Innate lymphoid cells (ILC) are abundant in mucosal tissues. They serve critical functions in anti-pathogen response and tissue homeostasis. However, the heterogenous composition of ILCs in mucosal ...sites and their various maturation trajectories are less well known. In this study, we characterize ILC types and functions from both the lung and the small intestine, and identify their tissue-specific markers. We find that ILC2s residing in the lung express CCR2, whereas intestinal ILC2s express CCR4. Through the use of CCR2 and CCR4 reporter mice, we show that ILC2s undergo translocation via the lung-gut axis upon IL-33 treatment. This trajectory of ILC2s is also observed at the postnatal stage. Allergen-induced activation of lung ILC2s affects the homeostasis of gut ILC2s. Together, our findings implicate that ILCs display tissue-specific features in both the lung and gut, and ILC2s mature along the lung-gut axis in particular homeostatic and inflammatory conditions.
SARS‐CoV‐2 is an emerging coronavirus that causes dysfunctions in multiple human cells and tissues. Studies have looked at the entry of SARS‐CoV‐2 into host cells mediated by the viral spike protein ...and human receptor ACE2. However, less is known about the cellular immune responses triggered by SARS‐CoV‐2 viral proteins. Here, we show that the nucleocapsid of SARS‐CoV‐2 inhibits host pyroptosis by blocking Gasdermin D (GSDMD) cleavage. SARS‐CoV‐2‐infected monocytes show enhanced cellular interleukin‐1β (IL‐1β) expression, but reduced IL‐1β secretion. While SARS‐CoV‐2 infection promotes activation of the NLRP3 inflammasome and caspase‐1, GSDMD cleavage and pyroptosis are inhibited in infected human monocytes. SARS‐CoV‐2 nucleocapsid protein associates with GSDMD in cells and inhibits GSDMD cleavage in vitro and in vivo. The nucleocapsid binds the GSDMD linker region and hinders GSDMD processing by caspase‐1. These insights into how SARS‐CoV‐2 antagonizes cellular inflammatory responses may open new avenues for treating COVID‐19 in the future.
SYNOPSIS
Cellular immune responses triggered by SARS‐CoV‐2 viral proteins are still elusive. This study finds that SARS‐CoV‐2 nucleocapsid inhibits host pyroptosis through blocking GSDMD cleavage. The nucleocapsid binds GSDMD linker region and hinders GSDMD processing by caspase‐1. SARS‐CoV‐2 infected monocytes have enhanced IL‐1β cellular expression level but decreased secretion of IL‐1β.
SARS‐CoV‐2 infected monocytes show altered inflammatory status.
SARS‐CoV‐2 infection causes NLRP3 inflammasome activation accompanied with diminished IL‐1β secretion.
SARS‐CoV‐2 nucleocapsid interacts with GSDMD and protects GSDMD linker from being cleaved by caspase‐1.
SARS‐CoV‐2 inhibits IL‐1β secretion and pyroptosis in human monocytes.
Despite caspase‐1 and NLRP3 inflammasome activation, pyroptotic cell death of SARS‐CoV2‐infected human monocytes is prevented by cleavage site masking in the key effector GSDMD by a viral protein.
The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune surveillance remains poorly ...understood. Here, we analyzed the intratissue bacteria from CRC patient colon tissues. We found that the commensal bacteria belonging to the Lachnospiraceae family, including Ruminococcus gnavus (Rg), Blautia producta (Bp), and Dorea formicigenerans (Df), were enriched in normal tissues, while Fusobacterium nucleatum (Fn) and Peptostreptococcus anaerobius (Pa) were abundant in tumor tissues. Tissue-resident Rg and Bp reduced colon tumor growth and promoted the activation of CD8+ T cells in immunocompetent mice. Mechanistically, intratissue Rg and Bp degraded lyso-glycerophospholipids that inhibited CD8+ T cell activity and maintained the immune surveillance function of CD8+ T cells. Lyso-glycerophospholipids alone promoted tumor growth that was abrogated with Rg and Bp injection. Collectively, intratissue Lachnospiraceae family bacteria facilitate the immune surveillance function of CD8+ T cells and control colorectal cancer progression.
Display omitted
•Identification of tissue-resident microbiota in colon tissues of CRC patients•Ruminococcus gnavus (Rg) and Blautia producta (Bp) are enriched in normal colon tissues•Rg and Bp suppress CRC and promote activation of tumor-infiltrating CD8+ T cells•Rg and Bp degrade lyso-glycerophospholipids and restore CD8+ T cell function
Zhang et al. identify the tissue-resident microbiota in colon tissues of CRC patients and show that the Lachnospiraceae family bacteria R. gnavus and B. producta are enriched in normal colon tissue and suppress CRC development in mice. These bacteria degrade lyso-glycerophospholipids and restore immune surveillance functions of CD8+ T cells.
Drought and flood are two frequent natural disasters in the world. Identification of temporal-spatial variability and its scale-dependence for drought-flood correlation can help to predict, hence to ...alleviate the losses. The correlations of drought with flood at 1, 3, 5, 10, 50 and 100-year scales at moving window of 30years during recent 500years were analyzed by spatial statistics based on geographical information system in Inner Mongolia, China. The results demonstrated that the frequency and intensity of two disasters increased generally during last 500years. The drought-flood correlations indicated a rhythm of alternate positive and negative relation with unspecific timescale, enlarged by prolonging of time scale from 1year to 5years, for either frequency or intensity. A lag effect, flood always occurred at the 4 or 5year following drought was observed. Located in the climatic marginal zone, eastern study region was strongly affected by the East Asia monsoon, showed a weak drought-flood correlation; western study region was controlled by continental climate, showed a significant drought-flood correlation. These correlations were also affected by periodic ENSO disturbance and mountain terrains. With the climatic changes, the drought-flood correlations also change in recent decades. These long-range correlations at various temporal-spatial scales provide a theoretical basis for the scientific prediction of drought and flood outbreaks, for a long term as well as a short wavelet.
Display omitted
•The temporal-spatial patterns of drought and flood frequency and intensity during recent 500years were disclosed.•The drought-flood correlations demonstrated a rhythm of alternate positive and negative relation with unspecific timescale.•The variability in drought-flood correlations across various sub-climatic regions were affected by global climatic changes
Gastric cancer displays marked molecular heterogeneity with aggressive behavior and treatment resistance. Therefore, good in vitro models that encompass unique subtypes are urgently needed for ...precision medicine development. Here, we have established a primary gastric cancer organoid (GCO) biobank that comprises normal, dysplastic, cancer, and lymph node metastases (n = 63) from 34 patients, including detailed whole-exome and transcriptome analysis. The cohort encompasses most known molecular subtypes (including EBV, MSI, intestinal/CIN, and diffuse/GS, with CLDN18-ARHGAP6 or CTNND1-ARHGAP26 fusions or RHOA mutations), capturing regional heterogeneity and subclonal architecture, while their morphology, transcriptome, and genomic profiles remain closely similar to in vivo tumors, even after long-term culture. Large-scale drug screening revealed sensitivity to unexpected drugs that were recently approved or in clinical trials, including Napabucasin, Abemaciclib, and the ATR inhibitor VE-822. Overall, this new GCO biobank, with linked genomic data, provides a useful resource for studying both cancer cell biology and precision cancer therapy.
Display omitted
•Living biobank includes 17 normal and 46 gastric cancer organoid lines•Organoid biobank encompasses most of the known molecular subtypes of gastric cancer•Organoids recapitulate the genomic and transcriptomic features of original tumors•High-throughput screen revealed potential target drugs for personalized therapy
Leung and colleagues established a biobank of patient-derived gastric cancer organoids that encompasses a diverse array of subtypes and maintained long-term similarity to the original tumors. They used the organoids to perform large-scale drug screening that identified potential target drugs and could guide patient drug selection.
Hydrolysis of materials in water can be a promising solution of onsite hydrogen generation for realization of hydrogen economy. In this work, it was the first time that the MgH2-LiNH2 composites were ...explored as air-stable hydrolysis system for hydrogen generation. The MgH2-LiNH2 composites with different composition ratios were synthesized by ball milling with various durations and the hydrogen generation performances of the composite samples were investigated and compared. X-ray diffraction, X-ray photoelectron spectroscopy and scanning electron microscopy techniques were adopted to elucidate the performance improvement mechanisms. The hydrolysis properties of MgH2 were found to be significantly enhanced by the introduction of LiNH2. The 4MgH2-LiNH2 composite ball milled for 5 h can generate 887.2 mL g−1 hydrogen in 1 min and 1016 mL g−1 in 50 min, one of the best results so far for Mg based hydrolysis materials. The LiOH·H2O and NH4OH phases of hydrolysis products from LiNH2 may prevent formation of Mg(OH)2 passivation layer on the surface and supply enough channels for hydrolysis of MgH2. The MgH2-LiNH2 composites appeared to be very stable in air and no obvious negative effect on kinetics and hydrogen generation yield was observed. These good performances demonstrate that the studied MgH2-LiNH2 composites can be a promising and practicable hydrogen generation system.
•Air-stable hydrolysis material of MgH2-LiNH2 composites is studied for the first time.•The hydrolysis properties of MgH2 were significantly enhanced by introduction of LiNH2.•The hydrolysis mechanism of xMgH2-yLiNH2 composites is also reported.•Air-stable MgH2-LiNH2 system means easy handling and good practicability for hydrolysis.
This study analyzed the environmental field, physical quantify fields, convection parameters and radar echo characteristics of a severe hailstorm that occurred on June 18, 2013, due to a mesoscale ...convective system. The analysis was performed using ground meteorological data, sounding data and GFS-ANL (gfs 0.5° × 0.5°) reanalysis data in combination with satellite cloud imagery and Doppler radar observations. The results showed that this rare hailstorm event was generated under the influence of a weakening and eastwardly moving low vortex over Lake Balkhash; and a distinct shear line in the middle and lower troposphere over the western South Xinjiang. Strong vertical wind shears, deep conditionally unstable stratification, ample water vapor in the lower troposphere and suitable wet-bulb zero heights are important contributors to the formation of severe hailstorms. An increase in convective available potential energy (CAPE) and a decrease in the lifting index are strong indicators of a severe hailstorm. For the studied hailstorm event, the time corresponding to the maximum value of the normalized CAPE was close to the timing of the actual hailstorm. The severe hailstorm, consisting of multiple supercells, exhibited notable characteristics of hail clouds and supercells. The formation, disappearance and replacement of strong convection cells occurred while the supercells were sustained. The tracking and forecasting results obtained using the Thunderstorm Identification, Tracking, Analysis and Nowcasting system are found to be, to a certain extent, able to indicate of the direction of the supercell storms during this severe hailstorm event.
PDF
