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"Wang, Fu-Sheng"
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What to do next to control the 2019-nCoV epidemic?
Notably, 159 confirmed cases have been reported in 23 other countries beyond China, including Japan, Thailand, Singapore, South Korea, Australia, the USA, Malaysia, and Germany. Because of the seriousness of this outbreak, WHO declared it a public health emergency of international concern on Jan 30, 2020, followed by the USA announcing a public health emergency on Jan 31, 2020. [...]it is important to understand the lung microenvironment and the map of immune responses against 2019-nCoV infection, which might help to define clinical stages and uncover the pathogenesis of the disease. First-line medical staff and scientists in China have had a leading role in fighting the outbreak of 2019-nCoV-associated pneumonia.
Journal Article
Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Shenzhen, China, 2020
Since early January 2020, after the outbreak of coronavirus infection in Wuhan, China, ≈365 confirmed cases have been reported in Shenzhen, China. The mode of community and intrafamily transmission is threatening residents in Shenzhen. Strategies to strengthen prevention and interruption of these transmissions should be urgently addressed.
Journal Article
Neutrophils in liver diseases: pathogenesis and therapeutic targets
Previously, it was assumed that peripheral neutrophils are a homogeneous population that displays antimicrobial functions. However, recent data have revealed that neutrophils are heterogeneous and are additionally involved in tissue damage and immune regulation. The phenotypic and functional plasticity of neutrophils has been identified in patients with cancer, inflammatory disorders, infections, and other diseases. Currently, neutrophils, with their autocrine, paracrine, and immune modulation functions, have been shown to be involved in liver diseases, including viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, cirrhosis, liver failure, and liver cancer. Accordingly, this review summarizes the role of neutrophils in liver diseases.
Journal Article
A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2
An outbreak of coronavirus disease 2019 (COVID-19)
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, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
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, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus–receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.
Two monoclonal antibodies isolated from a patient with COVID-19 are shown to interfere with SARS-CoV-2–receptor binding, and one displays potent action against this virus in vitro and in a rhesus macaque model.
Journal Article
BLiMP: The Benchmark of Linguistic Minimal Pairs for English
We introduce The Benchmark of Linguistic Minimal Pairs (BLiMP),
a challenge set for evaluating the linguistic knowledge of language models (LMs) on major grammatical phenomena in English. BLiMP consists of 67 individual datasets, each containing 1,000 minimal pairs—that is, pairs of minimally different sentences that contrast in grammatical acceptability and isolate specific phenomenon in syntax, morphology, or semantics. We generate the data according to linguist-crafted grammar templates, and human aggregate agreement with the labels is 96.4%. We evaluate
-gram, LSTM, and Transformer (GPT-2 and Transformer-XL) LMs by observing whether they assign a higher probability to the acceptable sentence in each minimal pair. We find that state-of-the-art models identify morphological contrasts related to agreement reliably, but they struggle with some subtle semantic and syntactic phenomena, such as negative polarity items and extraction islands.
Journal Article
Overcoming the energy gap law in near-infrared OLEDs by exciton–vibration decoupling
The development of high-performance near-infrared organic light-emitting diodes is hindered by strong non-radiative processes as governed by the energy gap law. Here, we show that exciton delocalization, which serves to decouple the exciton band from highly vibrational ladders in the S0 ground state, can bring substantial enhancements in the photoluminescence quantum yield of emitters, bypassing the energy gap law. Experimental proof is provided by the design and synthesis of a series of new Pt(ii) complexes with a delocalization length of 5–9 molecules that emit at 866–960 nm with a photoluminescence quantum yield of 5–12% in solid films. The corresponding near-infrared organic light-emitting diodes emit light with a 930 nm peak wavelength and a high external quantum efficiency up to 2.14% and a radiance of 41.6 W sr−1 m−2. Both theoretical and experimental results confirm the exciton–vibration decoupling strategy, which should be broadly applicable to other well-aligned molecular solids.Pt(ii) complexes allow the fabrication of efficient near-infrared organic light-emitting diodes that operate beyond the 900 nm region.
Journal Article
Single-cell RNA sequencing reveals intrahepatic and peripheral immune characteristics related to disease phases in HBV-infected patients
ObjectiveA comprehensive immune landscape for HBV infection is pivotal to achieve HBV cure.DesignWe performed single-cell RNA sequencing of 2 43 000 cells from 46 paired liver and blood samples of 23 individuals, including six immune tolerant, 5 immune active (IA), 3 acute recovery (AR), 3 chronic resolved and 6 HBV-free healthy controls (HCs). Flow cytometry and histological assays were applied in a second HBV cohort for validation.ResultsBoth IA and AR were characterised by high levels of intrahepatic exhausted CD8+ T (Tex) cells. In IA, Tex cells were mainly derived from liver-resident GZMK+ effector memory T cells and self-expansion. By contrast, peripheral CX3CR1+ effector T cells and GZMK+ effector memory T cells were the main source of Tex cells in AR. In IA but not AR, significant cell–cell interactions were observed between Tex cells and regulatory CD4+ T cells, as well as between Tex and FCGR3A+ macrophages. Such interactions were potentially mediated through human leukocyte antigen class I molecules together with their receptors CANX and LILRBs, respectively, contributing to the dysfunction of antiviral immune responses. By contrast, CX3CR1+GNLY+ central memory CD8+ T cells were concurrently expanded in both liver and blood of AR, providing a potential surrogate marker for viral resolution. In clinic, intrahepatic Tex cells were positively correlated with serum alanine aminotransferase levels and histological grading scores.ConclusionOur study dissects the coordinated immune responses for different HBV infection phases and provides a rich resource for fully understanding immunopathogenesis and developing effective therapeutic strategies.
Journal Article
Immunological and inflammatory profiles in mild and severe cases of COVID-19
COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.
Immunophenotyping of patients with COVID-19 is ongoing, but much remains to be learned. Here the authors analyze 41 hospitalized patients with COVID-19 and show a higher degree of lymphopenia in various immune cell subsets as well as cytotoxicity and T cell inhibitory marker expression in severe cases compared with mild.
Journal Article