Host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

Synergistic Effect of Hydroxyl and Carboxyl Groups on Promoting Nanoparticle Occlusion within Calcite.

Direct occlusion of guest nanoparticles into host crystals enables the straightforward preparation for various of nanocomposite materials with emerging properties. Therefore, it is highly desirable to elucidate the 'design rules' that govern efficient nanoparticle occlusion. Herein, a series of sterically-stabilized nanoparticles are rationally prepared, where the surface stabilizer chains of such nanoparticles are composed of either poly(methacrylic acid), or poly(glycerol monomethacrylate), or poly((2-hydroxy-3-(methacryloyloxy)propyl)serine). Systematic investigation reveals that hydroxyl groups and carboxyl groups play a synergistic role in driving nanoparticle incorporation into calcite crystals, where the hydroxyl groups enhance colloidal stability of the nanoparticles and the carboxyl groups provide binding sites for efficient occlusion. The generality of these findings is further validated by extending it to polymer-stabilized gold nanoparticles. This study demonstrates that precision synthesis of polymer stabilizers comprising of synergistic functional groups can significantly promote nanoparticle occlusion, thus enabling the efficient construction of organic-inorganic hybrid materials via nanoparticle occlusion strategy.

Phase Transformation from Amorphous RuSx to Ru-RuS2 Hybrid Nanostructure for Efficient Water Splitting in Alkaline Media.

Ruthenium (Ru)-based materials, as a class of efficient hydrogen evolution reaction (HER) catalysts, play an important role in hydrogen generation by electrolysis of water in an alkaline solution for clean hydrogen energy. Hybrid nanostructure (HN) materials, which include two or more components with distinct functionality, show better performance than their individual materials, since HN materials can potentially integrate their advantages and overcome the weaknesses. However, it remains a challenge to construct Ru-based HN materials with desired crystal phases for enhanced HER performances. Herein, a series of new Ru-based HN materials (t-Ru-RuS2, S-Ru-RuS2, and T-Ru-RuS2) through phase engineering of nanomaterials (PEN) and chemical transformation are designed to achieve highly efficient HER properties. Owing to the plentiful formation of heterojunctions and amorphous/crystalline interfaces, the t-Ru-RuS2 HN delivers the most outstanding overpotential of 16 mV and owns a small Tafel slope of 29 mV dec-1 at a current density of 10 mA cm-2, which exceeds commercial Pt/C catalysts (34 mV, 38 mV dec-1). This work shows a new insight for HN and provides alternative opportunities in designing advanced electrocatalysts with low cost for HER in the hydrogen economy.

Integrated analysis of gut microbiome and host immune responses in COVID-19.

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

PathogenTrack and Yeskit: tools for identifying intracellular pathogens from single-cell RNA-sequencing datasets as illustrated by application to COVID-19.

Pathogenic microbes can induce cellular dysfunction, immune response, and cause infectious disease and other diseases including cancers. However, the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods. Taking advantage of single-cell RNA-sequencing (scRNA-seq) analysis, we can assess the transcriptomic features at the single-cell level. Still, the tools used to interpret pathogens (such as viruses, bacteria, and fungi) at the single-cell level remain to be explored. Here, we introduced PathogenTrack, a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level. In addition, we established an R package named Yeskit to import, integrate, analyze, and interpret pathogen abundance and transcriptomic features in host cells. Robustness of these tools has been tested on various real and simulated scRNA-seq datasets. PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track, and the first tools for identifying bacteria at the single-cell level. Using the raw data of bronchoalveolar lavage fluid samples (BALF) from COVID-19 patients in the SRA database, we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages. SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module. Additionally, we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells, indicating a co-infection of the bacterium in some severe cases of COVID-19. The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub.

Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19.

The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circulatory factors within the first 30 days post-illness onset and during convalescence. We show that hypercortisolemia represents one of the probable causes of acute lymphocytopenia at the onset of severe/critical conditions. Comparison of the transcriptomes of the bronchoalveolar microenvironment and peripheral blood indicates alveolar macrophages, alveolar epithelial cells, and monocytes in lungs as the potential main sources of elevated cytokines mediating systemic immune responses and organ damages. In addition, the transcriptomes of patient blood cells are characterized by distinct gene regulatory networks and alternative splicing events. Our study provides a panorama of the host responses in COVID-19, which may serve as the basis for developing further diagnostics and therapy.

Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection.

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered ß Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4+ and CD8+ cells were increased upon SARS-CoV-2 antigen stimulation. Together, these results indicate that durable anti-SARS-CoV-2 immunity is common in convalescent population, and vaccines developed from 614D variant may offer protection from the currently predominant 614D variant of SARS-CoV-2.

Transcriptome Analysis Provides Novel Insights into the Capacity of the Ectomycorrhizal Fungus Amanita pantherina To Weather K-Containing Feldspar and Apatite.

Ectomycorrhizal (ECM) fungi, symbiotically associated with woody plants, markedly improve the uptake of mineral nutrients such as potassium (K) and phosphorus (P) by their host trees. Although it is well known that ECM fungi can obtain K and P from soil minerals through biological weathering, the mechanisms regulating this process are still poorly understood at the molecular level. Here, we investigated the transcriptional regulation of the ECM fungus Amanita pantherina in weathering K-containing feldspar and apatite using transcriptome sequencing (RNA-seq) and validated these results for differentially expressed genes using real-time quantitative PCR. The results showed that A. pantherina was able to improve relevant metabolic processes, such as promoting the biosynthesis of unsaturated fatty acids and steroids in the weathering of K-containing feldspar and apatite. The expression of genes encoding ion transporters was markedly enhanced during exposure to solid K-containing feldspar and apatite, and transcripts of the high-affinity K transporter ApHAK1, belonging to the HAK family, were significantly upregulated. The results also demonstrated that there was no upregulation of organic acid biosynthesis, reflecting the weak weathering capacity of the A. pantherina isolate used in this study, especially its inability to utilize P in apatite. Our findings suggest that under natural conditions in forests, some ECM fungi with low weathering potential of their own may instead enhance the uptake of mineral nutrients using their high-affinity ion transporter systems.IMPORTANCE In this study, we revealed the molecular mechanism and possible strategies of A. pantherina with weak weathering potential in the uptake of insoluble mineral nutrients by using transcriptome sequencing (RNA-seq) technology and found that ApHAK1, a K transporter gene of this fungus, plays a very important role in the acquisition of K and P. Ectomycorrhizal (ECM) fungi play critical roles in the uptake of woody plant nutrients in forests that are usually characterized by nutrient limitation and in maintaining the stability of forest ecosystems. However, the regulatory mechanisms of ECM fungi in acquiring nutrients from minerals/rocks are poorly understood. This study investigated the transcriptional regulation of A. pantherina weathering K-containing feldspar and apatite and improves the understanding of fungal-plant interactions in promoting plant nutrition enabling increased productivity in sustainable forestry.