Nod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 ...undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIIND
-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIIND
-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIIND
. Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells-a process that is greatly enhanced by NLRP1-FIIND
which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 Å, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes.
There has been significant interest in the photosensitivity, or photo-resistance, of Japanese rice cultivars, which synthesize tocols (Vitamin E), a class of phytochemicals including tocol ...derivatives tocopherol (T) and tocotrienol (T3). In the present study, the distribution of tocols in the leaves, seeds, stems, and roots of six Japanese rice cultivars was investigated. The relationship between the different tocols in cultivars and their ultraviolet B sensitivity index (USB–SI) was analyzed. The leaves contained the highest average total amount of tocols at 230 μg.fresh-g−1, followed by seeds, stems, and roots. In leaves and stems, the most abundant component was α-T which was more than 85%. On the other hand, the tocols in seeds were 38% δ-T3, 32% α-T, and 20% α-T3. The tocols in roots were 55% α-T, 14% γ-T, and 13% δ-T3. The total tocol content in four plant parts exhibited a negative correlation (P < 0.05) in stem and root, and a negative relationship (r < −0.70) with the UVB-SI of the cultivars, suggesting that the total tocol contents were closely related to the resistance to UVB in Japanese rice plants.
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•There was a difference in tocol composition in plant parts of Japanese rice cultivars.•The total tocols were decreased in order of leaves, seeds, stems, and roots.•In leaves and stems, the highest component of tocol was α-T (>85%).•In seeds, T3 components of α-T3 and γ-T3 were increased to 20% and 38%.•The tocols of the cultivars in four parts were negatively correlated with UBV-SI
Inland aquaculture contributed by three major fish groups, including carps, tilapias, and catfish plays a vital role in global food security and nutrition, particularly in low and middle‐income ...countries. However, the sustainable development of this sector is hampered by disease epidemics, especially those caused by bacteria such as Aeromonas species. At least eight pathogenic motile Aeromonas species (A. hydrophila, A. veronii, A. jandaei, A. caviae, A. sobria, A. bestiarum, A. dhakensis and A. schubertii) have been reported in aquaculture with some causing up to 100% mortality during disease outbreaks. Simultaneously, emerging multidrug‐resistant Aeromonas due to a long‐inappropriate use of antibiotics is alarming and highlights a global public health concern and negative socioeconomic impacts. Here, we provide a comprehensive overview of motile Aeromonas infections, antibiotic use and antimicrobial resistance of Aeromonas species. This contribution also highlights the non‐antibiotic approaches (the solutions for preventing or treating of bacterial diseases without resorting to antibiotic use) to control motile Aeromonas infections. In addition to the current state of knowledge and limitations of each prophylaxis/therapy, perspectives for future research are discussed critically, including oral/immersion multivalent vaccines, microencapsulated synbiotics, exogenous metabolites, and novel lytic bacteriophage cocktails. Some emerging applicable nanotechnology themes such as nanovaccines, nanobioactive compounds, and nanobubbles are also included in this review. In summary, combating motile Aeromonas infections in aquaculture, including multidrug‐resistant aeromonads, as well as other bacterial diseases, is a lengthy battle that requires a strategic combination of multiple non‐antibiotic approaches coherent with the One Health philosophy.
Tilapia Lake Virus (TiLV) is reported as a threat to tilapia aquaculture in 16 countries on four continents with outbreaks causing up to 90% mortality. This research is one of the first studies on ...TiLVs from Vietnam. We propagated successfully one TiLV isolate HB196‐VN‐2020 from a diseased tilapia sample using an E‐11 cell line and evaluated its virulence in two different weights of red hybrid tilapia and three serial 10‐fold diluted viral titers. Smaller fish (4.5 ± 1.98 g) were proved to be more susceptible to TiLV infection at the viral titre of 9.1 × 105 TCID50 fish−1 than larger fish (20.8 ± 7.5 g) with the mortalities of 92.5% and 12.5%, respectively. Reassortant detection analysis revealed seven potential reassortment events among 23 TiLV genomes, indicating the mixed infection of multiple TiLV isolates at the farms and the fish movement among different regions. Seven maximum likelihood phylogenetic trees based on the individual segments or the concatenated coding regions of some segments showed the genetically distant relationship of the Southern Vietnamese isolate RIA2‐VN‐2019 with the 21 reference isolates, and suggest the different origins of two Vietnamese TiLV isolates (RIA2‐VN‐2019 and HB196‐VN‐2020). However, additional sequences from various sampling locations and times are required to better understand the impacts of genetic diversity and reassortments on the evolution, migration and natural selection of TiLVs in Vietnam and other countries.
Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited.
We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an ...infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing.
Between 11th–25th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8–33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.043). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms.
Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals.
Wellcome and NIH/NIAID
The aim of this study was to estimate the cost-effectiveness of a very low-protein diet (VLPD) supplemented with ketoanalogues of essential amino acids compared with a conventional low-protein diet ...(LPD) in Vietnam.
The study was conducted from payer (base case), patient, and societal perspectives. A Markov model simulated costs and quality-adjusted life-years (QALYs) for patients with chronic kidney disease stage 4 or 5 (CKD4+) who were followed up during their lifetimes. Patients received a VLPD (0.3- to 0.4-g/kg/d diet) supplemented with ketoanalogues (5 kg/d 1 tablet) versus LPD (0.6 g/kg/d, mixed proteins). In each model cycle, patient transitions among the health states—CKD4+ (nondialysis), dialysis, and death—were based on transition probabilities taken from the published literature. The time horizon covered the cohort's lifetime. Utilities and costs were estimated from literature review and projected for the lifespan considered in the model. Probabilistic and deterministic sensitivity analyses were performed.
The ketoanalogue-supplemented VLPD increased survival and QALYs compared with the LPD. From a payer's perspective, total cost of care in Vietnam was ₫216,854,268 (€8684/$9242) per patient with LPD versus ₫200,928,819 (€8046/$8563) per patient with a supplemented VLPD (sVLPD) (difference, −₫15,925,449 −€638/−$679). From a patient's perspective, total cost of care in Vietnam was ₫217,872,043 (€8724/$9285) per patient with LPD versus ₫116,015,672 (€4646/$4944) per patient with sVLPD (difference, -₫101,856,371 −€4,079/ −$4341). From a societal perspective, total cost of care in Vietnam was ₫434,726,312 (€17,408/−$18,527) per patient with LPD versus ₫316,944,491 (€12,692/ $13,508) per patient with sVLPD (difference, -₫117,781,820 −€4716 €/$5020).
Ketoanalogue-supplemented VLPD lowered costs compared with LPD in all 3 perspectives considered.
The relationship between age and seroprevalence can be used to estimate the annual attack rate of an infectious disease. For pathogens with multiple serologically distinct strains, there is a need to ...describe composite exposure to an antigenically variable group of pathogens. In this study, we assay 24,402 general-population serum samples, collected in Vietnam between 2009 to 2015, for antibodies to eleven human influenza A strains. We report that a principal components decomposition of antibody titer data gives the first principal component as an appropriate surrogate for seroprevalence; this results in annual attack rate estimates of 25.6% (95% CI: 24.1% - 27.1%) for subtype H3 and 16.0% (95% CI: 14.7% - 17.3%) for subtype H1. The remaining principal components separate the strains by serological similarity and associate birth cohorts with their particular influenza histories. Our work shows that dimensionality reduction can be used on human antibody profiles to construct an age-seroprevalence relationship for antigenically variable pathogens.
We studied the immunogenicity of the Oxford-AstraZeneca vaccine in health-care workers of a major infectious diseases hospital in Vietnam. We measured neutralizing antibodies before and 14 days after ...each dose, and at day 28 and month 3 after dose 1. A total of 554 workers (136 men and 418 women; age range, 22-71 years; median age, 36 years) participated with the study. Of the 144 participants selected for follow-up after dose 1, 104 and 94 gave blood for antibody measurement at weeks 6 and 8, and at month 3 after dose 1, respectively. The window time between the two doses was 6 weeks. At baseline, none had detectable neutralizing antibodies. After dose 1, the proportion of participants with detectable neutralizing antibodies increased from 27.3% (151 of 554) at day 14 to 78.0% (432 of 554) at day 28. Age correlated negatively with the development and the levels of neutralizing antibodies. However, at day 28, these differences were less profound, and women had a greater seroconversion rate and greater levels of neutralizing antibodies than men. After dose 2, these age and gender associations were not observable. In addition, the proportion of study participants with detectable neutralizing antibodies increased from 70.2% (73 of 104) before dose 2 (week 6, after dose 1) to 98.1% (102 of 104) 14 days later. At month 3, neutralizing antibodies decreased and 94.7% (89 of 94) of the study participants remained seropositive. The Oxford-AstraZeneca COVID-19 vaccine is immunogenic in Vietnamese health-care workers. These data are critical to informing the deployment of the COVID-19 vaccine in Vietnam and in Southeast Asia, where vaccination coverage remains inadequate.
In this work, the central composite design in response surface methodology by the Design-Expert software was used for optimizing the removal of Pb(II) ions from aqueous solution by pine leaves (Pinus ...kesiya). Effects of pHsolution, adsorption time and initial Pb(II) ions concentration on adsorption capacity were investigated. Experimental data were fitted by using five nonlinear isotherm models including Langmuir, Freundlich, Sips, Temkin and Dubinin–Radushkevich. The maximum Pb(II) adsorption capacity (qmax) estimated from the Langmuir isotherm model was 31.04 mg/g, which is higher than other biomaterials such as barley straw, Cucumis sativus peel, coconut tree sawdust, etc. Kinetic studies indicated that the uptake of Pb(II) occurred on the Elovich model within two stages. Thermodynamic studies at different temperatures showed the biosorption to be endothermic and spontaneous. The study concluded that P. kesiya can be a good adsorbent for removing Pb(II) from aqueous solution.
Uterine arteriovenous malformation (UAVM) is a rare condition and is classified as either congenital or acquired UAVM. Patients with UAVMs usually experience miscarriages or recurrent menorrhagia. ...Ultrasound is used for the initial estimation of UAVMs. Computed tomography and magnetic resonance imaging are noninvasive and valuable methods that provide good compatibility with digital subtraction angiography to support the diagnosis and treatment of UAVM. Timely diagnosis is crucial to provide appropriate treatment for alleviating complications. This article presents a pictorial and literature review of the current evidence of the diagnosis and management of UAVM.
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