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1.
少颖-focus reverse aging (2025-07-05 05:54):
#paper doi: https://doi.org/10.1101/2025.06.11.659105 标题:X-Atlas/Orion: Genome-wide Perturb-seq Datasets via a Scalable Fix-Cryopreserve Platform for Training Dose-Dependent Biological Foundation Models 发表年份:2025年 总结:目前虚拟细胞的技术因为数据集的发表得到了比较大的提升,解决了大约40-50%的核心数据问题。X-Atlas/Orion 数据集的构建大约18-25人参与,其中有斯坦福大学教授的学生和谷歌公司的高管, 也有参与过药物研发整个流程的人,开发这个数据集的公司里面大佬云集,有斯坦福大学前教授,也有诺奖获得者,也有强生公司前CEO,阵容堪称世界顶尖。感悟:虚拟细胞的设计是顶尖科学家做的事情,所以这件事情会让人很有成就感。我可以参与,但是需要做好投入大量时间的准备。 公众号文章有更详细解读和分析:https://mp.weixin.qq.com/s/evVxdkRds8ZCbXVgnlmWAg
Abstract:
AbstractThe rapid expansion of massively parallel sequencing technologies has enabled the development of foundation models to uncover novel biological findings. While these have the potential to significantly accelerate scientific discoveries … >>>
AbstractThe rapid expansion of massively parallel sequencing technologies has enabled the development of foundation models to uncover novel biological findings. While these have the potential to significantly accelerate scientific discoveries by creating AI-driven virtual cell models, their progress has been greatly limited by the lack of large-scale high-quality perturbation data, which remains constrained due to scalability bottlenecks and assay variability. Here, we introduce “Fix-Cryopreserve-ScRNAseq” (FiCS) Perturb-seq, an industrialized platform for scalable Perturb-seq data generation. We demonstrate that FiCS Perturb-seq exhibits high sensitivity and low batch effects, effectively capturing perturbation-induced transcriptomic changes and recapitulating known biological pathways and protein complexes. In addition, we release X-Atlas: Orion edition (X-Atlas/Orion), the largest publicly available Perturb-seq atlas. This atlas, generated from two genome-wide FiCS Perturb-seq experiments targeting all human protein-coding genes, comprises eight million cells deeply sequenced to over 16,000 unique molecular identifiers (UMIs) per cell. Furthermore, we show that single guide RNA (sgRNA) abundance can serve as a proxy for gene knockdown (KD) efficacy. Leveraging the deep sequencing and substantial cell numbers per perturbation, we also show that stratification by sgRNA expression can reveal dose-dependent genetic effects. Taken together, we demonstrate that FiCS Perturb-seq is an efficient and scalable platform for high-throughput Perturb-seq screens. Through the release of X-Atlas/Orion, we highlight the potential of FiCS Perturb-seq to address current scalability and variability challenges in data generation, advance foundation model development that incorporates gene-dosage effects, and accelerate biological discoveries. <<<
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2.
少颖-focus reverse aging (2025-06-06 14:30):
#paper Socioeconomic Status and Cardiovascular Outcomes: Challenges and Interventions doi: 10.1161/CIRCULATIONAHA.117.029652 推荐原因:能学到一些规避心血管病的方法; 论文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5958918 论文重点内容:穷人更容易得心血管病,原因: 1.没钱买优质食物,便宜的食物通常高油高盐; 2.没条件运动,没公园没健身房; 3.没钱体检和买药; 4.压力大长期压抑; 5.保养意识健康意识差; 6. 穷人区环境污染大。
Abstract:
Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease … >>>
Socioeconomic status (SES) has a measurable and significant effect on cardiovascular health. Biological, behavioral, and psychosocial risk factors prevalent in disadvantaged individuals accentuate the link between SES and cardiovascular disease (CVD). Four measures have been consistently associated with CVD in high-income countries: income level, educational attainment, employment status, and neighborhood socioeconomic factors. In addition, disparities based on sex have been shown in several studies. Interventions targeting patients with low SES have predominantly focused on modification of traditional CVD risk factors. Promising approaches are emerging that can be implemented on an individual, community, or population basis to reduce disparities in outcomes. Structured physical activity has demonstrated effectiveness in low-SES populations, and geomapping may be used to identify targets for large-scale programs. Task shifting, the redistribution of healthcare management from physician to nonphysician providers in an effort to improve access to health care, may have a role in select areas. Integration of SES into the traditional CVD risk prediction models may allow improved management of individuals with high risk, but cultural and regional differences in SES make generalized implementation challenging. Future research is required to better understand the underlying mechanisms of CVD risk that affect individuals of low SES and to determine effective interventions for patients with high risk. We review the current state of knowledge on the impact of SES on the incidence, treatment, and outcomes of CVD in high-income societies and suggest future research directions aimed at the elimination of these adverse factors, and the integration of measures of SES into the customization of cardiovascular treatment. <<<
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3.
少颖-focus reverse aging (2025-06-02 00:22):
#paper Cardiovascular aging: from cellular and molecular changes to therapeutic interventions doi: 10.20517/jca.2023.09 论文网址:https://pmc.ncbi.nlm.nih.gov/articles/PMC10238104/#S16 公众号阅读笔记链接:https://mp.weixin.qq.com/s/O9IqSEJpAwSGIlaAMap3mQ
Abstract:
Progressive age-induced deterioration in the structure and function of the cardiovascular system involves cardiac hypertrophy, diastolic dysfunction, myocardial fibrosis, arterial stiffness, and endothelial dysfunction. These changes are driven by complex … >>>
Progressive age-induced deterioration in the structure and function of the cardiovascular system involves cardiac hypertrophy, diastolic dysfunction, myocardial fibrosis, arterial stiffness, and endothelial dysfunction. These changes are driven by complex processes that are interconnected, such as oxidative stress, mitochondrial dysfunction, autophagy, inflammation, fibrosis, and telomere dysfunction. In recent years, the advances in research of cardiovascular aging, including the wide use of animal models of cardiovascular aging, elucidated an abundance of cell signaling pathways involved in these processes and brought into sight possible interventions, which span from pharmacological agents, such as metformin, sodium-glucose cotransporter 2-inhibitors, rapamycin, dasatinib and quercetin, to lifestyle changes. <<<
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