Most of SARS-CoV-2 neutralizing antibodies (nAbs) targeted the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, mutations at RBD sequences found in the emerging SARS-CoV-2 ...variants greatly reduced the effectiveness of nAbs. Here we showed that four nAbs, S2-4D, S2-5D, S2-8D, and S2-4A, which recognized a conserved epitope in the S2 subunit of the S protein, can inhibit SARS-CoV-2 infection through blocking the S protein-mediated membrane fusion. Notably, these four nAbs exhibited broadly neutralizing activity against SARS-CoV-2 Alpha, Gamma, Delta, and Epsilon variants. Antisera collected from mice immunized with the identified epitope peptides of these four nAbs also exhibited potent virus neutralizing activity. Discovery of the S2-specific nAbs and their unique antigenic epitopes paves a new path for development of COVID-19 therapeutics and vaccines.
The spike (S) protein on the surface of SARS-CoV-2 mediates receptor binding and virus-host cell membrane fusion during virus entry. Many neutralizing antibodies (nAbs), which targeted the receptor binding domain (RBD) of S protein, lost the neutralizing activity against the newly emerging SARS-CoV-2 variants with sequence mutations at the RBD. In contrast, the nAb against the highly conserved S2 subunit, which plays the key role in virus-host cell membrane fusion, was poorly discovered. We showed that four S2-specific nAbs, S2-4D, S2-5D, S2-8D, and S2-4A, inhibited SARS-CoV-2 infection through blocking the S protein-mediated membrane fusion. These nAbs exhibited broadly neutralizing activity against Alpha, Gamma, Delta, and Epsilon variants. Antisera induced by the identified epitope peptides also possessed potent neutralizing activity. This work not only unveiled the S2-specific nAbs but also discovered an immunodominant epitope in the S2 subunit that can be rationally designed as the broad-spectrum vaccine against the SARS-like coronaviruses.
In the present study, a new water-soluble polysaccharide (LJP-11) was obtained from Laminaria japonica by anion exchange DEAE-cellulose chromatography and Sephacryl S-500 chromatography. The average ...molecular weight of this polysaccharide was estimated to be about 2.89×106Da by high performance liquid chromatography system. Gas chromatography showed that LJP-11 was composed of arabinose, mannose and glucose in a molar ratio of 1.0:1.16:6.33. LJP-11 contains a long backbone consisting of (1→4)-β-d-GlcpAc, (1→4)-α-d-Glcp, (1→6)-β-d-Glcp and (1→3,6)-α-d-Manp. The 1-linked β-l-Araf was linked to the C-6 of (1→3)-α-d-Manp and the sulfate group was attached to the C-4 of (1→6)-β-d-Glcp. Pharmacological tests displayed that LJP-11 can stimulate macrophages to release NO, IL-6, TNF-α and IL-10 as well as the up-regulation of their gene expressions, indicating LJP-11 has beneficial effects on immunostimulation. Moreover, LJP-11 exhibited positive effects on the translocation of NF-κB p65 from cytoplasm to nucleus and the phosphorylation of IκBα, ERK1/2, JNK1/2 and P38 in macrophages. These results suggested that the activation of MAPK and NF-κB signaling pathways is one of the mechanisms responsible for the immunostimulating activity of LJP-11.
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Complex quantum electronic circuits can be used to design noise-protected qubits, but their complexity may exceed the capabilities of classical simulation. In such cases, quantum ...computers are necessary for efficient simulation. In this work, we demonstrate the use of variational quantum computing on a transmon-based quantum processor to simulate a superconducting quantum electronic circuit and design a new type of qubit called “Plasmonium”, which operates in the plasmon-transition regime. The fabricated Plasmonium qubits show a high two-qubit gate fidelity of 99.58(3)%, as well as a smaller physical size and larger anharmonicity compared to transmon qubits. These properties make Plasmonium a promising candidate for scaling up multi-qubit devices. Our results demonstrate the potential of using quantum computers to aid in the design of advanced quantum processors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
As we known, reproducing kernel method (RKM) has been presented for solving differential equations for initial and boundary value problems. However, the direct application of the RKM presented in the ...previous works cannot produce good numerical results for Burgers’ equation. To solve this problem, this paper give a modified reproducing kernel method by piecewise technique. The exact solution is given by reproducing kernel functions in a series expansion form, the approximation solution is expressed by n-term summation of reproducing kernel functions. The three numerical experiments results show that the piecewise method is more easily implemented and effective. Some numerical results are also compared with the results obtained by other methods.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In higher plants, the shoot apical meristem produces lateral organs in a regular spacing (phyllotaxy) and timing (plastochron). Molecular analysis of mutants associated with phyllotaxy and ...plastochron would increase understanding of the mechanism of shoot architecture. In this study, we identified mutant mnd8ynp5 showing an increased rate of leaf emergence, larger number of nodes in combination with a dwarfed growth habit from an EMS-treated population of the elite barley cultivar Yangnongpi 5. Using a map-based cloning strategy, the mnd8 gene was narrowed down to a 6.7-kb genomic interval on the long arm of chromosome 5H. Sequence analysis revealed that a C to T single-nucleotide mutation happened at the first exon (position 953) of HORVU5Hr1G118820, leading to an Alamine (Ala) to Valine (Val) substitution at 318th amino acid site. Next, HORVU5Hr1G118820 was defined as the candidate gene of MND8 encoding 514 amino acids and containing two multidrug and toxic compound extrusion (MATE) domains, which is highly homologous to maize Bige1 and has a conserved function in regulation of plant development by controlling leaf initiation rate. Examination of modern barely varieties showed that the Hap-1 was the dominant haplotype and was selected in barley breeding across the world. Collectively, our results indicated that the mnd8ynp5 was a novel allele of HORVU5Hr1G118820 gene that was possibly responsible for shortened plastochron and many noded dwarf phenotype in barley.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Information on the use of lacosamide and concomitant antiepileptic and non-antiepileptic drugs (non-AEDs) is available from clinical trials and observational studies with small sample sizes. ...This retrospective cohort study was conducted to gain insight into the use of lacosamide in a large number of patients with epilepsy in real-life clinical practice with less restrictive selection criteria compared with clinical trial participants. The Truven Health MarketScan (Commercial Claims and Medicare Supplemental) database was used to identify patients with a prior diagnosis of epilepsy with at least one prescription claim for lacosamide between June 2009 and September 2013 and continuous health insurance enrolment with medical and pharmacy coverage during the 1-year pre-index baseline period. A total of 8859 eligible patients were identified, of whom, at index (lacosamide initiation), 16.8% received lacosamide as monotherapy and 54.0% as polytherapy. The median prescription duration was 196 days (Interquartile range 69–476 days). Levetiracetam was the most frequently prescribed concomitant AED across all age groups, followed by phenytoin among older (> 65 years) and lamotrigine among younger patients. Older patients who had LCM monotherapy at initiation, were prescribed fewer concomitant AEDs, but more non-AEDs. The most common non-AED medications were prescribed for pain, psychiatric conditions, hyperlipidemia and gastrointestinal diseases across all age groups. Overall, results suggest that the lacosamide use is driven predominantly by age and that there is substantial use of lacosamide monotherapy (16.8%), despite lack of indication at the time of the study. Results also reveal substantial use of concomitant non-AEDs; 90.4% among patients > 65 years of age and 54.3% among those ≤ 17 years, confirming the high prevalence of comorbidities among patients with epilepsy across all ages. Despite the availability of numerous newer AEDs, older AEDs are still being frequently prescribed, especially for elderly patients, notably phenytoin. This warrants careful consideration, given the strong propensity of enzyme-inducing AEDs to interact with other drugs, producing unwanted side effects. These results highlight the value of real-life prescription patterns and the potential in informing treatment decisions to ensure patients receive appropriate treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
With a large number of patients and high mortality, diabetic kidney disease (DKD) imposes a significant burden on US health care. Although diabetes is the leading cause of chronic kidney disease and ...complications, the epidemiology of DKD in the contemporary US veteran population is generally unknown.
We aimed to estimate the rate of DKD progression and to measure the general epidemiology of DKD in the United States veteran population.
We performed a retrospective observational research using electronic health-care records and administrative databases.
The DKD patient cohort was abstracted from the Veterans Health Administration health-record data from January 2016 to March 2022.
We defined DKD patients using the laboratory test data based on Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines.
Summary statistics include the five-year cumulative incidence of progression to an advanced stage from the DKD stage at the cohort entry date and prevalence at a series of single time points.
A total of 685,288 patients (male 96%, mean age 62 years, Caucasian 64%, non-Hispanic 87%) met our eligibility criteria. The 5-year cumulative incidence of progression to an advanced DKD stage or all-cause death from DKD stages G1 A2/A3, G2 A2/A3, G3a, and G3b were 52.0%, 47.4%, 50.5%, and 60.9%, respectively. In sum, 594,082 patients were classified as moderate or high risk as per KDIGO guidelines in 2021, and stages G3a and G3b accounted for 51.2% and 25.3%, respectively, of cases.
More than half of DKD patients underwent a stage progression or death within 5 years. A substantial number of DKD patients at an earlier stage might be left undetermined. The study findings warrant a revision of DKD patient identification and management in US veterans.
Carminic acid (CA) extracted from cochineal is widely used in food additives as a natural colorant, and its potential risk to human health makes its detection important. In this work, a layered ...doubled hydroxide (LDH)–luminol–H2O2 system-based chemiluminescence (CL) platform has been successfully applied for CA sensing. The principle detection consists of two steps: first, LDH adsorbs CA onto the surface via electrostatic attraction; second, CA quenches the CL of the LDH–luminol–H2O2 system via the synergistic effect of CL resonance energy transfer, reduction of reactive oxygen species, and occupation of positively charged centers of brucite-like layers. With this CL approach, 0.5 μM CA is detectable using a CL spectrometer, and the limit of detection is 0.03 μM. This CL system exhibited a linear response to CA in the concentration range from 0.5 to 10 μM. In addition, the practical application of the designed CL sensing system is evaluated with dried pork slice samples.
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Upward continuous casting is the key process in the production of contact wire for electric railway. The stability of the process and the quality of the produced billet are directly related to the ...performance of the contact wire and ultimately the safety of the railway operation. To ensure the quality of continuous-casting billet, the optimal process conditions need to be experimentally determined, which is not only costly but also time-consuming. To facilitate this optimisation process, the simulation of the solidification process of Cu-0.45%Sn alloy in upward continuous casting is described in this paper to assess the influence of casting temperature, upward continuous casting speed, the time of stop-pull, and primary cooling water flow rate on the liquid core length. The results show that the speed of upward continuous casting exhibits a great influence on the liquid core length, while the casting temperature has only little influence. In a certain range of the ratio of stopping time to pulling time, the quality of updraft Cu-0.45%Sn alloy billet is improved; exceeding a certain ratio results in a decrease of the surface quality and an increase in internal and external defects. The liquid core length of the continuous casting rod decreases with the increase of the cold water flow rate, and properties are stable when the flow rate reaches 0.45 m3·h−1. For a billet with a diameter of 20 mm, the appropriate upward continuous casting process parameters are determined as a casting temperature of 1175 °C, an upward continuous casting speed not exceeding 25 cm·min−1, a ratio of stopping time to pulling time not exceeding 2.13, and a cooling water flow rate of 0.45 m3·h−1.
Advanced battery systems with high energy density have attracted enormous research enthusiasm with potential for portable electronics, electrical vehicles, and grid‐scale systems. To enhance the ...performance of conversion‐type batteries, various catalytic materials are developed, including metals and transition‐metal dichalcogenides (TMDs). Metals are highly conductive with catalytic effects, but bulk structures with low surface area result in low atom utilization, and high chemical reactivity induces unfavorable dendrite effects. TMDs present chemical adsorption with active species and catalytic activity promotes conversion processes, suppressing shuttle effect and improving energy density. But they suffer from inferior conductivity compared with metal, and limited sites mainly concentrate on edges and defects. Single‐atom materials with atomic sizes, good conductivity, and individual sites are promising candidates for advanced batteries because of a large atom utilization, unsaturated coordination, and unique electronic structure. Single‐atom sites with high activity chemically trap intermediates to suppress shuttle effects and facilitate electron transfer and redox reactions for achieving high capacity, rate capability, and conversion efficiency. Herein, single‐atom catalytic electrodes design for advanced battery systems is addressed. Major challenges and promising strategies concerning electrochemical reactions, theoretical model, and in situ characterization are discussed to shed light on future research of single‐atom material‐based energy systems.
Single‐atom catalytic materials with atomic sizes, good conductivity, and individual catalytic sites are designed for advanced battery systems, including lithium–sulfur batteries, zinc–air batteries, fuel cells, and other energy‐storage systems. A systematic review on challenges and strategies related to synthesis, theoretical models, and in situ characterization of single‐atom materials is presented to shed light on next‐generation battery systems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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