Abstract
Background
The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)–based ...technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19.
Methods
The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort.
Results
The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days, while IgG was detected 14 (IQR, 10–18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%).
Conclusions
The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.
The time kinetics of humoral responses against the novel coronavirus (SARS-CoV-2) are characterized in patients with COVID-19 by nucleocapsid-based enzyme-linked immunosorbent assay. The antibody testing can aid in the diagnosis of COVID-19 when combined with quantitative polymerase chain reaction, including in subclinical cases.
Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular ...carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
Structural instability and inferior storage property are bottlenecks of the Ni-rich cathodes. Herein, a coating and doping co-modified Ni-rich cathode, in which La and Al is homogeneously doped in ...the inner and an epitaxial layer is distributed in the outer surface region of secondary particle, is constructed. The outer surface layer tightly integrates a La2O3 coating layer, an epitaxial grown LaAl doped atomic structure and a Ni concentration gradient into the bulk phase. The La and Al act as a pillar ion enlarging c axis spacing and a positively charged center, enhancing Li+ transportation and suppressing the phase transition. The outer surface region with La-enriched layer and decreased Ni concentration suppresses the side reactions between organic electrolyte and oxidizing Ni4+ and improves the storage stability in air. During cycling, the modified material exhibits enhanced rate capability and cycling stability with capacity retention of 80.0% after 480 cycles at 10C in the cell potential range of 2.7–4.3 V.
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•Ni-rich cathode is modified with synergy of coating and doping by La and Al.•Lower lattice expansion and higher Li+ transportation due to La doping.•The coating layer suppresses erosion of electrolyte and improve storage stability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Demands for large‐scale energy storage systems have driven the development of layered transition‐metal oxide cathodes for room‐temperature rechargeable sodium ion batteries (SIBs). Now, an abnormal ...layered‐tunnel heterostructure Na0.44Co0.1Mn0.9O2 cathode material induced by chemical element substitution is reported. By virtue of beneficial synergistic effects, this layered‐tunnel electrode shows outstanding electrochemical performance in sodium half‐cell system and excellent compatibility with hard carbon anode in sodium full‐cell system. The underlying formation process, charge compensation mechanism, phase transition, and sodium‐ion storage electrochemistry are clearly articulated and confirmed through combined analyses of in situ high‐energy X‐ray diffraction and ex situ X‐ray absorption spectroscopy as well as operando X‐ray diffraction. This crystal structure engineering regulation strategy offers a future outlook into advanced cathode materials for SIBs.
An abnormal layered‐tunnel heterostructure Na0.44Co0.1Mn0.9O2 cathode material induced by chemical element substitution is described. The crystal‐structure engineering strategy that was used gives an outlook into high‐performance sodium ion batteries.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are ...important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils.
Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly ...conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Spinal cord injury (SCI) is one of the most common devastating injuries, which causes permanent disabilities such as paralysis and loss of movement or sensation. The precise pathogenic mechanisms of ...the disease remain unclear, and, as of yet, there is no effective cure. Mesenchymal stem cells (MSCs) show promise as an effective therapy in the experimental models of SCI. MSCs secrete various factors that can modulate a hostile environment, which is called the paracrine effect. Among these paracrine molecules, exosome is considered to be the most valuable therapeutic factor. Thus, exosomes from MSCs (MSCs-exosomes) can be a potential candidate of therapeutic effects of stem cells. The present study was designed to investigate the effect of whether systemic administration of exosomes generated from MSCs can promote the function recovery on the rat model of SCI in vivo. In the present study, we observed that systemic administration of MSCs-exosomes significantly attenuated lesion size and improved functional recovery post-SCI. Additionally, MSCs-exosomes treatment attenuated cellular apoptosis and inflammation in the injured spinal cord. Expression levels of proapoptotic protein (Bcl-2-associated X protein) and proinflammatory cytokines (tumor necrosis factor alpha and interleukin IL-1β) were significantly decreased after MSCs-exosomes treatment, whereas expression levels of antiapoptotic (B-cell lymphoma 2) and anti-inflammatory (IL-10) proteins were upregulated. Further, administration of MSCs-exosomes significantly promoted angiogenesis. These results show, for the first time, that systemic administration of MSCs-exosomes attenuated cell apoptosis and inflammation, promoted angiogenesis, and promoted functional recovery post-SCI, suggesting that MSCs-exosomes hold promise as a novel therapeutic strategy for treating SCI.
Abstract
Motivation
Protein carbonylation is one of the most important oxidative stress-induced post-translational modifications, which is generally characterized as stability, irreversibility and ...relative early formation. It plays a significant role in orchestrating various biological processes and has been already demonstrated to be related to many diseases. However, the experimental technologies for carbonylation sites identification are not only costly and time consuming, but also unable of processing a large number of proteins at a time. Thus, rapidly and effectively identifying carbonylation sites by computational methods will provide key clues for the analysis of occurrence and development of diseases.
Results
In this study, we developed a predictor called iCarPS to identify carbonylation sites based on sequence information. A novel feature encoding scheme called residues conical coordinates combined with their physicochemical properties was proposed to formulate carbonylated protein and non-carbonylated protein samples. To remove potential redundant features and improve the prediction performance, a feature selection technique was used. The accuracy and robustness of iCarPS were proved by experiments on training and independent datasets. Comparison with other published methods demonstrated that the proposed method is powerful and could provide powerful performance for carbonylation sites identification.
Availability and implementation
Based on the proposed model, a user-friendly webserver and a software package were constructed, which can be freely accessed at http://lin-group.cn/server/iCarPS.
Supplementary information
Supplementary data are available at Bioinformatics online.
A novel method of achieving a single-feed circularly polarized (CP) microstrip antenna with both broad impedance bandwidth and axial ratio (AR) bandwidth is presented. The CP characteristics are ...generated by employing a resonator to excite the two orthogonal modes of the patch via two coupling paths and the required 90° phase difference is achieved by using the different orders of the two paths. The presented method, instead of conventional methods that power dividers and phase delay lines are usually required, not only significantly enhances the bandwidths of the antenna but also results in a compact feed, reduced loss and high gain. Based on this method, a dual-band shared-aperture CP array antenna is implemented for C-/X-band satellite communications. The antenna aperture includes a 2 × 2 array at C-band and a 4 × 4 array at X-band. To accommodate the C-X-band elements into the same aperture while achieving a good isolation between them, the C-band circular patches are etched at the four corners. The measured results agree well with the simulations, showing a wide impedance bandwidth of 21% and 21.2% at C-band and X-band, respectively. The C-band and X-band 3 dB AR bandwidths are 13.2% and 12.8%. The array also exhibits a high aperture efficiency of over 55%, low sidelobe (C-band: -12.5 dB and X-band: -15 dB), and high gain (C-band: 14.5 dBic and X-band: 17.5 dBic).
The development of lithium-sulfur (Li-S) batteries is hindered by capacity loss due to lithium polysulfide (LIPS) dissolution into electrolyte solutions (known as the "shuttle effect"). MXenes with ...excellent electrical conductivity, high mechanical strength and multiple possible active two-dimensional surface terminations are attracting much attention as anchoring materials of Li-S batteries. Here, the S-functionalized V
2
C (V
2
CS
2
) is designed and demonstrated to have not only dynamic and thermal stability, but also metallic character. Compared with bare V
2
C and V
2
CO
2
, V
2
CS
2
exhibits a moderate adsorption effect to suppress the "shuttle effect" and can preserve the structure of LIPSs without any decomposition. Moreover, the metallic properties of V
2
CS
2
are maintained after LIPSs are adsorbed, which can promote the electrochemical activity during the charge and discharge process. The low energy barriers of Li
2
S decomposition and Li diffusion on the V
2
CS
2
surface promise the phase transformation of LIPSs and assist the electrochemical process. Based on these remarkable results, we can conclude that V
2
CS
2
is a promising anchoring material for lithium-sulfur batteries. Our work may also inspire the exploration of other MXenes and new surface functionalization methods to improve the performance of MXenes as host materials for high performance Li-S batteries.
S-functionalized V
2
C (V
2
CS
2
) was designed and the properties of it act as anchoring material for Li-S batteries' cathode were investigated by first-principles calculations. Compared with bare V
2
C and V
2
CO
2
, V
2
CS
2
is more suitable as anchoring material.
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