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Self-assembled protein cages are attractive scaffolds for organizing various proteins of interest (POIs) toward applications in synthetic biology and medical science. However, specifically attaching multiple POIs to a single protein cage remains challenging, resulting in diversity among the functionalized particles. Here, we present the engineering of a self-assembled protein cage, DTMi3ST, capable of independently recruiting two different POIs using SpyCatcher (SC)/SpyTag (ST) and DogCatcher (DC)/DogTag (DT) chemistries, thereby reducing variability between assemblies. Using fluorescent proteins as models, we demonstrate controlled targeting of two different POIs onto DTMi3ST protein cages both in vitro and inside living cells. Furthermore, dual functionalization of the DTMi3ST protein cage with a membrane-targeting peptide and ß-galactosidase resulted in the construction of membrane-bound enzyme assemblies in Escherichia coli, leading to a 69.6% enhancement in substrate utilization across the membrane. This versatile protein cage platform provides dual functional nanotools for biological and biomedical applications.
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Escherichia coli , Engenharia de Proteínas , Escherichia coli/genética , Peptídeos/química , beta-Galactosidase/química , beta-Galactosidase/metabolismo , HumanosRESUMO
Naturally evolved metabolons have the ability to assemble and disassemble in response to environmental stimuli, allowing for the rapid reorganization of chemical reactions in living cells to meet changing cellular needs. However, replicating such capability in synthetic metabolons remains a challenge due to our limited understanding of the mechanisms by which the assembly and disassembly of such naturally occurring multienzyme complexes are controlled. Here, we report the synthesis of chemical- and light-responsive protein cages for assembling synthetic metabolons, enabling the dynamic regulation of enzymatic reactions in living cells. Particularly, a chemically responsive domain was fused to a self-assembled protein cage subunit, generating engineered protein cages capable of displaying proteins containing cognate interaction domains on their surfaces in response to small molecular cues. Chemical-induced colocalization of sequential enzymes on protein cages enhances the specificity of the branched deoxyviolacein biosynthetic reactions by 2.6-fold. Further, by replacing the chemical-inducible domain with a light-inducible dimerization domain, we created an optogenetic protein cage capable of reversibly recruiting and releasing targeted proteins onto and from the exterior of the protein cages in tens of seconds by on-off of blue light. Tethering the optogenetic protein cages to membranes enables the formation of light-switchable, membrane-bound metabolons, which can repeatably recruit-release enzymes, leading to the manipulation of substrate utilization across membranes on demand. Our work demonstrates a powerful and versatile strategy for constructing dynamic metabolons in engineered living cells for efficient and controllable biocatalysis.
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Complexos Multienzimáticos , Proteínas , Proteínas/química , Complexos Multienzimáticos/químicaRESUMO
Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies. Here we employ scRNA-seq, RNA-seq and various molecular and cellular approaches to characterize mouse models of classical experimental autoimmune uveitis (EAU), revealing that EAU causes broad retinal neuron degeneration and marker downregulation, and that Müller glia may act as antigen-presenting cells. Moreover, EAU immune response is primarily driven by Th1 cells, and results in dramatic upregulation of CC chemokines, especially CCL5, in the EAU retina. Accordingly, overexpression of CCR5, a CCL5 receptor, in mesenchymal stem cells (MSCs) enhances their homing capacity and improves their immunomodulatory outcomes in preventing EAU, by reducing infiltrating T cells and activated microglia and suppressing Nlrp3 inflammasome activation. Taken together, our data not only provide valuable insights into the molecular characteristics of EAU but also open an avenue for innovative MSC-based therapy.
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Células-Tronco Mesenquimais , Camundongos Endogâmicos C57BL , Receptores CCR5 , Análise de Célula Única , Uveíte , Animais , Camundongos , Células-Tronco Mesenquimais/metabolismo , Uveíte/imunologia , Receptores CCR5/metabolismo , Receptores CCR5/genética , Doenças Autoimunes/terapia , Perfilação da Expressão Gênica , Modelos Animais de Doenças , Feminino , Análise da Expressão Gênica de Célula ÚnicaRESUMO
Severe pneumonia caused by respiratory viruses has become a major threat to humans, especially with the SARS-CoV-2 outbreak and epidemic. The aim of this study was to investigate the universal molecular mechanism of severe pneumonia induced by multiple respiratory viruses and to search for therapeutic strategies targeting this universal molecular mechanism. The common differential genes of four respiratory viruses, including respiratory syncytial virus (RSV), rhinovirus, influenza, and SARS-CoV-2, were screened by GEO database, and the hub gene was obtained by Sytohubba in Cytoscape. Then, the effect of hub genes on inflammasome and pyrodeath was investigated in the model of RSV infection in vitro and in vivo. Finally, through virtual screening, drugs targeting the hub gene were obtained, which could alleviate severe viral pneumonia in vitro and in vivo. The results showed that CMPK2 is one of the hub genes after infection by four respiratory viruses. CMPK2 activates the inflammasome by activating NLRP3, and promotes the releases of inflammatory factors interleukin (IL)-1ß and IL-18 to induce severe viral pneumonia. Z25 and Z08 can reduce the expression level of CMPK2 mRNA and protein, thereby inhibiting NLRP3 and alleviating the development of severe viral pneumonia. In conclusion, the inflammatory response mediated by CMPK2 is the common molecular mechanism of severe pneumonia induced by viral infection, and Z25 and Z08 can effectively alleviate viral infection and severe pneumonia through this mechanism.
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Inflamassomos , Piroptose , Piroptose/efeitos dos fármacos , Humanos , Animais , Inflamassomos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Interleucina-18/metabolismo , Interleucina-18/genética , SARS-CoV-2 , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologiaRESUMO
This paper aims to study the therapeutic effect and safety of Bushen Culuan Formula in the treatment of patients with infertility caused by hyperprolactinemia. Sixty patients with infertility caused by hyperprolactinemia of kidney deficiency and blood stasis were divided into the treatment group(Bushen Culuan Formula + Bromocriptine Mesylate Tablets placebo) and the control group(Bromocriptine Mesylate Tablets + Bushen Culuan Formula placebo), and ovulation rate, pregnancy rate, serum sex hormones, basal body temperature(BBT), and traditional Chinese medicine(TCM) symptom scores were observed. The results showed the clinical effective rate was 90.00% in the treatment group and 80.00% in the control group. The treatment group was able to significantly reduce the PRL level and increase the pregnancy rate, and it was superior to the control group in increasing the BBT biphasic ratio, improving the TCM symptom scores, and enhancing the ovulation rate. The results show that Bushen Culuan Formula is safe and reliable in treating ovulatory disorder infertility caused by hyperprolactinemia, with remarkable effects.
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Medicamentos de Ervas Chinesas , Hiperprolactinemia , Infertilidade Feminina , Ovulação , Hiperprolactinemia/tratamento farmacológico , Hiperprolactinemia/complicações , Humanos , Feminino , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Adulto , Ovulação/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Gravidez , Adulto JovemRESUMO
Transcriptomics was used to investigate the mechanism of action of Bushen Culuan Formula in the treatment of infertility caused by hyperprolactinemia(HPRL), and animal experiments were carried out to verify the results. After establishing an animal model of HPRL-induced infertility, the mice were divided into normal group, model group, Bushen Culuan Formula groups with high-, medium-, and low-doses, and bromocriptine group, and they were observed in terms of the estrous cycle, gonadal index, serum sex hormones, morphology of ovary and mammary gland, follicle count, and fertility. The results showed that the Bushen Culuan Formula could effectively restore the estrous cycle, down-regulate the levels of prolactin(PRL), follicle-stimulating hormone(FSH), and luteinizing hormone(LH), up-regulate the level of estradiol(E_2), increase the number of primordial follicles and sinus follicles, and improve the ovulation rate and fertility of mice. Through RNA sequencing combined with biosignature analysis, Bushen Culuan Formula may regulate the metabolism of lipids, antioxidant enzymes, and other substances in the cells of the ovary and pituitary gland through the signaling pathways of cAMP-PKA, Kiss-1/GPR54, and Hippo and exert therapeutic effects. The results of animal experiments showed that Bushen Culuan Formula could up-regulate serum dopamine(DA) level and pituitary DRD2 expression, down-regulate hypothalamus and ovary cAMP levels, as well as protein expressions of the pituitary gland and ovary PKA, CREB, and p-CREB, and treat HPRL-induced infertility by regulating the cAMP-PKA signaling pathway.
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Medicamentos de Ervas Chinesas , Hormônios Esteroides Gonadais , Hiperprolactinemia , Ovulação , Animais , Feminino , Camundongos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Hiperprolactinemia/tratamento farmacológico , Ovulação/efeitos dos fármacos , Humanos , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ciclo Estral/efeitos dos fármacos , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genéticaRESUMO
This study aims to observe the efficacy and safety of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS) and to explore the mechanism using metabolomics. Ninety-four patients with infertility caused by PCOS with the syndrome of kidney deficiency and blood stasis were selected and assigned into treatment and control groups(n=47). The basal body temperature(BBT) was measured, and B-ultrasonography was employed to monitor follicles, ovarian volume, endometrium, ovulation, and pregnancy. The serum levels of sex hormones including follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(PRL), estradiol(E_2), progestin(P), testosterone(T), free testosterone(FT), androstenedione(A2), inhibin B(INHB), and anti-Müllerian hormone(AMH) were measured. The coagulation function, traditional Chinese medicine(TCM) symptom scores, blood and urine routine, liver and kidney functions and other safety indicators were determined. Metabolomics was employed to comparatively analyze the serum metabolites of 26 patients(13 patients in each group) in the clinical study. The results showed that the total response rate and pregnancy rate of the treatment group were higher than those of the control group(P<0.001), suggesting that Bushen Culuan Formula regulated the sex hormones and ovarian function. Specifically, it reduced the levels of LH, T, FT, A2, and INHB(P<0.05 or P<0.01) and the LH/FSH ratio(P<0.05), elevated the level of P(P<0.05), promoted ovulation, increased endothelial thickness, and lowered TCM symptom scores without causing adverse reactions. A total of 24 differential metabolites were screened by metabolomics, and there were correlations between sex hormones and differential metabolites in the PCOS-induced infertility patients with kidney deficiency and blood stasis. In conclusion, Bushen Culuan Formula may regulate hormone levels through lipid and amino acid metabolism.
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Medicamentos de Ervas Chinesas , Infertilidade Feminina , Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/fisiopatologia , Síndrome do Ovário Policístico/complicações , Medicamentos de Ervas Chinesas/administração & dosagem , Adulto , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Infertilidade Feminina/fisiopatologia , Adulto Jovem , Gravidez , Hormônio Luteinizante/sangueRESUMO
Uterine fibroids are a prevalent factor that impacts fertility in women of reproductive age. This study discusses the theoretical foundation and formula principles of Professor MA Kun's clinical treatment for infertility caused by uterine fibroids. The kidney stores essence and is responsible for reproduction, while blood serves as a vital material basis for women's physiological functions. Kidney deficiency is the fundamental pathogenesis of infertility, and imbalances in kidney Qi and essence or deficiencies in kidney Yin and Yang can result in blood stasis. Blood stasis plays a significant role throughout this condition by impeding the flow of blood, which is crucial for nourishing Qi. Therefore, both kidney deficiency and blood stasis are key factors contributing to infertility caused by uterine fibroids. Professor MA Kun treats infertility caused by uterine fibroids using an approach that involves tonifying the kidneys and activating blood circulation based on changes in Qi and blood during the menstrual cycle as well as follicular growth processes. By identifying stage-specific evidence, appropriate treatments can be applied accordingly. During menstruation when the uterus opens and menstrual blood flows out, promoting follicular development through nourishing kidney Yin and activating blood circulation becomes essential. In later stages of menstruation, additional measures are taken to remove blood stasis, alleviate symptoms, disperse knots, attack pathogens while simultaneously replenishing vital energy. During intermenstrual periods when Yin holds greater importance than Yang, tonifying the kidneys and activating blood circulation helps facilitate smooth discharge of eggs by promoting transformation between Yin and Yang energies. Premenstrual period to warm kidney Yang to promote pregnant egg implantation, and at the same time to dredge the liver and regulate Qi, Qi elimination stagnation, complementary in the line, with the symptoms of additional subtractions. Clinical effect is remarkable, for the reference of colleagues.
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Medicamentos de Ervas Chinesas , Infertilidade Feminina , Rim , Leiomioma , Humanos , Feminino , Rim/fisiopatologia , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Infertilidade Feminina/fisiopatologia , Medicamentos de Ervas Chinesas/uso terapêuticoRESUMO
How to efficiently activate peroxymonosulfate (PMS) in a complex water matrix to degrade organic pollutants still needs greater efforts, and cobalt-based bimetallic nanomaterials are desirable catalysts. In this paper, sea urchin-like NiCo2O4 nanomaterials were successfully prepared and comprehensively characterized for their structural, morphological and chemical properties via techniques, such as X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), among others. The sea urchin-like NiCo2O4 nanomaterials exhibited remarkable catalytic performance in activating PMS to degrade phenol. Within the NiCo2O4/PMS system, the removal rate of phenol (50 mg L-1, 250 mL) reached 100% after 45 min, with a reaction rate constant k of 0.091 min-1, which was 1.4-times higher than that of the monometallic compound Co3O4/PMS system. The outstanding catalytic activity of sea urchin-like NiCo2O4 primarily arises from the synergistic effect between Ni and Co ions. Additionally, a comprehensive analysis of key parameters influencing the catalytic activity of the sea urchin-like NiCo2O4/PMS system, including reaction temperature, initial pH of solution, initial concentration, catalyst and PMS dosages and coexisting anions (HCO3-, Cl-, NO3- and humic acid), was conducted. Cycling experiments show that the material has good chemical stability. Electron paramagnetic resonance (EPR) and quenching experiments verified that both radical activation (SO4â¢-, â¢OH, O2â¢-) and nonradical activation (1O2) are present in the NiCo2O4/PMS system. Finally, the possible degradation pathways in the NiCo2O4/PMS system were proposed based on gas chromatography-mass spectrometry (GC-MS). Favorably, sea urchin-like NiCo2O4-activated PMS is a promising technology for environmental treatment and the remediation of phenol-induced water pollution problems.
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Diabetic retinopathy (DR) is a severe ocular complication of diabetes which can leads to irreversible vision loss in its late-stage. Chronic inflammation results from long-term hyperglycemia contributes to the pathogenesis and progression of DR. In recent years, the interleukin-17 (IL-17) family have attracted the interest of researchers. IL-17A is the most widely explored cytokine in IL-17 family, involved in various acute and chronic inflammatory diseases. Growing body of evidence indicate the role of IL-17A in the pathogenesis of DR. However, the pro-inflammatory and pro-angiogenic effect of IL-17A in DR have not hitherto been reviewed. Gaining an understanding of the pro-inflammatory role of IL-17A, and how IL-17A control/impact angiogenesis pathways in the eye will deepen our understanding of how IL-17A contributes to DR pathogenesis. Herein, we aimed to thoroughly review the pro-inflammatory role of IL-17A in DR, with focus in how IL-17A impact inflammation and angiogenesis crosstalk.
Assuntos
Retinopatia Diabética , Inflamação , Interleucina-17 , Neovascularização Patológica , Retinopatia Diabética/metabolismo , Retinopatia Diabética/imunologia , Humanos , Interleucina-17/metabolismo , Animais , Inflamação/metabolismo , Neovascularização Patológica/metabolismo , AngiogêneseRESUMO
BACKGROUND: TRP protein is sensitive to external temperature changes, but its pathogenic mechanism in the upper airway mucosa is still unclear. OBJECTIVE: To investigate the mechanism of TRPV1and TRPA1 in regulating the secretion of inflammatory factors in nasal epithelial cells. METHODS: The expression of TRPV1 and TRPA1 in nasal mucosal epithelial cells was investigated using immunofluorescence assays. Epithelial cells were stimulated with TRPV1 and TRPA1 agonists and antagonists, and changes in Ca2+ release and inflammatory factor secretion in epithelial cells were detected. TSLP secretion stimulated with the calcium chelating agent EGTA was evaluated. The transcription factor NFAT was observed by immunofluorescence staining. RESULTS: TRPV1 and TRPA1 expression was detected in nasal epithelial cells, and Ca2+ influx was increased after stimulation with agonists. After the activation of TRPV1 and TRPA1, the gene expression of TSLP, IL-25, and IL-33 and the protein expression levels of TSLP and IL-33 were increased, and only TSLP could be inhibited by antagonists and siRNAs. After administration of EGTA, the secretion of TSLP was inhibited significantly, and the expression of the transcription factor NFAT in the nucleus was observed after activation of the TRPV1 and TRPA1 proteins in epithelial cells. CONCLUSION: Activation of TRPV1 and TRPA1 on nasal epithelial cells stimulates the generation of TSLP through the Ca2+/NFAT pathway. It also induces upregulation of IL-25 and IL-33 gene expression levels and increased levels of IL-33 protein, leading to the development of airway inflammation.
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Interleucina-33 , Canais de Cátion TRPV , Canais de Cátion TRPV/metabolismo , Canal de Cátion TRPA1/genética , Canal de Cátion TRPA1/metabolismo , Interleucina-33/metabolismo , Ácido Egtázico/metabolismo , Expressão Gênica , Mucosa Nasal/metabolismo , Células Epiteliais/metabolismo , Fatores de Transcrição/genéticaRESUMO
Antibiotics play a vital role in safeguarding people's health since most bacterial infection can be efficiently controlled and cured by treating with suitable antibiotics. However, excessive use of antibiotics in husbandry and aquaculture leaded to the pollution of eco-environment. Thus, it is important to develop simple facile methods and effective functional materials for quick on-site analysis of antibiotics. Covalent organic frameworks (COFs), as a kind of porous crystalline covalent bond linked polymers, have demonstrated its power in multiple fields. Herein, we will discuss COFs-based materials utilized as antibiotics sensors with fluorescence method. For each sensor, we will mainly discuss the mechanism for antibiotics recognition, the preparation, characterization and fluorescence sensing performance of specific antibiotics. The mechanism to illustrate the interaction between sensors and antibiotics analytes would also be stressed.
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As a tool of brain network analysis, the graph kernel is often used to assist the diagnosis of neurodegenerative diseases. It is used to judge whether the subject is sick by measuring the similarity between brain networks. Most of the existing graph kernels calculate the similarity of brain networks based on structural similarity, which can better capture the topology of brain networks, but all ignore the functional information including the lobe, centers, left and right brain to which the brain region belongs and functions of brain regions in brain networks. The functional similarities can help more accurately locate the specific brain regions affected by diseases so that we can focus on measuring the similarity of brain networks. Therefore, a multi-attribute graph kernel for the brain network is proposed, which assigns multiple attributes to nodes in the brain network, and computes the graph kernel of the brain network according to Weisfeiler-Lehman color refinement algorithm. In addition, in order to capture the interaction between multiple brain regions, a multi-attribute hypergraph kernel is proposed, which takes into account the functional and structural similarities as well as the higher-order correlation between the nodes of the brain network. Finally, the experiments are conducted on real data sets and the experimental results show that the proposed methods can significantly improve the performance of neurodegenerative disease diagnosis. Besides, the statistical test shows that the proposed methods are significantly different from compared methods.
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Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Algoritmos , Córtex CerebralRESUMO
Atherosclerosis is a significant risk factor for developing cardiovascular disease and a leading cause of death worldwide. The occurrence of atherosclerosis is closely related to factors such as endothelial injury, lipid deposition, immunity, and inflammation. Conventional statins, currently used in atherosclerosis treatment, have numerous adverse side effects that limit their clinical utility, prompting the urgent need to identify safer and more effective therapeutic alternatives. Growing evidence indicates the significant potential of Chinese herbs in atherosclerosis treatment. Herbal monomer components, such as natural flavonoid compounds extracted from herbs like Coptis chinensis and Panax notoginseng, have been utilized for their lipid-lowering and inflammation-inhibiting effects in atherosclerosis treatment. These herbs can be used as single components in treating diseases and with other Chinese medicines to form herbal combinations. This approach targets the disease mechanism in multiple ways, enhancing the therapeutic effects. Thus, this review examines the roles of Chinese herbal medicine monomers and Chinese herbal compounds in inhibiting atherosclerosis, including regulating lipids, improving endothelial function, reducing oxidative stress, regulating inflammation and the immune response, and apoptosis. By highlighting these roles, our study offers new perspectives on atherosclerosis treatment with Chinese herbs and is anticipated to contribute to advancements in related research fields.
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Aterosclerose , Medicamentos de Ervas Chinesas , Estresse Oxidativo , Aterosclerose/tratamento farmacológico , Aterosclerose/imunologia , Aterosclerose/prevenção & controle , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Imunomodulação , Apoptose/efeitos dos fármacos , Fitoterapia , Inflamação/tratamento farmacológico , Panax notoginseng/química , Endotélio Vascular/efeitos dos fármacos , Animais , Coptis/química , FlavonoidesRESUMO
BACKGROUND: Selectively prioritizing some emotion regulation (ER) strategies over others has been shown to predict well-being; however, it is unclear what mechanisms underlie this process. Impulsivity, which captures both top-down control of and bottom-up reactivity to emotions, is one potential mechanism of interest. METHODS: Using multilevel mediation modeling, we investigated whether lower ER strategy prioritization (i.e., lower between-strategy variability) mediates the relationship between greater momentary impulsivity and lower ER success in 82 individuals with remitted depression or no history of a mental disorder (1558 observations). To determine the specific effect of impulsivity, we covaried for mean regulatory effort and negative affect. RESULTS: The indirect effect of impulsivity on ER success was significant at the within-person, but not between-person, level. Specifically, in moments when individuals endorsed more impulsivity than usual, they showed less ER strategy prioritization than usual, which predicted less successful ER. Individuals who, on average, reported more impulsivity indicated lower ER strategy prioritization, but no difference in ER success. CONCLUSION: ER strategy prioritization mediated the within-person relationship between greater impulsivity and lower ER success. Interventions focused on training individuals to selectively prioritize ER strategies may improve ER success, particularly when individuals are feeling more impulsive than usual.
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Regulação Emocional , Transtornos Psicóticos , Humanos , Depressão , Emoções/fisiologia , Comportamento Impulsivo/fisiologia , Avaliação Momentânea EcológicaRESUMO
Variability in coral hosts susceptibility to Vibrio coralliilyticus is well-documented; however, the comprehensive understanding of tolerance of response to pathogen among coral species is lacked. Herein, we investigated the microbial communities and transcriptome dynamics of two corals in response to Vibrio coralliilyticus. Favites halicora displayed greater resistance to Vibrio coralliilyticus challenge than Pocillopora damicornis. Furthermore, the relative abundances of Flavobacteriaceae, Vibrionacea, Rhodobacteraceae, and Roseobacteraceae increased significantly in Favites halicora following pathogen stress, whereas that of Akkermansiaceae increased significantly in Pocillopora damicornis, leading to bacterial community imbalance. In contrast to the previous results, pathogen infection did not have much effect on the community structures of Symbiodiniaceae and fungi, but led to a decrease in the density of Symbiodiniaceae. Transcriptome analysis indicated that Vibrio infection triggered a coral immune response, resulting in higher expression of immune-related genes, which appeared to have higher transcriptional plasticity in Favites halicora than in Pocillopora damicornis. Specifically, the upregulated genes of Favites halicora were predominantly involved in the apoptosis pathway, whereas Pocillopora damicornis were significantly enriched in the nucleotide excision repair and base excision repair pathways. These findings suggest that coral holobionts activate different mechanisms across species in response to pathogens through shifts in microbial communities and transcriptomes, which provides novel insight into assessing the future coral assemblages suffering from disease outbreaks.
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Antozoários , Microbiota , Vibrio , Animais , Antozoários/genética , Vibrio/fisiologia , Transcriptoma , Recifes de CoraisRESUMO
BACKGROUND: It is a well-established fact that post-stroke depression (PSD) is a prevalent condition that affects a significant proportion of individuals who have suffered a stroke. Hence, our research endeavors to explore the safety, efficacy and the potential molecular mechanism of transcutaneous auricular vagus nerve stimulation (ta-VNS) for the treatment of depression in PSD patients by conducting a double-blind, sham-controlled, randomized trial. METHODS: Patients who had experienced strokes and exhibited depressive symptoms, with a Hamilton Depression Scale (HAMD-17) score of ≥8 and met the DSM-IV criteria, were diagnosed with PSD. A volunteer sample of participants (N = 80) were randomly divided into either the ta-VNS group (which received ta-VNS in addition to conventional treatment) or the control group (which received conventional treatment only), in a 1:1 ratio. The effectiveness of the interventions was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and Barthel Index (BI) scores. Furthermore, Plasma BDNF, CREB1, and 5-HT levels were measured before and after treatment. RESULTS: The concomitant application of ta-VNS demonstrated a remarkable reduction in HAMD-17 and SDS scores, leading to noteworthy enhancements in patients' daily functioning, as evidenced by improved activities of daily living, at all assessed time points, in contrast to the control group (p < 0.0001). Notably, the ta-VNS group exhibited superior effects in modulating the measured neurotrophic biomarkers when compared to the control group (p < 0.05). CONCLUSIONS: The synergistic approach of combining ta-VNS with conventional treatment has demonstrated remarkable efficacy and tolerability in managing depression following a stroke.
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Acidente Vascular Cerebral , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Depressão/etiologia , Depressão/terapia , Estimulação do Nervo Vago/efeitos adversos , Atividades Cotidianas , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Método Duplo-Cego , Nervo Vago , Resultado do TratamentoRESUMO
Monkeypox has been spreading worldwide since May 2022, when the World Health Organization (WHO) declared the outbreak a "public health emergency of international concern." The spread of monkeypox has posed a serious threat to the health of people around the world, but few studies have been conducted, and the molecular mechanism of monkeypox after infection remains unclear. We therefore implemented a transcriptome analysis to identify signaling pathways and biomarkers in monkeypox-infected cells to help understand monkeypox-host cell interactions. In this study, datasets GSE36854 and GSE11234 were obtained from GEO. Of these, 84 significantly different genes were identified in the dataset GSE36854, followed by KEGG, GO analysis protein-protein interaction (PPI) construction, and Hub gene extraction. We also analyzed the expression regulation of hub genes and screened for drugs targeting hub genes. The results showed that monkeypox-infected cells significantly activated the cellular immune response. The top 10 hub genes are IER3, IFIT2, IL11, ZC3H12A, EREG, IER2, NFKBIE, FST, IFIT1 and AREG. AP-26113 and itraconazole can be used to counteract the inhibitory effect of monkeypox on IFIT1 and IFIT2 and serve as candidate drugs for the treatment of monkeypox virus infection. IRF1 may also be a transcription factor of IFIT. Our results provide a new entry point for understanding how monkeypox virus interacts with its host.
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Spontaneous mind-wandering has been theorized to increase susceptibility for rumination, contributing to risk for major depressive disorder (MDD). Clarifying whether-and under what circumstances-mind-wandering leads to rumination could inform the development of targeted interventions to reduce risk for ruminative sequelae. Using intensively sampled data in 44 young adults with remitted MDD and 38 healthy volunteers with 1,558 total observations collected from 2018 to 2022, we conducted multilevel models to investigate temporal relationships between mind-wandering and rumination. Contextual factors (e.g., intensity of negative affect; momentary impulsivity) and individual factors (e.g., MDD history) were examined as moderators of these relationships. Mind-wandering predicted increased rumination, whereas rumination did not predict increased mind-wandering. When individuals experienced greater negative affect or acted more impulsively compared to their usual levels, they showed a stronger relationship between mind-wandering and subsequent rumination. Depression history did not significantly moderate temporal relationships between mind-wandering and rumination. Spontaneous mind-wandering may transition into rumination, particularly during moments when people experience more negative affect or impulsivity compared to usual. Delivering interventions in these moments could reduce risk for ruminative sequelae. The tendency to ruminate in response to mind-wandering is suggested to be consistent regardless of depression history, suggesting the transdiagnostic and dimensional nature of rumination as a possible consequence of mind-wandering. Future work is needed to determine whether these associations are generalizable across the lifespan. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Elastography is a noninvasive technique for characterizing the mechanical properties of biological tissues. Conventional methods have limitations in resolution and sensitivity, hindering disease detection in clinical diagnostics. To address these issues, this study developed an optical-resolution photoacoustic microelastography (OR-PAME) system. Using an agar tissue phantom with varying agar concentrations and contrast agents, PAME evaluated elasticity distribution under compression in both lateral and axial dimensions. It indirectly measured elastic properties by correlating photoacoustic responses, temporal lags, and induced displacement. We also applied the system to the study of the distribution of elastic characteristics of the liver tissue after ablation, which confirmed the potential of OR-PAME in the study of elastic characteristics. Quantitative analysis showed greater lateral displacement in regions with reduced agar concentrations, indicating decreased stiffness. PAME also detected vertical displacement along the axial plane, validating its efficacy in elastographic imaging. By improving resolution and penetration, PAME provides superior visualization of elasticity distribution. Its methodology correlates microstructural alterations with tissue biomechanics, holding potential implications in medical diagnostics.