Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated ...with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection.
Methods
In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2.
Results
To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively.
Conclusions
Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.
A peptide-based magnetic chemiluminescence enzyme immunoassay for the detection of SARS-CoV-2 antibodies was developed; 71.4% (197 of 276) and 57.2% (158 of 276) of the COVID-19 inpatients were positive for IgG and IgM against SARS-CoV-2.
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). ...Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
Plasma cell-free DNA (cfDNA) are small molecules generated through a non-random fragmentation procedure. Despite commendable translational values in cancer liquid biopsy, however, the biology of ...cfDNA, especially the principles of cfDNA fragmentation, remains largely elusive. Through orientation-aware analyses of cfDNA fragmentation patterns against the nucleosome structure and integration with multidimensional functional genomics data, here we report a DNA methylation - nuclease preference - cutting end - size distribution axis, demonstrating the role of DNA methylation as a functional molecular regulator of cfDNA fragmentation. Hence, low-level DNA methylation could increase nucleosome accessibility and alter the cutting activities of nucleases during DNA fragmentation, which further leads to variation in cutting sites and size distribution of cfDNA. We further develop a cfDNA ending preference-based metric for cancer diagnosis, whose performance has been validated by multiple pan-cancer datasets. Our work sheds light on the molecular basis of cfDNA fragmentation towards broader applications in cancer liquid biopsy.
Due to their intrinsic structural features, the design and synthesis of a new type of zeolite-like metal–organic frameworks (ZMOFs) is highly desirable but challenging. Herein, solvothermal reactions ...between an angular dicarboxylate linker and rare-earth (RE) ions afforded two RE-MOFs, namely, Tb-ZMOF-2 and Tb-ZMOF-3, respectively. Structural analyses reveal that Tb-ZMOF-2 encompasses a novel 446482 cage, while Tb-ZMOF-3 contains nonanuclear (i.e., D6R) and hexanuclear (i.e., D4R) RE clusters simultaneously, subsequently resulting in two new zeolitic topologies. Thanks to its high surface area and pore volume, Tb-ZMOF-2 demonstrates considerably high gravimetric and volumetric methane storage working capacities.
The novel multitargeted tyrosine kinase inhibitor sunitinib is used as an antiangiogenic agent for the treatment of several types of cancer, including metastatic renal cell carcinoma (RCC). Sunitinib ...was shown to positively change the immunosuppressive phenotype in RCC patients. To improve its antitumor efficacy, and offer strategies for its combination with other approaches, it is critical to fully elucidate its mechanisms of action. We show that sunitinib induces tumor cell apoptosis and growth arrest in RCC tumor cells, which correlates with signal transducer and activator of transcription 3 (Stat3) activity inhibition. Sunitinib-mediated direct effects on tumor cells occur regardless of von Hippel-Lindau tumor suppressor gene status and hypoxia-inducible transcription factor-2alpha levels. Reduction of Stat3 activity enhances the antitumor effects of sunitinib, whereas expression of a constitutively activated Stat3 mutant rescues tumor cell death. Intravital multiphoton microscopy data show that sunitinib induces mouse Renca tumor cell apoptosis in vivo before tumor vasculature collapse. Sunitinib also inhibits Stat3 in Renca tumor-associated myeloid-derived suppressor cells (MDSC), down-regulates angiogenic gene expression, and reduces MDSCs and tumor T regulatory cells. These results suggest that Stat3 activity is important for RCC response to sunitinib, and Stat3 inhibition permits the direct proapoptotic activity of sunitinib on tumor cells and positive effects on tumor immunologic microenvironment.
Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal ...characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.
Thickness reduction or loss of the calcareous eggshell is one of major phenotypic changes in the transition from oviparity to viviparity. Whether the reduction of eggshells in viviparous squamates is ...associated with specific gene losses is unknown. Taking advantage of a newly generated high‐quality genome of the viviparous Chinese crocodile lizard (Shinisaurus crocodilurus), we found that ovocleidin‐17 gene (OC‐17), which encodes an eggshell matrix protein that is essential for calcium deposition in eggshells, is not intact in the crocodile lizard genome. Only OC‐17 transcript fragments were found in the oviduct transcriptome, and no OC‐17 peptides were identified in the eggshell proteome of crocodile lizards. In contrast, OC‐17 was present in the eggshells of the oviparous Mongolia racerunner (Eremias argus). Although the loss of OC‐17 is not common in viviparous species, viviparous squamates show fewer intact eggshell‐specific proteins than oviparous squamates. Our study implies that functional loss of eggshell‐matrix protein genes may be involved in the reduction of eggshells during the transition from oviparity to viviparity in the crocodile lizard.
Could gene loss play a role in the evolution of eggshell reduction in viviparous squamates? The functional loss of OC‐17 in the Chinese crocodile lizard provides new clues.
Late-stage cancer metastasis remains incurable in the clinic and is the major cause death in patients. Circulating tumor cells (CTCs) are thought to be metastatic precursors shed from the primary ...tumor or metastatic deposits and circulate in the blood. The molecular network regulating CTC survival, extravasation, and colonization in distant metastatic sites is poorly defined, largely due to challenges in isolating rare CTCs. Recent advances in CTC isolation and
ex vivo
culture techniques facilitates single-cell omics and the development of related animal models to study CTC-mediated metastatic progression. With these powerful tools, CTCs can potentially be used as non-invasive biomarkers predicting therapeutic response. These studies may open a new avenue for CTC-specific drug discoveries. In this short review, we aim to summarize recent progress in the characterization of CTCs and their clinical relevance in various cancers, setting the stage for realizing personalized therapies against metastases.
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•Ultralight, robust and high Prussian blue (PB)-loading polyacrylonitrile (PAN) aerogel is prepared.•As-prepared PAN/PB aerogel shows higher PB-loading than reported composite ...adsorbents.•The aerogel overcomes the poor water stability of PB and shows excellent Cs+ adsorption selectivity.•The aerogel works well for highly efficient adsorption/removal of Cs+ from seawater and brine.•Co-spinning active groups in nanofibers is demonstrated to be a promising way for preparing high-performance aerogels.
Highly efficient and selective adsorption/removal of Cs+ is greatly essential for both resource utilization and radioactive pollution control. To overcome the poor water stability of Prussian blue (PB), a highly selective Cs+ adsorbent, PB-based polyacrylonitrile (PAN) aerogel was prepared using PB-loaded PAN nanofibers. Pre-doping of Fe3+ in PAN nanofibers through electrospinning provides abundant and evenly distributed active sites for the in-situ growth of PB, thus endowing resultant PAN/PB aerogel with much higher PB-loading capacity than reported PB-based composite adsorbents. Systematic structure characterization and property investigation show that as-prepared PAN/PB aerogel has interconnected porous structure, ultralight density, greatly improved water stability, increased thermal stability, robust mechanical elasticity, high hydrophilicity, excellent Cs+ adsorption selectivity. Its practical application potential was well demonstrated by the excellent performances in highly efficient, rapid and selective adsorption/removal of Cs+ from simulated seawater and salt lake brine. The maximum Cs+ adsorption amount of PAN/PB aerogel reached up to 152.67 mg∙g−1 within 1 min. In this work, co-spinning active groups (e.g., Fe3+) in PAN nanofibers is demonstrated to be an effective strategy for increasing the PB-loading of aerogel, which not only provides an excellent Cs+ adsorbent, but also paves a promising way for preparing high-performance aerogels.
As an isothermal nucleic acid amplification technique, strand displacement amplification (SDA) reaction has been introduced in G-quadruplex DNAzyme-based sensing system to improve the sensing ...performance. To further provide useful information for the design of SDA-amplified G-quadruplex DNAzyme-based sensors, the effects of nicking site number in SDA template DNA were investigated. With the increase of the nicking site number from 1 to 2, enrichment of G-quadruplex DNAzyme by SDA is changed from a linear amplification to an exponential amplification, thus greatly increasing the amplification efficiency and subsequently improving the sensing performance of corresponding sensing system. The nicking site number cannot be further increased because more nicking sites might result in high background signals. However, we demonstrated that G-quadruplex DNAzyme enrichment efficiency could be further improved by introducing a cross-triggered SDA strategy, in which two templates each has two nicking sites are used. To validate the proposed cross-triggered SDA strategy, we used it to develop a sensing platform for the detection of uracil-DNA glycosylase (UDG) activity. The sensor enables sensitive detection of UDG activity in the range of 1×10−4–1U/mL with a detection limit of 1×10−4U/mL.
•G-quadruplex amplification-sensitized DNAzyme-based sensing system is optimized.•The tolerance number of nicking site in DNA template is demonstrated to be two.•A cross-triggered amplification is introduced to improve the sensing performance.•A sensitive and selective sensor is designed for uracil-DNA glycosylase detection.•The work might provide useful information for G-quadruplex DNAzyme-based sensors.
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