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Bacillus pumilus exhibits substantial economic significance, with its metabolism, adaptability, and ecological functions regulated by its bacteriophages. Here, we isolated and characterized a novel temperate phage vB_BpuM-ZY1 from B. pumilus derived from mangrove sediments by mitomycin C induction. Phage vB_BpuM-ZY1 is a typical myophage, which has an icosahedral head with a diameter of 43.34 ± 2.14 nm and a long contractible tail with a length of 238.58 ± 5.18 nm. Genomic analysis indicated that vB_BpuM-ZY1 encodes genes for lysogeny control, and its life cycle may be intricately regulated by multiple mechanisms. vB_BpuM-ZY1 was predicted to employ P2-like 5'-extended-cos packaging strategy. In addition, genome-wide phylogenetic tree and proteome tree analyses indicated that vB_BpuM-ZY1 belongs to the Peduoviridae family but forms a separate branch at a deeper taxonomic level. Particularly, the comparative genomic analysis showed that vB_BpuM-ZY1 has less than 70% intergenomic similarities with its most similar phages. Thus, we propose that vB_BpuM-ZY1 is a novel Bacillus phage belonging to a new genus under the Peduoviridae family. The protein-sharing network analysis identified 44 vB_BpuM-ZY1-related phages. Interestingly, these evolutionarily related myophages infect a broad range of hosts across different phyla, which may be explained by the high structural variations of the host recognition domain in their central spike proteins. Collectively, our study will contribute to our understanding of Bacillus phage diversity and Bacillus-phage interactions, as well as provide essential knowledge for the industrial application of B. pumilus. IMPORTANCE: Although recent metagenomics research has obtained a wealth of phage genetic information, much of it is considered "dark matter" because of the lack of similarity with known sequences in the database. Therefore, the isolation and characterization of novel phages will help to interpret the vast unknown viral metagenome data and improve our understanding of phage diversity and phage-host interactions. Bacillus pumilus shows high economic relevance due to its wide applications in biotechnology, industry, biopharma, and environmental sectors. Since phages influence the abundance, metabolism, evolution, fitness, and ecological functions of bacteria through complex interactions, the significance of isolation and characterization of novel phages infecting B. pumilus is apparent. In this study, we isolated and characterized a B. pumilus phage belonging to a novel viral genus, which provides essential knowledge for phage biology as well as the industrial application of B. pumilus.
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Background: Patients with inflammatory bowel disease (IBD) often experience worries related to travel due to frequent bowel movements. However, there is currently limited research focusing on the travel worries of patients with IBD. The aim of this study was to assess the level of worry regarding out-of-home activities in patients with IBD and identify factors associated with worry. Methods: This study included patients with IBD who visited the outpatient clinics between September 2020 and March 2022, during the COVID-19 pandemic. Participants completed a self-designed questionnaire, providing general clinical data and indicating their level of worry for out-of-home activities. Results: A total of 529 patients with IBD completed the questionnaire. Patients with Crohn's disease (CD) had a higher proportion of individuals under 40 years old and males compared to patients with ulcerative colitis (UC). Regarding out-of-home activities, patients with UC expressed greater worry about going out and taking buses than patients with CD. However, there were no significant differences observed between the two groups in terms of travel worries and worries about finding public washrooms. A significant majority (85.4%) of patients with clinically active IBD expressed worries about not finding public washrooms when going out, while 46.7% of patients in clinical remission had similar worries. Moreover, the worry about finding public washrooms was higher in patients with UC compared to those with CD, both during the clinical activity and remission. Conclusion: This survey conducted during the COVID-19 pandemic reported worries among patients with IBD about out-of-home activities. The patients with clinically active IBD, especially UC, expressed worries about not finding public washrooms when going out. We highlight the actual psychological and quality of life challenges faced by patients with IBD.
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BACKGROUND: Patients with polycystic ovary syndrome (PCOS) have a higher risk of obstetric complications. The association between anti-Müllerian hormone (AMH) and gestational hypertension in these patients is poorly understood. OBJECTIVE: To determine the association between serum AMH levels and gestational hypertension in patients with PCOS undergoing fresh embryo transfer. METHODS: This retrospective study included 649 patients with PCOS who had singleton live births after undergoing fresh embryo transfers. The association of AMH with gestational hypertension in these patients was estimated before and after propensity score matching (PSM). RESULTS: Patients with gestational hypertension had higher AMH levels than those without gestational hypertension. In single-factor logistic regression, the odds of gestational hypertension increased by 11.7% and 18.6% for every 1â ng/mL increase in AMH before and after adjusting for confounding factors [OR 1.117, 95% CI(1.025, 1.217), P = 0.012; adjusted OR 1.186, 95% CI(1.061, 1.327), adjusted P = 0.003], respectively. The odds of gestational hypertension increased more than 100% [adjusted OR 2.635, 95% CI(1.132, 6.137), adjusted P = 0.025] in the 75th percentile group (>9.30â ng/ml) and more than thrice [adjusted OR 4.75, 95% CI(1.672, 13.495), adjusted P = 0.003] in the 90th percentile group (>12.31â ng/ml) as compared to the without-gestational hypertension group. AMH level was still associated with gestational hypertension after PSM. The area under the curve of AMH predicting gestational hypertension was 0.654 [95% CI (0.532, 0.776), P = 0.011] with an optimal cutoff value of 11.975â ng/mL. CONCLUSIONS: High serum AMH level pre-pregnancy (especially at levels > 9.30â ng/mL) indicates a high odds of gestational hypertension in patients with PCOS undergoing fresh embryo transfer.
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Seamounts are globally distributed across the oceans and form one of the major oceanic biomes. Here, we utilized combined analyses of bulk metagenome and virome to study viral communities in seamount sediments in the western Pacific Ocean. Phylogenetic analyses and the protein-sharing network demonstrate extensive diversity and previously unknown viral clades. Inference of virus-host linkages uncovers extensive interactions between viruses and dominant prokaryote lineages, and suggests that viruses play significant roles in carbon, sulfur, and nitrogen cycling by compensating or augmenting host metabolisms. Moreover, temperate viruses are predicted to be prevalent in seamount sediments, which tend to carry auxiliary metabolic genes for host survivability. Intriguingly, the geographical features of seamounts likely compromise the connectivity of viral communities and thus contribute to the high divergence of viral genetic spaces and populations across seamounts. Altogether, these findings provides knowledge essential for understanding the biogeography and ecological roles of viruses in globally widespread seamounts.
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Vírus , Filogenia , Oceanos e Mares , Ecossistema , Genes ViraisRESUMO
This study explored the effects of a Bacillus subtilis and Lactobacillus acidophilus mixture containing the co-fermented products of the two probiotics on growth performance, serum immunity and cecal microbiota of Cherry Valley ducks. This study included 480 one-day-old Cherry Valley ducks divided into four feeding groups: basal diet (control group) and basal diet supplemented with 300, 500, or 700 mg/kg of the probiotic powder; the ducks were raised for 42 days. Compared with the control group, body weight on day 42 and the average daily gain on days 15-42 significantly increased (p < 0.05), and the feed conversion rate significantly decreased (p < 0.05) in the experimental groups. Furthermore, the serum immunoglobulin (Ig) A, IgG, IgM, and interleukin (IL)-4 levels increased significantly (p < 0.05), and IL-1ß, IL-2, and tumor necrosis factor-α decreased significantly (p < 0.05) in the experimental groups. Finally, Sellimonas, Prevotellaceae NK3B31 group, Lachnospiraceae NK4A136 group and Butyricoccus played an important role in the cecal microbiota of the experimental group. Thus, the probiotic powder has impacts on the growth performance, serum immunity and cecal microbiota of Cherry Valley Ducks.
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Bacillus subtilis , Ceco , Patos , Lactobacillus acidophilus , Probióticos , Animais , Probióticos/administração & dosagem , Ceco/microbiologia , Patos/crescimento & desenvolvimento , Patos/microbiologia , Patos/imunologia , Patos/sangue , Microbioma Gastrointestinal , Dieta/veterinária , Ração Animal , Imunoglobulinas/sangue , Suplementos NutricionaisRESUMO
Diabetes increases the likelihood of germ cell damage, hypogonadism, and male infertility. Diabetes leads to lower zinc (Zn) levels, an important micronutrient for maintaining male fertility, and zinc deficiency can lead to decreased male fertility through multiple mechanisms. The aim of this study was to investigate the effect of combined metformin and zinc administration on epididymis in diabetic mice; 10 of 50 male mice were randomly selected as the control group (group C), and the remaining 40 mice were randomly divided into untreated diabetes group (group D), diabetes + zinc group (group Z), diabetes + metformin group (group M), and diabetes + metformin + zinc group (group ZM) with 10 mice each. Diabetic mice in group Z received oral zinc (10 mg/kg) once daily for 4 weeks; diabetic mice in group M received oral metformin (200 mg/kg) once daily for 4 weeks; diabetic mice in group ZM received oral metformin and zinc once daily for 4 weeks; and groups C and D received the same amount of sterile water by gavage. Overnight fasted mice were sacrificed, and blood samples, mouse epididymides, and sperm were collected for further experiments. In group D, fasting blood glucose and insulin resistance index increased significantly, semen quality, serum insulin, and testosterone decreased, and epididymal structure was disordered. In group D, epididymal tissue zinc, free zinc ions in the caput, and cauda of epididymis and zinc transporter (ZnT2) decreased significantly, while ZIP12, metallothionein (MT), and metal transcription factor (MTF1) increased significantly. In addition, the expressions of blood-epididymal barrier (BEB)-related molecules (including ZO-1 ß-catenin and N-cadherin) and aquaporins (AQPs, including AQP3, AQP9, and AQP11) in the epididymis of mice in group D were significantly decreased. In addition, compared with groups D, Z, and M, in the ZM group, the expression of BEB-related molecules (including ZO-1, ß-catenin, and N-cadherin) and aquaporins (AQP3, AQP9, and AQP11) in epididymis tissue were significantly increased, and sperm motility and serum testosterone were significantly increased. It was concluded that male diabetic mice have a disturbed epididymal structure and decreased semen quality by causing an imbalance in epididymal zinc homeostasis, BEB, and impaired absorptive function. The combination of zinc and metformin is an effective and safe alternative treatment and provides additional benefits over metformin alone.
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Zinc is an important trace element involved in the biochemical and physiological functions of the organism and is essential in the human body. It has been reported that 17.3% of people around the world are at risk of many diseases due to zinc deficiency, which has already affected people's healthy lives. Currently, mild zinc deficiency is difficult to diagnose early due to the lack of typical clinical manifestations, so finding zinc biomarkers is crucial for people's health. The present article reviews the main representative zinc biomarkers, such as body fluid zinc levels, zinc-dependent proteins, tissue zinc, and zinc-containing enzymes, to provide a reference for actively promoting the study of zinc nutritional status and early clinical diagnosis.
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BACKGROUND: Patients with decompensated cirrhosis face poor prognosis and increased mortality risk. Rifaximin, a non-absorbable antibiotic, has been shown to have beneficial effects in preventing complications and improving survival in these patients. However, the underlying mechanisms of rifaximin's effects remain unclear. METHODS: We obtained fecal samples from decompensated cirrhotic patients undergoing rifaximin treatment and controls, both at baseline and after 6 months of treatment. Shotgun metagenome sequencing profiled the gut microbiome, and untargeted metabolomics analyzed fecal metabolites. Linear discriminant and partial least squares discrimination analyses were used to identify differing species and metabolites between rifaximin-treated patients and controls. RESULTS: Forty-two patients were enrolled and divided into two groups (26 patients in the rifaximin group and 16 patients in the control group). The gut microbiome's beta diversity changed in the rifaximin group but remained unaffected in the control group. We observed 44 species with reduced abundance in the rifaximin group, including Streptococcus_salivarius, Streptococcus_vestibularis, Haemophilus_parainfluenzae, etc. compared to only four in the control group. Additionally, six species were enriched in the rifaximin group, including Eubacterium_sp._CAG:248, Prevotella_sp._CAG:604, etc., and 14 in the control group. Furthermore, rifaximin modulated different microbial functions compared to the control. Seventeen microbiome-related metabolites were altered due to rifaximin, while six were altered in the control group. CONCLUSION: Our study revealed distinct microbiome-metabolite networks regulated by rifaximin intervention in patients with decompensated cirrhosis. These findings suggest that targeting these specific metabolites or related bacteria might be a potential therapeutic strategy for decompensated cirrhosis.
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Cirrose Hepática , Metagenoma , Humanos , Rifaximina/uso terapêutico , Cirrose Hepática/complicações , Resultado do Tratamento , Antibacterianos/uso terapêuticoRESUMO
Multiple myeloma (MM) is an accumulated disease of malignant plasma cells, which is still incurably owing to therapeutic resistance and disease relapse. Herein, we synthesized a novel 2-iminobenzimidazole compound, XYA1353, showing a potent anti-myeloma activity both in vitro and in vivo. Compound XYA1353 dose-dependently promoted MM cell apoptosis via activating caspase-dependent endogenous pathways. Moreover, compound XYA1353 could enhance bortezomib (BTZ)-mediated DNA damage via elevating γH2AX expression levels. Notably, compound XYA1353 interacted synergistically with BTZ and overcame drug resistance. RNA sequencing analysis and experiments confirmed that compound XYA1353 inhibited primary tumor growth and myeloma distal infiltration by disturbing canonical NF-κB signaling pathway via decreasing expression of P65/P50 and p-IκBα phosphorylation level. Due to its importance in regulating MM progression, compound XYA1353 alone or combined with BTZ may potentially exert therapeutic effects on multiple myeloma by suppressing canonical NF-κB signaling.
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Antineoplásicos , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/patologia , NF-kappa B/metabolismo , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Transdução de Sinais , Apoptose , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
As the most abundant biological entities, viruses are the major players in marine ecosystems. However, our knowledge on virus diversity and virus-host interactions in the deep sea remains very limited. In this study, vB_BteM-A9Y, a novel bacteriophage infecting Bacillus tequilensis, was isolated from deep-sea sediments in the South China Sea. vB_BteM-A9Y has a hexametric head and a long, complex contractile tail, which are typical features of myophages. vB_BteM-A9Y initiated host lysis at 60 min post infection with a burst size of 75 PFU/cell. The phage genome comprises 38,634 base pairs and encodes 54 predicted open reading frames (ORFs), of which 27 ORFs can be functionally annotated by homology analysis. Interestingly, abundant ORFs involved in DNA damage repair were identified in the phage genome, suggesting that vB_BteM-A9Y encodes multiple pathways for DNA damage repair, which may help to maintain the stability of the host/phage genome. A BLASTn search of the whole genome sequence of vB_BteM-A9Y against the GenBank revealed no existing homolog. Consistently, a phylogenomic tree and proteome-based phylogenetic tree analysis showed that vB_BteM-A9Y formed a unique branch. Further comparative analysis of genomic nucleotide similarity and ORF homology of vB_BteM-A9Y with its mostly related phages showed that the intergenomic similarity between vB_BteM-A9Y and these phages was 0-33.2%. Collectively, based on the comprehensive morphological, phylogenetic, and comparative genomic analysis, we propose that vB_BteM-A9Y belongs to a novel genus under Caudoviricetes. Therefore, our study will increase our knowledge on deep-sea virus diversity and virus-host interactions, as well as expanding our knowledge on phage taxonomy.
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BACKGROUND: Fecal microbiota transplantation (FMT) has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis (UC). FMT modulates the Toll-like receptor 4 (TLR4) signaling pathway to treat some other diseases. However, it remains unknown whether this modulation is also involved in the treatment of UC. AIM: To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate (DSS)-induced mice and explain the mechanism of FMT on UC, through association analysis of gut microbiota with colon transcriptome in mice. METHODS: A mouse colitis model was constructed with wild-type (WT) and TLR4-knockout (KO) mice. Fecal microbiota was transplanted by gavage. Colon inflammation severity was measured by disease activity index (DAI) scoring and hematoxylin and eosin staining. Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing. Gene expression in the mouse colon was obtained by transcriptome sequencing. RESULTS: The KO (DSS + Water) and KO (DSS + FMT) groups displayed indistinguishable body weight loss, colon length, DAI score, and histology score, which showed that FMT could not inhibit the disease in KO mice. In mice treated with FMT, the relative abundance of Akkermansia decreased, and Lactobacillus became dominant. In particular, compared with those in WT mice, the scores of DAI and colon histology were clearly decreased in the KO-DSS group. Microbiota structure showed a significant difference between KO and WT mice. Akkermansia were the dominant genus in healthy KO mice. The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia. Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus. The top nine genes correlating with Akkermansia included Aqp4, Clca4a, Dpm3, Fau, Mcrip1, Meis3, Nupr1 L, Pank3, and Rps13 (|R| > 0.9, P < 0.01). CONCLUSION: FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway. TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment. Akkermansia bear great therapeutic potential for colitis.
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Colite Ulcerativa , Colite , Receptor 4 Toll-Like , Animais , Camundongos , Colite/induzido quimicamente , Colite/terapia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Transdução de Sinais , Receptor 4 Toll-Like/genéticaRESUMO
Nitrous oxide (N2O) emitted from agricultural soils destroys stratospheric ozone and contributes to global warming. A promising approach to reduce emissions is fertilizing the soil using organic wastes augmented by non-denitrifying N2O-reducing bacteria (NNRB). To realize this potential, we need a suite of NNRB strains that fulfill several criteria: efficient reduction of N2O, ability to grow in organic waste, and ability to survive in farmland soil. In this study, we enriched such organisms by sequential anaerobic batch incubations with N2O and reciprocating inoculation between the sterilized substrates of anaerobic manure digestate and soils. 16S rDNA amplicon sequencing and metagenomics analysis showed that a cluster of bacteria containing nosZ genes encoding N2O-reductase, was enriched during the incubation process. Strains of several dominant members were then isolated and characterized, and three of them were found to harbor the nosZ gene but none of the other denitrifying genes, thus qualifying as NNRB. The selected isolates were tested for their capacities to reduce N2O emissions from three different typical Chinese farmland soils. The results indicated the significant mitigation effect of these isolates, even in very acidic red soil. In conclusion, this study demonstrated a strategy to engineer the soil microbiome with promising NNRB with high adaptability to livestock manure digestate as well as different agricultural soils, which would be suitable for developing novel fertilizer for farmland application to efficiently mitigate the N2O emissions from agricultural soils.
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Regulating of pore environment is an efficient way to improve the performance of covalent organic frameworks (COFs) for specific application requirements. Herein, the design and synthesis of two pyrene-based 2D COFs with -H or -Me substituents, TFFPy-PPD-COF and TFFPy-TMPD-COF are reported. Both of them show long order structure and high porosity, in which TFFPy-PPD-COF displays a larger pore volume and bigger BET surface area (2587 m2 g-1 , 1.17 cm3 g-1 ). Interestingly, TFPPy-TMPD-COF exhibits a much higher vapor iodine capacity (4.8 g g-1 ) than TFPPy-PPD-COF (2.9 g g-1 ), in contrast to their pore volume size. By using multiple techniques, the better performance of TFPPy-TMPD-COF in iodine capture is ascribed to the altered pore environment by introducing methyl groups, which contributes to the formation of polyiodide anions and enhances the interactions between the frameworks and iodine. These results will be helpful for understanding the effect of pore environment in COFs for iodine uptake and constructing novel structure with high iodine capture performance.
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Iodo , Estruturas Metalorgânicas , Adsorção , PirenosRESUMO
De novo assembly of next generation metagenomic reads is widely used to provide taxonomic and functional information of genomes in a microbial community. As strains are functionally specific, recovery of strain-resolved genomes is important but still a challenge. Unitigs and assembly graphs are mid-products generated during the assembly of reads into contigs, and they provide higher resolution for sequences connection information. In this study, we propose a new approach UGMAGrefiner (a unitig level assembly graph-based metagenome-assembled Genome refiner), which uses the connection and coverage information from unitig level assembly graphs to recruit unbinned unitigs to MAGs, adjust binning result, and infer unitigs shared by multiple MAGs. In two simulated datasets (Simdata and CAMI data) and one real dataset (GD02), it outperforms two state-of-the-art assembly graph-based binning refine tools in the refinement of MAGs' quality by stably increasing the completeness of genomes. UGMAGrefiner can identify genome specific clusters of genomes with below 99% average nucleotide identity for homologous sequences. For MAGs mixed with 99% similarity genome clusters, it could distinguish 8 out of 9 genomes in Simdata and 8 out of 12 genomes in CAMI data. In GD02 data, it could identify 16 new unitig clusters representing genome specific regions of mixed genomes and 4 unitig clusters representing new genomes from total 135 MAGs for further functional analysis. UGMAGrefiner provides an efficient way to obtain more complete MAGs and study genome specific functions. It will be useful to improve taxonomic and functional information of genomes after de novo assembly.
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Exosome is a subgroup of extracellular vesicles, which has been serving as an efficient therapeutic tool for various diseases. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. After appropriate modification, engineered exosomes are able to deliver antitumor drugs to tumor sites efficiently and precisely with fewer treatment-related adverse effects. However, there still exist many challenges for the clinical translation of engineered exosomes. For instance, what sources and modification strategies could endow exosomes with the most efficient antitumor activity is still poorly understood. Additionally, how to choose appropriately engineered exosomes in different antitumor therapies is another unresolved problem. In this review, we summarized the characteristics of engineered exosomes, especially the spatial and temporal properties. Additionally, we concluded the recent advances in engineered exosomes in the cancer fields, including the sources, isolation technologies, modification strategies, and labeling and imaging methods of engineered exosomes. Furthermore, the applications of engineered exosomes in different antitumor therapies were summarized, such as photodynamic therapy, gene therapy, and immunotherapy. Consequently, the above provides the cancer researchers in this community with the latest ideas on engineered exosome modification and new direction of new drug development, which is prospective to accelerate the clinical translation of engineered exosomes for cancer-targeted therapy.
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Exossomos , Vesículas Extracelulares , Neoplasias , Humanos , Exossomos/genética , Exossomos/patologia , Estudos Prospectivos , Neoplasias/tratamento farmacológico , Neoplasias/genética , ImunoterapiaRESUMO
BACKGROUND: This study aimed to evaluate the cut-off value of anti-Müllerian hormone (AMH) combined with body mass index (BMI) in the diagnosis of polycystic ovary syndrome (PCOS) and polycystic ovary morphology (PCOM). METHODS: This retrospective study included 15,970 patients: 3775 women with PCOS, 2879 women with PCOM, and 9316 patients as controls. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for AMH. We randomly divided the patients into two data sets. In dataset 1, a receiver operating characteristic (ROC) curve was generated to analyze the accuracy of basic AMH levels in diagnosing PCOS and PCOM. The optimal cut-off value was calculated in dataset 1 and validated in dataset 2, expressed as sensitivity and specificity. RESULTS: In the PCOS group, obese patients had the lowest AMH levels, while underweight patients had the highest AMH level (P < 0.001). After adjusting for age, the ratio of luteinizing hormone (LH) and follicle stimulating hormone (FSH), serum testosterone level, and BMI, AMH was an independent predictor of PCOS and PCOM. In the group with BMI < 18.5 kg/m2, the optimistic AMH cut-off value was 5.145 ng/mL with a sensitivity of 84.3% and specificity of 89.1%, whereas in the BMI ≥ 28 kg/m2 group, the optimistic AMH cut-off value was 3.165 ng/mL with a sensitivity of 88.7% and specificity of 74.6%. For the BMI range categories of 18.5-24, 24.0-28 kg/m2, the optimistic AMH cut-off values were 4.345 ng/mL and 4.115 ng/mL, respectively. The tendency that the group with lower weight corresponded to higher AMH cut-off values was also applicable to PCOM. In the same BMI category, patients with PCOM had a lower AMH diagnosis threshold than those with PCOS (< 18.5 kg/m2, 5.145 vs. 4.3 ng/mL; 18.5-24 kg/m2, 4.345 vs. 3.635 ng/mL; 24.0-28 kg/m2, 4.115 vs. 3.73 ng/mL; ≥ 28 kg /m2, 3.165 vs. 3.155 ng/mL). These cut-off values had a good diagnostic efficacy in the validation dataset. Based on different phenotypes and severity of ovulation disorders, the distribution of AMH in PCOS were also significantly different (P < 0.001). CONCLUSIONS: AMH is a potential diagnostic indicator of PCOS and is adversely associated with BMI. The AMH cut-off value for diagnosing PCOS was significantly higher than that for PCOM.
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Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/diagnóstico , Estudos Retrospectivos , Hormônio Antimülleriano , Índice de Massa Corporal , Valores de ReferênciaRESUMO
Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.
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Benzilisoquinolinas , Colite Ulcerativa , Colite , Animais , Camundongos , Humanos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Macrófagos , Colo/metabolismo , Benzilisoquinolinas/farmacologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Colite/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Mangrove is among the most carbon-rich biomes on earth, and viruses are believed to play a significant role in modulating local and global carbon cycling. However, few viruses have been isolated from mangrove sediments to date. Here, we report the isolation of a novel Bacillus phage (named phage vB_BviS-A10Y) from mangrove sediments. Phage vB_BviS-A10Y has a hexameric head with a diameter of ~ 79.22 nm and a tail with a length of ~ 548.56 nm, which are typical features of siphophages. vB_BviS-A10Y initiated host lysis at 3.5 h postinfection with a burst size of 25 plaque-forming units (PFU)/cell. The genome of phage vB_BviS-A10Y is 162,435 bp long with 225 predicted genes, and the GC content is 34.03%. A comparison of the whole genome sequence of phage vB_BviS-A10Y with those of other phages from the NCBI viral genome database showed that phage vB_BviS-A10Y has the highest similarity (73.7% identity with 33% coverage) to Bacillus phage PBC2. Interestingly, abundant auxiliary metabolic genes (AMGs) were identified in the vB_BviS-A10Y genome. The presence of a ß-1,3-glucosyltransferase gene in the phage genome supported our previous hypothesis that mangrove viruses may manipulate carbon cycling directly through their encoded carbohydrate-active enzyme (CAZyme) genes. Therefore, our study will contribute to a better understanding of the diversity and potential roles of viruses in mangrove ecosystems.
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Fagos Bacilares , Bacteriófagos , Vírus , Bacteriófagos/genética , Ecossistema , Genoma Viral/genética , Vírus/genética , Fagos Bacilares/genética , Genômica , FilogeniaRESUMO
Lipopolysaccharides (LPS) is one of the most potent pathogen-associated signals for the immune system of vertebrates. In addition to the canonical pathway of LPS detection mediated by toll-like receptor 4 (TLR4) signaling pathway, TRP channel-mediated pathways endow sensory neurons and epithelial cells with the ability to detect and react to bacterial endotoxins. Previous work revealed that LPS triggers TRPV4-dependent calcium influx in urothelial cells (UCs) and mouse tracheobronchial epithelial cells (mTEC). In marked contrast, here we show that most subtypes of LPS could not directly activate TRPV4 channel. Although LPS from Salmonella enterica serotype Minnesota evoked a [Ca2+]i response in freshly isolated human bronchial epithelial cells (ECs), freshly isolated mouse ear skin single-cell suspensions, or HEK293T cells transiently transfected with mTRPV4, this activation occurred in a TRPV4-independent manner. Additionally, LPS from either E. coli strains or Salmonella enterica serotype Minnesota did not evoke significant difference in inflammation and pain hyperalgesia between wild type and TRPV4 deficient mice. In summary, our results demonstrate that in vitro and in vivo effects induced by LPS are independent of TRPV4, thus providing a clarity to the questioned role of LPS in TRPV4 activation.
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Sinalização do Cálcio , Lipopolissacarídeos , Canais de Cátion TRPV , Animais , Humanos , Camundongos , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Escherichia coli/patogenicidade , Células HEK293 , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/farmacologia , Salmonella enterica/patogenicidadeRESUMO
Cell death is generally classified into two categories: regulated cell death (RCD) and accidental cell death (ACD). In particular, RCD is a kind of genetically controlled process, including programmed apoptotic death and programmed necrotic death. Pyroptosis, an inflammatory form of programmed necrotic death, causes inflammation in cells. The influence of pyroptosis on tumor is complicated. On the one hand, pyroptosis triggers antitumor response. On the other hand, pyroptosis may induce carcinogenesis. Pyroptosis is initiated by various factors, especially non-coding RNAs. In this review, we discuss the effects of ncRNAs on pyroptosis and the mechanisms by which ncRNAs initiate pyroptosis. Moreover, we introduce the influence of ncRNA on tumor resistance via pyroptosis. Additionally, we summarize how ncRNA-associated pyroptosis modulates the tumor microenvironment (TME) and thereafter triggers antitumor immune response. Finally, pyroptosis-related ncRNAs are promising diagnostic and immunotherapeutic biomarkers and therapeutic targets.