The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses ...to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.
•SARS-CoV-2-specific antibodies are detected in COVID-19 convalescent subjects•Most COVID-19 convalescent individuals have detectable neutralizing antibodies•Cellular immune responses to SARS-CoV-2 are found in COVID-19 convalescent subjects•Neutralization antibody titers correlate with the numbers of virus-specific T cells.
In blood samples from COVID-19 convalescent subjects, Ni et al. have detected SARS-CoV-2-specific humoral and cellular immunity. Most subjects display serum neutralizing activities, which correlate with the numbers of virus-specific T cells.
In today’s business environment with fast growing communication and information technologies, knowledge management (KM) capabilities are a valuable source for innovation. However, little is known ...about the particular KM capabilities that lead to business model innovation (BMI) and whether their effect is dependent upon the firm’s orientation towards risk-taking. We examine the impact internal and external KM capabilities have on BMI and how these effects are moderated by its risk-taking tolerance. We empirically analyze a sample of 197 small and medium-sized enterprises (SMEs) applying structural equation modeling (SEM) and fuzzy-set qualitative comparative analysis (fsQCA). The results from the SEM indicate that particularly external KM capabilities stimulate BMI. This relationship is strengthened for firms with a high risk-taking tolerance. Internal knowledge is only effective for firms with a low risk-taking tolerance. The fsQCA results substantiate these findings and refine the SEM by providing particular antecedent conditions for high levels of BMI.
Tourism firms’ financial performance is determined by a complex interplay of factors, both internal and external to the firm. Predominant internal factors are their entrepreneurial behavior and ...financial resources. External factors refer to the network of actors contributing to the tourism product as well as market and competitive uncertainties. Employing fuzzy-set qualitative comparative analysis (fsQCA) on quantitative data from a survey of 113 owner-managers of small and medium-sized tourism firms from Austria, this study investigates configurations of factors that lead to high firm performance. Results reveal six different configurations, which can be grouped into high or low environmental uncertainty settings and highlight the relevance of multidimensional Entrepreneurial Orientation (EO), financial endowment, and personal and professional networks. Using a sequential mixed-methods approach, 13 qualitative follow-up interviews with owner-managers from the sample help to gain deeper insights into the identified configurations and to formulate successful paths to higher tourism firm performance.
•Tourism firm performance is driven by factor configurations, with no one factor being sufficient on its own•Fuzzy-set Qualitative Comparative Analysis enables the derivation of factor configurations leading to high performance•The degree of environmental uncertainty affects the solutions to achieve higher firm performance•Multidimensional entrepreneurial orientation, financial resources and networks promise higher firm performance•Qualitative follow-up interviews help to interpret findings, label configurations and develop implications
The performance drivers of family firms have spawned considerable research interest. Almost exclusively this research has relied on independent sets of explanatory variables in linear analyses. These ...analyses mask the complex interdependencies that are likely to exist among key success factors, leading to faulty theory and misspecified implications for practice. As treatment, the authors propose a configuration approach to family firm performance that accounts for complex interdependencies among entrepreneurial, innovation and family influence conditions. Using a fuzzy set qualitative comparative analysis of a sample of 129 Finnish family firms, the authors identify sufficient conditions with regard to the existence or absence of antecedent conditions to family firm performance. These conditions include entrepreneurial orientation, exploration and exploitation activities that form causal paths towards family firm performance. To enrich the analysis, the authors theorize and empirically analyse how these conditions might differ in family firms with high and low levels of family influence. They deepen the current understanding of configurations that promote the performance of family firms, offer important implications for theory and practice, and set new directions for future research on the strategic management of family firms. The results are also virtually identical and insensitive to change across subjective and objective performance measures.
In recent years, the rapidly growing attention on MXenes makes the material a rising star in the 2D materials family. Although most researchers' interests are still focused on the properties of bare ...MXenes, little attention has been paid to the surface chemistry of MXenes and MXene‐based nanocomposites. To this end, this Review offers a comprehensive discussion on surface modified MXene‐based nanocomposites for energy conversion and storage (ECS) applications. Based on the structure and reaction mechanism, the related synthesis methods toward MXenes are briefly summarized. After the discussion of existing surface modification techniques, the surface modified MXene‐based nanocomposites and their inherent chemical principles are presented. Finally, the application of these surface modified nanocomposites for supercapacitors (SCs), lithium/sodium–ion batteries (LIBs/SIBs), and electrocatalytic water splitting is discussed. The challenges and prospects of MXene‐based nanocomposites for future ECS applications are also presented.
Recently, MXenes have gained increasing attention in the field of energy conversion and storage (ECS). Meanwhile, the unique surface chemistry of MXenes endows them with great potential in the construction of 2D based nanocomposites. To this end, the present work offers a comprehensive summary of surface modified MXene‐based nanocomposites for ECS applications.
Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated ...multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution Ser139→Asn139 (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, ...and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
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•CH25H and its enzymatic product, 25HC, inhibit ZIKV entry in vitro•25HC attenuates ZIKV-associated viremia and disease in mice and non-human primates•25HC prevents ZIKV infection in human cortical organoids•25HC protects fetal mice from microcephaly caused by ZIKV infection
Zika virus (ZIKV) presents a major challenge to the global health system. Li et al. find that 25-hydroxycholesterol (25HC) inhibits ZIKV infection in monkeys and human cortical organoids and protects mice from microcephaly. 25HC has potential as a first-line antiviral agent to combat a broad array of pathogenic species, including ZIKV.
Herein, the authors present the development of novel 0D–2D nanohybrids consisting of a nickel‐based bimetal phosphorus trisulfide (Ni1−xFexPS3) nanomosaic that decorates on the surface of MXene ...nanosheets (denoted as NFPS@MXene). The nanohybrids are obtained through a facile self‐assemble process of transition metal layered double hydroxide (TMLDH) on MXene surface; followed by a low temperature in situ solid‐state reaction step. By tuning the Ni:Fe ratio, the as‐synthesized NFPS@MXene nanohybrids exhibit excellent activities when tested as electrocatalysts for overall water splitting. Particularly, with the initial Ni:Fe ratio of 7:3, the obtained Ni0.7Fe0.3PS3@MXene nanohybrid reveals low overpotential (282 mV) and Tafel slope (36.5 mV dec−1) for oxygen evolution reaction (OER) in 1 m KOH solution. Meanwhile, the Ni0.9Fe0.1PS3@MXene shows low overpotential (196 mV) for the hydrogen evolution reaction (HER) in 1 m KOH solution. When integrated for overall water splitting, the Ni0.7Fe0.3PS3@MXene || Ni0.9Fe0.1PS3@MXene couple shows a low onset potential of 1.42 V and needs only 1.65 V to reach a current density of 10 mA cm−2, which is better than the all noble metal IrO2 || Pt/C electrocatalyst (1.71 mV@10 mA cm−2). Given the chemical versatility of Ni1−xFexPS3 and the convenient self‐assemble process, the nanohybrids demonstrated in this work are promising for energy conversion applications.
Novel 0D–2D nanohybrids consisting of a nickel‐based bimetal phosphorus trisulfide (Ni1−xFexPS3) nanomosaic that decorates the surface of MXene nanosheets are obtained through a facile self‐assembly process. The Ni0.7Fe0.3PS3@MXene reveals low overpotential (282 mV) and Tafel slope (36.5 mV dec−1) for oxygen evolution reaction (OER) and the Ni0.7Fe0.3PS3@MXene || Ni0.9Fe0.1PS3@MXene couple shows good overall water splitting performance.
Traditionally, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a 91 kDa transcription factor, regulates lipid metabolism and long-chain fatty acid oxidation by upregulating the ...expression of several genes of the tricarboxylic acid cycle and the mitochondrial fatty acid oxidation pathway. In addition, PGC-1α regulates the expression of mitochondrial genes to control mitochondria DNA replication and cellular oxidative metabolism. Recently, new insights showed that several myokines such as irisin and myostatin are epigenetically regulated by PGC-1α in skeletal muscles, thereby modulating systemic energy balance, with marked expansion of mitochondrial volume density and oxidative capacity in healthy or diseased myocardia. In addition, in our studies evaluating whether PGC-1α overexpression in epicardial adipose tissue can act as a paracrine organ to improve or repair cardiac function, we found that overexpression of hepatic PGC-1α increased hepatic fatty acid oxidation and decreased triacylglycerol storage and secretion in vivo and in vitro. In this review, we discuss recent studies showing that PGC-1α may regulate mitochondrial fusion⁻fission homeostasis and affect the renal function in acute or chronic kidney injury. Furthermore, PGC-1α is an emerging protein with a biphasic role in cancer, acting both as a tumor suppressor and a tumor promoter and thus representing a new and unresolved topic for cancer biology studies. In summary, this review paper demonstrates that PGC-1α plays a central role in coordinating the gene expression of key components of mitochondrial biogenesis and as a critical metabolic regulator in many vital organs, including white and brown adipose tissue, skeletal muscle, heart, liver, and kidney.
Despite the growing interest in family firm internationalization, academics and practitioners still disagree about the role of external resources in family firms' internationalization processes. This ...study identifies configurations of external resources that lead to the successful internationalization of family firms. The study also explores how configurations differ depending on family firms' socioemotional wealth (SEW) endowment. Configurations are combinations of 1) external ownership, 2) the presence of a non-family CEO, 3) the presence of non-family members on the advisory board, and 4) international networks. By applying fuzzy-set qualitative comparative analysis to a sample of 426 family firms, the study highlights several optimal configurations of external resources that lead to the successful internationalization of family firms. These configurations relate to different degrees of SEW endowment, suggesting that family firms are willing to accept dependence on external resources by shifting their strategic reference point.