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The global outbreak of SARS in 2002-2003 was caused by the infection of a new human coronavirus SARS- CoV. The infection of SARS-CoV is mediated mainly through the viral surface glycoproteins, which consist of S1 and S2 subunits and form trimer spikes on the envelope of the virions. Here we report the ectodomain structures of the SARS-CoV surface spike trimer in different conformational states determined by single-particle cryo-electron microscopy. The conformation 1 determined at 4.3 A resolution is three-fold symmetric and has all the three recep- tor-binding C-terminal domain 1 （CTDls） of the S1 subunits in ＂down＂ positions. The binding of the ＂down＂ CTDls to the SARS-CoV receptor ACE2 is not possible due to steric clashes, suggesting that the conformation 1 represents a receptor-binding inactive state. Conformations 2-4 determined at 7.3, 5.7 and 6.8 A, resolutions are all asymmetric, in which one RBD rotates away from the ＂down＂ position by different angles to an ＂up＂ position. The ＂up＂ CTD1 exposes the receptor-binding site for ACE2 engagement, suggesting that the conformations 2-4 represent a recep- tor-binding active state. This eonformational change is also required for the binding of SARS-CoV neutralizing anti- bodies targeting the CTD1. This phenomenon could be extended to other betacoronaviruses utilizing CTD1 of the S1 subunit for receptor binding, which provides new insights into the intermediate states of coronavirus pre-fusion spike trimer during infection.

The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) from the full-length spike (S) protein that is stable in the prefusion conformation. NVX-CoV2373 S form 27.2-nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicit high titer anti-S IgG that blocks hACE2 receptor binding, neutralize virus, and protects against SARS-CoV-2 challenge with no evidence of vaccine-associated enhanced respiratory disease. NVX-CoV2373 also elicits multifunctional CD4 + and CD8 + T cells, CD4 + follicular helper T cells (Tfh), and antigen-specific germinal center (GC) B cells in the spleen. In baboons, low-dose levels of NVX-CoV2373 with Matrix-M was also highly immunogenic and elicited high titer anti-S antibodies and functional antibodies that block S-protein binding to hACE2 and neutralize virus infection and antigen-specific T cells. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2373 with Matrix-M (NCT04368988). Here, the authors characterize a SARS-CoV-2 subunit vaccine candidate that contains full-length spike protein stabilized in its prefusion conformation, and show immunogenicity in baboons and protection in mice with Matrix-M adjuvanted vaccine.

A recombinant SARS-CoV-2 spike protein nanoparticle vaccine delivered in the deltoid muscle on days 0 and 21 was found to be immunogenic at both 5 μg and 25 μg doses. When given with a saponin-based adjuvant, both doses were equally immunogenic, with little or no reactogenicity, and elicited neutralizing antibody titers higher than those in convalescent serum.

To address the diverse needs of enterprise users and the cold-start issue of recommendation system, this paper proposes a quality-service demand classification method—1D-CNN-CrossEntorpyLoss, based on cross-entropy loss and one-dimensional convolutional neural network (1D-CNN) with the comprehensive enterprise quality portrait labels. The main idea of 1D-CNN-CrossEntorpyLoss is to use cross-entropy to minimize the loss of 1D-CNN model and enhance the performance of the enterprise quality-service demand classification. The transaction data of the enterprise quality-service platform are selected as the data source. Finally, the performance of 1D-CNN-CrossEntorpyLoss is compared with XGBoost, SVM, and logistic regression models. From the experimental results, it can be found that 1D-CNN-CrossEntorpyLoss has the best classification results with an accuracy of 72.44%. In addition, compared to the results without the enterprise-quality portrait, the enterprise-quality portrait improves the accuracy and recall of 1D-CNN-CrossEntorpyLoss model. It is also verified that the enterprise-quality portrait can further improve the classification ability of enterprise quality-service demand, and 1D-CNN-CrossEntorpyLoss is better than other classification methods, which can improve the precision service of the comprehensive quality service platform for MSMEs.

Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies. Antibodies that target the N-terminal domain (NTD) of the MERS-CoV spike remain poorly characterized. Here, Zhou et al. report the structural and functional analysis of the NTD-targeting mAb 7D10 and show that it synergizes with antibodies targeting the receptor-binding domain against different MERS-CoV strains.

Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against SARS-CoV-2 Omicron XBB sub-variants. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4 + T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023–2024 COVID-19 vaccination campaign.

Background The geographic information science-based interactive map provided good prospects for the public health to study disease prevalence. The purpose of this study is to understand global spatial–temporal trends of childhood overweight and obesity and underlying causes help formulating intervention strategies. Methods This multiple cross-sectional study included data on childhood overweight and obesity prevalence, gross national income per capita, and urbanization rate for 191 countries from 1975–2016. Autoregressive integrated moving average model, standard deviational ellipse model and mixed-effects models were used to explore spatial–temporal trends of childhood overweight and obesity and associations with gross national income per capita and urbanization rate. Results Globally, childhood overweight and obesity rate would reach 30.0% in 2030 (boys: 34.2%, girls: 27.4%). By 2030, it would reach 58.3% in middle- and high-income countries and 68.1% in Western Pacific region. Spatial–temporal trendline for childhood overweight and obesity in 1975–2030 exhibited a “C” shape, migrating from 1975 (15.6 。 E, 24.6 。 N) to 2005 (10.6 。 E, 21.7 。 N), then to 2030 (14.8 。 E, 17.4 。 N). The trendline for urbanization rate was also an irregular \"C\", and the turning point appeared five years earlier than childhood overweight and obesity. Conclusions Globally, childhood overweight and obesity prevalence will continue to increase. Its weight mean center migrated from western countries to Asia and Africa following economic development.

The Bohai Sea is a large semi-enclosed shallow water basin, which receives extensive river discharges of various terrestrial and anthropogenic materials such as sediments, nutrients and contaminants. How these terrigenous inputs may influence the diversity, community structure, biogeographical distribution, abundance and ecophysiology of the sediment anaerobic ammonium oxidation (anammox) bacteria was unknown. To answer this question, an investigation employing both 16S rRNA and hzo gene biomarkers was carried out. Ca. Scalindua bacteria were predominant in the surface sediments of the Bohai Sea, while non-Scalindua anammox bacteria were also detected in the Yellow River estuary and inner part of Liaodong Bay that received strong riverine and anthropogenic impacts. A novel 16S rRNA gene sequence clade was identified, putatively representing an anammox bacterial new candidate species tentatively named \"Ca. Scalindua pacifica\". Several groups of environmental factors, usually with distinct physicochemical or biogeochemical natures, including general marine and estuarine physicochemical properties, availability of anammox substrates (inorganic N compounds), alternative reductants and oxidants, environmental variations caused by river discharges and associated contaminants such as heavy metals, were identified to likely play important roles in influencing the ecology and biogeochemical functioning of the sediment anammox bacteria. In addition to inorganic N compounds that might play a key role in shaping the anammox microbiota, organic carbon, organic nitrogen, sulfate, sulfide and metals all showed the potentials to participate in the anammox process, releasing the strict dependence of the anammox bacteria upon the direct availability of inorganic N nutrients that might be limiting in certain areas of the Bohai Sea. The importance of inorganic N nutrients and certain other environmental factors to the sediment anammox microbiota suggests that these bacteria were active for the in situ N transforming process and maintained a versatile life style well adapted to the varying environmental conditions of the studied coastal ocean.

Evidence for the prognostic impact of chest pain in acute pulmonary embolism (APE) is limited. This study aimed to assess the prognostic value of chest pain in a Chinese cohort of patients with APE. Consecutive hospitalized patients diagnosed with APE between January 2016 and December 2019 were retrospectively enrolled and followed prospectively for 2 years at West China Hospital of Sichuan University. The primary outcome was in-hospital all- cause mortality, while the secondary outcomes included 3-month, 6-month, and 2-year all-cause mortality, APE recurrence, mechanical ventilation, and length of hospital stay (LOS). A total of 737 APE patients met the study criteria, with 254 patients (34.5%) presented with chest pain at admission. Patients with chest pain had significantly lower in-hospital (3.1% vs. 11.2%), 3-month (3.7% vs. 7.5%), 6-month (5.3% vs. 10.0%), and 2-year (9.8% vs. 15.4%) all-cause mortality compared to patients without chest pain (all P  < 0.05). A lower rate of mechanical ventilation was observed in APE patients with chest pain, and no significant differences were identified in terms of APE recurrence and LOS between APE patients with and without chest pain. Chest pain was an independent predictor of in-hospital mortality in three separate multivariable models (range of odds ratios 0.390–0.423, all P  < 0.05). APE patients with chest pain had a lower short-term and long-term all-cause mortality compared to those without chest pain. Chest pain may be considered a strong, favorable prognostic marker in acute pulmonary embolism.

With the recent rise in cases of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b infection in humans and animals, there is an associated increase in the risk of human-to-human transmission. In this study, we characterize a recombinant A(H5N1) A/American Wigeon/South Carolina/22/000345-001/2021 (A/AW/SC/2021) clade 2.3.4.4b vaccine. Purified recombinant A/AW/SC/2021 HA trimers formulated with Matrix-M ® adjuvant, saponin-cholesterol-phospholipid combination arranged in cage-like particles, are found to non-covalently anchor to the vertices of the Matrix-M and form A(H5N1) HA – Matrix-M nanoparticles (H5-MNPs). In naïve female mice, two intranasal (IN) or intramuscular (IM) doses of A/AW/SC/2021 H5-MNP vaccine induces robust antibody- and cell-mediated immune responses, including neutralizing antibodies against A(H5N1). In non-human primates (NHPs) primed with seasonal influenza vaccine, a single IM or IN dose of the A/AW/SC/2021 H5-MNP vaccine induces geometric mean serum A(H5N1) clade 2.3.4.4b pseudovirus neutralizing titers of 1:1160 and 1:54, respectively; above the generally accepted seroconverting neutralizing titer of 1:40. Immunization with H5-MNP vaccine induces antibody responses against conserved epitopes in the A(H5N1) HA stem, vestigial esterase subdomain, and receptor binding site. This A(H5N1) H5-MNP IN and IM vaccine is immunogenic in female rodents and NHPs as a potential A(H5N1) pandemic single-dose vaccine. The rise in highly pathogenic avian influenza cases elevates the risk of human-to-human transmission. Here, the authors develop an adjuvanted protein-based vaccine that elicits robust antibody- and cell-mediated immune responses in mice and non-human primates, suggesting its potential to induce protective immunity in humans.