Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome‐coronavirus‐2 infection often results from alveolar injury that impedes airway capacity and ...multi‐organ failure—both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL‐6, IL‐1β, IL‐10, TNF, GM‐CSF, IP‐10 (IFN‐induced protein 10), IL‐17, MCP‐3, and IL‐1ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID‐19) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID‐19 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID‐19, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.
Reviews clinical data on leukocyte and cytokine changes during mild‐to‐severe infection, including a detailed overview of current therapy strategies targeting the cytokine storm.
We previously identified that the development of early-stage myeloid-derived suppressor cells (eMDSCs) in breast cancer with high IL-6 (IL-6
) expression was correlated with the SOCS3 ...deficiency-dependent hyperactivation of the JAK/STAT signaling pathway. However, the regulatory mechanisms have not yet been elucidated. In this study, we aimed to investigate how the posttranscriptional regulation mediated by cancer exosome-derived miRNAs affected the JAK/STAT signaling pathway and the development of eMDSCs. Using miRNA microarray, we screened miR-9 and miR-181a which were exclusively upregulated in eMDSCs and inversely associated with SOCS3 expression. We found both miRNAs promoted the amplification of immature eMDSCs with the strong suppression on T-cell immunity in mice and humans. Furthermore, miR-9 and miR-181a promoted 4T1 tumor growth and immune escape via enhancing eMDSCs infiltration in situ. But miR-9 and miR-181a stimulated eMDSCs development by separately inhibiting SOCS3 and PIAS3, two crucial regulators in the negative feedback loop of the JAK/STAT signaling pathway. Elevated miR-9 and miR-181a in eMDSCs was derived from tumor-derived exosomes, and blocking the exosome release could fully attenuate the miRNA-mediated regulation on eMDSCs development. In summary, our findings indicated that tumor exosome-derived miR-9 and miR-181a activated the JAK/STAT signaling pathway via targeting SOCS3 and PIAS3, respectively, and thus promoted the expansion of eMDSCs which might provide potential therapeutic target for IL-6
breast cancer treatment.
Single-cell RNA sequencing (scRNA-seq) technologies are poised to reshape the current cell-type classification system. However, a transcriptome-based single-cell atlas has not been achieved for ...complex mammalian systems. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using simple, inexpensive devices. Using Microwell-seq, we analyzed more than 400,000 single cells covering all of the major mouse organs and constructed a basic scheme for a mouse cell atlas (MCA). We reveal a single-cell hierarchy for many tissues that have not been well characterized previously. We built a web-based “single-cell MCA analysis” pipeline that accurately defines cell types based on single-cell digital expression. Our study demonstrates the wide applicability of the Microwell-seq technology and MCA resource.
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•Development of Microwell-seq, a high-throughput and low-cost scRNA-seq platform•Construction of a single-cell mouse cell atlas (scMCA) covering major cell types•Characterization of cellular heterogeneity with minimal batch effect•Characterization of cross-tissue cellular network at the single-cell level
Development of Microwell-seq allows construction of a mouse cell atlas at the single-cell level with a high-throughput and low-cost platform.
A gradual increase in population and urbanization has increased the demand for global resources, which ultimately burdens the depletion of resources and challenges environmental sustainability ...worldwide. In recent decades, nature sustainability has been the biggest challenge encountered by humankind. In addition, the changing lifestyle and consumption patterns have enormously played a key role. However, the consumption pattern from the employee’s perspective suffers from the lack of research. Therefore, grounded on the theory of planned behavior (TPB), this research explores the antecedents and consequences of employees’ buying intentions in the world’s emerging market (China). Data were collected using a web-based link shared
via
WeChat and Q.Q.; resultants into 451 valid responses and partial least square structural equation modeling (PLS-SEM) using SmartPLS 4 have been administered for the analysis. Besides the insignificant effect of descriptive norms on buying intention and environmental concerns on purchasing behavior, other factors significantly impact purchase intention and actual buying behavior. This research witnesses a significant mediating role of buying intention. This research suggests that practitioners (i.e., marketers, government, policymakers, and environmental focus companies) develop strategies for public advertisement and launch a general message and campaigns both in urban and rural areas to prevent environmental sustainability and increases awareness related to organic consumption.
Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems
. However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell ...mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a 'single-cell HCL analysis' pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology.
Efficient treatment of swine wastewater at a high rate would facilitate the development of a sustainable pig industry. In this study, to investigate methane fermentation and membrane filtration ...performance, an anaerobic membrane bioreactor was operated under mesophilic conditions for 207 days during four stages, with a hydraulic retention time (HRT) decreasing from 5 to 3, 2, and 1 day, and a changing of solid retention time/hydraulic retention time (SRT/HRT) ratio from 18,18 to 8 and 3.2. The results showed that a higher volumetric methane production of 1.63 L/(L·d) and a lower VFAs concentration (<200 mg/L at stable stage) could achieved when the HRT was 1 day and SRT/HRT ratio was only 3.2. The specific methanogenic activity slightly decreased under the shorter HRT, and with SRT/HRT shortening, hydrogenotrophic Methanocorpusculum tended to dominate in bulk sludge while acetoclastic Methanosaeta dominated in the biofilm. Membrane fouling was observed after 4 months with a flux decline and a significant increase in trans-membrane pressure. A serial cleaning test indicated that organic pollutants contributed highly to the membrane fouling.
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•HRT was successfully reduced to 1 day in the AnMBR.•The specific methanogenic activity decreased during the shortening of the HRT.•The biofilm attached to the membrane had higher acetoclastic methanogens.•Membrane fouling was almost completely removed by sodium hypochlorite.
This study investigates the problem of finite-time output feedback stabilization in probability for a class of stochastic high-order nonlinear systems with unknown output function. By combining the ...homogeneous domination techniques, backstepping method and sign function, we obtain the output feedback controller that includes state controller and recursive reduced-order observer. Subsequently, we present an analytical method to deal with the unknown output function within the stochastic high-order nonlinear system such that the designed output feedback controller can make the closed-loop system globally finite-time stabilization in probability when the unknown output function belongs to the maximum open sector <tex-math notation="LaTeX">$\Omega $ </tex-math>. The numerical simulation results show that the proposed scheme is feasible.
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•A hybrid AnMBR was developed to treat food waste with anti-fouling function.•About 21% of biomass attached on the carriers in the hybrid AnMBR.•Membrane fouling was largely ...alleviated in the hybrid AnMBR.•Thermophilic AD of food waste can maintain stability at high OLR.
The thermophilic anaerobic digestion of food waste was a long-term challenge for maintaining process stability. A hybrid submerged anaerobic membrane bioreactor (AnMBR), integrating 27%(v/v) polyurethane sponge as fixed carriers were therefore investigated at (50 ± 2) °C. The organics removal efficiencies, COD mass balance, and membrane filtration performance were investigated in a 75-days continuously operated experiment. The results showed that methane production reached 0.31 L/(kg·COD) under an organic loading rate of 7.3 kg·COD/(m3·d). The low concentration of total volatile fatty acids of 247 ~ 274 mg/L and a high proportion of Methanosarcina (>97%) represented the high stability of the thermophilic process. Approximately 21% of biomass grew on the carriers in the hybrid AnMBR and induced a much lower suspended solids concentration and viscosity of bulk sludge. Noticeable lower trans-membrane pressure was consequently observed. The affecting factors identified by PCA analysis proved the advantages of the hybrid AnMBR for alleviating membrane fouling formation.
The transcription factor Spi-1 proto-oncogene (SPI1, also known as PU.1) is a key regulator of signal communication in the immune system and is essential for the development of myeloid cells and ...lymphocytes. However, the potential role of SPI1 in gastric cancer (GC) and the correlations between SPI1 and immune infiltration remain unclear.
In the present study, multiple databases including ONCOMINE, TIMER, Kaplan-Meier Plotter, and The Cancer Genome Atlas were used to explore the expression levels and prognostic value of
in GC. cBioPortal was used to explore the possible reasons for the increased expression of SPI1 in GC. The correlations between SPI1 expression and tumor-infiltrating immune cells (TICs) were analyzed using CIBERSORT and TIMER. Gene set enrichment analysis was used to determine the biological function of SPI1 in the development of GC. In addition, a risk signature based on SPI1-related immunomodulators was constructed to accurately evaluate the prognosis of patients with GC. The upregulation of SPI1 expression in GC was further confirmed through immunohistochemistry, western blotting, and real-time quantitative PCR (RT-qPCR) assay.
The expression of SPI1 was increased significantly in GC according to multiple databases, and high expression of SPI1 was related to poor prognosis and progression of GC. The main factor influencing the high expression of SPI1 mRNA in GC may be diploidy, not DNA methylation. Moreover, immunohistochemistry, western blotting, and RT-qPCR assays also confirmed the upregulated expression of SPI1 in GC. CIBERSORT analysis revealed that SPI1 expression was correlated with seven types of TICs (naive B cells, resting memory CD4 T cells, activated memory CD4 T cells, activated natural killer cells, resting natural killer cells, M2 macrophages, and resting dendritic cells). Gene set enrichment analysis indicated that SPI1 might be related to immune activation in GC and participate in cell cycle regulation. In addition, based on SPI1-related immunomodulators, we developed multiple-gene risk prediction signatures and constructed a nomogram that can independently predict the clinical outcome of GC.
The results of the present study suggest that SPI1 has a critical role in determining the prognosis of GC patients and may be a potential immunotherapeutic target.
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