RESUMEN
Debates surrounding the efficacy of influenza vaccination for survival benefits persist, and there is a lack of data regarding its duration of protection. A self-controlled case series (SCCS) and a 1:4 matched case-control study were conducted using the National Health Interview Survey (NHIS) and public-use mortality data from 2005 to 2018 in the United States. The SCCS study identified participants who received influenza vaccination within 12 months before the survey and subsequently died within 1 year of postvaccination. The matched case-control study paired participants who died during the influenza season at the time of survey with four survivors. Among 1167 participants in the SCCS study, there was a 46% reduction in all-cause mortality and a 43% reduction in cardiovascular mortality within 29-196 days of postvaccination. The greatest protection was observed during days 29-56 (all-cause mortality: RI: 0.19; 95% CI: 0.12-0.29; cardiovascular mortality: RI: 0.28; 95% CI: 0.14-0.56). Among 626 cases and 2504 controls included in the matched case-control study, influenza vaccination was associated with a reduction in all-cause mortality (OR: 0.74, 95% CI: 0.60-0.92) and cardiovascular mortality (OR: 0.64, 95% CI: 0.44-0.93) during the influenza season. This study highlights the importance of influenza vaccination in reducing the risks of all-cause and cardiovascular mortality, with effects lasting for approximately 6 months.
Asunto(s)
Enfermedades Cardiovasculares , Vacunas contra la Influenza , Gripe Humana , Vacunación , Humanos , Estudios de Casos y Controles , Vacunas contra la Influenza/administración & dosificación , Masculino , Femenino , Gripe Humana/mortalidad , Gripe Humana/prevención & control , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Persona de Mediana Edad , Anciano , Vacunación/estadística & datos numéricos , Adulto , Estados Unidos/epidemiología , Anciano de 80 o más Años , Adulto JovenRESUMEN
Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) is a distinctive member of the serinethreonine protein AGC kinase family and an effective kinase for cAMP signal transduction. In recent years, scuticociliate has caused a lot of losses in domestic fishery farming, therefore, we have carried out morphological and molecular biological studies. In this study, diseased guppies (Poecilia reticulata) were collected from an ornamental fish market, and scuticociliate Philaster apodigitiformis Miao et al., 2009 was isolated. In our prior transcriptome sequencing research, we discovered significant expression of the ß-PKA gene in P. apodigitiformis during its infection process, leading us to speculate its involvement in pathogenesis. A complete sequence of the ß-PKA gene was cloned, and quantified by quantitative reverse transcription-polymerase chain reaction to analyse or to evaluate the functional characteristics of the ß-PKA gene. Morphological identification and phylogenetic analysis based on small subunit rRNA sequence, infection experiments and haematoxylineosin staining method were also carried out, in order to study the pathological characteristics and infection mechanism of scuticociliate. The present results showed that: (1) our results revealed that ß-PKA is a crucial gene involved in P. apodigitiformis infection in guppies, and the findings provide valuable insights for future studies on scuticociliatosis; (2) we characterized a complete gene, ß-PKA, that is generally expressed in parasitic organisms during infection stage and (3) the present study indicates that PKA plays a critical role in scuticociliate when infection occurs by controlling essential steps such as cell growth, development and regulating the activity of the sensory body structures and the irritability system.
Asunto(s)
Acuicultura , Proteínas Quinasas Dependientes de AMP Cíclico , Enfermedades de los Peces , Filogenia , Poecilia , Animales , Poecilia/parasitología , Poecilia/genética , Enfermedades de los Peces/parasitología , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/genética , Infecciones por Cilióforos/parasitología , Infecciones por Cilióforos/veterinaria , Secuencia de AminoácidosRESUMEN
Hydroxyectoine is an important compatible solute that holds potential for development into a high-value chemical with broad applications. However, the traditional high-salt fermentation for hydroxyectoine production presents challenges in treating the high-salt wastewater. Here, we report the rational engineering of Halomonas salifodinae to improve the bioproduction of hydroxyectoine under lower-salt conditions. The comparative transcriptomic analysis suggested that the increased expression of ectD gene encoding ectoine hydroxylase (EctD) and the decreased expressions of genes responsible for tricarboxylic acid (TCA) cycle contributed to the increased hydroxyectoine production in H. salifodinae IM328 grown under high-salt conditions. By blocking the degradation pathway of ectoine and hydroxyectoine, enhancing the expression of ectD, and increasing the supply of 2-oxoglutarate, the engineered H. salifodinae strain HS328-YNP15 (ΔdoeA::PUP119-ectD p-gdh) produced 8.3-fold higher hydroxyectoine production than the wild-type strain and finally achieved a hydroxyectoine titer of 4.9 g/L in fed-batch fermentation without any detailed process optimization. This study shows the potential to integrate hydroxyectoine production into open unsterile fermentation process that operates under low-salinity and high-alkalinity conditions, paving the way for next-generation industrial biotechnology. KEY POINTS: ⢠Hydroxyectoine production in H. salifodinae correlates with the salinity of medium ⢠Transcriptomic analysis reveals the limiting factors for hydroxyectoine production ⢠The engineered strain produced 8.3-fold more hydroxyectoine than the wild type.
Asunto(s)
Aminoácidos Diaminos , Fermentación , Halomonas , Ingeniería Metabólica , Halomonas/genética , Halomonas/metabolismo , Ingeniería Metabólica/métodos , Aminoácidos Diaminos/biosíntesis , Aminoácidos Diaminos/metabolismo , Aminoácidos Diaminos/genética , Ciclo del Ácido Cítrico/genética , Perfilación de la Expresión Génica , Cloruro de Sodio/metabolismo , Salinidad , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Ácidos Cetoglutáricos/metabolismoRESUMEN
Tetrahymenosis is caused by the ciliated protozoan Tetrahymena and is responsible for serious economic losses to the aquaculture industry worldwide. However, information regarding the molecular mechanism leading to tetrahymenosis is limited. In previous transcriptome sequencing work, it was found that one of the two ß-tubulin genes in T. pyriformis was significantly expressed in infected fish, we speculated that ß-tubulin is involved in T. pyriformis infecting fish. Herein, the potential biological function of the ß-tubulin gene in Tetrahymena species when establishing infection in guppies was investigated by cloning the full-length cDNA of this T. pyriformis ß-tubulin (BTU1) gene. The full-length cDNA of T. pyriformis BTU1 gene was 1873 bp, and the ORF occupied 1134 bp, whereas 5' UTR 434 bp, and 3' UTR 305 bp whose poly (A) tail contained 12 bases. The predicted protein encoded by T. pyriformis BTU1 gene had a calculated molecular weight of 42.26 kDa and pI of 4.48. Moreover, secondary structure analysis and tertiary structure prediction of BTU1 protein were also conducted. In addition, morphology, infraciliature, phylogeny, and histopathology of T. pyriformis isolated from guppies from a fish market in Harbin were also investigated. Furthermore, qRT-PCR analysis and experimental infection assays indicated that the expression of BTU1 gene resulted in efficient cell proliferation during infection. Collectively, our data revealed that BTU1 is a key gene involved in T. pyriformis infection in guppies, and the findings discussed herein provide valuable insights for future studies on tetrahymenosis.
Asunto(s)
Poecilia , Tetrahymena pyriformis , Tetrahymena , Animales , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Tetrahymena/genética , Poecilia/genética , ADN Complementario/metabolismo , Tetrahymena pyriformis/genética , Tetrahymena pyriformis/metabolismo , ARN Mensajero/metabolismoRESUMEN
To the best of our knowledge, no previous study has quantitatively estimated the dynamics and cumulative susceptibility to influenza infections after the widespread lifting of COVID-19 public health measures. We constructed an imitated stochastic susceptible-infected-removed model using particle-filtered Markov Chain Monte Carlo sampling to estimate the time-dependent reproduction number of influenza based on influenza surveillance data in southern China, northern China, and the United States during the 2022-2023 season. We compared these estimates to those from 2011 to 2019 seasons without strong social distancing interventions to determine cumulative susceptibility during COVID-19 restrictions. Compared to the 2011-2019 seasons without a strong intervention with social measures, the 2022-2023 influenza season length was 45.0%, 47.1%, and 57.1% shorter in southern China, northern China, and the United States, respectively, corresponding to an 140.1%, 74.8%, and 50.9% increase in scale of influenza infections, and a 60.3%, 72.9%, and 45.1% increase in population susceptibility to influenza. Large and high-intensity influenza epidemics occurred in China and the United States in 2022-2023. Population susceptibility increased in 2019-2022, especially in China. We recommend promoting influenza vaccination, taking personal prevention actions on at-risk populations, and monitoring changes in the dynamic levels of influenza and other respiratory infections to prevent potential outbreaks in the coming influenza season.
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COVID-19 , Gripe Humana , Humanos , Estados Unidos/epidemiología , Gripe Humana/epidemiología , Gripe Humana/prevención & control , COVID-19/epidemiología , Estaciones del Año , Pandemias , China/epidemiologíaRESUMEN
Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.
Asunto(s)
Suspensión Trasera , Mitocondrias Cardíacas , Ratones , Animales , Mitocondrias Cardíacas/metabolismo , Dinámicas Mitocondriales/genética , Proteína X Asociada a bcl-2/metabolismo , Apoptosis/fisiología , Autofagia , Miocitos Cardíacos/metabolismoRESUMEN
More than 30 months into the novel coronavirus 2019 (COVID-19) pandemic, efforts to bring this prevalence under control have achieved tentative achievements in China. However, the continuing increase in confirmed cases worldwide and the novel variants imply a severe risk of imported viruses. High-intensity non-pharmaceutical interventions (NPIs) are the mainly used measures of China's early response to COVID-19, which enabled effective control in the first wave of the epidemic. However, their efficiency is relatively low across China at the current stage. Therefore, this study focuses on whether measurable meteorological variables be found through global data to learn more about COVID-19 and explore flexible controls. This study first examines the control measures, such as NPIs and vaccination, on COVID-19 transmission across 189 countries, especially in China. Subsequently, we estimate the association between meteorological factors and time-varying reproduction numbers based on the global data by meta-population epidemic model, eliminating the aforementioned anthropogenic factors. According to this study, we find that the basic reproduction number of COVID-19 transmission varied wildly among Köppen-Geiger climate classifications, which is of great significance for the flexible adjustment of China's control protocols. We obtain that in southeast China, Köppen-Geiger climate sub-classifications, Cwb, Cfa, and Cfb, are more likely to spread COVID-19. In August, the RSIM of Cwb climate subclassification is about three times that of Dwc in April, which implies that the intensity of control efforts in different sub-regions may differ three times under the same imported risk. However, BSk and BWk, the most widely distributed in northwest China, have smaller basic reproduction numbers than Cfa, distributed in southeast coastal areas. It indicates that northwest China's control intensity could be appropriately weaker than southeast China under the same prevention objectives.
RESUMEN
Seed yield, determined mainly by seed numbers and seed weight, is the primary target of soybean breeding. Identifying the genes underlying yield-related traits is of great significance. Through joint linkage mapping and a genome-wide association study for 100-seed weight, we cloned GmGA3ox1, a gene encoding gibberellin 3ß-hydroxylase, which is the key enzyme in the gibberellin synthesis pathway. Genome resequencing identified a beneficial GmGA3ox1 haplotype contributing to high seed weight, which was further confirmed by soybean transformants. CRISPR/Cas9-generated gmga3ox1 mutants showed lower seed weight, but promoted seed yield by increasing seed numbers. The gmga3ox1 mutants reduced gibberellin biosynthesis while enhancing photosynthesis. Knockout of GmGA3ox1 resulted in the upregulation of numerous photosynthesis-related genes, particularly the GmRCA family encoding ribulose-1,5-bispho-sphate carboxylase-oxygenase (Rubisco) activases. The basic leucine zipper transcription factors GmbZIP97 and GmbZIP159, which were both upregulated in the gmga3ox1 mutants and induced by the gibberellin synthesis inhibitor uniconazole, could bind to the promoter of GmRCAß and activate its expression. Analysis of genomic sequences with over 2700 soybean accessions suggested that GmGA3ox1 is being gradually utilized in modern breeding. Our results elucidated the important role of GmGA3ox1 in soybean yield. These findings reveal important clues for future high-yield breeding in soybean and other crops.
Asunto(s)
Estudio de Asociación del Genoma Completo , Glycine max , Regulación hacia Abajo , Giberelinas/metabolismo , Oxigenasas de Función Mixta , Fotosíntesis , Fitomejoramiento , Sitios de Carácter Cuantitativo/genética , Semillas/genética , Glycine max/metabolismoRESUMEN
The conventional fabrication methods (for example, melting and powder metallurgy) of bulk thermoelectric materials are time- and energy-consuming, which restrict their large-scale application. In this work, ultra-fast self-propagating synthesis under a high-gravity field was used to prepare SnTe bulks, which shortened the synthesis time from several days to a few seconds. The grain growth was suppressed and some small pores were reserved in the matrix during the ultra-fast solidification process. The increased grain boundaries and pores (nanoscale to micron scale) enhanced phonon scattering, which greatly decreased the lattice thermal conductivity. The obtained minimum lattice thermal conductivity is 0.81 W m-1 K-1, and the maximum zT value is 0.5 (873 K), which is comparable to the best reported results of the undoped SnTe alloy. The ultra-fast non-equilibrium synthesis technique opens up new possibilities to prepare high-efficiency bulk thermoelectric materials with reduced time and energy consumption.
RESUMEN
BACKGROUND: Current methods for cervical cancer screening result in an increased number of referrals and unnecessary diagnostic procedures. This study aimed to develop and evaluate a more accurate model for cervical cancer screening. METHODS: Multiple predictors including age, cytology, high-risk human papillomavirus (hrHPV) DNA/mRNA, E6 oncoprotein, HPV genotyping, and p16/Ki-67 were used for model construction in a cross-sectional population including women with normal cervix (N = 1085), cervical intraepithelial neoplasia (CIN, N = 279), and cervical cancer (N = 551) to predict CIN2+ or CIN3+. A base model using age, cytology, and hrHPV was calculated, and extended versions with additional biomarkers were considered. External validations in two screening cohorts with 3-year follow-up were further conducted (NCohort-I = 3179, NCohort-II = 3082). RESULTS: The base model increased the area under the curve (AUC, 0.91, 95% confidence interval [CI] = 0.88-0.93) and reduced colposcopy referral rates (42.76%, 95% CI = 38.67-46.92) compared to hrHPV and cytology co-testing in the cross-sectional population (AUC 0.80, 95% CI = 0.79-0.82, referrals rates 61.62, 95% CI = 59.4-63.8) to predict CIN2+. The AUC further improved when HPV genotyping and/or E6 oncoprotein were included in the base model. External validation in two screening cohorts further demonstrated that our models had better clinical performances than routine screening methods, yielded AUCs of 0.92 (95% CI = 0.91-0.93) and 0.94 (95% CI = 0.91-0.97) to predict CIN2+ and referrals rates of 17.55% (95% CI = 16.24-18.92) and 7.40% (95% CI = 6.50-8.38) in screening cohort I and II, respectively. Similar results were observed for CIN3+ prediction. CONCLUSIONS: Compared to routine screening methods, our model using current cervical screening indicators can improve the clinical performance and reduce referral rates.
Asunto(s)
Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Estudios Transversales , Detección Precoz del Cáncer , Femenino , Humanos , Tamizaje Masivo , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiologíaRESUMEN
Ectoine and hydroxyectoine as typical representatives of compatible solutes are not only essential for extremophiles to survive in extreme environments, but also widely used in cosmetic and medical industries. Ectoine was traditionally produced by Halomonas elongata through a "bacterial milking" process, of which the marked feature is using a high-salt medium to stimulate ectoine biosynthesis and then excreting ectoine into a low-salt medium by osmotic shock. The optimal hydroxyectoine production was achieved by optimizing the fermentation process of Halomonas salina. However, high-salinity broth exacerbates the corrosion to fermenters, and more importantly, brings a big challenge to the subsequent wastewater treatment. Therefore, increasing attention has been paid to reducing the salinity of the fermentation broth but without a sacrifice of ectoine/hydroxyectoine production. With the fast development of functional genomics and synthetic biology, quite a lot of progress on the bioproduction of ectoine/hydroxyectoine has been achieved in recent years. The importation and expression of an ectoine producing pathway in a non-halophilic chassis has so far achieved the highest titer of ectoine (~ 65 g/L), while rational flux-tuning of halophilic chassis represents a promising strategy for the next-generation of ectoine industrial production. However, efficient conversion of ectoine to hydroxyectoine, which could benefit from a clearer understanding of the ectoine hydroxylase, is still a challenge to date.
Asunto(s)
Aminoácidos Diaminos/biosíntesis , Vías Biosintéticas , Fermentación , Halomonas/metabolismo , Aminoácidos Diaminos/análisis , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Reactores Biológicos/microbiología , Halomonas/genética , Presión Osmótica , SalinidadRESUMEN
OBJECTIVE: The Roche Cobas (Cobas) and BD Onclarity (Onclarity) human papillomavirus (HPV) assays are convenient, PCR-based, HPV DNA tests; currently, data on performance of Onclarity in Chinese women is limited. We aimed to evaluate the clinical performance of Onclarity for detecting cervical lesions in Chinese women. METHODS: In total, 1122 women were enrolled into this study. Exfoliated cervical cells were collected in PreservCyt medium and were tested using Cobas and Onclarity. Cytology and histology were interpreted by senior cytologists and a panel of pathologists, respectively, at Cancer Hospital, Chinese Academy of Medical Sciences. RESULTS: The assays showed excellent concordance for HPV16 (kappa = 0.91, 95% CI: 0.85-0.97) and for 12 other high-risk types (HPV31/33/35/39/45/51/52/56/58/59/66/68, kappa = 0.84, 95% CI: 0.78-0.90), and very good concordance for HPV18 (kappa = 0.75, 95% CI: 0.69-0.81). No difference for ≥CIN2 sensitivity was observed between Onclarity and Cobas (both 90.5%); and the Asunto(s)
Papillomaviridae/aislamiento & purificación
, Infecciones por Papillomavirus/virología
, Lesiones Precancerosas/virología
, Displasia del Cuello del Útero/virología
, Neoplasias del Cuello Uterino/virología
, Adulto
, Anciano
, China/epidemiología
, ADN Viral/análisis
, ADN Viral/genética
, Femenino
, Humanos
, Persona de Mediana Edad
, Papillomaviridae/genética
, Infecciones por Papillomavirus/epidemiología
, Lesiones Precancerosas/epidemiología
, Neoplasias del Cuello Uterino/epidemiología
, Adulto Joven
, Displasia del Cuello del Útero/epidemiología
RESUMEN
HPV-16 and -18 account for about 80% of cervical cancers. We evaluated the performance of HPV-16/18 oncoprotein to predict precancer and cancer in corresponding tissue biopsy specimens. 1,008 women attending cervical cancer screening program and 638 women referred to colposcopy with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from 4 hospitals were recruited (1,646 in total). All women were tested OncoE6 (AVC), Liquid-Based Cytology (Hologic) and cobas HPV test (Roche). Colposcopy was performed on women with any abnormal results. The final diagnoses were based on a consensus panel review of the histology. There were 919 normal, 69 CIN1, 53 CIN2, 91 CIN3,474 squamous cell carcinoma(SCC) and 40 adenocarcinoma (ADC) cases, the prevalence of OncoE6 was 1.7%, 10.1%, 13.2%, 44.0%, 80.4% and 65.0%, respectively. The percent positive for cobas was higher than that of OncoE6 in detection of HPV16/18 in entire population (p < 0.001). However, the disparity of positive rate between these two tests became tiny among cervical cancer patients (CIN2: 26.4% vs. 13.2%, CIN3: 73.6% vs. 44.0%, SCC: 84.0% vs. 80.4%, ADC: 67.5% vs. 65.0%). OncoE6 was less sensitive than cobas (73.9% vs. 93.6%, p < 0.001), but more specific (97.1% vs. 75.4%, p < 0.001) for CIN3+ in entire population; OncoE6 yielded a sensitivity of 77.7% and a specificity of 91.0% for CIN3+ among cobas positive women, which can reduce nearly half of the colposcopy referral numbers. OncoE6 can be considered as a useful tool for cervical cancer screening and a potential powerful biomarker for HPV positive triage.
Asunto(s)
Pruebas Genéticas/normas , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Triaje , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adenocarcinoma/virología , Adulto , Anciano , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Colposcopía , Estudios Transversales , ADN Viral/análisis , Detección Precoz del Cáncer/métodos , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Biopsia Líquida , Persona de Mediana Edad , Prueba de Papanicolaou , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
BACKGROUND: 2-phenylethanol (2-PE) is an important aromatic compound with a lovely rose-like scent. Saccharomyces cerevisiae is a desirable microbe for 2-PE production but its natural yield is not high, and one or two crucial genes' over-expression in S. cerevisiae did not improve 2-PE greatly. RESULTS: A new metabolic module was established here, in which, permease Gap1p for L-phenylalanine transportation, catalytic enzymes Aro8p, Aro10p and Adh2p in Ehrlich pathway respectively responsible for transamination, decarboxylation and reduction were assembled, besides, glutamate dehydrogenase Gdh2p was harbored for re-supplying another substrate 2-oxoglutarate, relieving product glutamate repression and regenerating cofactor NADH. Due to different promoter strengths, GAP1, ARO8, ARO9, ARO10, ADH2 and GDH2 in the new modularized YS58(G1-A8-A10-A2)-GDH strain enhanced 11.6-, 15.4-, 3.6-, 17.7-, 12.4- and 7.5-folds respectively, and crucial enzyme activities of aromatic aminotransferases and phenylpyruvate decarboxylase were 4.8- and 7-folds respectively higher than that of the control. CONCLUSIONS: Under the optimum medium and cell density, YS58(G1-A8-A10-A2)-GDH presented efficient 2-PE synthesis ability with ~ 6.3 g L-1 of 2-PE titer in 5-L fermenter reaching 95% of conversation ratio. Under fed-batch fermentation, 2-PE productivity at 24 h increased 29% than that of single-batch fermentation. Metabolic modularization with promoter strategy provides a new prospective for efficient 2-PE production.
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Fermentación , Ingeniería Metabólica/métodos , Alcohol Feniletílico/metabolismo , Regiones Promotoras Genéticas , Saccharomyces cerevisiae/metabolismo , Reactores Biológicos , Carboxiliasas/genética , Carboxiliasas/metabolismo , Microbiología Industrial , Ácidos Cetoglutáricos/farmacología , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Redes y Vías Metabólicas , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Transaminasas/genética , Transaminasas/metabolismoRESUMEN
Development of new drugs is one of the solutions to fight against the existing antimicrobial resistance threat. Cinnamaldehyde-amino acid Schiff base compounds, are newly discovered compounds that exhibit good antibacterial activity against gram-positive and gram-negative bacteria. Quantitative structureâ»activity relationship (QSAR) methodology was applied to explore the correlation between antibacterial activity and compound structures. The two best QSAR models showed R² = 0.9354, F = 57.96, and s² = 0.0020 against Escherichia coli, and R² = 0.8946, F = 33.94, and s² = 0.0043 against Staphylococcus aureus. The model analysis showed that the antibacterial activity of cinnamaldehyde compounds was significantly affected by the polarity parameter/square distance and the minimum atomic state energy for an H atom. According to the best QSAR model, the screening, synthesis, and antibacterial activity of three cinnamaldehyde-amino acid Schiff compounds were reported. The experiment value of antibacterial activity demonstrated that the new compounds possessed excellent antibacterial activity that was comparable to that of ciprofloxacin.
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Acroleína/análogos & derivados , Antibacterianos/síntesis química , Bases de Schiff/síntesis química , Acroleína/química , Antibacterianos/química , Antibacterianos/farmacología , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad Cuantitativa , Bases de Schiff/química , Bases de Schiff/farmacología , Staphylococcus aureus/efectos de los fármacosRESUMEN
The purpose of this study was to synthesize hydrophilic cinnamaldehyde Schiff base compounds and investigate those bioactivity. A total of 24 Schiff base compounds were synthesized using a simple approach with 3 cinnamaldehyde derivates and 8 amino acids as raw materials. The structures of synthesized compounds were confirmed using FTIR, (1)HNMR, HRMS purity and melting point. The antimicrobial activities of new compounds were evaluated with fluconazole and ciprofloxacin as the control against Aspergillus niger, Penicillium citrinum, Escherichia coli and Staphylococcus aureus. Findings show that major compounds exhibited significant bioactivity. Results from the structure-activity relationship suggest that both -p-Cl on benzene ring of cinnamaldehyde and the number of -COOK of amino acid salts significantly contributed to antimicrobial activity.
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Acroleína/análogos & derivados , Aminoácidos/química , Antiinfecciosos/síntesis química , Bases de Schiff/química , Acroleína/química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Aspergillus niger/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Penicillium/efectos de los fármacos , Bases de Schiff/síntesis química , Bases de Schiff/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Alzheimer's disease (AD) is a common neurodegenerative disease resulting in progressive dementia, and is a principal cause of dementia among older adults. Folate acts through one-carbon metabolism to support the methylation of multiple substrates. We hypothesized that folic acid supplementation modulates DNA methyltransferase (DNMT) activity and may alter amyloid ß-peptide (Aß) production in AD. Mouse Neuro-2a cells expressing human APP695 were incubated with folic acid (2.8-40 µmol/L), and with or without zebularine (the DNMT inhibitor). DNMT activity, cell viability, Aß and DNMTs expression were then examined. The results showed that folic acid stimulated DNMT gene and protein expression, and DNMT activity. Furthermore, folic acid decreased Aß protein production, whereas inhibition of DNMT activity by zebularine increased Aß production. The results indicate that folic acid induces methylation potential-dependent DNMT enzymes, thereby attenuating Aß production.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Ácido Fólico/uso terapéutico , Enfermedad de Alzheimer/enzimología , Animales , Línea Celular Tumoral , Metilación de ADN/efectos de los fármacos , Metilasas de Modificación del ADN/metabolismo , Activación Enzimática/efectos de los fármacos , Ácido Fólico/farmacología , Humanos , RatonesRESUMEN
Volcanic lava is an excellent model of primary succession, in which basalt-associated microorganisms drive the cycling of different elements such as nitrogen, carbon, and other nutrients. Microbial communities in volcanic soils are of particular interest for study on the emergence and evolution of life within special and extreme conditions. The initial processes of colonization and subsequent rock weathering by microbial communities are still poorly understood. We analyzed the soil bacterial and fungal communities and diversities associated with lava (LBL) and kipuka (BK) sites in Wudalianchi using 16S and ITS rRNA Illumina Miseq sequencing techniques. The results showed that soil physical and chemical properties (pH, MC, TOC, TN, TP, AP, DOC, and DON) significantly differed between LBL and BK. The Shannon, Ace, and Pd indexes of fungi in the two sites showed a significant difference (p < 0.05). The dominant bacterial phyla forming communities at LBL and BK sites were Acidobacteria, Proteobacteria, Actinobacteria, and Basidiomycota, and their differences were driven by Gemmatimonadetes and Verrucomicrobia. The dominant fungal phyla of LBL and BK sites were Ascomycota, Zygomycota, and Rozellomcota, which differed significantly between the two sites. The microbial communities showed extremely significant differences (p < 0.05), with MC, pH, and nitrogen being the main influencing factors according to RDA/CCA and correlation analysis. Microbial functional prediction analysis across the two sites showed that the relative abundance of advantageous functional groups was significantly different (p < 0.05). The combined results drive us to conclude that the volcanic soil differences in the deposits appear to be the main factor shaping the microbial communities in Wudalianchi (WDLC) volcanic ecosystems.
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The ongoing transmission of mpox in specific countries and regions necessitates urgent action. It is essential to implement targeted containment strategies that concentrate on high-risk populations and critical locations, such as college campuses, to effectively curb the spread of mpox. This study is dedicated to evaluating the performance of various vaccination and quarantine strategies in curbing the spread of mpox and estimating the outbreak risk. To accomplish this, we constructed a stochastic, agent-based, discrete-time susceptible-latent-infectious-recovered (SLIR) model, to examine mpox transmission on a simulated college campus. Our findings reveal that relying solely on PEP is insufficient in containing mpox effectively. To bolster the population immunity and protect the vulnerable, pre-exposure vaccination among high-risk populations prior to an outbreak is imperative. Our study demonstrates that a pre-exposure vaccination rate of 50% in high-risk populations can led to a remarkable 74.2% reduction of infections. This translated to a mere 1.0% cumulative infection incidence in the overall population. In cases where the desired vaccination coverage is not attainable, enhancing case detection and isolation measures can serve as an effective emergency response to contain mpox outbreaks. For pre-exposure vaccination coverage of 20% or lower, a 40% isolation ratio is necessary to keep the cumulative number of infections in check. However, when the coverage exceeds 30%, a reduced isolation ratio of 20% becomes sufficient to manage the outbreak effectively. These insights underscore the importance of strategic pre-exposure vaccination in conjunction with robust surveillance and isolation protocols to safeguard public health and prevent the escalation of mpox outbreaks.
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In order to understand the role of microorganisms in litter decomposition and the nutrient cycle in volcanic forest ecosystems, the dominant forest species Larix gmelinii in the volcanic lava plateau of the Wudalianchi volcano was considered as the research object. We analyzed the response of bacterial community structure and diversity to litter decomposition for 1 year, with an in situ decomposition experimental design using litter bags and Illumina MiSeq high-throughput sequencing. The results showed that after 365 days, the litter quality residual rate of Larix gmelinii was 77.57%, and the litter N, P, C:N, C:P, and N:P showed significant differences during the decomposition period (p < 0.05). The phyla Cyanobacteria and the genus unclassified_o_Chloroplast were the most dominant groups in early decomposition (January and April). The phyla Proteobacteria, Actinobacteriota, and Acidobacteriota and the genera Massilia, Pseudomonas, and Sphingomona were higher in July and October. The microbial communities showed extremely significant differences during the decomposition period (p < 0.05), with PCoa, RDA, and litter QRR, C:P, and N as the main factors driving litter bacteria succession. Microbial functional prediction analysis showed that Chloroplasts were the major functional group in January and April. Achemoheterotrophy and aerobic chemoheterotrophy showed a significant decrease as litter decomposition progressed.