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The precise role of the highly variable coronavirus S protein in modulating innate immune responses remains unclear. In this study, we demonstrated that the mutant strain of swine coronavirus porcine enteric diarrhea virus induced significantly lower levels of double-stranded RNA (dsRNA) accumulation, inhibited protein kinase R (PKR) activation and suppressed stress granule (SG) formation compared with the classical strain. The 29th amino acid at N-terminus of S was identified as the key functional site for regulation of SG formation, and found that mutant S inhibited PKR phosphorylation and SG formation by upregulating adenosine deaminase acting on RNA 1 (ADAR1)-p150. Notably, the Zα domain of ADAR1-p150 was essential for inhibiting SG formation. Upregulation of ADAR1-p150 also reduced accumulation of dsRNA depending on its RNA editing function. Virus rescue confirmed that the mutant carrying a substitution at amino acid 29 failed to induce ADAR1-p150, leading to dsRNA accumulation, PKR activation and SG formation. Interestingly, the latest severe acute respiratory syndrome coronavirus-2 strains exhibit a novel 25PPA27 deletion at N-terminus of S that was also shown to lead to altered ADAR1-p150 expression and SG inhibition. The transcription factor TCF7L2 was identified as a player in S-mediated transcriptional enhancement of ADAR1-p150. This study is the first to clarify the crucial role of N-terminus of S in immune regulation of coronaviruses.
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Variant Porcine epidemic diarrhea virus (PEDV), which causes diarrhea and high mortality in piglets, has become a major pathogen, and co-epidemics of different subtypes of the virus have become a very thorny problem for the clinical prevention and control of PEDV. However, cross-protection between epidemic G2a and G2b subtype strains has not been observed, and there is currently no vaccine against both G2a and G2b strains. In this study, we demonstrate the low cross-protection between G2a and G2b strains with piglet immunization and challenge tests. The trimeric full-length S proteins of G2a and G2b variants were purified and a bivalent subunit vaccine against PEDV G2a/G2b-S was developed. In active and passive immune protection tests, the bivalent subunit vaccine produced high neutralizing antibody titers and S-specific immunoglobulin G (IgG) and IgA titers against both the G2a and G2b strains in piglets and sows. In the attack phase of the viruses, the clinical symptoms and microscopic lesions in the immunized groups were significantly alleviated. Importantly, the PEDV G2a/G2b-S bivalent subunit vaccine conferred effective passive immunity against PEDV G2a and G2b challenges in the form of colostrum-derived antibodies from the immunized sows. In conclusion, our data demonstrate the low cross-protection of PEDV epidemic G2a and G2b strains and show that the G2a/G2b-S bivalent subunit vaccine is protective against both G2a and G2b strains. It is therefore a candidate vaccine for PEDV prevention. IMPORTANCE: The detection rate of PEDV G2a subtype strains is currently increasing. Although commercial vaccines are available, most vaccines do not exert an ideal protective effect against these strains. Furthermore, there is no definitive research into the cross-protection between G2a and G2b strains, and no bivalent vaccine provides joint protection against both. Therefore, in this study, we investigated the cross-protection between PEDV G2a and G2b strains and designed a candidate bivalent subunit vaccine combining the trimeric S proteins of the G2a and G2b subtypes. We demonstrate that the cross-protection between strains G2a and G2b is poor and that this bivalent subunit vaccine protects piglets from viral attack by inducing both active and passive immunity. This study emphasizes the effectiveness of the PEDV G2a/G2b-S bivalent subunit vaccine and provides a feasible method for the development of efficient PEDV vaccines.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por Coronavirus , Proteção Cruzada , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Vacinas de Subunidades Antigênicas , Vacinas Virais , Vírus da Diarreia Epidêmica Suína/imunologia , Animais , Suínos , Proteção Cruzada/imunologia , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/imunologia , Doenças dos Suínos/virologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Vacinas de Subunidades Antigênicas/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Chlorocebus aethiops , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Células Vero , Feminino , Glicoproteína da Espícula de Coronavírus/imunologia , Imunoglobulina A/imunologiaRESUMO
The follicle is the basic structural and functional unit of the ovary in female mammals. The excessive depletion of follicles will lead to diminished ovarian reserve or even premature ovarian failure, resulting in diminished ovarian oogenesis and endocrine function. Excessive follicular depletion is mainly due to loss of primordial follicles. Our analysis of published human ovarian single-cell sequencing results by others revealed a significant increase in rho-associated protein kinase 1 (ROCK1) expression during primordial follicle development. However, the role of ROCK1 in primordial follicle development and maintenance is not clear. This study revealed a gradual increase in ROCK1 expression during primordial follicle activation. Inhibition of ROCK1 resulted in reduced primordial follicle activation, decreased follicular reserve, and delayed development of growing follicles. This effect may be achieved through the HIPPO pathway. The present study indicates that ROCK1 is a key molecule for primordial follicular reserve and follicular development.NEW & NOTEWORTHY ROCK1, one of the Rho GTPases, plays an important role in primordial follicle reserve and follicular development. ROCK1 was primarily expressed in the cytoplasm of oocytes and granulosa cell in mice. Inhibition of ROCK1 significantly reduced the primordial follicle reserve and delayed growing follicle development. ROCK1 regulates primordial follicular reserve and follicle development through the HIPPO signaling pathway. These findings shed new lights on the physiology of sustaining female reproduction.
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Oócitos , Folículo Ovariano , Animais , Feminino , Humanos , Camundongos , Células da Granulosa/metabolismo , Mamíferos , Oogênese , Folículo Ovariano/metabolismo , Ovário/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismoRESUMO
Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.
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Apigenina , Transição Epitelial-Mesenquimal , Glucose , Histonas , Epitélio Pigmentado da Retina , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Animais , Apigenina/farmacologia , Acetilação/efeitos dos fármacos , Humanos , Glucose/metabolismo , Glucose/toxicidade , Histonas/metabolismo , Linhagem Celular , Camundongos , Fatores de Transcrição de p300-CBP/metabolismo , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Camundongos Endogâmicos C57BL , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Retinopatia Diabética/tratamento farmacológico , Proteína p300 Associada a E1A/metabolismo , Masculino , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Proteína de Ligação a CREB/metabolismo , Proteína de Ligação a CREB/genéticaRESUMO
Bicontinuous porous materials, which possess 3D interconnected network and pore channels facilitating the mass diffusion to the interior of materials, have demonstrated their promising potentials in a large variety of research fields. However, facile construction of such complex and delicate structures is still challenging. Here, an amine-mediated polymerization-induced fusion assembly strategy is reported for synthesizing polyphenol-based bicontinuous porous spheres with various pore structures. Specifically, the fusion of pore-generating template observed by TEM promotes the development of bicontinuous porous networks that are confirmed by 3D reconstruction. Furthermore, the resultant bicontinuous porous carbon particles after pyrolysis, with a diameter of ≈600 nm, a high accessible surface area of 359 m2 g-1, and a large pore size of 40-150 nm manifest enhanced performance toward the catalytic degradation of sulfamethazine in water decontamination. The present study expands the toolbox of interfacial tension-solvent-dependent porous spheres while providing new insight into their structure-property relationships.
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Converting carbon dioxide (CO2) into fuel and high-value-added chemicals is considered a green and effective way to solve global energy and environmental problems. Covalent triazine frameworks (CTFs) are extensively utilized as an emerging catalyst for photo/electrocatalytic CO2 reduction reaction (CO2RR) recently recognized for their distinctive qualities, including excellent thermal and chemical stability, π-conjugated structure, rich nitrogen content, and a strong affinity for CO2, etc. Nevertheless, single-component CTFs have the problems of accelerated recombination of photoexcited electron-hole pairs and restricted conductivity, which limit their application for photo/electrocatalytic CO2RR. Therefore, emphasis will then summarize the strategies for enhancing the photocatalytic and electrocatalytic efficiency of CTFs for CO2RR in this paper, including atom doping, constructing a heterojunction structure, etc. This review first illustrates the synthesis strategies of CTFs and the advantages of CTFs in the field of photo/electrocatalytic CO2RR. Subsequently, the mechanism of CTF-based materials in photo/electrocatalytic CO2RR is described. Lastly, the challenges and future prospects of CTFs in photo/electrocatalytic CO2RR are addressed, which offers a fresh perspective for the future development of CTFs in photo/electrocatalytic CO2RR.
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Future renewable energy supply and green, sustainable environmental development rely on various types of catalytic reactions. Copper single-atom catalysts (Cu SACs) are attractive due to their distinctive electronic structure (3d orbitals are not filled with valence electrons), high atomic utilization, and excellent catalytic performance and selectivity. Despite numerous optimization studies are conducted on Cu SACs in terms of energy conversion and environmental purification, the coupling among Cu atoms-support interactions, active sites, and catalytic performance remains unclear, and a systematic review of Cu SACs is lacking. To this end, this work summarizes the recent advances of Cu SACs. The synthesis strategies of Cu SACs, metal-support interactions between Cu single atoms and different supports, modification methods including modification for carriers, coordination environment regulating, site distance effect utilizing, and dual metal active center catalysts constructing, as well as their applications in energy conversion and environmental purification are emphatically introduced. Finally, the opportunities and challenges for the future Cu SACs development are discussed. This review aims to provide insight into Cu SACs and a reference for their optimal design and wide application.
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Rye (Secale cereale), a valuable relative of wheat, contains abundant powdery mildew resistance (Pm) genes. Using physical mapping, transcriptome sequencing, barley stripe mosaic virus-induced gene silencing, ethyl methane sulfonate mutagenesis, and stable transformation, we isolated and validated two coiled-coil, nucleotide-binding site and leucine-rich repeat (CC-NBS-LRR) alleles, PmTR1 and PmTR3, located on rye chromosome 6RS from different triticale lines. PmTR1 confers age-related resistance starting from the three-leaf stage, whereas its allele, PmTR3, confers typical all-stage resistance, which may be associated with their differential gene expression patterns. Overexpression in Nicotiana benthamiana showed that the CC, CC-NBS, and CC-LRR fragments of PMTR1 induce cell death, whereas in PMTR3 the CC and full-length fragments perform this function. Luciferase complementation imaging and pull-down assays revealed distinct interaction activities between the CC and NBS fragments. Our study elucidates two novel rye-derived Pm genes and their derivative germplasm resources and provides novel insights into the mechanism of age-related resistance, which can aid the improvement of resistance against wheat powdery mildew.
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Ascomicetos , Secale , Secale/genética , Resistência à Doença/genética , Triticum/genética , Proteínas de Repetições Ricas em Leucina , Ascomicetos/fisiologia , Nucleotídeos , Cromossomos de Plantas/genética , Sítios de Ligação , Doenças das Plantas/genéticaRESUMO
IMPORTANCE: Porcine epidemic diarrhea (PED) caused by PED virus (PEDV) remains a big threat to the swine industry worldwide. Vaccination with live attenuated vaccine is a promising method to prevent and control PED, because it can elicit a more protective immunity than the killed vaccine, subunit vaccine, and so on. In this study, we found two obvious deletions in the genome of a high passage of AH2012/12. We further confirmed the second deletion which contains seven amino acids at the carboxy-terminus of the S2 gene and the start codon of ORF3 can reduce its pathogenicity in vivo. Animal experiments indicated that the recombinant PEDV with deleted carboxy-terminus of S gene showed higher IgG, IgA, neutralization antibodies, and protection effects against virus challenge than the killed vaccine. These data reveal that the engineering of the carboxy-terminus of the S2 gene may be a promising method to develop live attenuated vaccine candidates of PEDV.
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Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Diarreia , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/patogenicidade , Suínos , Doenças dos Suínos/virologia , Vacinas Atenuadas/genética , Vacinas de Produtos Inativados , Vacinas Virais/genética , VirulênciaRESUMO
We propose a multimode interference-based optical fiber NHTSN sensor with a helical taper for simultaneous measurement of micro torsion and temperature. The sensor consists of single mode fiber (SMF), no-core fiber (NCF), and seven-core fiber (SCF). A helical taper is fabricated in the SCF using a flame heater, forming the SMF-NCF-Helical Taper SCF-NCF-SMF (NHTSN) structure. Theoretical analysis and experimental results demonstrate that the introduction of helical taper not only imparts directionality to the torsion measurement, but also results in a significant improvement in torsion sensitivity due to the increased inter-mode optical path difference (OPD) and enhanced inter-mode coupling. In the experiment, the torsion sensitivity of the NHTSN sensor reaches -1.255â nm/(rad/m) in the twist rate (TR) range of -3.931â rad/m to 3.931â rad/m, which is a 9-fold improvement over the original structure. Further reduction of the helical taper diameter increases the sensitivity to -1.690â nm/(rad/m). In addition, the sensor has a temperature sensitivity of up to 97 pm/°C from 20 °C to 90 °C, and simultaneous measurement of torsion and temperature is attainable through a dual-parameter measurement matrix. The NHTSN sensor possesses advantages of compact size, high sensitivity, good linearity, and strain-independence, endowing it with potential applications in structural health monitoring (SHM) and engineering machinery.
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BACKGROUND: The neuroanatomical alteration in bipolar II depression (BDII-D) and its associations with inflammation, childhood adversity, and psychiatric symptoms are currently unclear. We hypothesize that neuroanatomical deficits will be related to higher inflammation, greater childhood adversity, and worse psychiatric symptoms in BDII-D. METHODS: Voxel- and surface-based morphometry was performed using the CAT toolbox in 150 BDII-D patients and 155 healthy controls (HCs). Partial Pearson correlations followed by multiple comparison correction was used to indicate significant relationships between neuroanatomy and inflammation, childhood adversity, and psychiatric symptoms. RESULTS: Compared with HCs, the BDII-D group demonstrated significantly smaller gray matter volumes (GMVs) in frontostriatal and fronto-cerebellar area, insula, rectus, and temporal gyrus, while significantly thinner cortices were found in frontal and temporal areas. In BDII-D, smaller GMV in the right middle frontal gyrus (MFG) was correlated with greater sexual abuse (r = -0.348, q < 0.001) while larger GMV in the right orbital MFG was correlated with greater physical neglect (r = 0.254, q = 0.03). Higher WBC count (r = -0.227, q = 0.015) and IL-6 levels (r = -0.266, q = 0.015) was associated with smaller GMVs in fronto-cerebellar area in BDII-D. Greater positive symptoms was correlated with larger GMVs of the left middle temporal pole (r = 0.245, q = 0.03). CONCLUSIONS: Neuroanatomical alterations in frontostriatal and fronto-cerebellar area, insula, rectus, temporal gyrus volumes, and frontal-temporal thickness may reflect a core pathophysiological mechanism of BDII-D, which are related to inflammation, trauma, and psychiatric symptoms in BDII-D.
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Experiências Adversas da Infância , Transtorno Bipolar , Humanos , Transtorno Bipolar/diagnóstico por imagem , Depressão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Inflamação/diagnóstico por imagemRESUMO
Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Here we found that hydrogen sulfide (H2S) was required for Foxp3(+) Treg cell differentiation and function and that H2S deficiency led to systemic autoimmune disease. H2S maintained expression of methylcytosine dioxygenases Tet1 and Tet2 by sulfhydrating nuclear transcription factor Y subunit beta (NFYB) to facilitate its binding to Tet1 and Tet2 promoters. Transforming growth factor-ß (TGF-ß)-activated Smad3 and interleukin-2 (IL-2)-activated Stat5 facilitated Tet1 and Tet2 binding to Foxp3. Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in Foxp3 to establish a Treg-cell-specific hypomethylation pattern and stable Foxp3 expression. Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease. Thus, H2S promotes Tet1 and Tet2 expression, which are recruited to Foxp3 by TGF-ß and IL-2 signaling to maintain Foxp3 demethylation and Treg-cell-associated immune homeostasis.
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Colite/imunologia , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Sulfeto de Hidrogênio/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Fator de Ligação a CCAAT/metabolismo , Diferenciação Celular/genética , Colite/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Dioxigenases , Fatores de Transcrição Forkhead/genética , Homeostase/genética , Homeostase/imunologia , Humanos , Interleucina-2/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas/genética , Fator de Transcrição STAT5/metabolismo , Proteína Smad3/metabolismo , Linfócitos T Reguladores/transplante , Fator de Crescimento Transformador beta/imunologiaRESUMO
The self-oscillation of objects that perform continuous and periodic motions upon unchanging and constant stimuli is highly important for intelligent actuators, advanced robotics, and biomedical machines. Liquid crystalline elastomer (LCE) materials are superior to traditional stimuli-responsive polymeric materials in the development of self-oscillators because of their reversible, large and anisotropic shape-changing ability, fast response ability and versatile structural design. In addition, fiber-shaped oscillators have attracted much interest due to their agility, flexibility and diverse oscillation modes. Herein, we present a strategy for fabricating fiber-shaped LCE self-oscillators using soft tubes as molds. Through the settlement of different configuration states of the soft tubes, the prepared fiber-shaped LCE oscillators can perform continuous rotational self-oscillation or up-and-down shifting self-oscillation under constant light stimuli, which are realized by photoinduced repetitive self-winding motion and self-waving motion, respectively. The mechanism of self-oscillating movements is attributed to the local temperature oscillation of LCE fibers caused by repetitive self-shadowing effects. LCE self-oscillators can operate stably over many oscillating cycles without obvious performance attenuation, revealing good robustness. Our work offers a versatile way by which LCE self-oscillators can be conveniently designed and fabricated in bulk and at low cost, and broadens the road for developing self-oscillating materials for biological robotics and health care machines.
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GFRS is the conversion product of Panax ginseng Meyer berry after citric acid heat treatment, which is rich in rare ginsenosides. However, the anti-melanin role of GFRS in the regulation of skin pigmentation and its material basis remains unclear. To compare the anti-melanin activity before and after citric acid heat treatment, we determined the effects of GFS and GFRS on tyrosinase activity and melanin lever under α-MSH stimulation and found the potential anti-melanin effect of GFRS. Further, Western blot and immunofluorescence methods were used to reveal the mechanism by which GFRS detects anti-melanin activity by promoting autophagy flux levels. In zebrafish models, GFRS inhibited endogenous melanin and tyrosinase better than arbutin and promoted the accumulation of autophagy levels in vivo. To determine the material basis of the anti-melanin effect of GFRS, HPLC was used to isolate and prepare 12 ginsenosides from GFRS, and their activity evaluation and structure-activity relationship analysis were performed. The results showed that the inhibitory effect of GFRS on melanin was Rg3 > Rg5 > Rk1 > Rd. Molecular docking showed that their docking fraction with mushroom tyrosinase was significantly better than that of arbutin, but the presence of C-20 glycosylation decreased the anti-melanin activity of Rd. To maximize the content of Rg3, Rg5, and Rk1, we optimized the process by using citric acid heat treatment of ginsenoside Rd and found that citric acid heat treatment at 100°C almost completely transformed Rd and obtained a high content of active ingredients. In summary, our data demonstrated that GFRS exerted anti-melanin effects by inducing autophagy. It was further revealed that Rg3, Rg5, and Rk1, as effective active components, could be enriched by the improved process of converting ginsenoside Rd by citric acid heat treatment.
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Autofagia , Ácido Cítrico , Ginsenosídeos , Temperatura Alta , Melaninas , Panax , Peixe-Zebra , Panax/química , Melaninas/metabolismo , Melaninas/antagonistas & inibidores , Ginsenosídeos/farmacologia , Ginsenosídeos/química , Ginsenosídeos/isolamento & purificação , Animais , Relação Estrutura-Atividade , Autofagia/efeitos dos fármacos , Ácido Cítrico/química , Ácido Cítrico/farmacologia , Estrutura Molecular , Frutas/química , Simulação de Acoplamento Molecular , Relação Dose-Resposta a Droga , Monofenol Mono-Oxigenase/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidoresRESUMO
BACKGROUND Helicobacter pylori has a high infection rate worldwide, and epidemiological study of H. pylori is important. Artificial intelligence has been widely used in the field of medical research and has become a hotspot in recent years. This paper proposed a prediction model for H. pylori infection based on machine learning in adults. MATERIAL AND METHODS Adult patients were selected as research participants, and information on 30 factors was collected. The chi-square test, mutual information, ReliefF, and information gain were used to screen the feature factors and establish 2 subsets. We constructed an H. pylori infection prediction model based on XGBoost and optimized the model using a grid search by analyzing the correlation between features. The performance of the model was assessed by comparing its accuracy, recall, precision, F1 score, and AUC with those of 4 other classical machine learning methods. RESULTS The model performed better on the part B subset than on the part A subset. Compared with the other 4 machine learning methods, the model had the highest accuracy, recall, F1 score, and AUC. SHAP was used to evaluate the importance of features in the model. It was found that H. pylori infection of family members, living in rural areas, poor washing hands before meals and after using the toilet were risk factors for H. pylori infection. CONCLUSIONS The model proposed in this paper is superior to other models in predicting H. pylori infection and can provide a scientific basis for identifying the population susceptible to H. pylori and preventing H. pylori infection.
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Infecções por Helicobacter , Helicobacter pylori , Aprendizado de Máquina , Humanos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.
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Exossomos , Neomicina , Neomicina/toxicidade , Neomicina/metabolismo , Exossomos/metabolismo , Células Ciliadas Auditivas , Autofagia/fisiologiaRESUMO
Eddy current testing (ECT) is commonly used for the detection of defects inside metallic materials. In order to achieve the effective testing of CFRP materials, increasing the operating frequency or improving the coil structure is a common method used by researchers. Higher or wider operating frequencies make the design of the ADC's conditioning circuit complex and difficult to miniaturize. In this paper, an LC resonator based on inductance-to-digital converters (LDCs) is designed to easily detect the resonant frequency response to the state of the material under test. The reasonableness of the coil design is proven by simulation. The high signal-to-noise ratio (SNR) and detection sensitivity of the LC resonator are demonstrated through comparison experiments involving multiple probes. The anti-interference capability of the LC resonator in CFRP defect detection is demonstrated through various interference experiments.
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Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder that causes accelerated aging, due to a pathogenic variant in the LMNA gene. This pathogenic results in the production of progerin, a defective protein that disrupts the nuclear lamina's structure. In our study, we conducted a histopathological analysis of various organs in the LmnaG609G/G609G mouse model, which is commonly used to study HGPS. The objective of this study was to show that progerin accumulation drives systemic but organ-specific tissue damage and accelerated aging phenotypes. Our findings show significant fibrosis, inflammation, and dysfunction in multiple organ systems, including the skin, cardiovascular system, muscles, lungs, liver, kidneys, spleen, thymus, and heart. Specifically, we observed severe vascular fibrosis, reduced muscle regeneration, lung tissue remodeling, depletion of fat in the liver, and disruptions in immune structures. These results underscore the systemic nature of the disease and suggest that chronic inflammation and fibrosis play crucial roles in the accelerated aging seen in HGPS. Additionally, our study highlights that each organ responds differently to the toxic effects of progerin, indicating that there are distinct mechanisms of tissue-specific damage.
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Modelos Animais de Doenças , Fibrose , Inflamação , Lamina Tipo A , Progéria , Animais , Progéria/genética , Progéria/patologia , Progéria/metabolismo , Camundongos , Inflamação/patologia , Inflamação/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Especificidade de Órgãos , Pulmão/patologia , Pulmão/metabolismoRESUMO
The close-coupled selective catalytic reduction (cc-SCR) catalyst is an effective technology to reduce tailpipe NOx emission during cold start. This paper investigated the optimal ammonia storage under steady and transient state in the cc-SCR. The study showed that a trade-off between NOx conversion efficiency and ammonia slip is observed on the pareto solutions under steady state, and the optimal ammonia storage is calculated with ammonia slip less than 10 µL/L based on the China â ¥ emission legislation. The rapid temperature increase will lead to severe ammonia slip in the transient test cycle. A simplified 0-D calculation method on ammonia slip under transient state is proposed based on kinetic model of ammonia adsorption and desorption. In addition, the effect of ammonia storage, catalyst temperature and temperature increasing rate on ammonia slip are analyzed. The optimal ammonia storage is calculated with maximum ammonia slip less than 100 µL/L according to the oxidation efficiency of ammonia slip catalyst (ASC) downstream cc-SCR. It was found that the optimal ammonia storage under transient state is much lower than that under steady state in cc-SCR at lower temperature, and a phase diagram is established to analyze the influence of temperature and temperature increasing rate on optimal ammonia storage.
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Amônia , Temperatura Baixa , Oxirredução , Temperatura , CatáliseRESUMO
BBX proteins play important roles in all of the major light-regulated developmental processes. However, no systematic analysis of BBX gene family regarding the regulation of photoperiodic microtuber formation has been previously performed in yam. In this study, a systematic analysis on the BBX gene family was conducted in three yam species, with the results, indicating that this gene plays a role in regulating photoperiodic microtuber formation. These analyses included identification the BBX gene family in three yam species, their evolutionary relationships, conserved domains, motifs, gene structure, cis-acting elements, and expressional patterns. Based on these analyses, DoBBX2/DoCOL5 and DoBBX8/DoCOL8 showing the most opposite pattern of expression during microtuber formation were selected as candidate genes for further investigation. Gene expression analysis showed DoBBX2/DoCOL5 and DoBBX8/DoCOL8 were highest expressed in leaves and exhibited photoperiod responsive expression patterns. Besides, the overexpression of DoBBX2/DoCOL5 and DoBBX8/DoCOL8 in potato accelerated tuber formation under short-day (SD) conditions, whereas only the overexpression of DoBBX8/DoCOL8 enhanced the accelerating effect of dark conditions on tuber induction. Tuber number was increased in DoBBX8/DoCOL8 overexpressing plants under dark, as well as in DoBBX2/DoCOL5 overexpressing plants under SD. Overall, the data generated in this study may form the basis of future functional characterizations of BBX genes in yam, especially regarding their regulation of microtuber formation via the photoperiodic response pathway.