COVID‐19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID‐19 pathophysiology, we ...combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID‐19‐infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue‐specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN‐I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID‐19‐infected patients experiencing milder disease symptoms showed robust T‐cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS‐CoV‐2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID‐19.
SYNOPSIS
Proteomics, metabolomics and RNAseq data map immune responses in COVID‐19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue‐specific proteins.
A multi‐omics profiling of the host response to SARS‐CoV2 infection in 66 clinically diagnosed and laboratory confirmed COVID‐19 patients and 17 uninfected controls.
Significant correlations between multi‐omics data and key clinical parameters.
Alteration of tissue‐specific proteins and exRNAs.
Enhanced activation of immune responses is associated with COVID‐19 pathogenesis.
Biomarkers to predict COVID‐19 clinical outcomes pending clinical validation as prospective marker.
Proteomics, metabolomics and RNAseq data map immune responses in COVID‐19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue‐specific proteins.
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•A functionalized POSS-Ti3C2Tx has been prepared via a facile surface-manipulation approach.•Upon addition of 2 wt% of POSS-Ti3C2Tx, a 39.1 % reduction in the peak heat release rate ...of PS is obtained.•A 54.4 % reduction in the peak CO production rate of PS is achieved.•The initial temperatures of PS in nitrogen and air also increase by 22 °C and 39 °C, respectively.•The good fire safety is due to the adsorption, catalytic and barrier effects of POSS-Ti3C2Tx.
High-performance MXene-based polymer nanocomposites are highly desirable for diverse industry applications due to their exceptional mechanical, thermal and other properties. Nevertheless, it remains an intractable challenge to create flame retardant polymer/MXene nanocomposites due to the difficulty to achieve uniform dispersion of MXenes. Here, we reported a facile strategy for the surface manipulation of two-dimensional titanium carbide nanosheets (Ti3C2Tx) with 3-aminopropylheptaisobutyl-polyhedral oligomeric silsesquioxane (AP-POSS) (POSS-Ti3C2Tx) through electrostatic interactions. The POSS-Ti3C2Tx is steadily dispersed in many polar solvents. Upon incorporated into polystyrene (PS), the combined effect of AP-POSS and MXene makes the resultant PS nanocomposites exhibit significantly improved thermal and thermoxidative stability, e.g. 22 °C and 39 °C increases in the temperature at 5 wt% mass loss under nitrogen and air, respectively. Meanwhile, a 39.1 % reduction in the peak heat release rate, a respective 54.4 % and 35.6 % reduction in the peak CO production rate and the peak CO2 production rate was achieved, which are superior to those of its own and previous counterparts. This outstanding fire safety is attributed to the combination of adsorption, catalytic and barrier effects of POSS-Ti3C2Tx. Hence, as-designed functionalized MXenes can be effectively applied in PS to formulate multifunctional polymer nanocomposites attractive for wide potential applications.
Tumor immunotherapy is a promising therapeutic strategy for patients with advanced cancers. T cells are key mediators of antitumor function that specifically recognize and react to tumor-expressing ...antigens and have proven critical for cancer immunotherapy. However, T cells are not as effective against cancer as expected. This is partly because T cells enter a dysfunctional or exhausted state, which is characterized by sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T cells. T cell dysfunction induces the out of control of tumors. Recently, T cell dysfunction has been investigated in many experimental and clinical settings. The molecular definition of T cell dysfunction and the underlying causes of the T cell dysfunction has been advanced regardless of the fact that the pathways involved are not well elucidated, which proposing promising therapeutic opportunities in clinic. In this review, we will discuss the recent advances in the molecular mechanisms that affect TME and induce T cell dysfunction, and the development of promising immunotherapies to counteract the mechanisms of tumor-induced T cell dysfunction. Better understanding these underlying mechanisms may lead to new strategies to improve the clinical outcome of patients with cancer.
ABSTRACT
Vitamin D deficiency has been recognized as a major public health issue worldwide. Recent studies have indicated that genetic factors might play an important role in determining serum ...25‐hydroxyvitamin D 25(OH)D levels in Caucasians and African Americans. However, the genes that contribute to the variation in serum 25(OH)D levels in Chinese are unknown. In this study, we screened 15 key genes within the vitamin D metabolic pathway using 96 single‐nucleotide polymorphism (SNP) markers in a group of 2897 unrelated healthy Chinese subjects. Significant confounding factors that may influence the variability in serum 25(OH)D levels were used as covariates for association analyses. An association test for quantitative traits was performed to evaluate the association between candidate genes and serum 25(OH)D levels. In the present study, variants and/or haplotypes in GC, CYP2R1, and DHCR7/NADSYN1 were identified as being associated with 25(OH)D levels. Participants with three or four risk alleles of the two variants (GC‐rs4588 and CYP2R1‐rs10766197) had an increased chance of presenting with a 25(OH)D concentration lower than 20 ng/mL (odds ratio 2.121, 95% confidence interval 1.586–2.836, p = 6.1 × 10−8) compared with those lacking the risk alleles. Each additional copy of a risk allele was significantly associated with a 0.12‐fold decrease in the log‐25(OH)D concentration (p = 3.7 × 10−12). Haplotype TGA of GC rs705117‐rs2282679‐rs1491710, haplotype GAGTAC of GC rs842999‐rs705120‐rs222040‐rs4588‐rs7041‐rs10488854, haplotype CA of GC rs1155563‐rs222029, and haplotype AAGA of CYP2R1 rs7936142‐rs12794714‐rs2060793‐rs16930609 were genetic risk factors toward a lower 25(OH)D concentration. In contrast, haplotype TGGGCCC of DHCR7/NADSYN1 rs1790349‐rs7122671‐rs1790329‐rs11606033‐rs2276360‐rs1629220‐rs2282618 were genetic protective factors. The results suggest that the GC, CYP2R1, and DHCR7/NADSYN1 genes might contribute to variability in the serum 25(OH)D levels in a healthy Chinese population in Shanghai. These markers could be used as tools in Mendelian randomization analyses of vitamin D, and they could potentially be drug targets in the Chinese population in Shanghai.
Drawing upon prior research on proactive personality and person-environment fit, we examine the congruence effect of leader and follower proactive personality on leadermember exchange (LMX) quality, ...which in turn influences follower job satisfaction, affective commitment, and job performance. Results of cross-level polynomial regressions on 165 dyads supported the congruence effect hypothesis. Further, asymmetrical incongruence effects were found wherein followers had lower-quality LMX and poorer work outcomes when their proactive personality was lower than their leaders' as compared with when their proactive personality was higher. These findings highlight the pivotal role played by leaders in promoting employee proactivity at work.
Photocatalysis driven by solar energy is a feasible strategy to alleviate energy crises and environmental problems. In recent years, significant progress has been made in developing advanced ...photocatalysts for efficient solar‐to‐chemical energy conversion. Single‐atom catalysts have the advantages of highly dispersed active sites, maximum atomic utilization, unique coordination environment, and electronic structure, which have become a research hotspot in heterogeneous photocatalysis. This paper introduces the potential supports, preparation, and characterization methods of single‐atom photocatalysts in detail. Subsequently, the fascinating effects of single‐atom photocatalysts on three critical steps of photocatalysis (the absorption of incident light to produce electron‐hole pairs, carrier separation and migration, and interface reactions) are analyzed. At the same time, the applications of single‐atom photocatalysts in energy conversion and environmental protection (CO2 reduction, water splitting, N2 fixation, organic macromolecule reforming, air pollutant removal, and water pollutant degradation) are systematically summarized. Finally, the opportunities and challenges of single‐atom catalysts in heterogeneous photocatalysis are discussed. It is hoped that this work can provide insights into the design, synthesis, and application of single‐atom photocatalysts and promote the development of high‐performance photocatalytic systems.
Single‐atom catalysts (SACs) have the maximum atomic utilization, unique coordination environment, and electronic structure, which make them exhibit fascinating performance in the field of heterogeneous photocatalysis. This review summarizes the potential support, preparation, and characterization techniques of SACs. Notably, the unique properties of SACs in photocatalytic reaction and its latest research progress in energy conversion and environmental protection are discussed.
A growing number of studies have examined the "sharedness" of leadership processes in teams (i.e., shared leadership, collective leadership, and distributed leadership). We meta-analytically ...cumulated 42 independent samples of shared leadership and examined its relationship to team effectiveness. Our findings reveal an overall positive relationship (ρ = .34). But perhaps more important, what is actually shared among members appears to matter with regard to team effectiveness. That is, shared traditional forms of leadership (e.g., initiating structure and consideration) show a lower relationship (ρ = .18) than either shared new-genre leadership (e.g., charismatic and transformational leadership; ρ = .34) or cumulative, overall shared leadership (ρ = .35). In addition, shared leadership tends to be more strongly related to team attitudinal outcomes and behavioral processes and emergent team states, compared with team performance. Moreover, the effects of shared leadership are stronger when the work of team members is more complex. Our findings further suggest that the referent used in measuring shared leadership does not influence its relationship with team effectiveness and that compared with vertical leadership, shared leadership shows unique effects in relation to team performance. In total, our study not only cumulates extant research on shared leadership but also provides directions for future research to move forward in the study of plural forms of leadership.
Plant viruses have been used as rapid and cost-effective expression vectors for heterologous protein expression in genomic studies. However, delivering large or multiple foreign proteins in monocots ...and insect pests is challenging.
Here, we recovered a recombinant plant cytorhabdovirus, Barley yellow striate mosaic virus (BYSMV), for use as a versatile expression platform in cereals and the small brown plan-thopper (SBPH, Laodelphax striatellus) insect vector.
We engineered BYSMV vectors to provide versatile expression platforms for simultaneous expression of three foreign proteins in barley plants and SBPHs. Moreover, BYSMV vectors could express the c. 600-amino-acid β-glucuronidase (GUS) protein and a red fluorescent protein stably in systemically infected leaves and roots of cereals, including wheat, barley, foxtail millet, and maize plants. Moreover, we have demonstrated that BYSMV vectors can be used in barley to analyze biological functions of gibberellic acid (GA) biosynthesis genes. In a major technical advance, BYSMV vectors were developed for simultaneous delivery of CRISPR/Cas9 nuclease and single guide RNAs for genomic editing in Nicotiana benthamiana leaves.
Taken together, our results provide considerable potential for rapid screening of functional proteins in cereals and planthoppers, and an efficient approach for developing other insect-transmitted negative-strand RNA viruses.
Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as the renewable source of autologous cells. Whereas it has ...been generally assumed that these autologous cells should be immune-tolerated by the recipient from whom the iPSCs are derived, their immunogenicity has not been vigorously examined. We show here that, whereas embryonic stem cells (ESCs) derived from inbred C57BL/6 (B6) mice can efficiently form teratomas in B6 mice without any evident immune rejection, the allogeneic ESCs from 129/SvJ mice fail to form teratomas in B6 mice due to rapid rejection by recipients. B6 mouse embryonic fibroblasts (MEFs) were reprogrammed into iPSCs by either retroviral approach (ViPSCs) or a novel episomal approach (EiPSCs) that causes no genomic integration. In contrast to B6 ESCs, teratomas formed by B6 ViPSCs were mostly immune-rejected by B6 recipients. In addition, the majority of teratomas formed by B6 EiPSCs were immunogenic in B6 mice with T cell infiltration, and apparent tissue damage and regression were observed in a small fraction of teratomas. Global gene expression analysis of teratomas formed by B6 ESCs and EiPSCs revealed a number of genes frequently overexpressed in teratomas derived from EiPSCs, and several such gene products were shown to contribute directly to the immunogenicity of the B6 EiPSC-derived cells in B6 mice. These findings indicate that, in contrast to derivatives of ESCs, abnormal gene expression in some cells differentiated from iPSCs can induce T-cell-dependent immune response in syngeneic recipients. Therefore, the immunogenicity of therapeutically valuable cells derived from patient-specific iPSCs should be evaluated before any clinic application of these autologous cells into the patients.
CsPbI2Br is emerging as a promising all‐inorganic material for perovskite solar cells (PSCs) due to its more stable lattice structure and moisture resistance compared to CsPbI3, although its device ...performance is still much behind this counterpart. Herein, a preannealing process is developed and systematically investigated to achieve high‐quality CsPbI2Br films by regulating the nucleation and crystallization of perovskite. The preannealing temperature and time are specifically optimized for a dopant‐free poly(3‐hexylthiophene) (P3HT)‐based device to target dopant‐induced drastic performance degradation for spiro‐OMeTAD‐based devices. The resulting P3HT‐based device exhibits comparable power conversion efficiency (PCE) to spiro‐OMeTAD‐based devices but much enhanced ambient stability with over 95% PCE after 1300 h. A diphenylamine derivative is introduced as a buffer layer to improve the energy‐level mismatch between CsPbI2Br and P3HT. A record‐high PCE of 15.50% for dopant‐free P3HT‐based CsPbI2Br PSCs is achieved by alleviating the open‐circuit voltage loss with the buffer layer. These results demonstrate that the preannealing processing together with a suitable buffer layer are applicable strategies for developing dopant‐free P3HT PSCs with high efficiency and stability.
High‐efficiency and stable dopant‐free poly(3‐hexylthiophene) (P3HT)‐based CsPbI2Br solar cells are achieved by introducing an optimized preannealing process to engineer the nucleation and crystallization of CsPbI2Br films. Further incorporation of an ultrathin wide‐bandgap diphenylamine derivative layer (poly(9,9‐dioctylfluorenyl‐2,7‐diyl)‐co‐(4,4′‐(N‐(4‐sec‐butylphenyl)diphenylamine)) to regulate the band alignment of CsPbI2Br and P3HT delivers a record‐high efficiency of 15.50% for dopant‐free P3HT‐based CsPbI2Br solar cells.
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