Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host ...response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.
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•SARS-CoV-2 infection induces low IFN-I and -III levels with a moderate ISG response•Strong chemokine expression is consistent across in vitro, ex vivo, and in vivo models•Low innate antiviral defenses and high pro-inflammatory cues contribute to COVID-19
In comparison to other respiratory viruses, SARS-CoV-2 infection drives a lower antiviral transcriptional response that is marked by low IFN-I and IFN-III levels and elevated chemokine expression, which could explain the pro-inflammatory disease state associated with COVID-19.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not ...recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.
This study presents new secondary-ion mass spectrometry (SIMS) rutile and laser ablation–inductively coupled plasma–mass spectrometry (LA–ICP–MS) zircon U-Pb geochronological and whole-rock ...geochemical data for amphibolites of the Heilongjiang Complex, located within the Yilan area of NE China, to constrain the tectonic evolution of the Mudanjiang Ocean between the Songnen–Zhangguangcai Range and Jiamusi massifs. Magmatic zircon from amphibolites collected from the Yilan Marble Quarry yields a weighted mean 206Pb/238U age of 274 ± 2 Ma, which is interpreted as the protolithic age. Amphibolites from the Longlangang and Tuanshanzi areas yield rutile U-Pb ages of 177 ± 11 Ma and 172 ± 5 Ma, respectively, which are interpreted to reflect the cooling of these rocks below the closure temperature of Pb diffusion in rutile. Amphibolites from the Yilan Marble Quarry are enriched in light rare earth elements (LREEs) and depleted in high field strength elements (HFSEs; e.g., Nb, Ta and P) relative to large ion lithophile elements (LILEs). Amphibolites from the Longlangang and Tuanshanzi areas have relatively flat chondrite-normalized rare earth element (REE) patterns, and remarkable negative Nb and Ta anomalies. Moreover, all of the amphibolites from the Heilongjiang Complex in the Yilan area have tholeiitic and arc-type geochemical affinities. These amphibolites formed by similar petrogenetic processes, but from distinct mantle sources. The magmas that formed these units were generated by the partial melting of mantle sources metasomatized by subducted slab fluids, and the magma that formed the amphibolites within the Yilan Marble Quarry may have also incorporated sedimentary material. Mantle peridotite from the garnet-spinel transition zone is a possible source for the protolith of amphibolites in the Yilan Marble Quarry, and spinel-peridotites may have been the magma sources for the protoliths of amphibolites in the Longlangang and Tuanshanzi areas. Combining our data for amphibolites from the Heilongjiang Complex in the Yilan area with the results of previous research on Late Paleozoic–Early Mesozoic arc magmatism and metamorphism, we infer that the Late Paleozoic–Early Mesozoic tectonic evolution of the Mudanjiang Ocean was characterized by double-sided subduction. These data indicate that the Mudanjiang Ocean closed during the Jurassic (180–160 Ma).
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•Magmatic zircon from the amphibolite yielded protolithic age of 274 ± 2 Ma.•Rutile from the amphibolite yielded metamorphic ages of 177 ± 11 Ma and 172 ± 5 Ma.•The Mudanjiang Ocean closed during the Jurassic (180–160 Ma).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We propose and analyze a new approach based on parity-time (PT) symmetric microcavities with balanced gain and loss to enhance the performance of cavity-assisted metrology. We identify the conditions ...under which PT-symmetric microcavities allow us to improve sensitivity beyond what is achievable in loss-only systems. We discuss the application of PT-symmetric microcavities to the detection of mechanical motion, and show that the sensitivity is significantly enhanced near the transition point from unbroken- to broken-PT regimes. Our results open a new direction for PT-symmetric physical systems and it may find use in ultrahigh precision metrology and sensing.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Head and neck squamous cell carcinomas (HNSCCs) are generally associated with tobacco consumption, alcohol abuse or both. Mucins (MUCs) are high‐molecular‐weight glycoproteins produced by many ...epithelial tissues. Many studies have indicated that MUCs play an important role in cancer metastasis. MUC6 expression has been observed in gastric and oncocytic phenotypes and plays an important role during cancer progression. We found that levels of MUC6 are lower in Asian HNCC patients and affect the disease‐free survival of HNCC patients. Next, we investigated the combined effect of MUC6 polymorphisms and exposure to environmental carcinogens on the susceptibility to and clinicopathological characteristics of HNCC. Three single‐nucleotide polymorphisms (SNPs) of MUC6 (rs7481521, rs6597947 and rs61869016) were analysed using real‐time PCR. After adjusting for other co‐variants, we found that carrying a CC genotype at MUC6 rs6597947 led to a lower risk of developing oral squamous cell carcinoma (OSCC) than wild‐type carriers among non‐betel‐quid chewers. Moreover, male oral cancer patients who carried the AA + CC genotype at MUC6 rs6597947 had a lower risk of lymph node metastasis than other genotypes, suggesting a significant functional compromise and decompensated disease. Therefore, our findings suggest that genetic variations in MUC6 may correlate to OSCC and indicate the progression in OSCC patients.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To achieve plasmonically induced transparency (PIT), general near-field plasmonic systems based on couplings between localized plasmon resonances of nanostructures rely heavily on the well-designed ...interantenna separations. However, the implementation of such devices and techniques encounters great difficulties mainly to due to very small sized dimensions of the nanostructures and gaps between them. Here, we propose and numerically demonstrate that PIT can be achieved by using two graphene layers that are composed of a upper sinusoidally curved layer and a lower planar layer, avoiding any pattern of the graphene sheets. Both the analytical fitting and the Akaike Information Criterion (AIC) method are employed efficiently to distinguish the induced window, which is found to be more likely caused by Autler-Townes splitting (ATS) instead of electromagnetically induced transparency (EIT). Besides, our results show that the resonant modes cannot only be tuned dramatically by geometrically changing the grating amplitude and the interlayer spacing, but also by dynamically varying the Fermi energy of the graphene sheets. Potential applications of the proposed system could be expected on various photonic functional devices, including optical switches, plasmonic sensors.
The nephrotoxicity of sofosbuvir (SOF) on human immunodeficiency virus and hepatitis C virus (HIV/HCV)‐coinfected patients receiving antiretroviral therapy (ART) remains controversial. We ...prospectively compared the estimated glomerular filtration rate (eGFR) changes in 167 patients receiving SOF‐based direct‐acting antivirals (DAAs) who also received tenofovir disoproxil fumarate (TFV)‐based (n = 116) and TFV‐free ART (n = 51). The eGFR was assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation, and the eGFR changes between ART regimens were compared by the generalized estimated equation. During DAA treatment, participants on TFV‐based ART had a higher eGFR decline than those on TFV‐free ART (slope coefficient difference: −0.82 ml/min/1.73 m2/month 95% CI: −1.21 to −0.43; p < 0.001), whereas the eGFR changes did not differ between groups (slope coefficient difference: 0.13 ml/min/1.73 m2/month 95% CI: −0.32 to 0.58; p = 0.42) after discontinuing DAAs. Participants on TFV TDF‐based ART had a higher eGFR decline than those on TFV alafenamide fumarate (TAF)‐based ART (slope coefficient difference: −0.31 ml/min/1.73 m2/month 95% CI: −0.50 to −0.12; p = 0.01). After discontinuing DAAs, the eGFR changes did not differ between groups (slope coefficient difference: 0.06 ml/min/1.73 m2/month 95% CI: −0.98 to 1.10; p = 0.91). In conclusion, HIV/HCV‐coinfected patients on TFV‐based ART had a slight eGFR decline compared to those on TFV‐free ART during SOF‐based DAA therapy. A similar trend between TDF‐based and TAF‐based ART was also observed. Because the differences of eGFR changes are limited, the physicians should not discourage the use of SOF‐based DAAs in HIV‐positive patients on TFV‐based ART.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Carbonaceous materials are promising candidates as anode materials for non-lithium-ion batteries (NLIBs) due to their appealing properties such as good electrical conductivity, low cost, and high ...safety. However, graphene, a classic two-dimensional (2D) carbon material, is chemically inert to most metal atoms, hindering its application as an electrode material for metal-ion batteries. Inspired by the unique geometry of a four-penta unit, we explore a metallic 2D carbon allotrope C5-10-16 composed of 5-10-16 carbon rings. The C5-10-16 monolayer is free from any imaginary frequencies in the whole Brillouin zone. Due to the introduction of a non-sp2 hybridization state into C5-10-16, the extended conjugation of π-electrons is disrupted, leading to the enhanced surface activity toward metal ions. We investigate the performance of C5-10-16 as the anode for sodium/potassium-ion batteries by using first-principles calculations. The C5-10-16 sheet has high theoretical specific capacities of Na (850.84 mA h g−1) and K (743.87 mA h g−1). Besides, C5-10-16 exhibits a moderate migration barrier of 0.63 (0.32) eV for Na (K), ensuring rapid charging/discharging processes. The average open-circuit voltages of Na and K are 0.33 and 0.62 V, respectively, which are within the voltage acceptance range of anode materials. The fully sodiated (potassiated) C5-10-16 shows tiny lattice expansions of 1.4% (1.3%), suggesting the good reversibility. Moreover, bilayer C5-10-16 significantly affects both the adsorption strength and the mobility of Na or K. All these results show that C5-10-16 could be used as a promising anode material for NLIBs.
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