The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus ...into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including
, a broad-spectrum antiviral drug that interferes with the viral replication, and
, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.
Nanopipettes provide a promising confined space that enables advances in electrochemical, optical, and mass spectrometric measurements at the nanoscale. They have been employed to reveal the hidden ...population properties and dynamics of single molecules and single particles. Moreover, new detection mechanisms based on nanopipettes have led to detailed information on single cells at high spatial and temporal resolution. In this Minireview, we focus on the fabrication and characterization of nanopipettes, summarize their wide applications for the analysis of single entities, and conclude with an outlook for advanced practical sensing.
The preparation and characterization of nanopipettes—promising devices for electrochemical, optical, and mass spectrometric measurements at the nanoscale—are the themes of this Minireview. Their application enables the dynamics and properties of single molecules and particles to be uncovered. Furthermore, new detection mechanisms based on nanopipettes have led to detailed information on single cells at high resolution.
Abstract
Tuning metal–support interaction has been considered as an effective approach to modulate the electronic structure and catalytic activity of supported metal catalysts. At the atomic level, ...the understanding of the structure–activity relationship still remains obscure in heterogeneous catalysis, such as the conversion of water (alkaline) or hydronium ions (acid) to hydrogen (hydrogen evolution reaction, HER). Here, we reveal that the fine control over the oxidation states of single-atom Pt catalysts through electronic metal–support interaction significantly modulates the catalytic activities in either acidic or alkaline HER. Combined with detailed spectroscopic and electrochemical characterizations, the structure–activity relationship is established by correlating the acidic/alkaline HER activity with the average oxidation state of single-atom Pt and the Pt–H/Pt–OH interaction. This study sheds light on the atomic-level mechanistic understanding of acidic and alkaline HER, and further provides guidelines for the rational design of high-performance single-atom catalysts.
Recent transcriptome analyses have revealed that noncoding RNAs (ncRNAs) are broadly expressed in mammalian cells and abundant in the CNS, with tissue and cell type-specific expression patterns. ...Moreover, ncRNAs have been found to intricately and dynamically regulate various signaling pathways in neurodegeneration. As such, some antisense transcripts and microRNAs are known to directly affect neurodegeneration in disease contexts. The functions of ncRNAs in pathogenesis are unique for each disorder, as are the pertinent networks of ncRNA/miRNA/mRNA that mediate these functions. Thus, further understanding of ncRNA biogenesis and effects might aid the discovery of diagnostic biomarkers or development of effective therapeutics for neurodegenerative disorders. Here, we review the ncRNAs that have so far been identified in major neurodegenerative disease etiology and the mechanisms that link ncRNAs with disease-specific phenotypes, such as HTT aggregation in HD, α-synuclein in PD, and Aβ plaques and hyperphosphorylated Tau in AD. We also summarize the known lncRNA/miRNA/mRNA networks that participate in neurodegenerative diseases, and we discuss ncRNA-related treatments shown to delay disease onset and prolong lifespan in rodent models.
Single-molecule measurements have greatly enhanced our understanding of living systems. Biological systems offer nanopores, a sub-class of membrane proteins, the well-defined confined space for ...accommodating a single molecule. The biological nanopore acts as a single-biomolecule interface for capturing and identifying a single molecule of interest, and thus it can be used as a single-molecule sensor. In this Perspective, we focus on biological nanopore-based single-biomolecule interfaces for single-biomolecule detection. First, we outline the design of the nanopore-based single-biomolecule interface, which provides rich stochastic information regarding each biomolecule. Next, we highlight future research directions beyond DNA sequencing, including detection of rare species, identification of hidden intermediates, spectral analysis of covalent/noncovalent interactions, and tracing of the dynamic pathways of single-biopolymer behaviors. The concept of a “single-molecule ionic spectrum” is discussed, which may allow mapping of noncovalent interactions at an atomic level in the future. We also discuss the challenges and goals for the future to make this measurement possible for addressing entirely new types of biological questions, which would be an exciting area of future research.
Proteins are responsible for the occurrence and treatment of many diseases, and therefore protein sequencing will revolutionize proteomics and clinical diagnostics. Biological nanopore approach has ...proved successful for single‐molecule DNA sequencing, which resolves the identities of 4 natural deoxyribonucleotides based on the current blockages and duration times of their translocations across the nanopore confinement. However, open challenges still remain for biological nanopores to sequentially identify each amino acid (AA) of single proteins due to the inherent complexity of 20 proteinogenic AAs in charges, volumes, hydrophobicity and structures. Herein, we focus on recent exciting advances in biological nanopores for single‐molecule protein sequencing (SMPS) from native protein unfolding, control of peptide translocation, AA identification to applications in disease detection.
Nanopore electrochemistry offers a bright prospect for single‐molecule protein sequencing by measuring specific interactions between amino acids based on their natural structure and chemistry continuity and diversity. This Minireview focusses on recent advances in biological nanopores from protein unfolding, peptide translocation, amino acid identification to diagnostic application.
The coronavirus disease of 2019 (COVID-19) has quickly spread to all corners of the world since its emergence in Wuhan, China in December of 2019. The disease burden has been heterogeneous across ...regions of the world, with Americas leading in cumulative cases and deaths, followed by Europe, Southeast Asia, Eastern Mediterranean, Africa and Western Pacific. Initial responses to COVID-19 also varied between governments, ranging from proactive containment to delayed intervention. Understanding these variabilities allow high burden countries to learn from low burden countries on ways to create more sustainable response plans in the future.
This study used a mixed-methods approach to perform cross-country comparisons of pandemic responses in the United States (US), Brazil, Germany, Australia, South Korea, Thailand, New Zealand, Italy and China. These countries were selected based on their income level, relative COVID-19 burden and geographic location. To rationalize the epidemiological variability, a list of 14 indicators was established to assess the countries' preparedness, actual response, and socioeconomic and demographic profile in the context of COVID-19.
As of 1 April 2021, the US had the highest cases per million out of the nine countries, followed by Brazil, Italy, Germany, South Korea, Australia, New Zealand, Thailand and China. Meanwhile, Italy ranked first out of the nine countries' total deaths per million, followed by the US, Brazil, Germany, Australia, South Korea, New Zealand, China and Thailand. The epidemiological differences between these countries could be explained by nine indicators, and they were 1) leadership, governance and coordination of response, 2) communication, 3) community engagement, 4) multisectoral actions, 5) public health capacity, 6) universal health coverage, 7) medical services and hospital capacity, 8) demography and 9) burden of non-communicable diseases.
The COVID-19 pandemic manifests varied outcomes due to differences in countries' vulnerability, preparedness and response. Our study rationalizes why South Korea, New Zealand, Thailand, Australia and China performed better than the US, Italy and Brazil. By identifying the strengths of low burden countries and weaknesses of hotspot countries, we elucidate factors constituting an effective pandemic response that can be adopted by leaders in preparation for re-emerging public health threats.
Accumulating evidence indicates that circular RNAs (circRNAs) are abundant in the human transcriptome. However, their involvement in biological processes, including pluripotency, remains mostly ...undescribed. We identified a subset of circRNAs that are enriched in undifferentiated human embryonic stem cells (hESCs) and demonstrated that two, circBIRC6 and circCORO1C, are functionally associated with the pluripotent state. Mechanistically, we found that circBIRC6 is enriched in the AGO2 complex and directly interacts with microRNAs, miR-34a, and miR-145, which are known to modulate target genes that maintain pluripotency. Correspondingly, circBIRC6 attenuates the downregulation of these target genes and suppresses hESC differentiation. We further identified hESC-enriched splicing factors (SFs) and demonstrated that circBIRC6 biogenesis in hESCs is promoted by the SF ESRP1, whose expression is controlled by the core pluripotency-associated factors, OCT4 and NANOG. Collectively, our data suggest that circRNA serves as a microRNA "sponge" to regulate the molecular circuitry, which modulates human pluripotency and differentiation.
Visible-light persistent phosphors are being widely used as self-sustained night-vision materials because of their sufficiently strong and long afterglow (>10 h) and their ability to be excited by ...sunlight as well as room light. In contrast, persistent phosphors for near-infrared (NIR) wavelengths are lacking. Here we report a series of Cr(3+)-doped zinc gallogermanate NIR persistent phosphors that exhibit strong emission at 650-1,000 nm, extending beyond the typical 690-750 nm, and with a super-long afterglow of more than 360 h. These new NIR persistent phosphors are all-weather materials that can be rapidly, effectively and repeatedly charged by natural sunlight in almost all kinds of outdoor environment. Seconds to minutes of sunlight activation can result in more than two weeks of persistent NIR light emission. This new series of NIR persistent materials have potential applications in night-vision surveillance, solar energy utilization and in vivo bio-imaging.
Conclusions about human behavior are primarily based upon observations from western, educated, industrialized, rich, and democratic (WEIRD) samples, especially from the United States. One consequence ...may be the promotion of assumptions that research findings from these populations are more generalizable to humankind than findings from non-WEIRD populations. We tested this with an archival study comparing the extent to which titles of over 5,000 published psychology articles specify samples’ racial/ethnic/national/cultural characteristics—a practice that implies constraints to generalizability. We observed that samples from the United States were less frequently specified in titles compared to both other WEIRD and non-WEIRD regions. Yet, samples from the United States (compared to other regions) were more frequently specified in titles if they referred to racial/ethnic/cultural minorities who may be perceived as exceptions to assumed generalizability of the White American population. These findings suggest that one consequence of a USA-centric sampling bias in psychology may be biased assumptions of (White) people from the United States as especially reflective of humankind.
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