N6-methyladenosine modification of the mRNA for a key gene in purine nucleotide metabolism regulates virus proliferation in an insect vector.

The titer of viruses that persist and propagate in their insect vector must be high enough for transmission yet not harm the insect, but the mechanism of this dynamic balance is unclear. Here, expression of inosine monophosphate dehydrogenase (LsIMPDH), a rate-limiting enzyme for guanosine triphosphate (GTP) synthesis, is shown to be downregulated by increased levels of N6-methyladenosine (m6A) on LsIMPDH mRNA in rice stripe virus (RSV)-infected small brown planthoppers (SBPHs; Laodelphax striatellus), the RSV vector, which decreases GTP content, thus limiting viral proliferation. Moreover, planthopper methyltransferase-like protein 3 (LsMETTL3) and m6A reader protein LsYTHDF3 are found to catalyze and recognize the m6A on LsIMPDH mRNA, respectively, and cooperate in destabilizing LsIMPDH transcripts. Co-silencing assays show that negative regulation of viral proliferation by both LsMETTL3 and LsYTHDF3 is partially dependent on LsIMPDH. This distinct mechanism limits virus replication in an insect vector, providing a potential gene target to block viral transmission.

Public acceptance of COVID-19 control measures and associated factors during Omicron-dominant period in China: a cross-sectional survey.

OBJECTIVES: This study aims to evaluate the public acceptance of coronavirus disease 2019 (COVID-19) control measures during the Omicron-dominant period and its associated factors. METHODS: A cross-sectional design was conducted and 1391 study participants were openly recruited to participate in the questionnaire survey. Logistic regression model was performed to assess the association between the public acceptance and potential factors more specifically. RESULTS: By August 26, 2022, 58.9% of the study participants were less acceptive of the control measures while 41.1% expressed higher acceptance. Factors associated with lower acceptance included young age, such as < 18 (OR = 8.251, 95% CI: 2.009 to 33.889) and 18-29 (OR = 2.349, 95% CI: 1.564 to 3.529), and household per capita monthly income lower than 5000 yuan (OR = 1.512, 95% CI: 1.085 to 2.105). Furthermore, individuals who perceived that the case fatality rate (CFR) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was very low (OR = 6.010, 95% CI: 2.475 to 14.595) and that the restrictions could be eased once the CFR dropped to 2-3 times of the influenza (OR = 2.792, 95% CI: 1.939 to 4.023) showed greater oppositional attitudes. Likewise, respondents who were dissatisfied with control measures (OR = 9.639, 95% CI: 4.425 to 20.998) or preferred fully relaxation as soon as possible (OR = 13.571, 95% CI: 7.751 to 23.758) had even lower acceptability. By contrast, rural residents (OR = 0.683, 95% CI: 0.473 to 0.987), students (OR = 0.510, 95% CI: 0.276 to 0.941), public (OR = 0.417, 95% CI: 0.240 to 0.727) and private (OR = 0.562, 95% CI: 0.320 to 0.986) employees, and vaccinated participants (OR = 0.393, 95% CI: 0.204 to 0.756) were more compliant with control measures. CONCLUSION: More than half of the Chinese public were less supportive of COVID-19 control measures during Omicron-dominant period, which varied based on their different demographic characteristics, cognition and overall attitude towards SARS-CoV-2 infection. Control measures that struck a balance between public safety and individual freedom would be more acceptable during the pandemic.

A Novel Diffusion Tensor Image Analysis Along the Perivascular Space Method to Evaluate Glymphatic Alterations in Alzheimer's Disease.

Alzheimer 's disease (AD) is the most prevalent neurodegenerative disorder worldwide. The glymphatic system is considered to be associated with the pathogenesis of AD. However, the alterations of glymphatic system along the AD continuum are still unknown. In this study, we used a novel DTI analysis method, diffusion tensor image analysis along the perivascular space (DTI-ALPS), to evaluate the difference in the activity of the glymphatic system among normal control (NC) subjects, mild cognitive impairment (MCI) and AD patients. The data utilized in the study was obtained from Tongji Hospital in Shanghai, China, including 65 NCs, 58 MCIs and 36 ADs. First, we calculated the ALPS-index to evaluate the activity of the glymphatic system. Then, analysis of variance (ANOVA) was used to find the differences of ALPS-index among different groups, and to explore the correlation between ALPS-index and the three clinical scales: Minimum Mental State Examination (MMSE), Montreal Cognitive Assessment-Basic (MoCA-B) and Instrumental Activity of Daily Living (IADL). Receiver operating characteristic curve (ROC) analysis was used to evaluate the role of the ALPS-index in disease classification. The findings indicated a significant difference in the ALPS-index between the groups of participants with normal cognition, MCI, and AD. In addition, we found that ALPS-index was significantly correlated with the scores of the three clinical scales (with MoCA-B: r=0.233, p=0.001). Furthermore, with ALPS-index, Fractional Anisotropy (FA) values achieved best classification results (AUC=0.8899). Cognitive dysfunction is closely associated with the activity of the glymphatic system, and ALPS-index can be used as a biomarker for alterations along the AD continuum.

Higher critical closing pressure is independently associated with enlarged basal ganglia perivascular spaces.

Objective: This study aimed to explore the association between cerebral hemodynamic parameters focused on the critical closing pressure (CCP) and enlarged perivascular spaces (EPVS). Methods: Cerebral blood velocity in the middle cerebral artery (MCAv) and non-invasive continuous blood pressure (NIBP) were measured using a transcranial Doppler (TCD) and Finometer, followed by the calculation of cerebral hemodynamic parameters including CCP, resistance area product (RAP), pulsatility index (PI), and pulse pressure (PP). EPVS were graded separately in the basal ganglia (BG) and centrum semiovale (CSO), using a visual semiquantitative ordinal scale. Patients with EPVS >10 were classified into the severe BG-EPVS group and severe CSO-EPVS group, and the remainder into the mild BG-EPVS group and the mild CSO-EPVS group. Spearman's correlation and binary logistic regression analysis were performed to analyze the relationship between hemodynamic parameters and BG-EPVS and CSO-EPVS, respectively. Results: Overall, 107 patients were enrolled. The severe BG-EPVS group had higher CCP, mean arterial blood pressure (MABP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) than that in the mild BG-EPVS group (p < 0.05). There was no statistical difference in hemodynamic parameters between the severe CSO-EPVS group and the mild CSO-EPVS group. Spearman's correlation analysis showed that CCP was positively associated with BG-EPVS (rho = 0.331, p < 0.001) and CSO-EPVS (rho = 0.154, p = 0.044). The binary logistic regression analysis showed that CCP was independently associated with severe BG-EPVS (p < 0.05) and not with CSO-EPVS (p > 0.05) after adjusting for confounders. Conclusion: CCP representing cerebrovascular tension was independently associated with BG-EPVS.

Maternal antibody transfer rate of vaccination against SARS-CoV-2 before or during early pregnancy and its protective effectiveness on offspring.

This study focuses on maternal antibody transfer following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before or during early pregnancy and its potential protective effects on infants, providing scientific evidence for vaccination strategies. This prospective study tested the samples for SARS-CoV-2 IgG antibody titers and neutralizing capacity and tracked the infections after birth. Perform multivariate analysis of factors influencing antibody transfer rate, newborn antibody titers, and infant infection. Total 87.1% (122/140) women received coronavirus disease 2019 (COVID-19) vaccine before or during early pregnancy, and 28 of them had breakthrough infection. The maternal and neonatal IgG positive rates at delivery were 60.7% (85/140) and 60.8% (87/143), respectively. A positive correlation was found between neonatal and maternal IgG antibody titers. Compared with the median IgG antibody transfer rate of infected pregnant women, that of vaccinated but not infected pregnant women was higher (1.21 versus: 1.53 [two doses], 1.71 [three doses]). However, neonatal IgG antibodies were relatively low (174.91 versus: 0.99 [two doses], 8.18 [three doses]), and their neutralizing capacity was weak. The overall effectiveness of maternal vaccination in preventing infant infection was 27.0%, and three doses had higher effectiveness than two doses (64.3% vs. 19.6%). Multivariate analysises showed that in vaccination group women receiving three doses or in infection group women with longer interval between infection and delivery had a higher antibody transfer rate and neonatal IgG antibody titer. More than half of women vaccinated before or during early pregnancy can achieve effective antibody transfer to newborns. However, the neonatal IgG antibody titer is low and has a weak neutralizing capacity, providing limited protection to infants.

The Combination of a Graph Neural Network Technique and Brain Imaging to Diagnose Neurological Disorders: A Review and Outlook.

Neurological disorders (NDs), such as Alzheimer's disease, have been a threat to human health all over the world. It is of great importance to diagnose ND through combining artificial intelligence technology and brain imaging. A graph neural network (GNN) can model and analyze the brain, imaging from morphology, anatomical structure, function features, and other aspects, thus becoming one of the best deep learning models in the diagnosis of ND. Some researchers have investigated the application of GNN in the medical field, but the scope is broad, and its application to NDs is less frequent and not detailed enough. This review focuses on the research progress of GNNs in the diagnosis of ND. Firstly, we systematically investigated the GNN framework of ND, including graph construction, graph convolution, graph pooling, and graph prediction. Secondly, we investigated common NDs using the GNN diagnostic model in terms of data modality, number of subjects, and diagnostic accuracy. Thirdly, we discussed some research challenges and future research directions. The results of this review may be a valuable contribution to the ongoing intersection of artificial intelligence technology and brain imaging.

Effectiveness of Maternal Inactivated COVID-19 Vaccination against Omicron Infection in Infants during the First 12 Months of Life: A Test-Negative Case-Control Study.

This study aims to evaluate the effectiveness of maternal inactivated COVID-19 vaccination before delivery for infants against Omicron infection in Guangzhou, China. A test-negative case-control design was conducted. This study selected infants born from 1 November 2021 to 23 November 2022 and tested for SARS-CoV-2 between 13 April 2022 and 30 November 2022 during outbreaks in Guangzhou. Multivariable logistic regression was performed to compare the maternal vaccination status of inactivated COVID-19 vaccines before delivery in cases and controls to estimate vaccine effectiveness (VE) for infants within 12 months. According to eligibility criteria, we finally selected 205 test-positive and 114 test-negative infants, as well as their mothers. The effectiveness of inactivated COVID-19 vaccines among fully vaccinated mothers was 48.4% (7.3% to 71.7%) for infants within 12 months, with the effectiveness of partial and booster vaccination showing no significant difference. Effectiveness for full vaccination presented a slight increase according to infants' age at testing, with 49.6% (-12.3% to 78.4%) for 0-6 months and 59.9% (-0.6% to 84.4%) for over 6 months. A greater protective effect of two-dose vaccination was manifested in infants whose mother had received the second dose during the first trimester (65.9%, 95% CI: 7.7% to 87.9%) of pregnancy rather than preconception (43.5%, 95% CI: -8.7% to 71.1%). Moreover, VE could be improved to 77.1% (11.1% to 95.3%) when mothers received two doses both during pregnancy and 91.8% (41.1% to 99.6%) with receipt of a booster dose during pregnancy. Maternal vaccination with two doses of inactivated COVID-19 vaccines before delivery was moderately effective against Omicron infection in infants during the first 12 months of life. Full vaccination or a booster dose during pregnancy could confer better protection against Omicron for infants, although it might be overestimated due to the insufficient sample size in subgroups.

Validation of quenching effectiveness and pollutant degradation ability of singlet oxygen through model reaction system.

Quenching method is widely used to assess the contribution of specified reactive species through the probe inhibition efficiency (IE) caused by adding excessive quencher. However, for reactive species with weak ability such as singlet oxygen (1O2), the quenching results are prone to ambiguity. In this study, an 1O2 system using furfuryl alcohol (FFA) as a probe was successfully constructed by methylene-blue-N vis-photosensitization, to discuss the quenching, interference elimination and pollutant degradation ability of 1O2. Inhibition of FFA transformation caused by both quenching and interrupting of 1O2 production was found. The quenching is affected by quencher dosage and ability, which depends on the second-order-rate constant (k). A high k means a strong ability, and less dosage is required to achieve the same IE. Comparison between the calculated ratio of reactive species consumed by quencher and experimental IE helps to judge the interruption of 1O2 production. None of the organic-solvents (methanol, ethanol, iso-propanol, n-butanol, iso-butanol, tert-butanol, tetrahydrofuran, acetonitrile, acetone and chloroform) scavenged 1O2, which would be used as screening-agent for other reactive species (e.g., hydroxyl radicals) that would interrupt 1O2 contribution assessment. Besides, 1O2 was powerless to degrade most selected pollutants. These results encourage proper use of quenchers and better experimental design.

Unlocking the enigma: unraveling multiple cognitive dysfunction linked to glymphatic impairment in early Alzheimer's disease.

Background: Alzheimer's disease (AD) is one of the world's well-known neurodegenerative diseases, which is related to the balance mechanism of production and clearance of two proteins (amyloid-ß and tau) regulated by the glymphatic system. Latest studies have found that AD patients exhibit impairments to their glymphatic system. However, the alterations in the AD disease continuum, especially in the early stages, remain unclear. Moreover, the relationship between the glymphatic system and cognitive dysfunction is still worth exploring. Methods: A novel diffusion tensor image analysis method was applied to evaluate the activity of the glymphatic system by an index for diffusivity along the perivascular space (ALPS-index). Based on this method, the activity of the glymphatic system was noninvasively evaluated in 300 subjects, including 111 normal controls (NC), 120 subjects with mild cognitive impairment (MCI), and 69 subjects with AD. Partial correlation analysis was applied to explore the association between glymphatic system and cognitive impairment based on three domain-general scales and several domain-specific cognitive scales. Receiver operating characteristic curve analysis was used to evaluate the classification performance of ALPS-index along the AD continuum. Results: ALPS-index was significantly different among NC, MCI and AD groups, and ALPS-index decreased with cognitive decline. In addition, ALPS-index was significantly correlated with the scores of the clinical scales (p<0.05, FDR corrected), especially in left hemisphere. Furthermore, combination of ALPS and fractional anisotropy (FA) values achieved better classification results (NC vs. MCI: AUC = 0.6610, NC vs. AD: AUC = 0.8214). Conclusion: Here, we show that the glymphatic system is closely associated with multiple cognitive dysfunctions, and ALPS-index can be used as a biomarker for alterations along the AD continuum. This may provide new targets and strategies for the treatment of AD, and has the potential to assist clinical diagnosis.

Correction: Marginal zinc deficiency alters the heart proteome of rats.

Correction for 'Marginal zinc deficiency alters the heart proteome of rats' by Yongzhi Sun et al., Food Funct., 2023, https://doi.org/10.1039/d2fo03815c.

Marginal zinc deficiency alters the heart proteome of rats.

Zinc deficiency is closely related to cardiovascular diseases (CVDs), but the effects of marginal zinc deficiency (MZD) after birth on the heart are unknown. In this study, 4-week-old male rats were fed a low zinc diet (10 mg kg-1, 1/3 recommended nutrient intake, RNI) for 8 weeks. Echocardiography and histopathology were performed to assess the functional and morphological alterations of the heart. High-throughput proteomics was used to study the effects of MZD on cardiac protein expression. We found that MZD reduced food intake, body weight, serum zinc, and heart weight; however, the coefficient, zinc concentration, function, and histopathology of the heart were not changed. The heart proteome was altered in the marginal zinc-deficient diet group (MZG), compared with the normal zinc diet group (NZG). A total of 310 differentially expressed proteins (P < 0.05) were significantly changed by MZD, among which 163 proteins were up-regulated and 147 were down-regulated. Of these, 43 proteins are related to CVDs and 18 proteins are zinc-associated proteins. Gene Ontology and Pathway analysis revealed that 74 biological processes (BPs) and 37 pathways were significantly changed by MZD. This included six CVD-related BPs, such as regulation of heart rate, cardiac muscle contraction, regulation of ventricular cardiac muscle cell action potential, and regulation of blood pressure, and eight CVD-related pathways, such as dilated cardiomyopathy, diabetic cardiomyopathy, and hypertrophic cardiomyopathy. Our data show that marginal zinc deficiency after birth significantly alters cardiac protein expression and pathways related to CVDs.

Protective Effect of Inactivated COVID-19 Vaccines against Omicron BA.2 Infection in Guangzhou: A Test-Negative Case-Control Real-World Study.

This study aims to explore the relationship between the doses of inactivated COVID-19 vaccines received and SARS-CoV-2 Omicron infection in the real-world setting, so as to preliminarily evaluate the protective effect induced by COVID-19 vaccination. We conducted a test-negative case-control study and recruited the test-positive cases and test-negative controls in the outbreak caused by Omicron BA.2 in April 2022 in Guangzhou, China. All the participants were 3 years and older. The vaccination status between the case group and the control group was compared in the vaccinated and all participants, respectively, to estimate the immune protection of inactivated COVID-19 vaccines. After adjusting for sex and age, compared with a mere single dose, full vaccination of inactivated COVID-19 vaccines (OR = 0.191, 95% CI: 0.050 to 0.727) and booster vaccination (OR = 0.091, 95% CI: 0.011 to 0.727) had a more superior protective effect. Compared with one dose, the second dose was more effective in males (OR = 0.090), as well as two doses (OR = 0.089) and three doses (OR = 0.090) among individuals aged 18-59. Whereas, when compared with the unvaccinated, one dose (OR = 7.715, 95% CI: 1.904 to 31.254) and three doses (OR = 2.055, 95% CI: 1.162 to 3.635) could contribute to the increased risk of Omicron infection after adjusting for sex and age. Meanwhile, by contrast with unvaccinated individuals, the result of increased risk was also manifested in the first dose in males (OR = 12.400) and one dose (OR = 21.500), two doses (OR = 1.890), and a booster dose (OR = 1.945) in people aged 18-59. In conclusion, the protective effect of full and booster vaccination with inactivated COVID-19 vaccines exceeded the incomplete vaccination, of which three doses were more effective. Nevertheless, vaccination may increase the risk of Omicron infection compared with unvaccinated people. This may result from the transmission traits of BA.2, the particularity and stronger protection awareness of the unvaccinated population, as well as the ADE effect induced by the decrease of antibody titers after a long time of vaccination. It is crucial to explore this issue in depth for the formulation of future COVID-19 vaccination strategies.

Epstein-Barr virus envelope glycoprotein 110 inhibits NF-κB activation by interacting with NF-κB subunit p65.

Epstein-Barr virus (EBV) is a member of the lymphotropic virus family and is highly correlated with some human malignant tumors. It has been reported that envelope glycoprotein 110 (gp110) plays an essential role in viral fusion, DNA replication, and nucleocapsid assembly of EBV. However, it has not been established whether gp110 is involved in regulating the host's innate immunity. In this study, we found that gp110 inhibits tumor necrosis factor α-mediated NF- κB promoter activity and the downstream production of NF- κB-regulated cytokines under physiological conditions. Using dual-luciferase reporter assays, we showed that gp110 might impede the NF-κB promoter activation downstream of NF-κB transactivational subunit p65. Subsequently, we used coimmunoprecipitation assays to demonstrate that gp110 interacts with p65 during EBV lytic infection, and that the C-terminal cytoplasmic region of gp110 is the key interaction domain with p65. Furthermore, we determined that gp110 can bind to the N-terminal Rel homologous and C-terminal domains of p65. Alternatively, gp110 might not disturb the association of p65 with nontransactivational subunit p50, but we showed it restrains activational phosphorylation (at Ser536) and nuclear translocation of p65, which we also found to be executed by the C-terminal cytoplasmic region of gp110. Altogether, these data suggest that the surface protein gp110 may be a vital component for EBV to antagonize the host's innate immune response, which is also helpful for revealing the infectivity and pathogenesis of EBV.

Effect of Vaccination Time Intervals on SARS-COV-2 Omicron Variant Strain Infection in Guangzhou: A Real-World Matched Case-Control Study.

In April 2022, a COVID-19 outbreak caused by the Omicron variant emerged in Guangzhou. A case-control study was conducted to explore the relationship between vaccination intervals and SARS-CoV-2 infection in the real world. According to the vaccination dose and age information of the cases, a 1:4 matched case-control sample was established, finally including n = 242 for the case group and n = 968 for the control group. The results indicated that among the participants who received three vaccine doses, those with an interval of more than 300 days between the receipt of the first vaccine dose and infection (or the first contact with a confirmed case) were less likely to be infected with SARS-CoV-2 than those with an interval of less than 300 days (OR = 0.67, 95% CI = 0.46-0.99). After age-stratified analysis, among participants aged 18-40 years who received two doses of vaccine, those who received the second dose more than 30 days after the first dose were less likely to be infected with SARS-CoV-2 (OR = 0.53, 95% CI = 0.30-0.96). Our findings suggest that we need to extend the interval between the first dose and the second dose and further explore the optimal interval between the first and second and between the second and third doses in order to improve vaccine efficacy.

Zinc and COVID-19: Immunity, Susceptibility, Severity and Intervention.

During the coronavirus disease 2019 (COVID-19) pandemic and continuing emergence of viral mutants, there has been a lack of effective treatment methods. Zinc maintains immune function, with direct and indirect antiviral activities. Zinc nutritional status is a critical factor in antiviral immune responses. Importantly, COVID-19 and zinc deficiency overlap in high-risk population. Hence, the potential effect of zinc as a preventive and adjunct therapy for COVID-19 is intriguing. Here, this review summarizes the immune and antiviral function of zinc, the relationship between zinc levels, susceptibility, and severity of COVID-19, and the effect of zinc supplementation on COVID-19. Existing studies have confirmed that zinc deficiency was associated with COVID-19 susceptibility and severity. Zinc supplementation plays a potentially protective role in enhancing immunity, decreasing susceptibility, shortening illness duration, and reducing the severity of COVID-19. We recommend that zinc levels should be monitored, particularly in COVID-19 patients, and zinc as a preventive and adjunct therapy for COVID-19 should be considered for groups at risk of zinc deficiency to reduce susceptibility and disease severity.

Transplacental Transfer of Maternal Antibody against SARS-CoV-2 and Its Influencing Factors: A Review.

Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, the disease has rapidly become a global threat. The constant emergence of new variants has increased the difficulty of controlling this disease. Vaccination is still considered the most effective method to prevent COVID-19. Vaccination has expanded to include children aged 3-17 years old, and some countries have lowered the age of vaccination to 6 months (for example, the United States). However, children under 3 years old are still not able to be vaccinated in most countries. In this study, we summarize the COVID-19 vaccination status in pregnant women, comprehensively elaborate on the status of maternal immune response and maternal antibody transfer after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, and further analyze the possible influencing factors of maternal antibody transfer according to the currently available evidence on the topic. It was concluded that pregnant women develop an immune response and produce antibodies that can be transmitted through the placenta after vaccination, but more data are needed to determine the transfer rate and duration of these maternal antibodies and potential factors. The results provide a scientific basis for studying the protective effect of maternal antibodies on infants, formulating a vaccination strategy for pregnant women, and preventing SARS-CoV-2 infection in infants.

Effects of marginal zinc deficiency on learning and memory ability after birth.

Zinc deficiency during pregnancy and severe zinc deficiency after birth both impaired learning and memory ability, but the effects of marginal zinc deficiency (MZD) after birth on learning and memory are unclear. In the first experiment, 4-week-old male rats were randomly divided into three groups: the marginal zinc-deficient group (MZG, 10 mg kg-1, 1/3 RNI), normal zinc group (NZG, 30 mg kg-1, RNI), and paired zinc group (PZG, 30 mg kg-1). After a 4-week feeding period, the brain weight, brain coefficient, and serum zinc concentration were measured, and hippocampal proteomics analysis was performed. In the second experiment, 4-week-old male rats were fed the same diet for 8 weeks. In addition to the previously mentioned indicators, the Morris water maze results, brain pathology, post-translational modifications (PTMs) of hippocampal proteins, and the concentrations of indicators known to be related to learning and memory were analyzed. In both experiments, compared with those of the NZG, the food intake, body weight and serum zinc of the MZG were significantly decreased, and the brain weight was unchanged, but the brain coefficient was increased. Two hippocampal proteomics analyses and PTM screening showed that MZD did not change the expression and PTM of proteins. The brain pathology, learning, memory and the concentrations of indicators known to be related to learning and memory were not changed by MZD. Our study confirmed that marginal zinc deficiency (10 mg kg-1, 1/3 RNI) had no effect on the learning and memory abilities of rats after birth.

Qualitative and Quantitative Analysis of Six Fatty Acid Amides in 11 Edible Vegetable Oils Using Liquid Chromatography-Mass Spectrometry.

Fatty acid amides (FAAs) are endogenous lipid molecules that exhibit various physiological activities. FAAs are usually present at nanomolar levels in biological samples. In this study, a method for the qualitative and quantitative determination of six FAAs (linoleamide, linoleoyl ethanolamide, oleoyl ethanolamide, palmitic amide, oleamide, and octadecanamide) in edible vegetable oils was established. All six FAAs were detected in sesame, peanut, soybean (decolorized and non-decolorized), and blended oils; five in sunflower oil; four in rice oil; three in linseed and olive oils; and two in corn and canola oils. The total contents of FAAs were highest in sesame oil (104.88 ± 3.01 µg/mL), followed by peanut oil (34.96 ± 3.87 µg/mL), soybean oil (16.75 ± 1.27 µg/mL), and blended oil (13.33 ± 0.77 µg/mL), and the contents in the other edible vegetable oils were all <1.03 µg/mL. The concentrations of linoleoyl ethanolamide and oleoyl ethanolamide were highest in non-decolorized soybean oil, while the other four FAAs (linoleamide, palmitic amide, oleamide, and octadecanamide) showed the highest concentrations in sesame oil. The total contents of these FAAs in eight different oils were higher than those in biological fluids and tissue. Our study confirmed that edible vegetable oils are rich in FAAs, and provides reliable data for evaluating the nutritive value of vegetable oils.

The Molecular Mechanism of Herpes Simplex Virus 1 UL31 in Antagonizing the Activity of IFN-ß.

Virus infection triggers intricate signal cascade reactions to activate the host innate immunity, which leads to the production of type I interferon (IFN-I). Herpes simplex virus 1 (HSV-1), a human-restricted pathogen, is capable of encoding over 80 viral proteins, and several of them are involved in immune evasion to resist the host antiviral response through the IFN-I signaling pathway. Here, we determined that HSV-1 UL31, which is associated with nuclear matrix and is essential for the formation of viral nuclear egress complex, could inhibit retinoic acid-inducible gene I (RIG-I)-like receptor pathway-mediated interferon beta (IFN-ß)-luciferase (Luc) and (PRDIII-I)4-Luc (an expression plasmid of IFN-ß positive regulatory elements III and I) promoter activation, as well as the mRNA transcription of IFN-ß and downstream interferon-stimulated genes (ISGs), such as ISG15, ISG54, ISG56, etc., to promote viral infection. UL31 was shown to restrain IFN-ß activation at the interferon regulatory factor 3 (IRF3)/IRF7 level. Mechanically, UL31 was demonstrated to interact with TANK binding kinase 1 (TBK1), inducible IκB kinase (IKKi), and IRF3 to impede the formation of the IKKi-IRF3 complex but not the formation of the IRF7-related complex. UL31 could constrain the dimerization and nuclear translocation of IRF3. Although UL31 was associated with the CREB binding protein (CBP)/p300 coactivators, it could not efficiently hamper the formation of the CBP/p300-IRF3 complex. In addition, UL31 could facilitate the degradation of IKKi and IRF3 by mediating their K48-linked polyubiquitination. Taken together, these results illustrated that UL31 was able to suppress IFN-ß activity by inhibiting the activation of IKKi and IRF3, which may contribute to the knowledge of a new immune evasion mechanism during HSV-1 infection. IMPORTANCE The innate immune system is the first line of host defense against the invasion of pathogens. Among its mechanisms, IFN-I is an essential cytokine in the antiviral response, which can help the host eliminate a virus. HSV-1 is a double-stranded DNA virus that can cause herpes and establish a lifelong latent infection, due to its possession of multiple mechanisms to escape host innate immunity. In this study, we illustrate for the first time that the HSV-1-encoded UL31 protein has a negative regulatory effect on IFN-ß production by blocking the dimerization and nuclear translocation of IRF3, as well as promoting the K48-linked polyubiquitination and degradation of both IKKi and IRF3. This study may be helpful for fully understanding the pathogenesis of HSV-1.

[Molecular mechanism of Ganoderma against gastric cancer based on network pharmacology and experimental test].

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between ß-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. ß-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that ß-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.