题提供了希望。 总的来说,这项研究为基因编辑技术的发展提供了新的视角,也为未来的生物医学研究开辟了新的可能性。
2.
惊鸿 (2024-05-25 20:25):
#paper Pub Date : 2024-02-15 DOI : 10.1017/bap.2023.34 本研究认为韩国经济治国之道的核心是(1)高科技产业供应链多元化,以主动减轻经济胁迫的脆弱性,(2)追求技术主权,以提高先进技术的自给自足,(3) )治理改革以增强供应链的弹性,以及(4)产业政策以增强先进产业的竞争力。上述四种战略的共同点是都以高科技的战略运用为基础。基于这些特征,我将韩国的新经济安全战略定义为技术经济治国之道。韩国的技术经济治国之道有两个特点。首先,韩国利用高科技作为经济和安全之间的纽带。其次,韩国利用高科技作为衔接国内外政策的纽带。
Abstract:
<jats:title>Abstract</jats:title> <jats:p>This study identifies the core of Korea’s economic statecraft as (1) diversification of the supply chain of high-tech industries to proactively mitigate vulnerability to economic coercion, (2) the pursuit … >>>
<jats:title>Abstract</jats:title> <jats:p>This study identifies the core of Korea’s economic statecraft as (1) diversification of the supply chain of high-tech industries to proactively mitigate vulnerability to economic coercion, (2) the pursuit of technological sovereignty to increase self-sufficiency in advanced technologies, (3) governance reforms to strengthen supply chain resilience, and (4) industrial policies to enhance the competitiveness of advanced industries. The four strategies mentioned above all have in common that they are predicated on the strategic utilization of high technology. Based on these traits, I define Korea’s new economic security strategy as techno-economic statecraft. Korea’s techno-economic statecraft has two features. First, Korea utilizes high technology as a nexus between economy and security. Second, Korea uses high technology as a nexus to link domestic and foreign policies.</jats:p> <<<
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3.
惊鸿 (2024-04-24 18:51):
#paper DNA origami mediated electrically connected metal—semiconductor junctions Pub Date : 2020-02-19 DOI : 10.1007/s12274-020-2672-5 无机纳米结构的基于DNA的纳米加工在电子,催化和等离激元学中具有潜在的应用。先前的DNA金属化已经产生了导电的DNA组装的纳米结构。然而,半导体的使用以及DNA纳米结构上良好连接的纳米级金属-半导体结的开发仍处于早期阶段。本文中,我们报告了通过金和碲纳米棒的位置特异性结合在单个DNA折纸上首次制造多个电连接的金属-半导体结。纳米棒附着到DNA折纸上的方法是通过DNA杂交获得Au,通过静电相互作用获得Te。化学镀金用于通过填充Au和Te纳米棒之间的间隙来创建纳米级金属-半导体界面。两点电特性表明,Au-Te-Au结已电连接,电流-电压特性与肖特基结一致。基于DNA的金属-半导体结的纳米加工为纳米电子学打开了潜在的机遇,证明了这种自下而上方法的强大功能。
4.
惊鸿 (2024-01-31 20:12):
#paper Pub Date  : 2024-01-15 DOI : 10.1016/j.str.2023.12.012 tRNA 衍生片段 (tRF) 已成为免疫调节的关键参与者。一些RNase A 超家族成员参与 tRF 群体的形成。通过比较野生型和敲除型巨噬细胞系,我们之前的工作揭示了 RNase 2 可以选择性切割 tRNA。在这里,我们通过筛选合成 tRNA、单突变体和反密码子环 DNA/RNA 发夹来确认体外蛋白质切割模式。通过对 tRF 产物进行测序,我们确定了重组 RNase 2 的切割选择性,在 B 1 (U/C) 和 B 2 (A) 位点具有碱基特异性,这与之前的细胞研究一致。最后,通过MD模拟预测了蛋白质-发夹复合物。结果揭示了 α1、环 3 和环 4 以及 β6 RNase 2 区域的贡献,其中残基 Arg36/Asn39/Gln40/Asn65/Arg68/Arg132 提供相互作用,跨越对反密码子至关重要的P -1到 P 2位点循环识别。对 RNase 2 特异性 tRF 生成的了解可能会指导传染病和免疫相关疾病的新治疗方法。
Abstract:
tRNA-derived fragments (tRFs) have emerged as key players of immunoregulation. Some RNase A superfamily members participate in the shaping of the tRFs population. By comparing wild-type and knockout macrophage cell … >>>
tRNA-derived fragments (tRFs) have emerged as key players of immunoregulation. Some RNase A superfamily members participate in the shaping of the tRFs population. By comparing wild-type and knockout macrophage cell lines, our previous work revealed that RNase 2 can selectively cleave tRNAs. Here, we confirm the in vitro protein cleavage pattern by screening of synthetic tRNAs, single-mutant variants, and anticodon-loop DNA/RNA hairpins. By sequencing of tRF products, we identified the cleavage selectivity of recombinant RNase 2 with base specificity at B (U/C) and B (A) sites, consistent with a previous cellular study. Lastly, protein-hairpin complexes were predicted by MD simulations. Results reveal the contribution of the α1, loop 3 and loop 4, and β6 RNase 2 regions, where residues Arg36/Asn39/Gln40/Asn65/Arg68/Arg132 provide interactions, spanning from P to P sites that are essential for anticodon loop recognition. Knowledge of RNase 2-specific tRFs generation might guide new therapeutic approaches for infectious and immune-related diseases. <<<
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5.
惊鸿 (2023-12-30 08:42):
#paper The quantum house of cards 10.1073/pnas.2313269120 Pub Date  : 2023-12-26 量子计算机已被提议解决许多重要问题,例如发现新药、肥料生产的新催化剂、破解加密协议、优化金融投资组合或实施新的人工智能应用。然而,迄今为止,诸如 3 乘以 5 之类的简单任务超出了现有的量子硬件的能力。本文探讨了量子计算机兑现其承诺需要解决的困难。我讨论了构建量子计算机的整个技术堆栈,从顶层(实际算法和相关应用程序)到最底层(量子硬件、其控制电子设备、低温等),而不是忘记了量子纠错的关键中间层。
Abstract:
Quantum computers have been proposed to solve a number of important problems such as discovering new drugs, new catalysts for fertilizer production, breaking encryption protocols, optimizing financial portfolios, or implementing … >>>
Quantum computers have been proposed to solve a number of important problems such as discovering new drugs, new catalysts for fertilizer production, breaking encryption protocols, optimizing financial portfolios, or implementing new artificial intelligence applications. Yet, to date, a simple task such as multiplying 3 by 5 is beyond existing quantum hardware. This article examines the difficulties that would need to be solved for quantum computers to live up to their promises. I discuss the whole stack of technologies that has been envisioned to build a quantum computer from the top layers (the actual algorithms and associated applications) down to the very bottom ones (the quantum hardware, its control electronics, cryogeny, etc.) while not forgetting the crucial intermediate layer of quantum error correction. <<<
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6.
惊鸿 (2023-11-29 11:58):
#paper DOI : 10.1007/s00417-023-06158-2 Pub Date  : 2023-06-30 Comparisons of the protein expressions between high myopia and moderate myopia on the anterior corneal stroma in human 这篇论文的结论为,与中度近视角膜相比,高度近视角膜在前角膜基质上有 36 个 DEP。高度近视眼角膜的角质形成细胞迁移和细胞骨架的结构成分减弱,这可能部分解释了高度近视眼角膜生物力学较低的原因。较低表达的KRT16在高度近视角膜中发挥重要作用。
7.
惊鸿 (2023-10-30 11:51):
#paper DOI:10.1007/s00417-023-06158-2 Pub Date:2023-06-30 Comparisons of the protein expressions between high myopia and moderate myopia on the anterior corneal stroma in human 这篇文章告诉了前角膜基质上存在高度近视和中度近视之间的36个DEP,其中11个蛋白上调,25个蛋白下调。GO分析显示,高度近视角膜中角质细胞迁移和细胞骨架结构成分发生显着变化,大部分蛋白质减少。角蛋白 16 (KRT16) 和红细胞膜蛋白带 4.1 样蛋白 4B 是仅有的两种参与这两种功能的蛋白。PPI 分析显示角蛋白 II 型细胞骨架 6A (KRT6A) 和 KRT16 具有很强的联系。免疫球蛋白lambda变量8-61(IGLV8-61)和烟酰胺磷酸核糖转移酶(NAMPT)与TMT的结果一致。 得出结论为与中度近视角膜相比,高度近视角膜在前角膜基质上有 36 个 DEP。高度近视眼角膜的角质形成细胞迁移和细胞骨架的结构成分减弱,这可能部分解释了高度近视眼角膜生物力学较低的原因。较低表达的KRT16在高度近视角膜中发挥重要作用。
Abstract:
PURPOSE: To investigate the differentially expressed proteins (DEP) between high myopia and moderate myopia on the anterior corneal stroma. METHODS: Tandem mass tag (TMT) quantitative proteomics was utilized to reveal … >>>
PURPOSE: To investigate the differentially expressed proteins (DEP) between high myopia and moderate myopia on the anterior corneal stroma. METHODS: Tandem mass tag (TMT) quantitative proteomics was utilized to reveal proteins. DEPs were screened by the multiple change of more than 1.2 times or less than 0.83 and the P value < 0.05. The DEPs were functional annotated by Gene Ontology (GO) terms. Proteins and protein interaction (PPI) networks were conducted with String online tool. Parallel reaction monitoring (PRM) data processing was used to verify the TMT proteomics results. RESULTS: There are 36 DEPs between high myopia and moderate myopia on the anterior corneal stroma, of which 11 proteins are upregulated, 25 proteins are downregulated. The GO analysis demonstrated keratinocyte migration and structural constituent of cytoskeleton that are significantly changed with most of the proteins decreased in high myopic corneas. Keratin 16 (KRT16) and erythrocyte membrane protein band 4.1-like protein 4B are the only two proteins involved in both functions. The PPI analysis showed keratin type II cytoskeletal 6A (KRT6A) and KRT16 that have strong connections. Immunoglobulin lambda variable 8-61(IGLV8-61) and nicotinamide phosphoribosyl transferase (NAMPT) have consistent results with the TMT. CONCLUSIONS: The high myopic corneas have 36 DEPs compared to the moderate myopic corneas on the anterior corneal stroma. Keratinocyte migrations and structural constituent of cytoskeleton are weakened in high myopic corneas, which may partly account for the lower corneal biomechanics in high myopic eyes. The lower expressed KRT16 plays important roles in high myopic corneas. <<<
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8.
惊鸿 (2023-09-30 19:52):
#paper Fear of the dark The invisible enemy. 27 September 2023 https://doi.org/10.1038/d41586-023-03002-9 这篇文章描述了一个军官与一位教授的对话,讨论了关于暗物质中的生物存在和潜在威胁的问题。故事中,教授向军官解释了暗物质的存在和性质,并透露他们已经发现了一些暗物质的聚集体,里面有活动的“事物”。这些事物不仅仅是无生命的物质,它们还拥有技术,并且暗物质的力量比我们所知的力量更为强大。教授担心这些暗物质生物可能会利用他们的技术建造引力武器,对人类构成威胁。因此,他建议采取行动,并使用一个小型黑洞来消灭他们。最后,军官同意了这个建议,并表示将动用军队来执行任务。
9.
惊鸿 (2023-08-28 23:29):
#paper DOI : 10.7150/thno.82228 2023-06-12 Lipid nanoparticles-loaded with toxin mRNA represents a new strategy for the treatment of solid tumors. 癌症治疗在过去十年中取得了显着发展,提供了使用免疫调节抑制癌细胞生长的新策略,无论是否使用基因治疗。具体而言,已经研究了自杀基因疗法和免疫毒素通过直接癌细胞细胞毒性治疗肿瘤。mRNA递送的最新进展也证明了基于mRNA的疫苗和免疫调节剂通过利用纳米载体进行mRNA递送而具有癌症治疗的潜力。
Abstract:
: Cancer therapy have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. Specifically, suicide gene therapies … >>>
: Cancer therapy have evolved remarkably over the past decade, providing new strategies to inhibit cancer cell growth using immune modulation, with or without gene therapy. Specifically, suicide gene therapies and immunotoxins have been investigated for the treatment of tumors by direct cancer cell cytotoxicity. Recent advances in mRNA delivery also demonstrated the potential of mRNA-based vaccines and immune-modulators for cancer therapeutics by utilizing nanocarriers for mRNA delivery. We designed a bacterial toxin-encoding modified mRNA, delivered by lipid nanoparticles into a B16-melanoma mouse model. : We showed that local administration of LNPs entrapping a modified mRNA that encodes for a bacterial toxin, induced significant anti-tumor effects and improved overall survival of treated mice. We propose mmRNA-loaded LNPs as a new class of anti-tumoral, toxin-based therapy. <<<
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10.
惊鸿 (2023-07-29 17:48):
#paper CAR T therapy beyond cancer: the evolution of a living drug DOI : 10.1038/s41586-023-06243-w 2023-07-26 通过改造患者自身的 T 细胞来选择性地靶向并消除肿瘤细胞,已经治愈了患有无法治疗的血液癌症的患者。这些结果推动了嵌合抗原受体 (CAR) T 疗法在整个肿瘤学领域的应用。然而,临床和临床前研究的证据强调了 CAR T 疗法在肿瘤学之外治疗自身免疫、慢性感染、心脏纤维化、衰老相关疾病和其他疾病方面的潜力。同时,新技术和平台的部署为 CAR T 疗法应用于非癌症病理提供了进一步的机会。在这里,我们回顾了 CAR T 疗法背后的基本原理、当前肿瘤学面临的挑战、非癌症疾病初步报告的概要,以及对相关新兴技术的讨论。我们研究了这种疗法在各种情况下的潜在应用。最后,我们强调了对特异性和安全性的担忧,并概述了 CAR T 疗法超越癌症的前进道路。
Abstract:
Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen … >>>
Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer. <<<
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11.
惊鸿 (2023-06-25 16:56):
#paper https://doi.org/10.1021/acssynbio.3c00216 Immortalized Bovine Satellite Cells for Cultured Meat Applications 为了使培养肉大规模成功,来自食品相关物种的肌肉细胞必须以快速可靠的方式在体外扩增,以每年产生数百万公吨的生物质。为了实现这一目标,遗传永生化细胞比原代细胞具有实质性的好处,包括快速生长、逃离细胞衰老以及一致的起始细胞群进行生产。在这里,我们通过牛端粒酶逆转录酶(TERT)和细胞周期蛋白依赖性激酶4(CDK4)的组成表达开发遗传永生化的牛卫星细胞(iBSC)。这些细胞在发表时实现了超过120倍的倍增,并保持其肌源分化的能力。因此,它们为该领域提供了有价值的工具,使进一步的研究和开发能够推进培养肉。
Abstract:
For cultured meat to succeed at scale, muscle cells from food-relevant species must be expanded in vitro in a rapid and reliable manner to produce millions of metric tons of … >>>
For cultured meat to succeed at scale, muscle cells from food-relevant species must be expanded in vitro in a rapid and reliable manner to produce millions of metric tons of biomass annually. Toward this goal, genetically immortalized cells offer substantial benefits over primary cells, including rapid growth, escape from cellular senescence, and consistent starting cell populations for production. Here, we develop genetically immortalized bovine satellite cells (iBSCs) via constitutive expression of bovine Telomerase reverse transcriptase (TERT) and Cyclin-dependent kinase 4 (CDK4). These cells achieve over 120 doublings at the time of publication and maintain their capacity for myogenic differentiation. They therefore offer a valuable tool to the field, enabling further research and development to advance cultured meat. <<<
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惊鸿 (2023-05-29 09:56):
#paper Date  : 2023-05-05 DOI : 10.1021/acssynbio.3c00216 Immortalized Bovine Satellite Cells for Cultured Meat Applications该论文提到,为了使培养肉在规模上成功,食用相关物种的肌肉细胞必须在体外快速可靠地扩展,从而每年生产数百万吨的生物量。基因不老化的细胞比原代细胞具有显着的优势,包括快速增长、逃避细胞衰老和始终一致的起始细胞群体生产。因此,研究人员通过持续表达牛端粒酶逆转录酶(TERT)和Cyclin-dependent kinase 4(CDK4)开发了基因不老化的牛卫星细胞(iBSCs)。这些细胞在发布时已经实现了超过120倍增殖,并保持了其肌肉分化能力。因此,它们为这一领域提供了有价值的工具,可以进一步推动培养肉的研究和开发。
Abstract:
For cultured meat to succeed at scale, muscle cells from food-relevant species must be expanded in vitro in a rapid and reliable manner to produce millions of metric tons of … >>>
For cultured meat to succeed at scale, muscle cells from food-relevant species must be expanded in vitro in a rapid and reliable manner to produce millions of metric tons of biomass annually. Toward this goal, genetically immortalized cells offer substantial benefits over primary cells, including rapid growth, escape from cellular senescence, and consistent starting cell populations for production. Here, we develop genetically immortalized bovine satellite cells (iBSCs) via constitutive expression of bovine Telomerase reverse transcriptase (TERT) and Cyclin-dependent kinase 4 (CDK4). These cells achieve over 120 doublings at the time of publication and maintain their capacity for myogenic differentiation. They therefore offer a valuable tool to the field, enabling further research and development to advance cultured meat. <<<
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13.
惊鸿 (2023-04-19 15:35):
#paper Pub Date : 2019-01-23 DOI : 10.1038/s41564-018-0355-8 Harnessing undomesticated life 在实验室中只能对细菌进行细微的培养和工程改造,这限制了我们在恶劣环境中部署细菌或使用细菌生产重要化合物的能力。最近的工作通过开发新的方法来表征和工程化各种未驯化的细菌物种,从而打开了这一领域。这些技术可用于环境改造,为人类以后殖民外太空有极大的帮助
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惊鸿 (2023-03-27 11:42):
#paper doi:https://ma.x-mol.com/paperRedirect/1639426668090503168 Thymidine nucleotide metabolism controls human telomere length 人类的端粒长度与寿命和严重疾病有关,但端粒长度的遗传决定因素仍未完全确定。在这里,我们进行了全基因组 CRISPR-Cas9 功能性端粒长度筛选,并将胸苷 (dT) 核苷酸代谢确定为人类端粒维持的限制因素。使用 CRISPR-Cas9 的靶向基因破坏揭示了胸苷核苷酸代谢途径中的多个端粒长度控制点:通过删除编码核胸苷激酶 ( TK1 ) 的基因减少 dT 核苷酸回收或通过敲除胸苷酸合酶基因 (TYMS )从头产生端粒长度减少,而脱氧核苷三磷酸水解酶编码基因SAMHD1失活延长的端粒。值得注意的是,单独补充 dT 可通过细胞中的端粒酶驱动端粒的稳健延伸,并且三磷酸胸苷在体外以底物非依赖性方式刺激端粒酶活性。在源自遗传性端粒生物学障碍患者的诱导多能干细胞中,补充 dT 或抑制SAMHD1可促进端粒恢复。我们的结果表明胸苷代谢在控制人端粒酶和端粒长度方面的关键作用,这可能对致命的退行性疾病患者具有治疗作用。
Abstract:
Telomere length in humans is associated with lifespan and severe diseases, yet the genetic determinants of telomere length remain incompletely defined. Here we performed genome-wide CRISPR-Cas9 functional telomere length screening … >>>
Telomere length in humans is associated with lifespan and severe diseases, yet the genetic determinants of telomere length remain incompletely defined. Here we performed genome-wide CRISPR-Cas9 functional telomere length screening and identified thymidine (dT) nucleotide metabolism as a limiting factor in human telomere maintenance. Targeted genetic disruption using CRISPR-Cas9 revealed multiple telomere length control points across the thymidine nucleotide metabolism pathway: decreasing dT nucleotide salvage via deletion of the gene encoding nuclear thymidine kinase (TK1) or de novo production by knockout of the thymidylate synthase gene (TYMS) decreased telomere length, whereas inactivation of the deoxynucleoside triphosphohydrolase-encoding gene SAMHD1 lengthened telomeres. Remarkably, supplementation with dT alone drove robust telomere elongation by telomerase in cells, and thymidine triphosphate stimulated telomerase activity in a substrate-independent manner in vitro. In induced pluripotent stem cells derived from patients with genetic telomere biology disorders, dT supplementation or inhibition of SAMHD1 promoted telomere restoration. Our results demonstrate a critical role of thymidine metabolism in controlling human telomerase and telomere length, which may be therapeutically actionable in patients with fatal degenerative diseases. <<<
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15.
惊鸿 (2023-02-28 21:15):
#paper DOI : 10.1021/acsnano.2c10477 Floating Seawater Splitting Device Based on NiFeCrMo Metal Hydroxide Electrocatalyst and Perovskite/Silicon Tandem Solar Cells 海水光伏制氢意义重大。太阳能驱动海水电解面临的析氯反应竞争、氯化物腐蚀、催化剂中毒等挑战严重制约了该技术的发展。在本文中,我们报道了一种由 Ni、Fe、Cr 和 Mo 元素组成的二维纳米片季金属氢氧化物催化剂。通过原位电化学活化,部分钼元素在催化剂中被浸出并发生形态转变。获得了更高的金属价态和许多 O 空位,在工业要求的 500 mA cm –2 电流密度下,在整体碱性海水电解中提供了优异的催化活性和耐腐蚀性在室温下 1.82 V 低电压下超过 1000 小时。漂浮的太阳能海水分解装置显示出 20.61 ± 0.77% 的太阳能制氢 (STH) 效率。这项工作展示了高效太阳能海水电解装置的发展,并可能促进清洁能源转换的研究。
ACS nano, 2023-Mar-14. DOI: 10.1021/acsnano.2c10477 PMID: 36808966
Abstract:
Photovoltaic hydrogen production from seawater is of great significance. Challenges of solar-driven seawater electrolysis, for example, competing among chlorine evolution reactions, chloride corrosion, and catalyst poisoning, seriously restrict the development … >>>
Photovoltaic hydrogen production from seawater is of great significance. Challenges of solar-driven seawater electrolysis, for example, competing among chlorine evolution reactions, chloride corrosion, and catalyst poisoning, seriously restrict the development of this technology. In this paper, we report a two-dimensional nanosheet quaternary metal hydroxide catalyst composed of Ni, Fe, Cr, and Mo elements. By in situ electrochemical activation, a partial Mo element was leached and morphologically transformed in the catalyst. The higher metal valence states and many O vacancies were obtained, providing excellent catalytic activity and corrosion resistance in overall alkaline seawater electrolysis operating at an industrial-required current density of 500 mA cm over 1000 h under 1.82 V low voltages at room temperature. The floating solar seawater splitting device shows a 20.61 ± 0.77% efficiency of solar energy to hydrogen (STH). This work demonstrates the development of efficient solar seawater electrolysis devices and potentially promotes research on clean energy conversion. <<<
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16.
惊鸿 (2023-01-07 21:44):
#paper DOI : 10.1038/s43587-022-00340-7 Pub Date:2022-12-30Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan 线粒体功能障碍在衰老中起着核心作用,但确切的生物学原因仍在确定中。在这里,我们展示了使用光激活质子泵在成年期通过光遗传学增加线粒体膜电位可改善与年龄相关的表型并延长秀丽隐杆线虫的寿命。我们的研究结果提供了直接的因果证据,表明挽救与年龄相关的线粒体膜电位下降足以减缓衰老速度并延长健康寿命和寿命。
Abstract:
Mitochondrial dysfunction plays a central role in aging but the exact biological causes are still being determined. Here, we show that optogenetically increasing mitochondrial membrane potential during adulthood using a … >>>
Mitochondrial dysfunction plays a central role in aging but the exact biological causes are still being determined. Here, we show that optogenetically increasing mitochondrial membrane potential during adulthood using a light-activated proton pump improves age-associated phenotypes and extends lifespan in . Our findings provide direct causal evidence that rescuing the age-related decline in mitochondrial membrane potential is sufficient to slow the rate of aging and extend healthspan and lifespan. <<<
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17.
惊鸿 (2022-12-29 15:54):
#paper DOI : 10.1126/science.abl6620 Glassfrogs conceal blood in their liver to maintain transparency 20221222 动物的透明体是一种复杂的伪装形式,涉及减少整个生物体的光散射和吸收的机制。在脊椎动物中,获得透明度很困难,因为它们的循环系统充满了强烈减弱光线的红细胞 (RBC)。在此,这个实验团队记录了玻璃蛙如何通过隐藏这些细胞。该实验团队使用光声成像在体内追踪红细胞,表明静息玻璃蛙通过从循环中去除约 89% 的红细胞并将其包装在肝脏中,从而将透明度提高两到三倍。因此,脊椎动物的透明性需要透明组织和从这些组织中“清除”呼吸色素的活跃机制。此外,玻璃蛙能够调节位置、密度。
Abstract:
Transparency in animals is a complex form of camouflage involving mechanisms that reduce light scattering and absorption throughout the organism. In vertebrates, attaining transparency is difficult because their circulatory system … >>>
Transparency in animals is a complex form of camouflage involving mechanisms that reduce light scattering and absorption throughout the organism. In vertebrates, attaining transparency is difficult because their circulatory system is full of red blood cells (RBCs) that strongly attenuate light. Here, we document how glassfrogs overcome this challenge by concealing these cells from view. Using photoacoustic imaging to track RBCs in vivo, we show that resting glassfrogs increase transparency two- to threefold by removing ~89% of their RBCs from circulation and packing them within their liver. Vertebrate transparency thus requires both see-through tissues and active mechanisms that "clear" respiratory pigments from these tissues. Furthermore, glassfrogs' ability to regulate the location, density, and packing of RBCs without clotting offers insight in metabolic, hemodynamic, and blood-clot research. <<<
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18.
惊鸿 (2022-11-28 10:33):
#paper CRISPRing future medicinesExpert Opin. Drug Discov.PubDate:2021-01-03DOI:10.1080/17460441.2021.1850687Laure Grand Moursel 1 , Mijke Visser 1 , Geraldine Servant 1 , Selvi Durmus 1 , Anne-Marie Zuurmond 1这是以快速且具有成本效益的方式设计哺乳动物基因组的能力导致 CRISPR 技术在生物医学研究中的快速适应。基于 CRISPR 的工程具有加速药物发现、支持降低药物开发中的高损耗率以及促进细胞和基因疗法的开发的潜力。CRISPR 技术正迅速成为基因组工程的首选工具,如今很难想象没有这项技术的药物发现管道。随着未来几年,CRISPR 技术无疑将得到进一步完善,并将蓬勃发展成为一项成熟的技术,它将在支持药物发现管道以及细胞和基因治疗开发中的基因组工程要求方面发挥关键作用。
Abstract:
: The ability to engineer mammalian genomes in a quick and cost-effective way has led to rapid adaptation of CRISPR technology in biomedical research. CRISPR-based engineering has the potential to … >>>
: The ability to engineer mammalian genomes in a quick and cost-effective way has led to rapid adaptation of CRISPR technology in biomedical research. CRISPR-based engineering has the potential to accelerate drug discovery, to support the reduction of high attrition rate in drug development and to enhance development of cell and gene-based therapies.: How CRISPR technology is transforming drug discovery is discussed in this review. From target identification to target validation in both and models, CRISPR technology is positively impacting the early stages of drug development by providing a straightforward way to genome engineering. This property also attracted attention for CRISPR application in the cell and gene therapy area.: CRISPR technology is rapidly becoming the preferred tool for genome engineering and nowadays it is hard to imagine the drug discovery pipeline without this technology. With the years to come, CRISPR technology will undoubtedly be further refined and will flourish into a mature technology that will play a key role in supporting genome engineering requirements in the drug discovery pipeline as well as in cell and gene therapy development. <<<
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19.
惊鸿 (2022-10-31 10:45):
#paper Clipping cancer with CRISPR Cancer Cytopathology ( IF 4.264 ) Pub Date : 2018-01-01 , DOI: 10.1002/cncy.21964 它是一种细菌自我保护,不然细菌就会在几分钟内死亡。许多细菌(和古生菌)可以扭转其病毒攻击的机制的侦查已迅速成为生物医学中最热门的研究领域之一。细菌 CRISPR(成簇的规则间隔短回文重复序列)-Cas9(CRISPR 相关蛋白 9)酶系统被重新用作精确的 DNA 编辑工具,已在广泛的应用中显示出早期前景,包括努力发现癌症通路和设计更有针对性的化疗药物。然而,科学家们敦促谨慎对待意外基因或产生脱靶效应的风险,以及永久改变遗传 DNA 的可能性;这让人想起 1990 年代后期围绕基因治疗的安全和伦理问题。在 CRISPR 系统的希望和严格审查中,最近的几项研究表明,新工具如何避免过去的一些陷阱,以及它如何在准备用于临床之前克服更多陷阱。该技术需要面临许多挑战,并且要避免对该项技术的过多幻想,否则将会给我们带来失望。
20.
惊鸿 (2022-09-27 09:09):
#paper doi:Volume 40, Issue 9, 12 September 2022, Pages 999-1009.e6Detection and localization of early- and late-stage cancers using platelet 这篇论文解释了RNA癌症患者受益于早期肿瘤检测,因为治疗结果对不太晚期的癌症更有利。血小板参与癌症进展,被认为是癌症检测的有前途的生物来源,因为它们根据局部和全身线索改变其RNA含量。我们表明,基于肿瘤的血小板(TEP)RNA血液测试能够检测18种癌症类型。血栓形成Seq在无症状对照组的特异性为99%,在I-IV期癌症患者的1,096份血液样本中有三分之二和352名I-III期肿瘤中的一半中正确检测到癌症的存在。对症对照组,包括炎症和心血管疾病以及良性肿瘤,假阳性检测结果增加,平均特异性为78%。此外,血栓形成Seq在超过80%的癌症患者中正确确定了五种不同肿瘤类型的肿瘤起源部位。这些结果突出了TEP衍生的RNA组合的潜在特性,以补充当前基于血液的癌症筛查方法。
Sjors G J G In 't Veld, Mohammad Arkani, Edward Post, Mafalda Antunes-Ferreira, Silvia D'Ambrosi, Daan C L Vessies, Lisa Vermunt, Adrienne Vancura, Mirte Muller, Anna-Larissa N Niemeijer, Jihane Tannous, Laura L Meijer, Tessa Y S Le Large, Giulia Mantini, Niels E Wondergem, Kimberley M Heinhuis, Sandra van Wilpe, A Josien Smits, Esther E E Drees, Eva Roos, Cyra E Leurs, Lee-Ann Tjon Kon Fat, Ewoud J van der Lelij, Govert Dwarshuis, Maarten J Kamphuis, Lisanne E Visser, Romee Harting, Annemijn Gregory, Markus W Schweiger, Laurine E Wedekind, Jip Ramaker, Kenn Zwaan, Heleen Verschueren, Idris Bahce, Adrianus J de Langen, Egbert F Smit, Michel M van den Heuvel, Koen J Hartemink, Marijke J E Kuijpers, Mirjam G A Oude Egbrink, Arjan W Griffioen, Rafael Rossel, T Jeroen N Hiltermann, Elizabeth Lee-Lewandrowski, Kent B Lewandrowski, Philip C De Witt Hamer, Mathilde Kouwenhoven, Jaap C Reijneveld, William P J Leenders, Ann Hoeben, Irma M Verdonck-de Leeuw, C René Leemans, Robert J Baatenburg de Jong, Chris H J Terhaard, Robert P Takes, Johannes A Langendijk, Saskia C de Jager, Adriaan O Kraaijeveld, Gerard Pasterkamp, Minke Smits, Jack A Schalken, Sylwia Łapińska-Szumczyk, Anna Łojkowska, Anna J Żaczek, Henk Lokhorst, Niels W C J van de Donk, Inger Nijhof, Henk-Jan Prins, Josée M Zijlstra, Sander Idema, Johannes C Baayen, Charlotte E Teunissen, Joep Killestein, Marc G Besselink, Lindsay Brammen, Thomas Bachleitner-Hofmann, Farrah Mateen, John T M Plukker, Michal Heger, Quirijn de Mast, Ton Lisman, D Michiel Pegtel, Harm-Jan Bogaard, Jacek Jassem, Anna Supernat, Niven Mehra, Winald Gerritsen, Cornelis D de Kroon, Christianne A R Lok, Jurgen M J Piek, Neeltje Steeghs, Winan J van Houdt, Ruud H Brakenhoff, Gabe S Sonke, Henk M Verheul, Elisa Giovannetti, Geert Kazemier, Siamack Sabrkhany, Ed Schuuring, Erik A Sistermans, Rob Wolthuis, Hanne Meijers-Heijboer, Josephine Dorsman, Cees Oudejans, Bauke Ylstra, Bart A Westerman, Daan van den Broek, Danijela Koppers-Lalic, Pieter Wesseling, R Jonas A Nilsson, W Peter Vandertop, David P Noske, Bakhos A Tannous, Nik Sol, Myron G Best, Thomas Wurdinger <<<
Abstract:
Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for … >>>
Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening. <<<
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