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1.
Proc Natl Acad Sci U S A ; 121(42): e2412016121, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39388275

RESUMO

In this study, we show that the potato (Solanum tuberosum) pattern recognition receptor (PRR) NEMATODE-INDUCED LEUCINE-RICH REPEAT (LRR)-RLK1 (StNILR1) functions as a dual receptor, recognizing both nematode-associated molecular pattern ascaroside #18 (Ascr18) and plant hormone brassinosteroid (BR) to activate two different physiological outputs: pattern-triggered immunity (PTI) and BR response. Ascr18/BR-StNILR1 signaling requires the coreceptor potato BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1 (StBAK1) and perception of either ligand strengthens StNILR1 interaction with StBAK1 in plant cells. Significantly, the parasitically successful potato cyst nematode (Globodera pallida) utilizes the effector RHA1B, which is a functional ubiquitin ligase, to target StNILR1 for ubiquitination-mediated proteasome-dependent degradation, thereby countering Ascr18/BR-StNILR1-mediated PTI in potato and facilitating nematode parasitism. These findings broaden our understanding of PRR specificity and reveal a nematode parasitic mechanism that targets a PTI signaling pathway.


Assuntos
Doenças das Plantas , Imunidade Vegetal , Solanum tuberosum , Animais , Solanum tuberosum/parasitologia , Solanum tuberosum/imunologia , Solanum tuberosum/metabolismo , Doenças das Plantas/parasitologia , Doenças das Plantas/imunologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/imunologia , Brassinosteroides/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Ligantes , Transdução de Sinais , Receptores de Reconhecimento de Padrão/metabolismo , Receptores de Reconhecimento de Padrão/imunologia , Tylenchoidea/fisiologia , Nematoides/metabolismo , Nematoides/imunologia
2.
Nucleic Acids Res ; 52(14): 8609-8627, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-38967005

RESUMO

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:G→T: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.


Assuntos
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 , Mutação
3.
FASEB J ; 38(10): e23668, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38742811

RESUMO

Podocyte injury plays a critical role in the progression of diabetic kidney disease (DKD), but the underlying cellular and molecular mechanisms remain poorly understanding. MicroRNAs (miRNAs) can disrupt gene expression by inducing translation inhibition and mRNA degradation, and recent evidence has shown that miRNAs may play a key role in many kidney diseases. In this study, we identified miR-4645-3p by global transcriptome expression profiling as one of the major downregulated miRNAs in high glucose-cultured podocytes. Moreover, whether DKD patients or STZ-induced diabetic mice, expression of miR-4645-3p was also significantly decreased in kidney. In the podocytes cultured by normal glucose, inhibition of miR-4645-3p expression promoted mitochondrial damage and podocyte apoptosis. In the podocytes cultured by high glucose (30 mM glucose), overexpression of miR-4645-3p significantly attenuated mitochondrial dysfunction and podocyte apoptosis induced by high glucose. Furthermore, we found that miR-4645-3p exerted protective roles by targeting Cdk5 inhibition. In vitro, miR-4645-3p obviously antagonized podocyte injury by inhibiting overexpression of Cdk5. In vivo of diabetic mice, podocyte injury, proteinuria, and impaired renal function were all effectively ameliorated by treatment with exogenous miR-4645-3p. Collectively, these findings demonstrate that miR-4645-3p can attenuate podocyte injury and mitochondrial dysfunction in DKD by targeting Cdk5. Sustaining the expression of miR-4645-3p in podocytes may be a novel strategy to treat DKD.


Assuntos
Quinase 5 Dependente de Ciclina , Diabetes Mellitus Experimental , Nefropatias Diabéticas , MicroRNAs , Mitocôndrias , Podócitos , Animais , Humanos , Masculino , Camundongos , Apoptose , Quinase 5 Dependente de Ciclina/metabolismo , Quinase 5 Dependente de Ciclina/genética , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/genética , Glucose , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Podócitos/metabolismo , Podócitos/patologia
4.
J Med Genet ; 61(11): 1053-1061, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39332896

RESUMO

BACKGROUND: GlcNAc2-epimerase (GNE) myopathy is a rare autosomal recessive disorder caused by pathogenic variants in the GNE gene, which is essential for the sialic acid biosynthesis pathway. OBJECTIVE: This multi-centre study aimed to delineate the clinical phenotype and GNE variant spectrum in Chinese patients, enhancing our understanding of the genetic diversity and clinical manifestation across different populations. METHODS: We retrospectively analysed GNE variants from 113 patients, integrating these data with external GNE variants from online databases for a global perspective, examining their consequences, distribution, ethnicity and severity. RESULTS: This study revealed 97 distinct GNE variants, including 35 (36.08%) novel variants. Two more patients with deep intronic variant c.862+870C>T were identified, while whole genome sequencing (WGS) uncovered another two novel intronic variants: c.52-8924G>T and c.1505-12G>A. Nanopore long reads sequencing (LRS) and further PCR analysis verified a 639 bp insertion at chr9:36249241. Missense variants predominantly located in the epimerase/kinase domain coding region, indicating the impairment of catalytic function as a key pathogenic consequence. Comparative studies with Japanese, Korean and Jewish, our cohorts showed later onset ages by 2 years. The high allele frequency of the non-catalytic GNE variant, c.620A>T, might underlie the milder phenotype of Chinese patients. CONCLUSIONS: Comprehensive techniques such as WGS and Nanopore LRS warrants the identifying of GNE variants. Patients with the non-catalytic GNE variant, c.620A>T, had a milder disease progression and later wheelchair use.


Assuntos
Estudos de Associação Genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Carboidratos Epimerases/genética , China/epidemiologia , Miopatias Distais/genética , Miopatias Distais/patologia , Miopatias Distais/epidemiologia , Estudos de Associação Genética/métodos , Mutação , Fenótipo , Estudos Retrospectivos , Sequenciamento Completo do Genoma , População do Leste Asiático/genética
5.
Neuroimage ; 291: 120584, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38522806

RESUMO

Memory is closely associated with neuronal activity and dendritic spine formation. Low-intensity transcranial ultrasound stimulation (TUS) improves the memory of individuals with vascular dementia (VD). However, it is unclear whether neuronal activity and dendritic spine formation under ultrasound stimulation are involved in memory improvement in VD. In this study, we found that seven days of TUS improved memory in VD model while simultaneously increasing pyramidal neuron activity, promoting dendritic spine formation, and reducing dendritic spine elimination. These effects lasted for 7 days but disappeared on 14 d after TUS. Neuronal activity and dendritic spine formation strongly corresponded to improvements in memory behavior over time. In addition, we also found that the memory, neuronal activity and dendritic spine of VD mice cannot be restored again by TUS of 7 days after 28 d. Collectively, these findings suggest that TUS increases neuronal activity and promotes dendritic spine formation and is thus important for improving memory in patients with VD.


Assuntos
Demência Vascular , Camundongos , Humanos , Animais , Demência Vascular/terapia , Neurônios , Células Piramidais , Ultrassonografia
6.
Am J Gastroenterol ; 119(1): 203-205, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37561055

RESUMO

INTRODUCTION: Proton pump inhibitors (PPI) are overused and carry harms in cirrhosis. Deprescribing is advocated but has not been trialed. METHODS AND FINDINGS: We emulated a clinical trial using Medicare data. All patients were receiving chronic PPI therapy before a compensated cirrhosis diagnosis. We compared the risk death/decompensation over 3 years between continuous users and deprescribers. We find that PPI deprescription is associated with less ascites and that cumulative PPI use is associated with more ascites and encephalopathy. Ultimately, 71% of deprescribers restart PPIs. DISCUSSION: PPI deprescribing has benefits but requires ongoing support and alternative therapies for gastrointestinal symptoms.


Assuntos
Desprescrições , Idoso , Estados Unidos , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Ascite/complicações , Medicare , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico
7.
Small ; : e2407464, 2024 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-39491516

RESUMO

Aromatic residues in assembling peptides play a crucial role in driving peptide self-assembly through π-π stacking and hydrophobic interactions. Although various aromatic capping groups have been extensively studied, systematic investigations into the effects of single aromatic amino acids in assembling peptides remain limited. In this study, the influence of aromatic-aromatic interactions on disulfide-rich assembling peptides is systematically investigated by incorporating three different aromatic amino acids. Their folding propensity, self-assembling properties, and rheological behaviors are evaluated. These results indicate that different aromatic-aromatic interactions have a significant effect on self-assembly abilities, as determined by critical aggregation concentration (CAC) measurements. Furthermore, the biocompatibility of these hydrogels is assessed, and their potential for 3D cell culture is explored. The injectable F1-ox hydrogel demonstrate excellent biocompatibility for SHED and NIH3T3 cells and exhibit a porous structure that facilitates nutrient and cellular metabolic waste exchange. This work provides new insights into the molecular design of peptide-based biomaterials, with a focus on the impact of aromatic residues on disulfide-rich assembling peptides.

8.
Nat Methods ; 18(1): 46-49, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33408404

RESUMO

We have developed a miniature two-photon microscope equipped with an axial scanning mechanism and a long-working-distance miniature objective to enable multi-plane imaging over a volume of 420 × 420 × 180 µm3 at a lateral resolution of ~1 µm. Together with the detachable design that permits long-term recurring imaging, our miniature two-photon microscope can help decipher neuronal mechanisms in freely behaving animals.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Miniaturização/métodos , Neuroimagem/métodos , Animais , Comportamento Animal , Encéfalo/citologia , Técnicas Citológicas , Locomoção , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
Appl Environ Microbiol ; 90(8): e0221023, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-39072624

RESUMO

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.


Assuntos
Percepção de Quorum , Vibrio alginolyticus , Vibrio alginolyticus/virologia , Vibrio alginolyticus/fisiologia , Bacteriófagos/fisiologia , Bacteriófagos/genética , Homosserina/análogos & derivados , Homosserina/metabolismo , Cápsulas Bacterianas/metabolismo , Podoviridae/genética , Podoviridae/fisiologia , Biofilmes/crescimento & desenvolvimento , Polissacarídeos Bacterianos/metabolismo
10.
Opt Express ; 32(12): 21077-21091, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859471

RESUMO

We propose a low-complexity frequency domain frame synchronization method for short-reach intensity modulation and direct detection (IM/DD) systems. A four-level pulse amplitude modulation-training sequence (PAM4-TS) is specially designed for the proposed method, which has an obvious peak in the amplitude spectrum that is higher than the normal signal. The proposed method comprises a coarse synchronization stage and a fine synchronization stage. Firstly, the coarse synchronization stage takes advantage of the feature of PAM4-TS to obtain the approximate position of the frame head by identifying the peak value in amplitude spectrum of the segmented received signal. Then, the fine synchronization stage calculates the correlation between the coarse synchronization result and PAM4-TS by multiplying the two in the frequency domain. Compared with the traditional sliding window correlation method realized in the time domain, both simulation and experimental results of C-band 50 Gbit/s PAM4 transmission demonstrate that the proposed method reduces the multiplication complexity by up to about 96.01% without any additional performance penalty.

11.
Syst Biol ; 72(2): 319-340, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-36130311

RESUMO

What happens when organisms actively modify their environment? Clarifying the role of construction behavior on a macroevolutionary scale is crucial to interpreting phenotypic evolution. Spiders, an extremely successful group of animals exhibiting a wide variety of functional, morphological, and behavioral diversity, are ideal candidates to test whether animal behaviors are related to their phenotypic evolution. Herein, we reconstructed the phylogenomic relationships of 303 spiders covering 105 families with 99 newly developed molecular markers that universally apply across Araneae, and explicitly tested the potential link between construction behavior and somatic evolution based on extensive morphological data from 3,342 extant species and 682 fossil species. Our dated molecular phylogeny provides the backbone for analyses, revealing the behavioral and ecological processes behind these spiders' morphological adaptations. Evolutionary model analyses showed the artifacts constructed by spiders, especially the suspending webs, expand the spider's ability to inhabit different habitats. These artifacts have more substantial impacts on their somatic traits than habitats and promote different trajectories of morphological evolution. Specifically, for spiders, silk-lined burrowing produced larger bodies, relatively shorter legs, and longer patellae, while web-building produced smaller bodies, relatively longer legs, and shorter patellae, and hunting promoted an intermediate morphological size. Molecular convergence analysis showed that genes related to morphogenesis or response to stimulus and stress are enriched in spiders with construction behavior. Our study demonstrated that the construction behavior of an animal plays a crucial role in determining the direction and intensity of the selection pressure imposed on it and provides strong evidence that construction behaviors are associated with phenotypic evolution on macroevolutionary timescales. [Araneae; body size; habitat change; molecular marker; leg length; phylogenomics.].


Assuntos
Evolução Biológica , Aranhas , Animais , Filogenia , Seda/genética , Ecossistema
12.
Mol Cell Biochem ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795212

RESUMO

Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.

13.
J Inherit Metab Dis ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227307

RESUMO

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts.

14.
Helicobacter ; 29(4): e13079, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984661

RESUMO

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.


Assuntos
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/microbiologia
15.
Fish Shellfish Immunol ; 154: 109917, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39307256

RESUMO

Galectins are a family of animal lectins involved in the immune response against pathogens. However, the roles of fish galectins during pathogen infection require comprehensive studies. In the present research, eight different galectin genes from Takifugu obscurus (named ToGalec1-8) were identified and characterized. ToGalec1-8 encoded proteins of 240, 182, 373, 145, 452, 135, 359 and 346 amino acids, respectively. All predicted ToGalec1-8 proteins possessed one or more conserved carbohydrate recognition domains (CRDs). Phylogenetic analysis revealed that ToGalec1-8 were evolutionarily closely related to their counterparts in other selected vertebrates, hinting their genetic relationship. Tissue distribution analysis showed that most ToGalec genes were distributed ubiquitously in all detected tissues, with relatively high expression in immune tissues. After stimulation by Vibrio harveyi and Staphylococcus aureus, the mRNA transcripts of ToGalec1-8 in liver and kidney were significantly upregulated. In addition, RNA interference experiments indicated that knockdown of ToGalec1 and ToGalec7 inhibited the clearance of bacteria in vivo. Taken together, these obtained results suggested that ToGalec1-8 play an important role in innate immunity and defense against bacterial infection in T. obscurus.

16.
Fish Shellfish Immunol ; 144: 109283, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38092094

RESUMO

L-type lectins (LTLs) contain a carbohydrate recognition domain homologous to leguminous lectins, and have functions in selective protein trafficking, sorting and targeting in the secretory pathway of animals. In this study, a novel LTL, designated as ToERGIC-53, was cloned and identified from obscure puffer Takifugu obscurus. The open reading frame of ToERGIC-53 contained 1554 nucleotides encoding 517 amino acid residues. The deduced ToERGIC-53 protein consisted of a signal peptide, a leguminous lectin domain (LTLD), a coiled-coil region, and a transmembrane region. Quantitative real-time PCR showed that ToERGIC-53 was expressed in all examined tissues, with the highest expression level in the liver. The expression of ToERGIC-53 was significantly upregulated after infection with Vibrio harveyi and Staphylococcus aureus. Recombinant ToERGIC-53-LTLD (rToERGIC-53-LTLD) protein could not only agglutinate and bind to one Gram-positive bacterium (S. aureus) and three Gram-negative bacteria (V. harveyi, V. parahaemolyticus and Aeromonas hydrophila), but also bind to glycoconjugates on the surface of bacteria such as lipopolysaccharide, peptidoglycan, mannose and galactose. In addition, rToERGIC-53-LTLD inhibited the growth of bacteria in vitro. All these results suggested that ToERGIC-53 might be a pattern recognition receptor involved in antibacterial immune response of T. obscurus.


Assuntos
Infecções Bacterianas , Lectinas , Animais , Lectinas/genética , Takifugu/genética , Takifugu/metabolismo , Staphylococcus aureus/metabolismo , Receptores de Reconhecimento de Padrão/genética , Filogenia , Imunidade Inata/genética , Lectinas Tipo C/genética
17.
Fish Shellfish Immunol ; 145: 109324, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38134977

RESUMO

Ameson portunus (Microsporidia) has caused serious economic losses to the aquaculture industry of swimming crab, Portunus trituberculatus. The hemolymph and hepatopancreas are the main immune organs of P. trituberculatus, and the main sites of A. portunus infection. Elucidating the response characteristics of hemolymph and hepatopancreas to microsporidian infection facilitates the development of microsporidiosis prevention and control strategy. This study performed comparative transcriptomic analysis of hemolymph (PTX/PTXA) and hepatopancreas (PTG/PTGA) of P. trituberculatus uninfected and infected with A. portunus. The results showed that there were 223 and 1309 differentially expressed genes (DEGs) in PTX/PTXA and PTG/PTGA, respectively. The lysosome pathway was significantly enriched after the invasion of the hemolymph by A. portunus. Also, immune-related genes were all significantly up-regulated in the hemolymph and hepatopancreas, suggesting that the invasion by A. portunus may activate host immune responses. Unlike hemolymph, antioxidant and detoxification-related genes were also significantly up-regulated in the hepatopancreas. Moreover, metabolism-related genes were significantly down-regulated in the hepatopancreas, suggesting that energy synthesis, resistance to pathogens, and regulation of oxidative stress were suppressed in the hepatopancreas. Hemolymph and hepatopancreas have similarity and tissue specificity to microsporidian infection. The differential genes and pathways identified in this study can provide references for the prevention and control of microsporidiosis.


Assuntos
Braquiúros , Microsporídios , Microsporidiose , Animais , Braquiúros/genética , Hemolinfa , Hepatopâncreas/metabolismo , Microsporídios/genética , Microsporidiose/metabolismo , Transcriptoma
18.
Arch Virol ; 169(6): 127, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789713

RESUMO

Herpesviruses adhere to a precise temporal expression model in which immediate-early (IE) genes play a crucial role in regulating the viral life cycle. However, there is a lack of functional research on the IE genes in Ictalurid herpesvirus 1 (IcHV-1). In this study, we identified the IcHV-1 ORF24 as an IE gene via a metabolic inhibition assay, and subcellular analysis indicated its predominant localisation in the nucleus. To investigate its function, we performed yeast reporter assays using an ORF24 fusion protein containing the Gal4-BD domain and found that BD-ORF24 was able to activate HIS3/lacZ reporter genes without the Gal4-AD domain. Our findings provide concrete evidence that ORF24 is indeed an IE gene that likely functions as a transcriptional regulator during IcHV-1 infection. This work contributes to our understanding of the molecular mechanisms underlying fish herpesvirus IE gene expression.


Assuntos
Regulação Viral da Expressão Gênica , Genes Precoces , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Transcrição Gênica , Proteínas Virais/genética , Proteínas Virais/metabolismo
19.
Nanotechnology ; 35(40)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38981451

RESUMO

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.

20.
BMC Gastroenterol ; 24(1): 335, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350033

RESUMO

BACKGROUND: The early diagnosis and treatment of Heliobacter pylori (H.pylori) gastrointestinal infection provide significant benefits to patients. We constructed a convolutional neural network (CNN) model based on an endoscopic system to diagnose H. pylori infection, and then examined the potential benefit of this model to endoscopists in their diagnosis of H. pylori infection. MATERIALS AND METHODS: A CNN neural network system for endoscopic diagnosis of H.pylori infection was established by collecting 7377 endoscopic images from 639 patients. The accuracy, sensitivity, and specificity were determined. Then, a randomized controlled study was used to compare the accuracy of diagnosis of H. pylori infection by endoscopists who were assisted or unassisted by this CNN model. RESULTS: The deep CNN model for diagnosis of H. pylori infection had an accuracy of 89.6%, a sensitivity of 90.9%, and a specificity of 88.9%. Relative to the group of endoscopists unassisted by AI, the AI-assisted group had better accuracy (92.8% [194/209; 95%CI: 89.3%, 96.4%] vs. 75.6% [158/209; 95%CI: 69.7%, 81.5%]), sensitivity (91.8% [67/73; 95%CI: 85.3%, 98.2%] vs. 78.6% [44/56; 95%CI: 67.5%, 89.7%]), and specificity (93.4% [127/136; 95%CI: 89.2%, 97.6%] vs. 74.5% [114/153; 95%CI: 67.5%, 81.5%]). All of these differences were statistically significant (P < 0.05). CONCLUSION: Our AI-assisted system for diagnosis of H. pylori infection has significant ability for diagnostic, and can improve the accuracy of endoscopists in gastroscopic diagnosis. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Daping Hospital (10/07/2020) (No.89,2020) and was registered with the Chinese Clinical Trial Registration Center (02/09/2020)   ( www.chictr.org.cn ; registration number: ChiCTR2000037801).


Assuntos
Inteligência Artificial , Infecções por Helicobacter , Helicobacter pylori , Redes Neurais de Computação , Sensibilidade e Especificidade , Humanos , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Endoscopia Gastrointestinal/métodos , Gastroscopia/métodos
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