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The exponential interest in covalent organic frameworks (COFs) arises from the direct correlation between their diverse and intriguing properties and the modular design principle. However, the insufficient interlamellar interaction among COF nanosheets greatly hinders the formation of defect-free membranes. Therefore, developing a methodology for the facile fabrication of these materials remains an enticing and highly desirable objective. Herein, ultrahigh proton conductivity and superior stability are achieved by taking advantage of COF composite membranes where 2D TB-COF nanosheets are linked by 1D lignocellulosic nanofibrils (LCNFs) through π-π and electrostatic interactions to form a robust and ordered structure. Notably, the high concentration of -SO3 H groups within the COF pores and the abundant proton transport paths at COFs-LCNFs interfaces impart composite membranes ultrahigh proton conductivity (0.348 S cm-1 at 80 °C and 100% RH). Moreover, the directional migration of protons along the stacked nanochannels of COFs is facilitated by oxygen atoms on the keto groups, as demonstrated by density functional theory (DFT) calculations. The simple design concept and reliable operation of the demonstrated mixed-dimensional composite membrane are expected to provide an ideal platform for next-generation conductive materials.
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BACKGROUND: As indigestible carbohydrates, milk oligosaccharides possess various benefits for newborns, mainly through intestinal microbiota, among which 2'-fucosyllactose (2'-FL) is the most predominant milk oligosaccharide. However, knowledge about the fermentative characteristics of 2'-FL in the gut remains limited, especially in the small intestine. The aim of this study is to explore the differential fermentability of 2'-FL by the small and large intestinal microbiota of piglets using fructo-oligosaccharide (FOS) and lactose as controls in an in vitro batch fermentation experiment. During fermentation, microbial composition was characterized along with gas production and short-chain fatty acid production. RESULTS: 2'-Fucosyllactose showed differential fermentability in jejunal and colonic fermentation. Compared with the colon, 2'-FL produced less gas in the jejunum than in the FOS and lactose groups (P < 0.05). Meanwhile, 2'-FL exhibited a different influence on the microbial composition and metabolism in the jejunum and colon compared with FOS and lactose. In the jejunum, compared with the FOS and lactose groups, the 2'-FL group showed a higher abundance of Bacteroides, Prevotella, and Blautia, but a lower abundance of Streptococcus and Lactobacillus (P < 0.05), with a higher level of propionate and a lower level of lactate during fermentation (P < 0.05). In the colon, compared with the FOS and lactose groups, 2'-FL increased the abundance of Blautia, Faecalibacterium, and Lachnospiraceae FCS020, but decreased the abundance of Prevotella_9, Succinivibrio, and Megasphaera (P < 0.05) with an increase in acetate production (P < 0.05). CONCLUSION: Overall, the results suggested that the small intestinal microbiota had the potential to ferment milk oligosaccharides. Meanwhile, in comparison with FOS and lactose, 2'-FL selectively stimulated the growth of propionate-producing bacteria in the jejunum and acetate-producing bacteria in the colon. These results demonstrated the differences in fermentation properties of 2'-FL by small and large intestinal microbiota and provided new evidence for the application of 2'-FL in optimizing gut microbiota. © 2023 Society of Chemical Industry.
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Microbioma Gastrointestinal , Animais , Suínos , Fermentação , Propionatos/farmacologia , Lactose/metabolismo , Oligossacarídeos/metabolismo , Acetatos/farmacologiaRESUMO
Succinate is a vital signaling metabolite produced by the host and gut microbiota. Succinate has been shown to regulate host metabolic homeostasis and inhibit obesity-associated inflammation in macrophages by engaging its cognate receptor, SUCNR1. However, the contribution of the succinate-SUCNR1 axis to intestinal barrier dysfunction in obesity remains unclear. In the present study, we explored the effects of succinate-SUCNR1 signaling on high-fat diet (HFD)-induced intestinal barrier dysfunction. Using a SUCNR1-deficient mouse model under HFD feeding conditions, we identified the effects of succinate-SUCNR1 axis on obesity-associated intestinal barrier impairment. Our results showed that HFD administration decreased goblet cell numbers and mucus production, promoted intestinal pro-inflammatory responses, induced gut microbiota composition imbalance, increased intestinal permeability, and caused mucosal barrier dysfunction. Dietary succinate supplementation was sufficient to activate a type 2 immune response, trigger the differentiation of barrier-promoting goblet cells, suppress intestinal inflammation, restore HFD-induced mucosal barrier impairment and intestinal dysbiosis, and eventually exert anti-obesity effects. However, SUNNR1-deficient mice failed to improve the intestinal barrier function and metabolic phenotype in HFD mice. Our data indicate the protective role of the succinate-SUCNR1 axis in HFD-induced intestinal barrier dysfunction.
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Gastroenteropatias , Enteropatias , Camundongos , Animais , Ácido Succínico , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Transdução de Sinais , Inflamação/metabolismo , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Vanishing white matter (VWM) is one of the most prevalent leukoencephalopathies and is caused by recessive mutations in gene eIF2B1-5. The onset may vary from an antenatal disorder that is rapidly fatal to an adult-onset disorder with chronic progressive deterioration. METHODS: Based on a comprehensive study of 14 juvenile/adult patients diagnosed in our department as well as a review of 71 previously reported cases of genetically confirmed juvenile/adult-onset VWM since 2001, we attempted to delineate the clinical symptoms, disease evolution, episodic aggravation, associated symptoms, MRI findings and genotypic characteristics of adult VWM. RESULTS: The onset age of neuropsychiatric symptoms was 23.4 ± 10.6 years, and the mean follow-up time was 8.1 ± 4.8 years. Major clinical symptoms included headache, epilepsy, cognitive decline, cerebellar ataxia, and urinary disturbances. Episodic aggravation was found in 42.9% of the patients in our series. Molecular studies revealed fourteen novel missense mutations. Diffuse abnormal signals characterized by T1-weighted hypointensity and T2-weighted hyperintensity were observed in the supratentorial white matter. CONCLUSIONS: The symmetrical leukoencephalopathy must be considered in patients of any age with premature ovarian failure or optic neuropathy. The VWM disease spectrum consists of characteristic imaging findings in combination with extremely wide variability in VWM patients.
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Leucoencefalopatias , Substância Branca , Adolescente , Adulto , Criança , China , Fator de Iniciação 2B em Eucariotos/genética , Feminino , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética , Mutação/genética , Gravidez , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: To investigate the serum creatinine (SCr) level in patients with sporadic amyotrophic lateral sclerosis (sALS) and to explore the relationship between the SCr level and the clinical characteristics. METHODS: A total of 80 patients with sALS, 80 patients with multiple system atrophy (MSA) and 80 patients with tension-type headache (TTH) were enrolled in the study. The SCr levels were compared among the three groups. The association between the SCr level and the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), the forced vital capacity (FVC) percentage of predicted (FVC%pred), the site of symptom onset, the duration of disease and the rate of disease progression was evaluated in the sALS group. RESULTS: The SCr level was significantly decreased in the sALS group than the other two groups [(60.86 ± 16.80) µmol/L vs (70.05 ± 12.79) µmol/L and (66.97 ± 14.14) µmol/L, P < 0.01].In the sALS group, the SCr level was positively correlated with the ALSFRS-R (r = 0.315, P = 0.005), while no correlation was found between the SCr level and the FVC%pred, the site of symptom onset, the duration of disease and the rate of disease progression (all P > 0.05). CONCLUSION: The SCr level is an important biochemical index in the patients with sALS and might play an important role in monitoring the disease progression.
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Esclerose Lateral Amiotrófica/sangue , Creatinina/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The optimal revascularization strategy for non-culprit vessels is still up for debate nowadays, particularly when it comes to individuals with different Killip classes. Therefore, the aim of our study was to investigate whether multivessel revascularization, as compared with infarct-related artery (IRA) alone revascularization, improves long-term prognosis in patients who have experienced an acute myocardial infarction (AMI) and have multivessel coronary artery disease (CAD). METHODS: A retrospective analysis was conducted on clinical data from 646 patients who presented with AMI and multivessel CAD at Beijing Chaoyang hospital between November 2014 and November 2020. Based on various revascularization strategies, patients were categorised into two groups: IRA-only revascularization (n = 416) and multivessel revascularization (n = 230). The primary endpoint was cardiovascular death. RESULTS: In the following 60.6 months (60.6 ± 23.9), the primary endpoint occurred in 3% of the multivessel revascularization group versus 9.6% in the IRA-only revascularization group (HR 0.284, CI 0.120-0.669, p = 0.002). For the Killip I-II patients (n = 533), the primary endpoint occurred in 2.6% of the multivessel revascularization group versus 9.5% in the IRA-only revascularization group (HR 0.236, CI 0.083-0.667, p = 0.003). For Killip III-IV patients (n = 113), there was no significance differences in the primary endpoint. After using the inverse probability weighted method, the benefit of complete revascularization was consistently observed. CONCLUSIONS: Multivessel revascularization significantly reduced the incidence of cardiovascular death for patients presenting with AMI and multivessel CAD, particularly for Killip I-II patients. There were no significant differences in the primary outcome across the groups of patients with Killip III-IV.
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Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/complicações , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio/diagnóstico , Idoso , Intervenção Coronária Percutânea/métodos , Revascularização Miocárdica/métodos , Resultado do Tratamento , Angiografia Coronária , Vasos Coronários/cirurgia , Vasos Coronários/diagnóstico por imagem , Seguimentos , Taxa de Sobrevida/tendências , PrognósticoRESUMO
Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease with high morbidity and an increased risk of cancer or death, resulting in a heavy societal medical burden. While current treatment modalities have been successful in achieving long-term remission and reducing the risk of complications, IBD remains incurable. Nanomedicine has the potential to address the high toxic side effects and low efficacy in IBD treatment. However, synthesized nanomedicines typically exhibit some degree of immune rejection, off-target effects, and a poor ability to cross biological barriers, limiting the development of clinical applications. The emergence of bionic materials and bionic technologies has reshaped the landscape in novel pharmaceutical fields. Biomimetic drug-delivery systems can effectively improve biocompatibility and reduce immunogenicity. Some bioinspired strategies can mimic specific components, targets or immune mechanisms in pathological processes to produce targeting effects for precise disease control. This article highlights recent research on bioinspired and biomimetic strategies for the treatment of IBD and discusses the challenges and future directions in the field to advance the treatment of IBD.
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Doenças Inflamatórias Intestinais , Neoplasias , Humanos , Biomimética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Previsões , Neoplasias/tratamento farmacológicoRESUMO
Previous studies have demonstrated that L. delbrueckii plays beneficial roles in modulating the gut microbiota, enhancing the intestinal barrier, and promoting animal growth. Postbiotics have a similar or even superior effect in protecting intestinal health compared to probiotics due to their excellent stability, extended shelf life, and safety. However, the protective effects and underlying mechanism of postbiotics from L. delbrueckii in intestinal inflammation remain unclear. In this study, we demonstrated the beneficial impact of postbiotics from L. delbrueckii on intestinal health by establishing a S. Typhimurium-induced intestinal inflammation model in mice, which included inactivated bacteria and supernatant. The results revealed that the probiotics and postbiotics from L. delbrueckii increased the survival rate and body weight of S. Typhimurium-induced mice, increased the level of IL-10, and decreased the levels of TNF-α and IL-6, thereby alleviating intestinal inflammation. Meanwhile, treatment with postbiotics decreased the levels of D-LA, DAO, and LPS and promoted the expression of Occludin, ZO-1, and Claudin-1 in the serum and jejunum, suggesting an improvement in intestinal barrier function by postbiotics. Additionally, the postbiotics modulated gut microbial diversity, increased the ratio of Firmicutes and Bacteroidetes, and restored the abundance of Muribaculaceae, Lachnospiraceae_NK4a136_groups, and Alloprevotella in S. Typhimurium-infected mice. Moreover, postbiotics from L. delbrueckii promoted the expansion of intestinal stem cells (ISCs) and increased the numbers of Paneth and Goblet cells. Taken together, these data revealed the beneficial role of postbiotics from L. delbrueckii in protecting against intestinal inflammation by promoting the expansion of ISCs.
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With multiscale hierarchical structure, wood is suitable for a range of high-value applications, especially as a chromatographic matrix. Here, we have aimed to provide a weak anion-exchange polymeric monolithic column based on natural wood with high permeability and stability for effectively separating the targeted protein. The wood-polymeric monolithic column was synthesized by in situ polymerization of glycidyl methacrylate and ethylene glycol dimethacrylate in wood, and coupled with diethylaminoethyl hydrochloride. The wood-polymeric monolithic column can be integrated with fast-protein liquid chromatography for large-scale protein purification. According to the results, the wood-polymeric monolithic column showed high hydrophilicity, permeability and stability. Separation experiments verified that the wood-polymeric monolithic column could purify the targeted protein (spike protein of SARS-COV-2 and ovalbumin) from the mixed proteins by ion exchange, and the static adsorption capacity was 33.04 mg mL-1 and the dynamic adsorption capacity was 24.51 mg mL-1. In addition, the wood-polymerized monolithic column had good stability, and a negligible decrease in the dynamic adsorption capacity after 20 cycles. This wood-polymerized monolithic column can provide a novel, efficient, and green matrix for monolithic chromatographic columns.
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Madeira , Madeira/química , Adsorção , Metacrilatos/química , Cromatografia por Troca Iônica/métodos , Polímeros/química , Ovalbumina/química , Ovalbumina/isolamento & purificação , Interações Hidrofóbicas e Hidrofílicas , SARS-CoV-2 , Polimerização , Compostos de EpóxiRESUMO
Gut hormones are produced by enteroendocrine cells (EECs) found along the intestinal epithelium, and these cells play a crucial role in regulating intestinal function, nutrient absorption and food intake. A hydrolyzed casein diet has been reported to promote the secretion of gut hormones through the regulation of EEC development, but the underlying mechanism remains unclear. Therefore, this study was conducted to investigate whether the hydrolyzed casein diet can regulate EEC differentiation by employing mouse and organoid models. Mice were fed diets containing either casein (casein group) or hydrolyzed casein (hydrolyzed casein group) as the sole protein source. The hydrolyzed casein diet upregulated the expression of transcription factors, induced EEC differentiation, increased fasting serum ghrelin concentrations and promoted gastrointestinal (GI) motility in the duodenum compared to the casein diet. Interestingly, these differences could be abolished when there is addition of antibiotics to the drinking water, suggesting a significant role of gut microbiota in the hydrolyzed casein-mediated EEC function. Further investigation showed that the hydrolyzed casein diet led to reduced microbial diversity, especially the abundance of Akkermansia muciniphila (A. muciniphila) on the duodenal mucosa. In contrast, gavage with A. muciniphila impaired EEC differentiation through attenuated neurog3 transcription factor (Ngn3) expression, mediated through the promotion of Notch signaling. Moreover, pasteurized A. muciniphila showed similar effects to enter organoids in vitro. Overall, we found that a hydrolyzed casein diet reduced the abundance of A. muciniphila and promoted Ngn3 controlling EEC differentiation and this pathway is associated with increased GI motility in mice. The findings provide new insights into the role of hydrolyzed casein in gut transit and guidelines for using hydrolyzed casein in safe formula milk.
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Caseínas , Hormônios Gastrointestinais , Camundongos , Animais , Caseínas/metabolismo , Diferenciação Celular , Células Enteroendócrinas , Dieta , Fatores de Transcrição/metabolismo , Hormônios Gastrointestinais/metabolismo , Motilidade GastrointestinalRESUMO
High-fat diet (HFD) feeding is known to cause intestinal barrier disruption, thereby triggering severe intestinal inflammatory disease. Indole-3-aldehyde (IAld) has emerged as a potential candidate for mitigating inflammatory responses and maintaining intestinal homeostasis. However, the role of IAld in the HFD-related intestinal disruption remains unclear. In this study, 48 7 week-old male C57BL/6J mice were assigned to four groups: the normal chow diet (NCD) group received a NCD; the HFD group was fed an HFD; the HFD + IAld200 group was supplemented with 200 mg/kg IAld in the HFD; and the HFD + IAld600 group was supplemented with 600 mg/kg IAld in the HFD. The results showed that dietary IAld supplementation ameliorated fat accumulation and metabolic disorders, which are associated with reduced intestinal permeability. This reduction potentially led to decreased systemic inflammation and enhanced intestinal barrier function in HFD-fed mice. Furthermore, we found that IAld promoted intestinal stem cell (ISC) proliferation by activating aryl hydrocarbon receptors (AHRs) in vivo and ex vivo. These findings suggest that IAld restores the HFD-induced intestinal barrier disruption by promoting AHR-mediated ISC proliferation.
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Viable microorganisms and a diverse microbial ecosystem found in human milk play a crucial role in promoting healthy immune system and shaping the microbial community in the infant's gut. Culturomics is a method to obtain a comprehensive repertoire of human milk microbiota. However, culturomics is an onerous procedure, and needs expertise, making it difficult to be widely implemented. Currently, there is no efficient and feasible culturomics method specifically designed for human milk microbiota yet. Therefore, the aim of this study was to develop a more efficient and feasible culturomics method specifically designed for human milk microbiota. We obtained fresh samples of human milk from healthy Chinese mothers and conducted a 27-day enrichment process using blood culture bottles. Bacterial isolates were harvested at different time intervals and cultured on four different types of media. Using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, we identified a total of 6601 colonies and successfully obtained 865 strains, representing 4 phyla, 21 genera, and 54 species. By combining CBA and MRS media, we were able to cultivate over 94.4% of bacterial species with high diversity, including species-specific microorganisms. Prolonged pre-incubation in blood culture bottles significantly increased the number of bacterial species by about 33% and improved the isolation efficiency of beneficial bacteria with low abundance in human milk. After optimization, we reduced the pre-incubation time in blood culture bottles and selected optimal picking time-points (0, 3, and 6 days) at 37°C. By testing 6601 colonies using MALDI-TOF MS, we estimated that this new protocol could obtain more than 90% of bacterial species, reducing the workload by 57.0%. In conclusion, our new culturomics strategy, which involves the combination of CBA and MRS media, extended pre-incubation enrichment, and optimized picking time-points, is a feasible method for studying the human milk microbiota. This protocol significantly improves the efficiency of culturomics and allows for the establishment of a comprehensive repertoire of bacterial species and strains in human milk.
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OBJECTIVES: The respiratory tract is the portal of entry for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a variety of respiratory pathogens other than SARS-CoV-2 have been associated with severe cases of COVID-19 disease, the dynamics of the upper respiratory microbiota during disease the course of disease, and how they impact disease manifestation, remain uncertain. METHODS: We collected 349 longitudinal upper respiratory samples from a cohort of 65 COVID-19 patients (cohort 1), 28 samples from 28 recovered COVID-19 patients (cohort 2), and 59 samples from 59 healthy controls (cohort 3). All COVID-19 patients originated from the earliest stage of the epidemic in Wuhan. Based on a modified clinical scale, the disease course was divided into five clinical disease phases (pseudotimes): "Healthy" (pseudotime 0), "Incremental" (pseudotime 1), "Critical" (pseudotime 2), "Complicated" (pseudotime 3), "Convalescent" (pseudotime 4), and "Long-term follow-up" (pseudotime 5). Using meta-transcriptomics, we investigated the features and dynamics of transcriptionally active microbes in the upper respiratory tract (URT) over the course of COVID-19 disease, as well as its association with disease progression and clinical outcomes. RESULTS: Our results revealed that the URT microbiome exhibits substantial heterogeneity during disease course. Two clusters of microbial communities characterized by low alpha diversity and enrichment for multiple pathogens or potential pathobionts (including Acinetobacter and Candida) were associated with disease progression and a worse clinical outcome. We also identified a series of microbial indicators that classified disease progression into more severe stages. Longitudinal analysis revealed that although the microbiome exhibited complex and changing patterns during COVID-19, a restoration of URT microbiomes from early dysbiosis toward more diverse status in later disease stages was observed in most patients. In addition, a group of potential pathobionts were strongly associated with the concentration of inflammatory indicators and mortality. CONCLUSION: This study revealed strong links between URT microbiome dynamics and disease progression and clinical outcomes in COVID-19, implying that the treatment of severe disease should consider the full spectrum of microbial pathogens present.
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COVID-19 , Microbiota , Humanos , SARS-CoV-2 , Nariz , Progressão da DoençaRESUMO
Considerable research has been devoted to finding a cost-effective chromatographic matrix with efficient adsorption and high throughput. Wood exhibits complex micro-network structures that make it a powerful contender for a novel environment-friendly chromatographic matrix material. We demonstrate a novel strategy to manufacture a wood monolithic column, which chemically modified the wood and imported diethyl aminoethyl, diethylamine, and amino groups. This wood monolithic column can maintain fully monolithic column performances and highly selective to spike glycoprotein of SARS-CoV-2 by ion exchange force. The wood monolithic column was evaluated by static adsorption, dynamic adsorption, and frontal analysis. The results showed that the static adsorption capacity of the wood monolithic column with 2-diethylaminoethylchloride hydrochloride for bovine serum albumin was 14.72 mg/g, and the adsorption process was chemisorption. In addition, it retained 80 % adsorption capacity after 110 repeated adsorption-elution cycles.
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COVID-19 , SARS-CoV-2 , Porosidade , Madeira , Glicoproteína da Espícula de Coronavírus , GlicoproteínasRESUMO
BACKGROUND: Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut. Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models. However, how gut microbes regulate intestinal serotonin production in piglets remains vague. To investigate the relationship between microbiota and serotonin specifically in the colon, microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion. Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investigate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells. RESULTS: Antibiotic infusion increased quantities of Lactobacillus amylovorus (LA) that positively correlated with increased serotonin concentrations in the colon, while no effects observed for Limosilactobacillus reuteri (LR). To understand how microbes regulate serotonin, representative strains of LA, LR, and Streptococcus alactolyticus (SA, enriched in feces from prior observation) were selected for cell culture studies. Compared to the control group, LA, LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1 (TPH1) expression and promoted serotonin production in IPEC-J2 cells, while in RIN-14B cells only LA exerted similar action. To investigate potential mechanisms mediated by microbe-derived molecules, microbial metabolites including lactate, acetate, glutamine, and γ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacterial supernatant. Among these metabolites, acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1. Similar effects were also recapitulated when treating the cells with AR420626, an agonist targeting free fatty acid receptor 3. CONCLUSIONS: Overall, these results suggest that Lactobacillus amylovorus showed a positive correlation with serotonin production in the pig gut and exhibited a remarkable ability to regulate serotonin production in cell cultures. These findings provide evidence that microbial metabolites mediate the dialogue between microbes and host, which reveals a potential approach using microbial manipulation to regulate intestinal serotonin biosynthesis.
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Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The clinical disease characteristics and case fatality rates of SFTSV may vary across distinct regions and among different variant genotypes. From 2018 to 2022, we surveyed and recruited 202 severe fever with thrombocytopenia syndrome (SFTS) patients in Hubei Province, a high-incidence area of the epidemic, and conducted timely and systematic research on the disease characteristics, SFTSV diversity, and the correlation between virus genome variation and clinical diseases. Our study identified at least 6 genotypes of SFTSV prevalent in Hubei Province based on the analysis of the S, M, and L genome sequences of 88 virus strains. Strikingly, the dominant genotype of SFTSV was found to change during the years, indicating a dynamic shift in viral genetic diversity in the region. Phylogenetic analysis revealed the genetic exchange of Hubei SFTSV strains was relatively frequent, including 3 reassortment strains and 8 recombination strains. Despite the limited sample size, SFTSV C1 genotype may be associated with higher mortality compared to the other four genotypes, and the serum amyloid A (SAA) level, an inflammatory biomarker, was significantly elevated in these patients. Overall, our data summarize the disease characteristics of SFTSV in Hubei Province, highlight the profound changes in viral genetic diversity, and indicate the need for in-depth monitoring and exploration of the relationship between viral mutations and disease severity.
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Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Infecções por Bunyaviridae/epidemiologia , Filogenia , Phlebovirus/genética , China/epidemiologia , Variação GenéticaRESUMO
Introduction: Pure ventricular hemorrhage is often secondary to Moyamoya disease, rarely caused by rupture of ventricular aneurysm. The surgical treatment of the latter is very challenging. 3D Slicer reconstruction technology can accurately locate small intracranial lesions and combined with minimally invasive surgery with transcranial neuroendoscope is a new attempt to treat the above diseases. Case presentation: We report a case of pure intraventricular hemorrhage secondary to rupture of a distal segment aneurysm of the anterior choroidal artery. Brain computed tomography (CT) before admission showed pure ventricular hemorrhage, and brain CT angiography (CTA) before operation showed a distal segment aneurysm of the anterior choroidal artery. We used 3D Slicer reconstruction and precise location of the focus before the operation and used the minimally invasive surgery technique with transcranial neuroendoscope to completely remove the hematoma in the ventricle, and found the responsible aneurysm located in the ventricle. Conclusion: Pure intraventricular hemorrhage requires vigilance against the distal segment aneurysm of the anterior choroidal artery. At present, conventional microscopic craniotomy and intravascular interventional therapy have limitations, and 3D Slicer reconstruction and precise positioning technology combined with transcranial neuroendoscope minimally invasive surgery may be a good choice.
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A phenylalanine (Phe)-restricted diet is indispensable for individuals suffering from phenylketonuria (PKU). Our previous study reported a low-Phe-containing whey protein hydrolysate (LPH) prepared from a selected whey protein hydrolysate (TA2H). This study aimed to investigate the osteogenic activity of LPH and TA2H in MC3T3-E1 preosteoblast cells and explore the underlying mechanism. Results showed that the treatment of TA2H and LPH (at the final concentrations of 100-1000 µg/mL) had a stimulatory effect on the proliferation, differentiation, and mineralization of MC3T3-E1 cells. The LPH of 1000 µg/mL significantly increased cell proliferation (2.15- ± 0.11-fold) and alkaline phosphatase activity (1.22- ± 0.07-fold), promoted the protein and mRNA levels of runt-related transcription factor 2 (Runx2, 2.50- ± 0.14-fold and 2.97- ± 0.23-fold, respectively), enhanced the expression of differentiation biomarkers (type-I collagen, osteocalcin, and osteopontin), increased calcium deposition (1.56- ± 0.08-fold), and upregulated the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand. The exploration of signaling pathways indicated that the activated p38-dependent Runx2 signaling contributed to the LPH-induced osteogenesis. These results provided evidence, for the first time, that a prepared low-Phe whey protein hydrolysate positively modulated the activity of osteoblasts through the p38/Runx2 pathway, thereby providing a new osteoinductive protein substitute to make functional PKU food.
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Subunidade alfa 1 de Fator de Ligação ao Core , Osteogênese , Diferenciação Celular , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Osteoblastos , Fenilalanina/metabolismo , Fenilalanina/farmacologia , Hidrolisados de Proteína/metabolismo , Hidrolisados de Proteína/farmacologia , Soro do Leite/metabolismoRESUMO
Succinate is produced by both the host and microbiota with pleiotropic functions in the modulation of intestinal inflammation and metabolic homeostasis, but the mechanisms remain elusive. This study aimed to determine whether dietary succinate influences the intestinal inflammatory response and to analyze the possible mechanisms by which succinate regulates enterohepatic metabolism. Sixteen growing barrows were randomly assigned to two groups, fed with a basal diet that consisted of a typical commercial diet or fed with a basal diet supplemented with 1% sodium succinate. Our data showed that dietary succinate activated the expression of succinate receptor 1 (SUCNR1) and increased the concentrations of pro-inflammatory cytokines in the intestine. Dietary succinate inhibited the expression levels of the ileal Farnesol X receptor (FXR) and its target genes, promoted hepatic bile acid secretion, and altered the bile acid metabolic profile. Then, we demonstrated that the pro-inflammatory cytokines triggered by succinate disrupted the ability of bile acids to activate FXR and fibroblast growth factor 19. Furthermore, dietary succinate reduced the abundance of bile-salt hydrolase enriched bacteria in the ileum. Taken together, dietary succinate activated the pro-inflammatory response via SUCNR1 in the intestine, and the pro-inflammatory cytokines induced by succinate blocked the activation of FXR and its target genes and disturbed bile acid enterohepatic circulation.
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Circulação Êntero-Hepática , Ácido Succínico , Suínos , Animais , Ácido Succínico/metabolismo , Ácidos e Sais Biliares/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Citocinas/genética , Citocinas/metabolismoRESUMO
Leptospirosis is an important zoonosis that is caused by pathogenic Leptospira, which is considered to be a re-emerging infectious disease in many countries. Rodents are the most important reservoirs for both human and animal infection. An epidemiological survey of pathogenic Leptospira in rodents is important for the prevention and control of leptospirosis. In this study, a total of 964 rodents were captured from six cities in Hubei Province, and two pathogenic Leptospira species (L. interrogans and L. borgpetersenii) were detected using nested PCR with an overall prevalence of 4.8%. L. interrogans was distributed in five sampling sites, which may be the dominant species of pathogenic Leptospira in Hubei Province. In addition, Rattus norvegicus showed a relatively high infection rate, which may play an important role in the transmission and infection of pathogenic Leptospira. This study reveals the prevalence of pathogenic Leptospira in wild rodents in Hubei Province, suggesting that the risk of leptospirosis infection in Hubei Province still exists.