A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not ...complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.
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•Detailed COVID-19 immune landscape depicted by integrated 1.46 million single cells•Peripheral immune subtypes differentially associated with distinct clinical features•SARS-CoV-2 RNA is present in diverse epithelial and immune cells•Megakaryocytes and monocyte subsets may contribute to cytokine storms
Analysis of the immune landscape in the lung and peripheral blood of COVID patients across different regions in China at the single-cell level documents the presence of viral RNAs in diverse cell types and highlights the potential contribution of megakaryocytes and monocyte subsets to cytokine storms.
We report a phosphine-directed ruthenium-catalyzed C8-selective alkylation of naphthalenes with alkenes. This protocol provides straightforward access to a large library of electron-rich C8-alkyl ...substituent 1-naphthphosphines, which outperformed common commercial phosphines and their precursors in the Pd-catalyzed Suzuki-Miyaura coupling of aryl bromides with alkylboronic acid.
We report a phosphine-directed ruthenium-catalyzed C8-selective alkylation of naphthalenes with alkenes.
Novel electrochromic (EC) and aggregation-enhanced emission (AEE)-active triphenylamine (TPA)-based polyamides were prepared with 4-cyanotriphenylamine ( TPA-CN ), 4-methoxytriphenylamine ( TPA-OMe ...), cyclohexane (CH) and tetraphenylethene (TPE) moieties via condensation polymerization. The emission from the polyamides could be quenched from the neutral to oxidized states effectively due to the structural planarization and optical absorption shift of TPA units during electrochemical switching. With the introduction of n -heptyl viologen (HV) into the device system as a counter EC layer for balancing charges, the resulting high-performance electrofluorochromic (EFC) devices based on TPA-CN-CH as a photoluminescent (with a fluorescence quantum yield of up to 46% in the film state) and redox-active layer showed a high fluorescence contrast ratio ( I off / I on ) of 105. The HV-containing TPA-OMe-TPE -based EFC device displayed the shortest response time of less than 4.9 s, and excellent improvement in reducing the switching recovery time and lowering the oxidation potential could also be achieved. Thus, judiciously designed multi-functional polymers with both redox- and AEE-active features are a crucial and feasible approach for preparing highly efficient EFC devices.
Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor microenvironment and contribute to lymph node (LN) metastasis. However, the precise mechanisms of ...TAMs-induced LN metastasis remain largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node Metastasis Associated Transcript 1 (LNMAT1), which is upregulated in LN-positive bladder cancer and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that LNMAT1 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, LNMAT1 epigenetically activates CCL2 expression by recruiting hnRNPL to CCL2 promoter, which leads to increased H3K4 tri-methylation that ensures hnRNPL binding and enhances transcription. Furthermore, LNMAT1-induced upregulation of CCL2 recruits macrophages into the tumor, which promotes lymphatic metastasis via VEGF-C excretion. These findings provide a plausible mechanism for LNMAT1-modulated tumor microenvironment in lymphatic metastasis and suggest that LNMAT1 may represent a potential therapeutic target for clinical intervention in LN-metastatic bladder cancer.
The basic helix-loop-helix (bHLH) proteins, a large transcription factors family, are involved in plant growth and development, and defensive response to various environmental stresses. The ...resurrection plant Myrothamnus flabellifolia is known for its extremely strong drought tolerance, but few bHLHs taking part in abiotic stress response have been unveiled in M. flabellifolia.
In the present research, we cloned and characterized a dehydration-inducible gene, MfbHLH38, from M. flabellifolia. The MfbHLH38 protein is localized in the nucleus, where it may act as a transcription factor. Heterologous expression of MfbHLH38 in Arabidopsis improved the tolerance to drought and salinity stresses, as determined by the studies on physiological indexes, such as contents of chlorophyll, malondialdehyde (MDA), proline (Pro), soluble protein, and soluble sugar, water loss rate of detached leaves, reactive oxygen species (ROS) accumulation, as well as antioxidant enzyme activities. Besides, MfbHLH38 overexpression increased the sensitivity of stomatal closure to mannitol and abscisic acid (ABA), improved ABA level under drought stress, and elevated the expression of genes associated with ABA biosynthesis and ABA responding, sucha as NCED3, P5CS, and RD29A.
Our results presented evidence that MfbHLH38 enhanced tolerance to drought and salinity stresses in Arabidopsis through increasing water retention ability, regulating osmotic balance, decreasing stress-induced oxidation damage, and possibly participated in ABA-dependent stress-responding pathway.
The plastisphere refers to biofilm formation on the microplastic (MP) surface, but its subsequent functions, especially driving the nitrogen biogeochemical cycle, are rarely studied. Here, MPs were ...incubated in the pelagic water and benthic water-sediment interface of an aquaculture pond, and the two corresponding microcosms amended with incubated plastisphere were simulated. The results showed decreased ammonia concentrations and increased nitrification rates in microcosms with either pelagic or benthic plastispheres. To uncover the possible mechanisms, the community structure and function of the plastisphere were investigated. As clarified by 16S rRNA, the community diversity of the pelagic plastisphere was significantly higher than that of the corresponding hydrosphere. Plastisphere communities, especially those incubated in pelagic water, were separated from the hydrosphere. Moreover, the abundance of Proteobacteria increased while the abundance of Cyanobacteria decreased in both plastispheres. Metagenome further revealed that the abundance of amoA and annotated Nitrososphaeraceae_archaeon and hao and affiliated Nitrosomonas_europaea, which contributed to ammonia oxidation to nitrite, was higher in the benthic plastisphere. Comparing the pelagic plastisphere with the corresponding hydrosphere, however, the abundance of nxrA and annotated Nitrobacter hamburgensis and nxrB and the affiliated Nitrospira moscoviensis, which are involved in nitrite oxidation, was more abundant in the plastisphere. These findings suggest that the plastisphere might selectively enrich functional microorganisms and genes in a habitat-dependent manner to promote nitrification in aquaculture ponds.
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•Plastisphere promoted nitrification in aquaculture ponds.•Plastisphere showed a habitat-dependent microbial community.•AOB tended to enrich in benthic MPs.•NOB preferred to concentrate on pelagic MPs.
This report outlines a highly sensitive and facile electrochemiluminescence (ECL) sensing platform based on a novel high-quantum-yield Au-nanocluster (AuNC) probe for glutathione (GSH) detection. ...Owing to the prominent quenching effect of GSH on the ECL of the AuNCs, the proposed ECL nanosensor showed a wide response to GSH in the ranges of 1.0 × 10-9–1.0 × 10-5M and 1.0 × 10-5–1.0 × 10-1M and a low detection limit of 3.2 × 10-10M. In addition, the proposed system exhibited good selectivity for GSH in the presence of other chemical/biological interferences. Moreover, since no further functionalization of AuNC-based sensor interface was necessary, together with the stability, high sensitivity and selectivity of the proposed nanosensor, this convenient approach was able to successfully detect GSH in both of human urine samples and blood samples with excellent recoveries, which indicated its promising application under physiological conditions. Of significant importance is that this study not only helps in gaining a better understanding of the applicability of the ECL properties of AuNCs, but also provides a new avenue for the design and development of ECL sensors based on the novel high-quantum-yield AuNC-based probe and other functional-metal-based NC probes.
•Facile ECL sensing platform based on high-quantum-yield AuNC probe.•A high performance ECL method for glutathione determination.•Detection of glutathione in human urine samples.•This sensing platform can be adapted to measure other physiologically important compounds.•A new avenue for design and development of other functional-metal NC probe-based ECL sensors.
Hepatocellular Carcinoma (HCC) is the fifth most prevalent cancer worldwide. Specially, Hepatitis B viurs X protein (HBx) is a leading factor in the progression of Hepatitis B viurs-related HCC. ...Nutrient-deprived tumor microenvironment also contributes to tumor development. However, the role of HBx in nutrient-deprived HCC has received little investigation. Here, we show that HBx elevates PINK1-Parkin mediating mitophagy in starvation. HBx not only increases the PINK1/Parkin gene expression but also accelerates Parkin recruitment to partial mitochondria. Further analysis indicates that, HBx either promotes mitochondrial unfolded protein response, with remarkable mitochondrial LONP1 increases, or reduces LONP1 expression in cytosol inducing LONP1-Parkin pathway, both consequently enhancing mitophagy. Moreover, the enhanced mitophagy lowers mitochondrial apoptosis in starved hepatoma cells, and Bax is implied in the machinery. In addition, we define differential centrifuge, 3000 g or 12,000 g to pellet mitochondria, as an effective method to obtain distinct mitochondria. In collect, HBx regulates diverse aspects of LONP1 and Parkin, enhancing mitophagy in starvation. This study may shed new insights into the machinery development of hepatocellular carcinoma.
•HBx induces the translocation of Parkin to partial mitochondria to elevate mitophagy.•HBx has diverse roles on mitochondrial and cytosolic LONP1 to enhance mitophagy.•HBx attenuates mitochondrial apoptosis in starvation through enhancing mitophagy.
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