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BACKGROUND: Venom glands play a key role in the predation and defense strategies of almost all spider groups. However, the spider family Uloboridae lacks venom glands and has evolved an adaptive strategy: they excessively wrap their prey directly with spider silk instead of paralyzing it first with toxins. This shift in survival strategy is very fascinating, but the genetic underpinnings behind it are poorly understood. RESULTS: Spanning multiple spider groups, we conducted multiomics analyses on Octonoba sinensis and described the adaptive evolution of the Uloboridae family at the genome level. We observed the coding genes of myosin and twitchin in muscles are under positive selection, energy metabolism functions are enhanced, and gene families related to tracheal development and tissue mechanical strength are expanded or emerged, all of which are related to the unique anatomical structure and predatory behavior of spiders in the family Uloboridae. In addition, we also scanned the elements that are absent or under relaxed purifying selection, as well as toxin gene homologs in the genomes of 2 species in this family. The results show that the absence of regions and regions under relaxed selection in these spiders' genomes are concentrated in areas related to development and neurosystem. The search for toxin homologs reveals possible gene function shift between toxins and nontoxins and confirms that there are no reliable toxin genes in the genome of this group. CONCLUSIONS: This study demonstrates the trade-off between different predation strategies in spiders, using either chemical or physical strategy, and provides insights into the possible mechanism underlying this trade-off. Venomless spiders need to mobilize multiple developmental and metabolic pathways related to motor function and limb mechanical strength to cover the decline in adaptability caused by the absence of venom glands.
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Evolução Molecular , Aranhas , Animais , Aranhas/genética , Aranhas/metabolismo , Venenos de Aranha/genética , Comportamento Predatório , Filogenia , Evolução Biológica , Genoma , Seleção Genética , Adaptação Fisiológica/genéticaRESUMO
The skin mucus of fish is equipped with immunological and antimicrobial peptides that confer protection against invading pathogens. The skin mucus has been studied in fish however information regarding its immunological roles in bacterial infection is rare. This study highlighted the proteins and peptides in the skin mucus of Obscure puffer Takifugu obscurus that quantitatively altered against Aeromonas hydrophila infection. We infected the fish through bath immersion, intraperitonially, and treated with PBS (control) then compared the level of proteins in the skin mucus among the groups using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The Tandem Mass Tag (TMT) based quantification showed that 4896 proteins were Deferentially Quantified Proteins (DQPs), based on 19,751 unique peptides. Of which 170 were depleted (decreased in abundance) and 69 were abundant in comparison of Bath Treated (BT) vs Control (C) groups. Similarly, 76 DQPs were depleted and 70 were abundant in comparison of Treated (T) vs BT groups. Further, 126 DQPs were depleted, and 34 were abundant in comparison to T vs C groups. The DQPs we report were mostly immunological and were involved in unique biological functions and pathways. The interesting protein we report, where some of the proteins are for the first time in fish, shows the protein-rich structure of the mucus of fish, which may act as a biomarker to be targeted for bacterial disease therapy in fish and ultimately hint to the way of making resistance in fish against bacterial pathogens.
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The nitrogen (N) cycle is the foundation of the biogeochemistry on Earth and plays a crucial role in global climate stability. It is one of the most important nutrient cycles in high-altitude lakes. The biogeochemistry of nitrogen is almost entirely dependent on redox reactions mediated by microorganisms. However, the nitrogen cycling of microbial communities in the high-altitude saline lakes of the Qinghai-Tibet Plateau (QTP), the world's "third pole" has not been investigated extensively. In this study, we used a metagenomic approach to investigate the microbial communities in four high-altitude pristine saline lakes in the Altun mountain on the QTP. We observed that Proteobacteria, Bacteroidota, and Actinobacteriota were dominant in these lakes. We reconstructed 1,593 bacterial MAGs and 8 archaeal MAGs, 1,060 of which were found to contain nitrogen cycle related genes. Our analysis revealed that nitrite reduction, nitrogen fixation, and assimilatory nitrate reduction processes might be active in the lakes. Denitrification might be a major mechanism driving the potential nitrogen loss, while nitrification might be inactive. A wide variety of microorganisms in the lake, dominated by Proteobacteria, participate together in the nitrogen cycle. The prevalence of the dominant taxon Yoonia in these lakes may be attributed to its well-established nitrogen functions and the coupled proton dynamics. This study is the first to systematically investigate the structure and nitrogen function of the microbial community in the high-altitude pristine saline lakes in the Altun mountain on the QTP. As such, it contributes to a better comprehension of biogeochemistry of high-altitude saline lakes.
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TMEM16 proteins, which function as Ca2+activated Cl channels are involved in regulating a wide variety of cellular pathways and functions. The modulators of Cl channels can be used for the moleculebased treatment of respiratory diseases, cystic fibrosis, tumors, cancer, osteoporosis and coronavirus disease 2019. The TMEM16 proteins link Ca2+ signaling, cellular electrical activity and lipid transport. Thus, deciphering these complex regulatory mechanisms may enable a more comprehensive understanding of the physiological functions of the TMEM16 proteins and assist in ascertaining the applicability of these proteins as potential pharmacological targets for the treatment of a range of diseases. The present review examined the structures, functions and characteristics of the different types of TMEM16 proteins, their association with the pathogenesis of various diseases and the applicability of TMEM16 modulatorbased treatment methods.
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Anoctaminas , Proteínas de Transferência de Fosfolipídeos , Humanos , Proteínas de Transferência de Fosfolipídeos/metabolismo , Anoctaminas/metabolismo , Anoctaminas/genética , Animais , Cálcio/metabolismo , Canais de Cloreto/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , COVID-19/metabolismo , SARS-CoV-2/metabolismo , Terapia de Alvo Molecular , Sinalização do Cálcio/efeitos dos fármacosRESUMO
Introduction: Pseudomonas aeruginosa is present throughout nature and is a common opportunistic pathogen in the human body. Carbapenem antibiotics are typically utilized as a last resort in the clinical treatment of multidrug-resistant infections caused by P. aeruginosa. The increase in carbapenem-resistant P. aeruginosa poses an immense challenge for the treatment of these infections. Bacteriophages have the potential to be used as antimicrobial agents for treating antibiotic-resistant bacteria. Methods and Results: In this study, a new virulent P. aeruginosa phage, Phage_Pae01, was isolated from hospital sewage and shown to have broad-spectrum antibacterial activity against clinical P. aeruginosa isolates (83.6%). These clinical strains included multidrug-resistant P. aeruginosa and carbapenem-resistant P. aeruginosa. Transmission electron microscopy revealed that the phage possessed an icosahedral head of approximately 80 nm and a long tail about 110 m, indicating that it belongs to the Myoviridae family of the order Caudovirales. Biological characteristic analysis revealed that Phage_Pae01 could maintain stable activity in the temperature range of 4~ 60°C and pH range of 4 ~ 10. According to the in vitro lysis kinetics of the phage, Phage_Pae01 demonstrated strong antibacterial activity. The optimal multiplicity of infection was 0.01. The genome of Phage_Pae01 has a total length of 93,182 bp and contains 176 open reading frames (ORFs). The phage genome does not contain genes related to virulence or antibiotic resistance. In addition, Phage_Pae01 effectively prevented the formation of biofilms and eliminated established biofilms. When Phage_Pae01 was combined with gentamicin, it significantly disrupted established P. aeruginosa biofilms. Conclusion: We identified a novel P. aeruginosa phage and demonstrated its effective antimicrobial properties against P. aeruginosa in both the floating and biofilm states. These findings offer a promising approach for the treatment of drug-resistant bacterial infections in clinical settings.
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While single-cell technologies have greatly advanced our comprehension of human brain cell types and functions, studies including large numbers of donors and multiple brain regions are needed to extend our understanding of brain cell heterogeneity. Integrating atlas-level single-cell data presents a chance to reveal rare cell types and cellular heterogeneity across brain regions. Here we present the Brain Cell Atlas, a comprehensive reference atlas of brain cells, by assembling single-cell data from 70 human and 103 mouse studies of the brain throughout major developmental stages across brain regions, covering over 26.3 million cells or nuclei from both healthy and diseased tissues. Using machine-learning based algorithms, the Brain Cell Atlas provides a consensus cell type annotation, and it showcases the identification of putative neural progenitor cells and a cell subpopulation of PCDH9high microglia in the human brain. We demonstrate the gene regulatory difference of PCDH9high microglia between hippocampus and prefrontal cortex and elucidate the cell-cell communication network. The Brain Cell Atlas presents an atlas-level integrative resource for comparing brain cells in different environments and conditions within the Human Cell Atlas.
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BACKGROUND: Arthroscopy-assisted closed reduction and percutaneous internal fixation is a minimally invasive technique for medial malleolus fracture treatment. The purpose of the study was to assess the quality and functional outcomes of this technique. METHODS: Seventy-eight patients with combined medial malleolus fractures were treated with arthroscopy-assisted closed reduction and percutaneous screw fixation technique. The surgical procedure was described in detail; the clinical efficacy of this method was evaluated in terms of time of operation, postoperative complications, and fracture healing time; and functional outcomes were analyzed. RESULTS: All of the patients were followed up for a minimum of 12 months without complications of the medial malleolus wound, and all of the medial malleolus fractures healed within 6 to 8 weeks. At the last follow-up, the visual analog scale scores ranged from 0 to 3 and the American Orthopaedic Foot and Ankle Society ankle and hindfoot function scores ranged from 75 to 95. CONCLUSIONS: Arthroscopy-assisted closed reduction and percutaneous internal fixation makes the treatment of medial malleolus fractures less invasive compared with traditional surgical methods and allows simultaneous exploration and management of the articular surface.
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Fraturas do Tornozelo , Artroscopia , Fixação Interna de Fraturas , Humanos , Artroscopia/métodos , Fixação Interna de Fraturas/métodos , Masculino , Fraturas do Tornozelo/cirurgia , Feminino , Adulto , Pessoa de Meia-Idade , Parafusos Ósseos , Resultado do Tratamento , Consolidação da Fratura/fisiologia , Adulto Jovem , Estudos Retrospectivos , Redução Fechada/métodos , Idoso , Seguimentos , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
As the amount of metagenomic sequencing continues to increase, there is a growing need for tools that help biologists make sense of the data. Specifically, researchers are often interested in the potential of a microbial community to carry out a metabolic reaction, but this analysis requires knitting together multiple software tools into a complex pipeline. Thanos offers a user-friendly R package designed for the pathway-centric analysis and visualization of the functions encoded within metagenomic samples. It allows researchers to go beyond taxonomic profiles and find out, quantitatively, which pathways are prevalent in an environment, as well as comparing different environments in terms of their functional potential. The analysis is based on the sequencing depth of the genes of interest, either in the metagenome-assembled genomes (MAGs) or in the assembled reads (contigs), using a normalization strategy that enables comparison across samples. The package can import the data from multiple formats and offers functions for the visualization of the results as bar plots of the functional profile, box plots of compare functions across samples, and annotated pathway graphs. By streamlining the analysis of the functional potential encoded in microbial communities, Thanos can enable impactful discoveries in all the fields touched by metagenomics, from human health to the environmental sciences.
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Due to shortcomings such as poor homogeneity of Al doping, precisely controlling the thickness, inability to conformally deposit on high aspect ratio devices and high pinhole rate, the applications of Al-doped ZnO (AZO) nanomembrane in integrated optoelectronic devices are remarkably influenced. Here, we reportin situmonitoring during the atomic layer deposition (ALD) of AZO nanomembrane by using an integrated spectroscopic ellipsometer. AZO nanomembranes with different compositions were deposited with real-time and precise atomic level monitoring of the deposition process. We specifically investigate the half-reaction and thickness evolution during the ALD processes and the influence of the chamber temperature is also disclosed. Structural characterizations demonstrate that the obtained AZO nanomembranes without any post-treatment are uniform, dense and pinhole-free. The transmittances of the nanomembranes in visible range are >94%, and the optimal conductivity can reach up to 1210 S cm-1. The output of current research may pave the way for AZO nanomembrane to become promising in integrated optoelectronic devices.
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The adult turtle spinal cord can generate multiple kinds of limb movements, including swimming, three forms of scratching, and limb withdrawal (flexion reflex), even without brain input and sensory feedback. There are many multifunctional spinal neurons, activated during multiple motor patterns, and some behaviorally specialized neurons, activated during only one. How do multifunctional and behaviorally specialized neurons each contribute to motor output? We analyzed in vivo intracellular recordings of multifunctional and specialized neurons. Neurons tended to spike in the same phase of the hip-flexor (HF) activity cycle during swimming and scratching, though one preferred opposite phases. During both swimming and scratching, a larger fraction of multifunctional neurons than specialized neurons were highly rhythmic. One group of multifunctional neurons was active during the HF-on phase and another during the HF-off phase. Thus, HF-extensor alternation may be generated by a subset of multifunctional spinal neurons during both swimming and scratching. Scratch-specialized neurons and flexion reflex-selective neurons may instead trigger their respective motor patterns, by biasing activity of multifunctional neurons. In phase-averaged membrane potentials of multifunctional neurons, trough phases were more highly correlated between swimming and scratching than peak phases, suggesting that rhythmic inhibition plays a greater role than rhythmic excitation. We also provide the first intracellular recording of a turtle swim-specialized neuron: tonically excited during swimming but inactive during scratching and flexion reflex. It displayed an excitatory postsynaptic potential following each swim-evoking electrical stimulus and thus may be an intermediary between reticulospinal axons and the swimming CPG they activate.
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Reflexo , Medula Espinal , Natação , Tartarugas , Animais , Tartarugas/fisiologia , Natação/fisiologia , Medula Espinal/fisiologia , Reflexo/fisiologia , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Neurônios Motores/fisiologiaRESUMO
PURPOSE: It is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA). METHODS: We included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality. RESULTS: There were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349-4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397-6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393-3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022-8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE. CONCLUSIONS: Our results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.
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Doenças Cardiovasculares , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Feminino , Idoso , Estudos Prospectivos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/mortalidade , Distúrbios do Início e da Manutenção do Sono/complicações , Apneia Obstrutiva do Sono/mortalidade , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Idoso de 80 Anos ou mais , Causas de Morte/tendências , Fatores de RiscoRESUMO
The utilization of lignocellulosic substrates for microbial oil production by oleaginous yeasts has been evidenced as an economically viable process for industrial-scale biodiesel preparation. Efficient sugar utilization and tolerance to inhibitors are critical for lipid production from lignocellulosic substrates. This study investigated the lignocellulosic sugar utilization and inhibitor tolerance characteristics of Rhodotorula toruloides C23. The results demonstrated that C23 exhibited robust glucose and xylose assimilation irrespective of their ratios, yielding over 21 g/L of lipids and 11 mg/L of carotenoids. Furthermore, C23 exhibited high resistance and efficiently degradation towards toxic inhibitors commonly found in lignocellulosic hydrolysates. The potential molecular mechanism underlying xylose metabolism in C23 was explored, with several key enzymes and signal regulation pathways identified as potentially contributing to its superior lipid synthesis performance. The study highlights R. toruloides C23 as a promising candidate for robust biofuel and carotenoid production through direct utilization of non-detoxified lignocellulosic hydrolysates.
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Carotenoides , Lignina , Lipídeos , Rhodotorula , Rhodotorula/metabolismo , Rhodotorula/efeitos dos fármacos , Lignina/metabolismo , Carotenoides/metabolismo , Glucose/metabolismo , Xilose/metabolismo , BiocombustíveisRESUMO
BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.
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Antibacterianos , Bismuto , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/terapia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Transplante de Microbiota Fecal/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Helicobacter pylori/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Estudos Prospectivos , Bismuto/uso terapêutico , Quimioterapia Combinada , China , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Resultado do Tratamento , Idoso , Fezes/microbiologiaRESUMO
High spontaneous mutation rate is crucial for obtaining ideal phenotype and exploring the relationship between genes and phenotype. How to break the genetic stability of organisms and increase the mutation frequency has become a research hotspot. Here, we present a practical and controllable evolutionary tool (oMut-Cgts) based on dual genetic level modification engineering for Corynebacterium glutamicum. Firstly, the modification engineering of transcription and replication levels based on RNA polymerase α subunit and DNA helicase Cgl0854 as the 'dock' of cytidine deaminase (pmCDA1) significantly increased the mutation rate, proving that the localization of pmCDA1 around transient ssDNA is necessary for genome mutation. Then, the combined modification and optimization of engineering at dual genetic level achieved 1.02 × 104-fold increased mutation rate. The genome sequencing revealed that the oMut-Cgts perform uniform and efficient C:GâT:A transitions on a genome-wide scale. Furthermore, oMut-Cgts-mediated rapid evolution of C. glutamicum with stress (acid, oxidative and ethanol) tolerance proved that the tool has powerful functions in multi-dimensional biological engineering (rapid phenotype evolution, gene function mining and protein evolution). The strategies for rapid genome evolution provided in this study are expected to be applicable to a variety of applications in all prokaryotic cells.
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Corynebacterium glutamicum , Genoma Bacteriano , Corynebacterium glutamicum/genética , Engenharia Genética/métodos , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Taxa de Mutação , Evolução Molecular , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , Replicação do DNA/genética , MutaçãoRESUMO
Circulating bat coronaviruses represent a pandemic threat. However, our understanding of bat coronavirus pathogenesis and transmission potential is limited by the lack of phenotypically characterized strains. We created molecular clones for the two closest known relatives of SARS-CoV-2, BANAL-52 and BANAL-236. We demonstrated that BANAL-CoVs and SARS-CoV-2 have similar replication kinetics in human bronchial epithelial cells. However, BANAL-CoVs have impaired replication in human nasal epithelial cells and in the upper airway of mice. We also observed reduced pathogenesis in mice and diminished transmission in hamsters. Further, we observed that diverse bat coronaviruses evade interferon and downregulate major histocompatibility complex class I. Collectively, our study demonstrates that despite high genetic similarity across bat coronaviruses, prediction of pandemic potential of a virus necessitates functional characterization. Finally, the restriction of bat coronavirus replication in the upper airway highlights that transmission potential and innate immune restriction can be uncoupled in this high-risk family of emerging viruses.
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COVID-19 , Quirópteros , Imunidade Inata , SARS-CoV-2 , Replicação Viral , Animais , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Quirópteros/virologia , Quirópteros/imunologia , COVID-19/transmissão , COVID-19/virologia , COVID-19/imunologia , Camundongos , Cricetinae , Evasão da Resposta Imune , Células Epiteliais/virologia , Células Epiteliais/imunologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Coronavirus/imunologia , Coronavirus/genética , Coronavirus/classificação , Coronavirus/fisiologia , Coronavirus/patogenicidade , Linhagem Celular , FemininoRESUMO
(R)-3-Hydroxybutyric acid (R-3HB) is an important chiral chemical with extensive applications in the agricultural, food, and chemical industries. The synthesis of R-3HB by microbial fermentation is of interest due to its remarkable stereoselectivity and economy. However, the low production of R-3HB failed to meet the needs of large-scale industrial production. In this study, an engineered strain for the efficient biosynthesis of R-3HB was constructed through a three-pronged approach encompassing biosynthetic pathway optimization, engineering of NADPH regenerators, and central metabolism regulation. The engineered strain Q5081 produced 75.7 g/L R-3HB, with a productivity of 1.26 g/L/h and a yield of 0.34 g/g glucose in fed-batch fermentation, showing the highest reported titer and productivity of R-3HB to date. We also performed transcriptome sequencing and annotation to illustrate the mechanism underlying the enhanced R-3HB production. The systematic metabolic engineering by a three-pronged approach demonstrated the feasibility of improving the biosynthesis, and the engineered strain Q5081 has the potential for widespread applications in the industrial production of R-3HB.
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Ácido 3-Hidroxibutírico , Escherichia coli , Fermentação , Engenharia Metabólica , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Ácido 3-Hidroxibutírico/biossíntese , Ácido 3-Hidroxibutírico/química , Vias BiossintéticasRESUMO
Quorum sensing (QS) orchestrates many bacterial behaviors, including virulence and biofilm formation, across bacterial populations. Nevertheless, the underlying mechanism by which QS regulates capsular polysaccharide (CPS)-dependent phage-bacterium interactions remains unclear. In this study, we report that QS upregulates the expression of CPS-dependent phage receptors, thus increasing phage adsorption and infection rates in Vibrio alginolyticus. We found that QS upregulated the expression of the ugd gene, leading to increased synthesis of Autographiviridae phage receptor CPS synthesis in V. alginolyticus. The signal molecule autoinducer-2 released by Vibrio from different sources can potentially enhance CPS-dependent phage infections. Therefore, our data suggest that inhibiting QS may reduce, rather than improve, the therapeutic efficacy of CPS-specific phages. IMPORTANCE: Phage resistance is a direct threat to phage therapy, and understanding phage-host interactions, especially how bacteria block phage infection, is essential for developing successful phage therapy. In the present study, we demonstrate for the first time that Vibrio alginolyticus uses quorum sensing (QS) to promote capsular polysaccharide (CPS)-specific phage infection by upregulating ugd expression, which is necessary for the synthesis of Autographiviridae phage receptor CPS. Although increased CPS-specific phage susceptibility is a novel trade-off mediated by QS, it results in the upregulation of virulence factors, promoting biofilm development and enhanced capsular polysaccharide production in V. alginolyticus. This suggests that inhibiting QS may improve the effectiveness of antibiotic treatment, but it may also reduce the efficacy of phage therapy.
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Objective: To investigate the short-term clinical efficacy of robot-assisted retrograde drilling and arthroscopic microfracture for osteochondral lesions of the talus (OCLT). Methods: This study was divided into two groups: experimental group: robot-assisted retrograde drilling group; control group: arthroscopic microfracture group. A total of 6 OCLT patients who were treated with robot navigation-assisted retrograde drilling and 10 OCLT patients who were treated with arthroscopic microfracture between October 2020 and October 2021 were retrospectively analyzed. There were 11 males and five females, with a mean age of 36 years. The patients were followed up for 6-12 months to compare the changes in the OCLT lesion area by magnetic resonance imaging (MRI), visual analogue scale/score (VAS) and American Orthopedic Foot and Ankle Society score (AOFAS) before and after surgery. Results: All 16 patients were followed up for an average of 8 months, and no complications such as joint infection, nerve injury, or active bleeding occurred during the follow-up period. Only one patient suffered discomfort involving transient postoperative pain in the operative area, but did not experience long-term numbness or chronic pain. Postoperative MRI revealed that none of the patients had severe signs of osteonecrosis, osteolysis or cystic changes of the talus, with lesion areas smaller than those before surgery. The difference was statistically significant (P < 0.01). The patients in the experimental group showed a more significant improvement in the last 3 months than in the first 3 months of the follow-up period. At the last follow-up, the VAS score was 3 points in the experimental group and 2.2 points in the control group, and the AOFAS score was 88.6 points in the experimental group and 88 points in the control group, all of which were significantly higher than those before operation, and the differences were statistically significant, but there was no statistically significant difference between the groups. Conclusion: Both robot navigation-assisted retrograde drilling and arthroscopic microfracture for bone marrow stimulation (BMS) to treat OCLT in all patients obtained satisfactory effects in the short term. In addition, the follow-up revealed that with excellent efficacy and few complications, robot navigation-assisted retrograde drilling was safe and minimally invasive, and greatly reduced operative time. Consequently, robot navigation-assisted retrograde drilling for BMS was a safe and effective procedure for the treatment of OCLT.
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Crystalline calcium fluoride (CaF2) is drawing significant attention due to its great potential of being the gate dielectric of two-dimensional (2D) material MOSFETs. It is deemed to be superior to boron nitride and traditional silicon dioxide (SiO2) because of its larger dielectric constant, wider band gap, and lower defect density. Nevertheless, the CaF2-based MOSFETs fabricated in the experiment still present notable reliability issues, and the underlying reason remains unclear. Here, we studied the various intrinsic defects and adsorbates in CaF2/molybdenum disulfide (MoS2) and CaF2/molybdenum disilicon tetranitride (MoSi2N4) interface systems to reveal the most active charge-trapping centers in CaF2-based 2D material MOSFETs. An elaborate Table comparing the importance of different defects in both n-type and p-type devices is provided. Most impressively, the oxygen molecules (O2) adsorbed at the interface or surface, which are inevitable in experiments, are as active as the intrinsic defects in channel materials, and they can even change the MoSi2N4 to p-type spontaneously. These results mean that it is necessary to develop a high-vacuum packaging process, as well as prepare high-quality 2D materials for better device performance.
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OBJECTIVES: The objective of this study was to analyze the occlusal contact characteristics of the food-impacted teeth using a new digital technique. METHODS: A 3D occlusal analysis method was developed for studying the occlusal contact characteristics of teeth affected by food impaction. In this self-controlled study, food-impacted molars from 20 participants constituted the experimental group. The corresponding healthy teeth on the opposite side served as the control group. Variables such as occlusal force (OF), occlusal contact area (OCA), and the number and distribution of occlusal contact points (OCN) in the mesio-distal directions were measured and compared between the two groups. RESULTS: There was no statistical significant difference in the values of OF, OCA and OCN between the food-impacted molars and the healthy control molars (P > 0.05). However, paired T-tests indicated significant difference in the proportion of mesial OF, OCA, and OCN in the second molars of the experimental group (0.22, 0.28 and 0.28, respectively) and the control group (0.66, 0.63, and 0.63 respectively) (P < 0.001). CONCLUSIONS: The abnormal distribution of occlusal contacts in the second molar, primarily characterized by excessive occlusal contact in the distal direction may contribute to the occurrence of food impaction. CLINICAL SIGNIFICANCE: The present study identified variations in the distribution of occlusal contacts and occlusal component force in food-impacted teeth. These findings can assist dentists in making more targeted occlusal adjustments, or applying other treatment modalities, to effectively address food impaction.