The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to ...analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.
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•Quantitative lipidomic and metabolomic profiling of COVID-19 plasma•Plasma metabolite panel distinguished COVID-19 from healthy controls (AUC = 0.975)•Differential correlation analyses uncovered metabolic dysregulation in COVID-19•GM3-enriched exosomes are positively correlated with COVID-19 pathogenesis
Plasma metabolite panel effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma monosialodihexosyl gangliosides (GM3s) were negatively correlated with CD4+ T cell count in COVID-19 patients, and GM3-enriched exosomes were positively correlated with disease severity. These observations suggest that GM3-enriched exosomes may participate in pathological processes associated with COVID-19 progression.
In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not ...fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4
effector-GNLY (granulysin), CD8
effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.
COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and ...immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.
Herein, we report a nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes through reductive decarboxylation of redox-active esters. The present reaction enables the ...preparation of functionalized
-difluoroalkenes with the formation of sterically hindered C(sp
)-C(sp
) bonds under very mild reaction conditions, while tolerating many sensitive functional groups and requiring minimal substrate protection. Therefore, this method provides an efficient and convenient approach for late-stage modification of biologically interesting molecules.
Metal-organic frameworks (MOFs), assembled by metal ions or their clusters and organic linkers, are one of the state-of-the-art crystalline materials. Their features such as ultra-high porosity, ...synthetic tailorability and relative ease of synthesis make them promising candidates for diversified applications. Controllable integration of MOFs and carbon-based materials not only leads to further enhancement of single-phase MOFs in terms of stability and electrical conductivity, but also surprisingly brings about a number of new functionalities like formation of new pores and template effects. These benefits allow the resultant MOF-carbon composites to be applied beyond the fields of single-phase MOFs. Increasing research interests have been aroused in this rapidly developing interdisciplinary area. This review aims to specifically group together the important reports focused on MOF-carbon composites till now. The methods used for composite synthesis and applications of the composites are investigated and categorized. The review also exclusively discusses the functionalities stemming from the synergistic effects of the two intriguing materials and pictures the future prospects at the end.
This review summarizes the recent progress in preparations, functionalities and applications of composites of metal-organic frameworks (MOFs) and carbon-based materials.
Single-photon imaging over 200 km Li, Zheng-Ping; Ye, Jun-Tian; Huang, Xin ...
Optica,
03/2021, Letnik:
8, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Long-range active imaging has widespread applications in remote sensing and target recognition. Single-photon light detection and ranging (lidar) has been shown to have high sensitivity and temporal ...resolution. On the application front, however, the operating range of practical single-photon lidar systems is limited to about tens of kilometers over the Earth’s atmosphere, mainly due to the weak echo signal mixed with high background noise. Here, we present a compact coaxial single-photon lidar system capable of realizing 3D imaging at up to 201.5 km. It is achieved by using high-efficiency optical devices for collection and detection, and what we believe is a new noise-suppression technique that is efficient for long-range applications. We show that photon-efficient computational algorithms enable accurate 3D imaging over hundreds of kilometers with as few as 0.44 signal photons per pixel. The results represent a significant step toward practical, low-power lidar over extra-long ranges.
An unprecedented type of reaction for Cu-catalyzed trifluoromethylation of terminal alkenes is reported. This reaction represents a rare instance of catalytic trifluoromethylation through C(sp3)–H ...activation. It also provides a mechanistically unique example of Cu-catalyzed allylic C–H activation/functionalization. Both experimental and theoretical analyses indicate that the trifluoromethylation may occur via a Heck-like four-membered-ring transition state.
Matrix attachment regions (MARs) are DNA fragments with specific motifs that enhance transgenic expression; however, the characteristics and functions of these elements remain unclear. In this study, ...we designed and synthesized three short chimeric MARs, namely, SM4, SM5, and SM6, with different numbers and orders of motifs on the basis of the features and motifs of previously reported MARs, namely, SM1, SM2, and SM3, respectively. Expression vectors with six synthetic MARs flanking the down or upstream of the expression cassette for enhanced green fluorescence protein (EGFP) were constructed and introduced into Chinese hamster ovary (CHO) cells. Results indicated that the EGFP expression of the CHO cells with transfection bySM4, SM5, or SM6‐containing vectors was higher than that of those containing SM1, SM2, or SM3 regardless of the MAR insertion position. The improving effect of SM5 was particularly pronounced. Transgenic expression was further enhanced with the increasing SM5 copy number. Bioinformatics analysis indicated that several arrangements of the DNA‐binding motifs for CEBP, FAST, Hox, glutathione, and NMP4 may help increase transgenic expression levels and the average population of highly expressed cells. Our findings on novel synthetic MARs will help establish stable expression systems in mammalian cells.
1. The three synthetic matrix attachment regions (MARs) can improve transient enhanced green fluorescence protein (EGFP) expression level in Chinese hamster ovary cell (CHO) cells. 2. The CHO cells transfected with p3‐SM5 vector improved stable transgenic expression by 5.3‐fold. 3. The enhancing effect was heightened with the increasing copy number of this synthetic MARs.
Background. Whether statins can reduce major cardiovascular adverse events (MACE) in patients with coronary artery spasm (CAS) is controversial. And most of the relevant research to date has been ...conducted in Asia. Methods. We systematically searched electronic databases for studies on the effect of statins on MACE in patients with CAS in Asia and published up to September 2022. We included data on MACE in a statin therapy patient group and a no-statin therapy control group. We then evaluated the effect of statin therapy on MACE in patients with CAS in Asia by meta-analysis and trial sequential analysis (TSA). All statistical analyses were performed using Stata 16.0 software and TSA software. Results. A total of 10 studies (n=9333 patients) were included in the final analysis. Meta-analysis showed that the use of statins had a significant effect on MACE in CAS patients (with RR, 0.70; 95% CI, 0.49-0.99), and the sensitivity analysis further confirmed this finding. Subgroup analysis suggested that the correlation between statin therapy and reduced MACE endpoint was stronger in Japanese patients and patients followed up for more than 4 years. But our TSA results indicated that the available samples were insufficient and further research is needed. Conclusions. Our meta-analysis suggests that statin therapy can reduce MACE in patients with CAS in Asia, and the correlation between the two was stronger in Japanese patients and patients followed up for more than 4 years.
Background
IBM Watson for Oncology (WFO), which can use natural language processing to evaluate data in structured and unstructured formats, has begun to be used in China. It provides physicians with ...evidence‐based treatment options and ranks them in three categories for treatment decision support. This study was designed to examine the concordance between the treatment recommendation proposed by WFO and actual clinical decisions by oncologists in our cancer center, which would reflect the differences of cancer treatment between China and the U.S.
Patients and Methods
Retrospective data from 362 patients with cancer were ingested into WFO from April 2017 to October 2017. WFO recommendations were provided in three categories: recommended, for consideration, and not recommended. Concordance was analyzed by comparing the treatment decisions proposed by WFO with those of the multidisciplinary tumor board. Concordance was achieved when the oncologists' treatment decisions were in the recommended or for consideration categories in WFO.
Results
Ovarian cancer showed the highest concordance, which was 96%. Lung cancer and breast cancer obtained a concordance of slightly above 80%. The concordance of rectal cancer was 74%, whereas colon cancer and cervical cancer showed the same concordance of 64%. In particular, the concordance of gastric cancer was very low, only 12%, and 88% of cases were under physicians choice.
Conclusion
Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major cause of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. ClinicalTrials.gov Identifier: NCT03400514.
Implications for Practice
IBM Watson for Oncology (WFO) has begun to be used in China. In this study, concordance was examined between the treatment recommendation proposed by WFO and clinical decisions for 362 patients in our cancer center, which could reflect the differences of cancer treatment between China and the U.S. Different cancer types showed different concordances, and only gastric cancers were significantly less likely to be concordant. Incidence and pharmaceuticals may be the major causes of discordance. To be comprehensively and rapidly applied in China, WFO needs to accelerate localization. This study may have a significant effect on application of artificial intelligence systems in China.
摘要
背景。IBM 沃森肿瘤 (WFO) 可以使用自然语言处理程序来评估结构化和非结构化格式的数据，我们已在中国开展使用。它可以提供各种基于证据的治疗选择并将它们划分为三个类别，以提供治疗决策支持。本研究旨在检验 WFO 提出的治疗建议与我们癌症中心的肿瘤医生制定的实际临床决策之间的一致性，这可以反映出中美之间的癌症治疗差异。
患者和方法。在 2017 年 4 月至 2017 年 10 月期间，WFO 输入了来自 362 名癌症患者的回顾性数据。按照三种类别提供 WFO 建议:建议、以供考虑和不建议。通过对比 WFO 与多学科肿瘤委员会建议的治疗决策，我们对一致性进行了分析。当肿瘤医生的治疗决策在 WFO 中属于建议或以供考虑的类别时，即表示实现了一致性。
结果。卵巢癌显示出最高的一致性，为 96%。肺癌和乳腺癌取得了略高于 80% 的一致性。直肠癌的一致性为 74%，而结肠癌和宫颈癌显示出相同的一致性，同为 64%。特别值得注意的是，胃癌的一致性非常低，仅为 12%，88% 的病例均由医生选择。
结论。不同的癌症类型显示出不同的一致性，只有胃癌明显不太可能一致。发病率和药物可能是导致不一致的主要原因。为了实现在中国的全面、快速应用，WFO 需要加速本地化。ClinicalTrials.gov 标识符:NCT03400514。
对临床实践的提示:我们现已在中国开始使用 IBM 沃森肿瘤 (WFO)。在本研究中，我们检验了针对我们癌症中心的 362 名患者的 WFO 治疗建议与临床决策之间的一致性，这可以反映出中美之间的癌症治疗差异。不同的癌症类型显示出不同的一致性，只有胃癌明显不太可能一致。发病率和药物可能是导致不一致的主要原因。为了实现在中国的全面、快速应用，WFO 需要加速本地化。本研究可能对人工智能系统在中国的应用产生重大影响。
Using the updated version of IBM Watson for Oncology, this study explored the concordance of the suggested therapeutic regimen between Watson and physicians in China. This article reports results and suggests some similarities and differences between the East and West in the treatment of cancer.
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