A long-term cohort study: the immune evasion and decreasing neutralization dominated the SARS-CoV-2 breakthrough infection

Most of vaccinees and COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, which helps preventing infection and alleviating symptoms. However, breakthrough viral infections caused by emerging SARS-CoV-2 variants, especially Omicron subvariants, still pose a serious threat to global health. By monitoring the viral infections and the sera neutralization ability of a long-tracked cohort, we found out that the immune evasion of emerging Omicron subvariants and the decreasing neutralization led to the mini-wave of SARS-CoV-2 breakthrough infections. Meanwhile, no significant difference had been found in the infectivity of tested SARS-CoV-2 variants, even though the affinity between human angiotensin-converting enzyme 2 (hACE2) and receptor-binding domain (RBDs) of tested variants showed an increasing trend. Notably, the immune imprinting of inactivated COVID-19 vaccine can be relieved by infections of BA.5.2 and XBB.1.5 variants sequentially. Our data reveal the rising reinfection risk of immune evasion variants like Omicron JN.1 in China, suggesting the importance of booster with updated vaccines

Emerging SARS-CoV-2 variants: Why, how, and what's next?

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in the Spike protein of the Omicron variant severely compromised the protective immunity elicited by either vaccination or prior infection. The persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, the virus recombination upon Delta and Omicron co-infections has been reported lately, although the impact remains to be assessed. This minireview summarizes the characteristics, evolution and mutation control, and immune evasion mechanisms of SARS-CoV-2 variants, which will be helpful for the in-depth understanding of the SARS-CoV-2 variants and policy-making related to COVID-19 pandemic control

Market investigation of basic parameters for exposure assessment of contact materials for nut-seed food in China

Objective To establish the basic parameters for exposure assessment of contact materials for nut-seed food in China. Methods The contact area method was used to study the contact materials of nut-seed food in this study. Based on the contact area values, ratio of contact areas and unit mass were obtained. Results Through investigation and analysis, 114 kinds of nut-seed food were sampled, and 3 648 related data were obtained. Food contact materials of nut-seed food on the market mainly included aluminum, polyethylene, polyethylene terephthalate, polypropylene, polystyrene and coating. The average contact area per unit mass or volume (S/V) was 21.29 dm2/kg, the median was 13.40 dm2/kg, P5 was 1.11 dm2/kg, and P95 was 67.46 dm2/kg. Conclusion The basic parameters of nut-seed food contact materials could provide data support for the safety assessment in China

Amorphous quaternary alloy nanoplates for efficient catalysis of hydrogen evolution reaction

Developing a highly efficient non-precious transition metal-based electrocatalyst via a facile approach toward the hydrogen evolution reaction (HER) is critical for large-scale hydrogen production but still remains challenging. Herein, a cost-effective electrochemical deposition strategy is rationally proposed to construct amorphous quaternary FeCoNiCu alloy nanosheets supported on nickel foam (NF) towards this challenge. Benefiting from the synergistic effect of multi-metal atoms interaction and the high exposure of active sites caused by abundant open voids, the as-synthesized FeCoNiCu/NF electrode exhibits high catalytic activity and robustness toward HER in alkaline solution, requiring an overpotential of only 35 mV to reach a current density of 10 mA cm–2. This study may pave a new avenue to design advanced electrocatalyst for energy conversion

N7-Methylation of the Coronavirus RNA Cap Is Required for Maximal Virulence by Preventing Innate Immune Recognition

The ongoing coronavirus (CoV) disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome CoV 2 (SARS-CoV-2) is associated with substantial morbidity and mortality. Understanding the immunological and pathological processes of coronavirus diseases is crucial for the rational design of effective vaccines and therapies for COVID-19. Previous studies showed that 2′-O-methylation of the viral RNA cap structure is required to prevent the recognition of viral RNAs by intracellular innate sensors. Here, we demonstrate that the guanine N7-methylation of the 5′ cap mediated by coronavirus nonstructural protein 14 (nsp14) contributes to viral evasion of the type I interferon (IFN-I)-mediated immune response and pathogenesis in mice. A Y414A substitution in nsp14 of the coronavirus mouse hepatitis virus (MHV) significantly decreased N7-methyltransferase activity and reduced guanine N7-methylation of the 5′ cap in vitro. Infection of myeloid cells with recombinant MHV harboring the nsp14-Y414A mutation (rMHVnsp14-Y414A) resulted in upregulated expression of IFN-I and ISG15 mainly via MDA5 signaling and in reduced viral replication compared to that of wild-type rMHV. rMHVnsp14-Y414A replicated to lower titers in livers and brains and exhibited an attenuated phenotype in mice. This attenuated phenotype was IFN-I dependent because the virulence of the rMHVnsp14-Y414A mutant was restored in Ifnar−/− mice. We further found that the comparable mutation (Y420A) in SARS-CoV-2 nsp14 (rSARS-CoV-2nsp14-Y420A) also significantly decreased N7-methyltransferase activity in vitro, and the mutant virus was attenuated in K18-human ACE2 transgenic mice. Moreover, infection with rSARS-CoV-2nsp14-Y420A conferred complete protection against subsequent and otherwise lethal SARS-CoV-2 infection in mice, indicating the vaccine potential of this mutant. IMPORTANCE Coronaviruses (CoVs), including SARS-CoV-2, the cause of COVID-19, use several strategies to evade the host innate immune responses. While the cap structure of RNA, including CoV RNA, is important for translation, previous studies indicate that the cap also contributes to viral evasion from the host immune response. In this study, we demonstrate that the N7-methylated cap structure of CoV RNA is pivotal for virus immunoevasion. Using recombinant MHV and SARS-CoV-2 encoding an inactive N7-methyltransferase, we demonstrate that these mutant viruses are highly attenuated in vivo and that attenuation is apparent at very early times after infection. Virulence is restored in mice lacking interferon signaling. Further, we show that infection with virus defective in N7-methylation protects mice from lethal SARS-CoV-2, suggesting that the N7-methylase might be a useful target in drug and vaccine development

TFEB Probably Involved in Midazolam-Disturbed Lysosomal Homeostasis and Its Induced β-Amyloid Accumulation

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, and β-amyloid (Aβ) plays a leading role in the pathogenesis of AD. The transcription factor EB (TFEB), a main regulating factor of autophagy and lysosome biosynthesis, is involved in the pathogenesis of AD by regulating autophagy-lysosomal pathways. To date, the choice of anesthetics during surgery in patients with neurodegenerative diseases and evaluation of the effects and underlying mechanisms in these patients have rarely been reported. In this study, the HEK293-APP cells overexpressing APP and Hela cells were used. The cells were treated with midazolam at different concentrations and at different times, then lysosomes were stained by lysotracker and their morphology was observed under a fluorescence microscope. The number and size of lysosomes were analyzed using the ImageJ software. The levels of TFEB in the nucleus and APP-cleaved intracellular proteins were detected by nuclear separation and Western Blot. Finally, ELISA was used to detect the levels of Aβ40 and Aβ42 in the cells after drug treatment. We found that 30 μM midazolam decreased the number of lysosomes and increased its size in HEK293 and HeLa cells. However, 15 μM midazolam transiently disturbed lysosomal homeostasis at 24 h and recovered it at 36 h. Notably, there was no significant difference in the extent to which lysosomal homeostasis was disturbed between treatments of different concentrations of midazolam at 24 h. In addition, 30 μM midazolam prevents the transport of TFEB to the nucleus in either normal or starved cells. Finally, the intracellular C-terminal fragment β (CTFβ), CTFα, Aβ40 and Aβ42 levels were all significantly elevated in 30 μM midazolam-treated HKE293-APP cells. Collectively, the inhibition of TFEB transport to the nucleus may be involved in midazolam-disturbed lysosomal homeostasis and its induced Aβ accumulation in vitro. The results indicated the risk of accelerating the pathogenesis of AD by midazolam and suggested that TFEB might be a candidate target for reduction of midazolam-dependent neurotoxicity

Oxygen Vacancy-Enriched Amorphous Transition Metal Ternary Oxides toward Highly Efficient Oxygen Evolution Reaction

Developing highly efficient oxygen evolution reaction (OER) electrocatalysts based on earth-abundant elements is critical to improve the efficiency of water electrolysis, but it remains a challenge. Herein, an amorphous ternary oxides composites FeNiCoOx/CoOx with rich oxygen vacancies are developed through a low-cost wet chemical deposition strategy toward this challenge. Benefiting from the synergistic effect of multimetal atom interaction and high exposure of active sites caused by oxygen vacancies and amorphous structure, the as-developed FeNiCoOx/CoOx electrocatalyst exhibits an exceptional catalytic performance with a low overpotential of only 221 mV at a current density of 100 mA cm-2 and negligible performance degradation over 240 h. Furthermore, the FeNiCoOx/CoOx-assembled anion exchange membrane water electrolyzer (AEMWE) can achieve a high current density of 1 A cm-2 at a low voltage of 1.765 V, demonstrating its great potential for practical application

Prognostic values of ALDOB expression and 18F-FDG PET/CT in hepatocellular carcinoma

PurposeThe glycolytic enzyme fructose 1,6-bisphosphate aldolase B (ALDOB) is aberrantly expressed and impacts the prognosis in hepatocellular carcinoma (HCC). Hepatic ALDOB loss leads to paradoxical upregulation of glucose metabolism, favoring hepatocellular carcinogenesis. Nevertheless, the relationship between ALDOB expression and 18F-fluorodeoxyglucose (18F-FDG) uptake, and their effects on HCC prognosis remain unclear. We evaluated whether ALDOB expression is associated with 18F-FDG uptake and their impacts on HCC prognosis prediction.MethodsChanges in ALDOB expression levels and the prognostic values in HCC were analyzed using data from The Cancer Genome Atlas (TCGA) database. Ultimately, 34 patients with HCC who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) preoperatively were enrolled in this retrospective study. ALDOB expression was determined using immunohistochemistry (IHC) staining, and the maximum standardized uptake value (SUVmax) of HCC was calculated from the 18F-FDG PET/CT scans. The relationship between ALDOB expression and SUVmax was examined, and their impacts on overall survival were evaluated using Cox proportional hazards models and Kaplan–Meier survival analysis. ALDOB overexpression in HUH7 and 7721 cells was used to analyze its role in tumor metabolism.ResultsAccording to TCGA database, the ALDOB mRNA level was downregulated in HCC compared to normal tissue, and significantly shortened overall survival in HCC patients. ALDOB protein expression was similarly decreased in IHC findings in HCC than that in adjacent normal tissues (P<0.05) and was significantly associated with tumor size (P<0.001), high tumor-node-metastasis stage (P=0.022), and elevated SUVmax (P=0.009). ALDOB expression in HCC was inversely correlated with SUVmax (r=-0.454; P=0.012), and the optimal SUVmax cutoff value for predicting its expression was 4.15. Prognostically, low ALDOB expression or SUVmax ≥3.9 indicated shorter overall survival time in HCC. Moreover, COX regression analysis suggested high SUVmax as an independent prognostic risk factor for HCC (P=0.036). HCC patients with negative ALDOB expression and positive SUVmax (≥3.9) were correlated with worse prognosis. ALDOB overexpression in HCC cells significantly decreases 18F-FDG uptake and lactate production.ConclusionSUVmax in HCC patients is inversely correlated with ALDOB expression, and 18F-FDG PET/CT may be useful for ALDOB status prediction. The combined use of ALDOB expression and 18F-FDG PET/CT data can provide additional information on disease prognosis in HCC patients

A transition of atmospheric emissions of particles and gases from on-road heavy-duty trucks

The transition, in extent and characteristics, of atmospheric emissions caused by the modernization of the heavy-duty on-road fleet was studied utilizing roadside measurements. Emissions of particle number (PN), particle mass (PM), black carbon (BC), nitrogen oxides (NOx), carbon monoxide (CO), hydrocarbon (HC), particle size distributions, and particle volatility were measured from 556 individual heavy-duty trucks (HDTs). Substantial reductions in PM, BC, NOx, CO, and to a lesser extent PN were observed from Euro III to Euro VI HDTs by 99 %, 98 %, 93 %, and 57 % for the average emission factors of PM, BC, NOx, and CO, respectively. Despite significant total reductions in NOx emissions, the fraction of NO2 in the NOx emissions increased continuously from Euro IV to Euro VI HDTs. Larger data scattering was evident for PN emissions in comparison to solid particle number (SPN) for Euro VI HDTs, indicating a highly variable fraction of volatile particle components. Particle size distributions of Euro III to enhanced environmentally friendly vehicle (EEV) HDTs were bimodal, whereas those of Euro VI HDTs were nucleation mode dominated. High emitters disproportionately contributed to a large fraction of the total emissions with the highest-emitting 10 % of HDTs in each pollutant category being responsible for 65 % of total PM, 70 % of total PN, and 44 % of total NOx emissions. Euro VI HDTs, which accounted for 53 % of total kilometres driven by Swedish HDTs, were estimated to only contribute to 2 %, 6 %, 12 %, and 47 % of PM, BC, NOx, and PN emissions, respectively. A shift to a fleet dominated by Euro VI HDTs would promote a transition of atmospheric emissions towards low PM, BC, NOx, and CO levels. Nonetheless, reducing PN, SPN, and NO2 emissions from Euro VI HDTs is still important to improve air quality in urban environments