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.
The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical ...isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
Macroautophagy/autophagy deficit induces intracellular MAPT/tau accumulation, the hallmark pathology in Alzheimer disease (AD) and other tauopathies; however, the reverse role of MAPT accumulation in ...autophagy and neurodegeneration is not clear. Here, we found that overexpression of human wild-type full-length MAPT, which models MAPT pathologies as seen in sporadic AD patients, induced autophagy deficits via repression of autophagosome-lysosome fusion leading to significantly increased LC3 (microtubule-associated protein 1 light chain 3)-II and SQSTM1/p62 (sequestosome 1) protein levels with autophagosome accumulation. At the molecular level, intracellular MAPT aggregation inhibited expression of IST1 (IST1 factor associated with ESCRT-III), a positive modulator for the formation of ESCRT (the Endosomal Sorting Complex Required for Transport) complex that is required for autophagosome-lysosome fusion. Upregulating IST1 in human MAPT transgenic mice attenuated autophagy deficit with reduced MAPT aggregation and ameliorated synaptic plasticity and cognitive functions, while downregulating IST1 per se induced autophagy deficit with impaired synapse and cognitive function in naïve mice. IST1 can facilitate association of CHMP2B (charged multivesicular body protein 2B) and CHMP4B/SNF7-2 to form ESCRT-III complex, while lack of IST1 impeded the complex formation. Finally, we demonstrate that MAPT accumulation suppresses IST1 transcription with the mechanisms involving the ANP32A-regulated mask of histone acetylation. Our findings suggest that the AD-like MAPT accumulation can repress autophagosome-lysosome fusion by deregulating ANP32A-INHAT-IST1-ESCRT-III pathway, which also reveals a vicious cycle of MAPT accumulation and autophagy deficit in the chronic course of AD neurodegeneration.Abbreviations: AAV: adeno-associated virus; Aβ: β-amyloid; aCSF: artificial cerebrospinal fluid; AD: Alzheimer disease; ANP32A: acidic nuclear phosphoprotein 32 family member A; ATG: autophagy related; AVs: autophagic vacuoles; CEBPB: CCAAT enhancer binding protein beta; CHMP: charged multivesicular body protein; DMEM: Dulbecco's modified eagle's medium; EBSS: Earle's balanced salt solution; EGFR: epidermal growth factor receptor; ESCRT: endosomal sorting complex required for transport; fEPSPs: field excitatory postsynaptic potentials; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSK3B: glycogen synthase kinase 3 beta; HAT: histone acetyl transferase; HDAC: histone deacetylase; INHAT: inhibitor of histone acetyl transferase; IST1: IST1 factor associated with ESCRT-III; LAMP2: lysosomal associated membrane protein 2; LTP: long-term potentiation; MAP1LC3: microtubule associated protein 1 light chain 3; MAPT/tau: microtubule associated protein tau; MVB: multivesicular bodies; MWM: Morris water maze; PBS: phosphate-buffered saline solution; RAB7: member RAS oncogene family; SNAREs: soluble N-ethylmaleimide-sensitive factor attachment protein receptors; SQSTM1/p62: sequestosome 1
The Nanwenghe Wetlands Reserve in the Yile'huli Mountains is a representative region of the Xing'an permafrost. The response of permafrost to climate change remains unclear due to limited field ...investigations. Thus, longer-term responses of the ground thermal state to climate change since 2011 have been monitored at four sites with varied surface characteristics: Carex tato wetland (P1) and shrub-C. tato wetland (P2) with a multi-year average temperatures at the depth of zero annual amplitude (TZAA) of −0.52 and −1.19 °C, respectively; Betula platyphylla-Larix gmelinii (Rupr.) Kuzen mixed forest (P3) with TZAA of 0.17 °C, and; the forest of L. gmelinii (Rupr.) Kuzen (P4) with TZAA of 1.65 °C. Continuous observations demonstrate that the ecosystem-protected Xing'an permafrost experienced a cooling under a warming climate. The temperature at the top of permafrost (TTOP) rose (1.8 °C per decade) but the TZAA declined (−0.14 °C per decade), while the active layer thickness (ALT) thinned from 0.9 m in 2012 to 0.8 m in 2014 at P1. Both the TTOP and TZAA increased (0.89 and 0.06 °C per decade, respectively), but the ALT thinned from 1.4 m in 2012 to 0.7 m in 2016 at P2. Vertically detached permafrost at P3 disappeared in summer 2012, with warming rates of +0.42 and + 0.17 °C per decade for TTOP and TZAA, respectively. However, up to date, the ground thermal state has remained stable at P4. We conclude that the thermal offset is crucial for the preservation and persistence of the Xing'an permafrost at the southern fringe.
The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide ...association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240-370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.
Under a warming climate, degrading permafrost profoundly and extensively affects arctic and alpine ecology. However, most existing relevant studies are more focused on the hydrothermal impacts of ...vegetation on the underlying permafrost, or symbiosis between vegetation and permafrost, only very few on ecological impacts of permafrost degradation. Additionally, there are much more pertinent investigations in arctic and boreal regions than those in alpine and high-plateau regions at mid- and low latitudes. This study emphasizes on the impact mechanisms of permafrost degradation on vegetation both at high and mid-to low latitudes, addressing vegetation succession trajectories and associated changes in soil hydrology and soil nutrient above degrading permafrost. Permafrost degradation influences vegetation by altering soil hydrology, soil biogeochemical processes and microbial communities, which further improve soil nutrient availability. Furthermore, under a warming climate, vegetation may take two successional trajectories, towards a wetter or drier ecosystem within a certain time period, but to a drier ecosystem in the end upon the thaw of permafrost in case of permeable soils and good drainage. Thus, with rapidly developing remote-sensing and other space- and ground-based and air-borne observational networks and numerical predictive models, the impacting mechanisms of permafrost degradation on vegetation should be timely and better monitored, evaluated and modeled at desired spatiotemporal scales and resolutions by terrestrial or integrated ecosystem models.
A
bstract
We derive the chiral kinetic equation in 8 dimensional phase space in non- Abelian SU(
N
) gauge field within the Wigner function formalism. By using the “covariant gradient expansion”, we ...disentangle the Wigner equations in four-vector space up to the first order and find that only the time-like component of the chiral Wigner function is independent while other components can be explicit derivative. After further decomposing the Wigner function or equations in color space, we present the non-Abelian covariant chiral kinetic equation for the color singlet and multiplet phase-space distribution functions. These phase-space distribution functions have non-trivial Lorentz transformation rules when we define them in different reference frames. The chiral anomaly from non-Abelian gauge field arises naturally from the Berry monopole in Euclidian momentum space in the vacuum or Dirac sea contribution. The anomalous currents as non-Abelian counterparts of chiral magnetic effect and chiral vortical effect have also been derived from the non-Abelian chiral kinetic equation.
Diminished ovarian reserve (DOR) is defined as a reduction in ovarian reserve and oocyte quality. The pathophysiology of DOR has not been completely explained as of yet. Scholars have uncovered a ...large number of exosomes that have been detected in follicular fluid, and exosomal miRNAs have been proven to play a critical role in controlling ovarian disorders and follicle formation. We focused on the expression profile of follicular fluid-derived exosomal microRNAs (miRNAs) and attempted to understand if their role is connected to the pathomechanism of DOR.
The follicular fluid-derived differentially expressed exosomal miRNAs (DEmiRs) between patients with DOR and those with normal ovarian function were investigated using the next-generation sequencing (NGS) method. The main metabolic and signaling pathways of DEmiRs were identified using the KEGG pathway database, disease ontology (DO) analysis, and gene ontology (GO) analysis. In the end, a Protein-Protein Interaction (PPI) network was built to search for exosomal miRNAs and their target genes that were potentially strongly connected with DOR.
In comparison to normal controls, 52 DEmiRs were discovered in follicular fluid-derived exosomes of DOR patients, of which 19 were up-regulated and 33 were down-regulated (|log2(fold change) |>2, P < 0.05). GO, DO analysis, and the KEGG pathway database revealed that many of these DEmiRs have broad biological roles that are connected to ovarian function and disorders. The top ten DEmiRs in terms of expression were then chosen for miRNA-mRNA interaction analysis. Totally, 8 experimentally supported miRNAs (hsa-miR-1246, hsa-miR-483-3p, hsa-miR-122-5p, hsa-miR-130b-3p, hsa-miR-342-3p, hsa-miR-625-3p, hsa-miR-675-3p, and hsa-miR-134-5p) and 126 target genes were filtrated by utilizing Cytoscape software. The module analysis findings of the PPI network showed that the main module cluster with a score > 6.0 (MCODE score = 15) had six hub genes, including IGFR, VEGFA, KRAS, ERBB2, RHOA, and PTEN (MCODE score = 11.472).
Our data suggested a special expression profile of follicular fluid-derived exosomal miRNAs in patients with DOR, which was probably correlated to ovarian dysfunction and follicle formation. These results may give a unique insight into a better understanding of the molecular process in the pathogenesis of DOR or other ovarian diseases.
Due to the increasing amounts of textile waste, textile to textile recycling is of prime concern. Polyethylene terephthalate (PET) represents the most extensively used type of chemical fiber. Its ...spinnability suffers from impurities and degradation in the processing, which limits its recycling to new fibers. Here, recycled polyester is blended with a small amount of recycled nylon, and the regenerated fibers, which demonstrated good mechanical properties, were obtained via a melt spinning machine. The mechanical properties, thermal properties, rheological properties, and chemical structure of the modified recycled fibers were investigated. It was found that when compared with rPET-T fibers, the elongation at break of rPET-A
fibers increased to 17.48%, and the strength at break decreased to 3.79 cN/dtex. The compatibility of PET and PA6 copolymer were enhanced by copolymers produced by in-situ reaction in the processing. Meanwhile, the existence of PA6 increases the crystallization temperature and improves the hydrophilicity of the fibers. This study realized the high-value recycling of waste PET fabric to new fibers, which opens a door for the large utilization of waste textiles.
NLRP3, a member of nucleotide-binding domain-(NOD) like receptor family, can be found in large varieties of immune and non-immune cells. Upon activation, the NLRP3, apoptosis-associated speck-like ...protein (ASC) and pro-caspase-1 would assemble into a multimeric protein, called the NLRP3 inflammasome. Then the inflammasome promotes inflammation (through specific cleavage and production of bioactive IL-1β and IL-18) and pyroptotic cell death. Previous studies have indicated the importance of NLRP3 in regulating innate immunity. Recently, numerous studies have revealed their significance in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) and inflammatory bowel disease (IBD). In this review, we will briefly discuss the biological features of NLRP3 and summarize the recent progression of the involvement of NLRP3 in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.
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