Harnessing ZIKV NS2A RNA for alleviating acute hepatitis and cytokine release storm by targeting translation machinery.

BACKGROUND AND AIMS: Hyperactivated inflammatory responses induced by cytokine release syndrome are the primary causes of tissue damage and even death. The translation process is precisely regulated to control the production of proinflammatory cytokines. However, it is largely unknown whether targeting translation can effectively limit the hyperactivated inflammatory responses during acute hepatitis and graft-versus-host disease. APPROACH AND RESULTS: By using in vitro translation and cellular overexpression systems, we have found that the nonstructural protein gene NS2A of Zika virus functions as RNA molecules to suppress the translation of both ectopic genes and endogenous proinflammatory cytokines. Mechanistically, results from RNA pulldown and co-immunoprecipitation assays have demonstrated that NS2A RNA interacts with the translation initiation factor eIF2α to disrupt the dynamic balance of the eIF2/eIF2B complex and translation initiation, which is the rate-limiting step of translation. In the acetaminophen-induced, lipopolysaccharide/D-galactosamine-induced, viral infection-induced acute hepatitis, and graft-versus-host disease mouse models, mice with myeloid cell-specific knock-in of NS2A show decreased levels of serum proinflammatory cytokines and reduced tissue damage. CONCLUSIONS: Zika virus NS2A dampens the production of proinflammatory cytokines and alleviates inflammatory injuries by interfering translation process as RNA molecules, which suggests that NS2A RNA is potentially used to treat numerous acute inflammatory diseases characterized by cytokine release syndrome.

Crystal Structure Regulation of CoSe2 Induced by Fe Dopant for Promoted Surface Reconstitution toward Energetic Oxygen Evolution Reaction.

Most nonoxide catalysts based on transition metal elements will inevitably change their primitive phases under anodic oxidation conditions in alkaline media. Establishing a relationship between the bulk phase and surface evolution is imperative to reveal the intrinsic catalytic active sites. In this work, it is demonstrated that the introduction of Fe facilitates the phase transition of orthorhombic CoSe2 into its cubic counterpart and then accelerates the Co-Fe hydroxide layer generation on the surface during electrocatalytic oxygen evolution reaction (OER). As a result, the Fe-doped cubic CoSe2 catalyst exhibits a significantly enhanced activity with a considerable overpotential decrease of 79.9 and 66.9 mV to deliver 10 mA·cm-2 accompanied by a Tafel slope of 48.0 mV·dec-1 toward OER when compared to orthorhombic CoSe2 and Fe-doped orthorhombic CoSe2, respectively. Density functional theory (DFT) calculations reveal that the introduction of Fe on the surface hydroxide layers will tune electron density around Co atoms and raise the d-band center. These findings will provide deep insights into the surface reconstitution of the OER electrocatalysts based on transition metal elements.

The impact of community services usage on geriatric depression: a ten-year follow-up study.

BACKGROUND: This study explores whether the impact of environmental factors (community services usage, CSU) on geriatric depression is mediated by psychological resilience and moderated by the COMT (catechol-O-methyltransferase) gene val158met polymorphism. METHODS: The data consists of 13,512 entries from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) collected in the years 2008, 2011, 2014, and 2018. The study employed a Random Intercept Cross-Lagged Panel Model (RI-CLPM) to examine the relationship between CSU and geriatric depression, including the mediating effect of psychological resilience and the moderating role of the comt gene val158met gene polymorphism in this relationship. RESULTS: Lower CSU at earlier assessments were significantly associated with more severe geriatric depression in subsequent evaluations.Psychological resilience was found to partially mediate the relationship between CSU and depression.Differential impacts were observed among various gene genotypes; specifically, the val genotype demonstrated a significantly greater influence of CSU on subsequent psychological resilience and on subsequent depression compared to the met genotype. CONCLUSION: Enhancement in CSU can predict subsequent geriatric depression. The relationship between the CSU and depression can be mediated by psychological resilience, with genetics modulating the pathway from CSU through psychological resilience to depression. Multidisciplinary interventions focused on enhancing community service quality, boosting psychological resilience, and mitigating depression are likely to benefit the older adults's emotional and psychological well-being.

XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity.

XIAP-associated factor 1 (XAF1) is an interferon (IFN)-stimulated gene (ISG) that enhances IFN-induced apoptosis. However, it is unexplored whether XAF1 is essential for the host fighting against invaded viruses. Here, we find that XAF1 is significantly upregulated in the host cells infected with emerging RNA viruses, including influenza, Zika virus (ZIKV), and SARS-CoV-2. IFN regulatory factor 1 (IRF1), a key transcription factor in immune cells, determines the induction of XAF1 during antiviral immunity. Ectopic expression of XAF1 protects host cells against various RNA viruses independent of apoptosis. Knockout of XAF1 attenuates host antiviral innate immunity in vitro and in vivo, which leads to more severe lung injuries and higher mortality in the influenza infection mouse model. XAF1 stabilizes IRF1 protein by antagonizing the CHIP-mediated degradation of IRF1, thus inducing more antiviral IRF1 target genes, including DDX58, DDX60, MX1, and OAS2. Our study has described a protective role of XAF1 in the host antiviral innate immunity against RNA viruses. We have also elucidated the molecular mechanism that IRF1 and XAF1 form a positive feedback loop to induce rapid and robust antiviral immunity. IMPORTANCE Rapid and robust induction of antiviral genes is essential for the host to clear the invaded viruses. In addition to the IRF3/7-IFN-I-STAT1 signaling axis, the XAF1-IRF1 positive feedback loop synergistically or independently drives the transcription of antiviral genes. Moreover, XAF1 is a sensitive and reliable gene that positively correlates with the viral infection, suggesting that XAF1 is a potential diagnostic marker for viral infectious diseases. In addition to the antitumor role, our study has shown that XAF1 is essential for antiviral immunity. XAF1 is not only a proapoptotic ISG, but it also stabilizes the master transcription factor IRF1 to induce antiviral genes. IRF1 directly binds to the IRF-Es of its target gene promoters and drives their transcriptions, which suggests a unique role of the XAF1-IRF1 loop in antiviral innate immunity, particularly in the host defect of IFN-I signaling such as invertebrates.

Treatment of immune thrombocytopenia with hetrombopag olamine tablets in a Kabuki syndrome patient with new KMT2D mutations.

Kabuki syndrome (KS) is a rare multisystem-affecting genetic disorder, and usually accompanied with autoimmune disorders such as immune thrombocytopenic purpura (ITP). Here, we report a 16-year-old patient with Kabuki syndrome with ITP and observe the therapeutic effect of TPO agonist hetrombopag olamine tablets. The duration of maintenance therapy and follow up were both 17 months. Whole exon sequencing (WES) of the patient's peripheral blood showed c.5775_5778del (p. Leu1926LysfsTer120) heterozygous mutation in the KMT2D gene, which was not reported before.

Serpentine Ni3 Ge2 O5 (OH)4 Nanosheets with Tailored Layers and Size for Efficient Oxygen Evolution Reactions.

Layered serpentine Ni3 Ge2 O5 (OH)4 is compositionally active and structurally favorable for adsorption and diffusion of reactants in oxygen evolution reactions (OER). However, one of the major problems for these materials is limited active sites and low efficiency for OER. In this regard, a new catalyst consisting of layered serpentine Ni3 Ge2 O5 (OH)4 nanosheets is introduced via a controlled one-step synthetic process where the morphology, size, and layers are well tailored. The theoretical calculations indicate that decreased layers and increased exposure of (100) facets in serpentine Ni3 Ge2 O5 (OH)4 lead to much lower Gibbs free energy in adsorption of reactive intermediates. Experimentally, it is found that the reduction in number of layers with minimized particle size exhibits plenty of highly surface-active sites of (100) facets and demonstrates a much enhanced performance in OER than the corresponding multilayered nanosheets. Such a strategy of tailoring active sites of serpentine Ni3 Ge2 O5 (OH)4 nanosheets offers an effective method to design highly efficient electrocatalysts.

Protein Hydrolysates' Absorption Characteristics in the Dynamic Small Intestine In Vivo.

Background: Dietary proteins are known for their wide range of nutritional, functional and biological properties. Although the total amount of proteins may be obtained from mixtures, its "availability" for absorption in the gut is in many cases quite uncertain or even varies for the same food depending on processing conditions, the presence of other components, and so on. Methods: To obtain accurate protein hydrolysate absorption data, we have developed a small intestine model (SIM) to test them. Results: The results indicated that the protein hydrolysates were absorbed rapidly during the first 15 min, and then decreased to 90 min, then they were absorbed again from 90 min to the endpoint. The protein absorption was also affected by the protein processing method used. The Enzyme + Ultrasound (EU) processing method group had a higher absorption rate than the Enzyme (E) processing method group, and the absorption of the Enzyme + Artificial gastric juice processing method (EH) and Enzyme + Ultrasound + Artificial gastric juice processing method (EUH) groups was reduced compared to the E group alone. The amino acid analysis results showed that the amino acids were reduced and absorbed by our SIM in almost all groups except for cysteine and methionine. In general, the Pearson relation value of the amino acid contents between before SIM and after SIM was 0.887, which indicated that single amino acid absorption was mainly related to its content in the whole amino acids. The single amino acid absorption ratio among different groups also displayed differences, which ranged from 31% to 46% (E group from 39% to 42%; EU group from 40% to 47%; EH group from 31% to 39%; EUH group from 35% to 41%). CONCLUSIONS: The protein hydrolysates' varied from startpoint to endpoint, and the protein absorption was affected by processing method.

Comparative transcriptomic analysis of Bombyx mori fat body tissue following dietary restriction.

Dietary restriction (DR) refers to a reduction in food intake to induce undernutrition but not malnutrition, which extends the lifespan of multiple species. Although there are invertebrate aging models, such as the Caenorhabditis elegans and Drosophila melanogaster, aging studies in Lepidoptera are few in number and the underlying life-extending molecular mechanisms are not clear. Research on a broader range of animals is necessary to support generalizations on mechanisms of aging and rates of aging. The aim of this study was to further investigate genes and pathways associated with DR in Bombyx mori. Here, we used mRNA deep sequencing (RNA-seq) to further investigate genes and pathways associated with DR. The transcriptome profiles showed that most of the differentially expressed genes were upregulated following DR, and genes involved in amino acid and protein metabolism, RNA metabolism and translation, energy metabolism, nitrogen metabolism, and juvenile hormone pathway-related proteins were particularly affected. DR also affects the metabolism of uric acid and urea, which accumulated in silkworm following DR. We speculate that this may not be due to activation of uric acid biosynthesis, but rather by downregulating the degradation of uric acid and urea. These results may help us to understand the mechanisms by which DR prolong lifespan in insects and other animals.

Influence of extremely low frequency magnetic fields on Ca2+ signaling and double messenger system in mice hippocampus and reversal function of procyanidins extracted from lotus seedpod.

This research investigated the influence of extremely low frequency magnetic fields (ELF-MF; 50 Hz, 8 mT, 4 h per day, for 28 days) on calcium ion signaling and the double messenger system in the hippocampus of mice. Messengers that were studied included: G-protein, Ins(1,4,5)P3 (IP3 ), diacylglycerol (DAG), cAMP-dependent protein kinase (PKA), and Ca2+ -dependent protein kinase C (PKC). The results showed that ELF-MF caused an increase in the levels of Gi protein, IP3, DAG, PKA and PKC beta, calcium and calmodulin-dependent protein phosphatase calcineuring (PP2B), and intracellular Ca2+ content, and a decrease in calcium/calmodulin-dependent protein kinase II (CaMK II) and PKC alpha. In addition, ELF-MF exposure decreased the level of brain-derived neurotrophic factor (BDNF), which played a key role in hippocampal neuronal cell death. However, oral administration of procyanidins from lotus seedpod (LSPCs) (especially 90 mg kg-1 ) significantly recovered these changes, and nearly reached normal levels. All these showed that LSPCs may mediate calcium signal and double messenger system through Ca2+ /CaMK II/CREB/BDNF and DG/PKC/MAPK signaling pathways to reverse the alteration caused by ELF-MF. Bioelectromagnetics. 38:436-446, 2017. © 2017 Wiley Periodicals, Inc.

Improvement of skin condition by oral administration of collagen hydrolysates in chronologically aged mice.

BACKGROUND: Collagen hydrolysates (CHs) have been demonstrated to have positive effects on skin photoaging by topical application or oral ingestion. However, there has been little research on their influence on skin chronological aging. In this study, 9-month-old female ICR mice were given normal AIN-93M diets containing CHs (2.5, 5 and 10% w/w) from Nile tilapia scale. RESULTS: After 6 months, the collagen content and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities increased significantly (P < 0.05), while the survival rate, viscera indices and contents of moisture, fat and non-collagenous protein in skin did not change (P > 0.05). The color, luster and quantity of hair were obviously ameliorated. Moreover, the structure of epidermis and dermis, the density and distribution of collagen fibers and the ratio of type I to type III collagen were improved in a dose-dependent manner as shown by histochemical staining. CONCLUSION: Oral ingestion of CHs increased the collagen content and antioxidant enzyme activities and improved the appearance and structure of skin. These results suggest the potential of CHs as an anti-skin-aging ingredient in nutraceuticals or functional foods. © 2016 Society of Chemical Industry.

Trace elements and rare earth elements in wet deposition of Lijiang, Mt. Yulong region, southeastern edge of the Tibetan Plateau.

In order to investigate the compositions and wet deposition fluxes of trace elements and rare earth elements (REEs) in the precipitation of the southeastern edge of the Tibetan Plateau, 38 precipitation samples were collected from March to August in 2012 in an urban site of Lijiang city in the Mt. Yulong region. The concentrations of most trace elements and REEs were higher during the non-monsoon season than during the monsoon season, indicating that the lower concentrations of trace elements and REEs observed during monsoon had been influenced by the dilution effect of increased precipitation. The concentrations of trace elements in the precipitation of Lijiang city were slightly higher than those observed in remote sites of the Tibetan Plateau but much lower than those observed in the metropolises of China, indicating that the atmospheric environment of Lijiang city was less influenced by anthropogenic emissions, and, as a consequence, the air quality was still relatively good. However, the results of enrichment factor and principal component analysis revealed that some anthropogenic activities (e.g., the increasing traffic emissions from the rapid development of tourism) were most likely important contributors to trace elements, while the regional/local crustal sources rather than anthropogenic activities were the predominant contributors to the REEs in the wet deposition of Lijiang city. Our study was relevant not only for assessing the current status of the atmospheric environment in the Mt. Yulong region, but also for specific management actions to be implemented for the control of atmospheric inputs and the health of the environment for the future.

Effect of fluoride on the proteomic profile of the hippocampus in rats.

Two-dimensional gel electrophoresis (2-DE) was used to detect fluoride-induced alterations in the proteome of the rat hippocampus. Male Sprague-Dawley rats (n=30) were subjected to treatments three weeks after weaning. Animals of the first group were injected intraperitoneally (i.p.) with aqueous NaF (20 mg/kg/body weight/day), the second group, injected with physiological saline, served as the control. After 30 days, the body weight of the fluoride-treated rats was lower than that of the control, and F- levels in serum were higher than in the control. The hippocampus was subjected to proteomic analysis, and the fluoride-treated group was found to contain 19 up-regulated and eight down-regulated proteins. The proteins, identified by mass-spectroscopic analysis of their fragments obtained after digestion, were found to be involved in amino acid biosynthesis, the insulin signaling pathway and various other crucial functions. Our results also provide useful information on the mechanism of the reduction of the learning ability and memory induced by F.

Determination of bioavailability and identification of collagen peptide in blood after oral ingestion of gelatin.

BACKGROUND: Gelatin has long been widely used in foods, pharmaceuticals, cosmetics, and other products. However, there are few reports on its bioavailability and bioavailable forms. In this study, the bioavailability of gelatin was indirectly evaluated by the determining the bioavailability of total hydroxyproline in gelatin using a pharmacokinetic method after oral administration to rats. RESULTS: The relative and absolute bioavailability of gelatin were 74.12% and 85.97%, respectively. The amino acid profile of plasma indicated that 41.91% of the digested gelatin was absorbed from the intestine in the form of peptide, and there was a good linear correlation between the absorbed amount of an amino acid and its content in gelatin (R(2) = 0.9566). Moreover, 17 types of collagen peptide were purified by multi-step chromatography and identified with ultra-performance liquid chromatography-electrospray ionisation-mass spectrometry. CONCLUSION: Gelatin had high oral bioavailability. Nearly half of digested gelatin was absorbed from the intestine in the form of various collagen peptides.

Analysis of herbaceous plant succession and dispersal mechanisms in deglaciated terrain on Mt. Yulong, China.

Ecological succession itself could be a theoretical reference for ecosystem restoration and reconstruction. Glacier forelands are ideal places for investigating plant succession because there are representative ecological succession records at long temporal scales. Based on field observations and experimental data on the foreland of Baishui number 1 Glacier on Mt. Yulong, the succession and dispersal mechanisms of dominant plant species were examined by using numerical classification and ordination methods. Fifty samples were first classified into nine community types and then into three succession stages. The three succession stages occurred about 9-13, 13-102, and 110-400 years ago, respectively. The earliest succession stage contained the association of Arenaria delavayi + Meconopsis horridula. The middle stage contained the associations of Arenaria delavayi + Kobresia fragilis, Carex capilliformis + Polygonum macrophyllum, Carex kansuensis, and also Pedicularis rupicola. The last stage included the associations of Kobresia fragilis + Carex capilliformis, Kobresia fragilis, Kobresia fragilis + Ligusticum rechingerana, and Kobresia fragilis + Ligusticum sikiangense. The tendency of the succession was from bare land to sparse vegetation and then to alpine meadow. In addition, three modes of dispersal were observed, namely, anemochory, mammalichory, and myrmecochory. The dispersal modes of dominant species in plant succession process were evolved from anemochory to zoochory.

Research on the death psychology among Chinese during and after the COVID-19 pandemic.

Under the threat of the novel coronavirus, people are compelled to contemplate some ultimate existential questions, such as life and death. This study collected texts related to the death psychology from Sina Weibo, and after data cleaning, a total of 3868 Weibo texts were included. Study 1 employed grounded theory from qualitative research to explore the core categories and evolutionary mechanisms of people's psychology when facing death threats in the context of the pandemic. Study 2 utilized big data mining techniques such as topic mining and semantic network analysis to validate the effectiveness of the death psychology theory developed in qualitative research. The findings demonstrate that within the "Emotion-Cognition-Behavior-Value" framework, the implications of death threats manifest in four aspects: death anxiety, death cognition, coping efficacy, and sense of meaning. As time progresses, the study of death psychology can be segmented into four distinct phases: the tranquil phase prior to lifting pandemic restrictions, the threat phase at lifting pandemic restrictions onset, the coping phase mid-lifting pandemic restrictions, and the reformative phase post-lifting pandemic restrictions. The calculated outcomes of topic mining and semantic network analysis corroborate the coding results and theories derived from the grounded theory. This reaffirms that data mining technology can be a potent tool for validating grounded theory.

Exploring the relationship between mindfulness and burnout among preschool teachers: the role of dispositional equanimity and empathy.

The objective of this study is to delve into the underlying mechanisms between mindfulness and burnout among preschool teachers. Employing a cross-sectional research design, this study surveyed 1,980 Chinese preschool teachers using the Mindful Attention Awareness Scale (MAAS), Preschool Teacher Dispositional Equanimity Questionnaire (PTDEQ), Empathy Scale (ME), and Maslach Burnout Inventory for Educators (MBI-ES). The results revealed a significant negative correlation between preschool teachers' mindfulness and burnout. A mediation analysis demonstrated that dispositional equanimity served as a mediator between mindfulness and preschool teacher burnout. Furthermore, a moderation analysis indicated that empathy moderated the influence of dispositional equanimity on preschool teacher burnout. These findings suggest that mindfulness can enable preschool teachers to better cope with workplace challenges with a more peaceful mindset.

Pulse potential mediated selectivity for the electrocatalytic oxidation of glycerol to glyceric acid.

Preventing the deactivation of noble metal-based catalysts due to self-oxidation and poisonous adsorption is a significant challenge in organic electro-oxidation. In this study, we employ a pulsed potential electrolysis strategy for the selective electrocatalytic oxidation of glycerol to glyceric acid over a Pt-based catalyst. In situ Fourier-transform infrared spectroscopy, quasi-in situ X-ray photoelectron spectroscopy, and finite element simulations reveal that the pulsed potential could tailor the catalyst's oxidation and surface micro-environment. This prevents the overaccumulation of poisoning intermediate species and frees up active sites for the re-adsorption of OH adsorbate and glycerol. The pulsed potential electrolysis strategy results in a higher glyceric acid selectivity (81.8%) than constant-potential electrocatalysis with 0.7 VRHE (37.8%). This work offers an efficient strategy to mitigate the deactivation of noble metal-based electrocatalysts.

Unilamellar MnO2 nanosheets confined Ru-clusters combined with pulse electrocatalysis for biomass electrooxidation in neutral electrolytes.

The electrochemical oxidation of 5-hydroxymethylfurfural (HMFOR) in alkaline electrolyte is a promising strategy for producing high-value chemicals from biomass derivatives. However, the disproportionation of aldehyde groups under strong alkaline conditions and the polymerization of HMF to form humic substances can impact the purity of 2,5-furandicarboxylic acid (FDCA) products. The use of neutral electrolytes offers an alternative environment for electrolysis, but the lack of OH- ions in the electrolyte often leads to low current density and low yields of FDCA. In this study, a sandwich-structured catalyst, consisting of Ru clusters confined between unilamellar MnO2 nanosheets (S-Ru/MnO2), was used in conjunction with an electrochemical pulse method to realize the electrochemical conversion of 5-hydroxymethylfurfural into FDCA in neutral electrolytes. Pulse electrolysis and the strong electron transfer between Ru clusters and MnO2 nanosheets help maintain Ru in a low oxidation state, ensuring high activity. The increased *OH generation led to a groundbreaking current density of 47 mA/cm2 at 1.55 V vs. reversible hydrogen electrode (RHE) and an outstanding yield rate of 98.7 % for FDCA in a neutral electrolyte. This work provides a strategy that combines electrocatalyst design with an electrolysis technique to achieve remarkable performance in neutral HMFOR.

Design of imaging keratometer with annular object and charge-coupled device detector.

A novel imaging keratometer by the aid of modern optoelectronic technology is proposed. The optical system consists of an annular object, a first imaging subsystem, a second imaging subsystem, and a CCD detector. The measurement range of corneal refraction is from 30D to 60D (5.5-11 mm in radius of curvature), and the accuracy reaches 0.156D, 0.072D, and 0.036D, respectively, for the corneal surface of the steepest, the radius of curvature of 7.8 mm, and the corneal surface of the flattest. The accuracy of corneal astigmatism is verified to be 0.05D for cylindrical refraction of 0.75D. Compared with the traditional keratometer, the proposed keratometer possesses advantages of high accuracy.

Proteomic profiling of liver from Elaphe taeniura, a common snake in eastern and southeastern Asia.

Snake liver has been implicated in the adaptation of snakes to a variety of habitats. However, to date, there has been no systematic analysis of snake liver proteins. In this study, we undertook a proteomic analysis of liver from the colubrid snake Elaphe taeniura using a combination of two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of flightmass spectrometry (MALDI-TOF MS). We also constructed a local protein sequence database based on transcriptome sequencing to facilitate protein identification. Of the 268 protein spots revealed by 2-DE 109 gave positive MS signals, 84 of which were identified by searching the NCBInr, Swiss-Prot and local databases. The other 25 protein spots could not be identified, possibly because their transcripts were not be stable enough to be detected by transcriptome sequencing. GO analysis showed that most proteins may be involved in binding, catalysis, cellular processes and metabolic processes. Forty-two of the liver proteins identified were found in other reptiles and in amphibians. The findings of this study provide a good reference map of snake liver proteins that will be useful in molecular investigations of snake physiology and adaptation.