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The widespread sulfonamide resistance genes sul1, sul2, and sul3 in food and gut bacteria have attracted considerable attention. In this study, we assessed the in vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli, using a murine model. High fitness costs were incurred for sul1 and sul3 gene-dependent E. coli strains in vivo. A fitness advantage was found in three of the eight mice after intragastric administration of sul2 gene-dependent E. coli strains. We isolated three compensatory mutant strains (CMSs) independently from three mice that outcompeted the parent strain P2 in vivo. Whole-genome sequencing revealed seven identical single nucleotide polymorphism (SNP) mutations in the three CMSs compared with strain P2, an additional SNP mutation in strain S2-2, and two additional SNP mutations in strain S2-3. Furthermore, tandem mass tag-based quantitative proteomic analysis revealed abundant differentially expressed proteins (DEPs) in the CMSs compared with P2. Of these, seven key fitness-related DEPs distributed in two-component systems, galactose and tryptophan metabolism pathways, were verified using parallel reaction monitoring analysis. The DEPs in the CMSs influenced bacterial motility, environmental stress tolerance, colonization ability, carbohydrate utilization, cell morphology maintenance, and chemotaxis to restore fitness costs and adapt to the mammalian gut environment.IMPORTANCESulfonamides are traditional synthetic antimicrobial agents used in clinical and veterinary medical settings. Their long-term excessive overuse has resulted in widespread microbial resistance, limiting their application for medical interventions. Resistance to sulfonamides is primarily conferred by the alternative genes sul1, sul2, and sul3 encoding dihydropteroate synthase in bacteria. Studying the potential fitness cost of these sul genes is crucial for understanding the evolution and transmission of sulfonamide-resistant bacteria. In vitro studies have been conducted on the fitness cost of sul genes in bacteria. In this study, we provide critical insights into bacterial adaptation and transmission using an in vivo approach.
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PURPOSE: To comprehensively evaluate and compare all the available reference guides for the safe use of drugs during pregnancy, with the goal of determining the scientificity and reliability of these reference guides. METHODS: We searched PubMed, EMbase, CNKI, Wanfang Database, and VIP database to comprehensively identify the available reference guides. Moreover, we selected 103 drugs based on relevant literatures, and compared the recommendations of each drug from different reference guides. RESULTS: A total of 14 available reference guides were identified. However, none of these reference guides assessed the risk of bias of original studies or the quality of current evidence. Seven reference guides adopted expert consensus method to formulate pregnancy recommendations, while the rest reference guides did not report the formation method. Moreover, 77.7% of the selected drugs had inconsistent recommendations among different reference guides. In addition, the referenced human and animal studies for the same drug differed among different reference guides. CONCLUSION: Our results indicate that current reference guides for the safe use of drugs during pregnancy are less scientific and reliable, and there are considerable discrepancies in recommendations from different reference guides concerning drug use during pregnancy. The reasons for the discrepancies in recommendations include â the literature search in most reference guides was not comprehensive, â¡ none of the available reference guides assessed the risk of bias of original studies or the quality of current evidence, and ⢠the method adopted by current reference guides to formulate recommendations had obvious subjectivity and lacked of scientificity.
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BACKGROUND: Adenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles. RESULTS: Differences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse. CONCLUSIONS: The vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.
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Adenomiose , Ciclo Menstrual , Microbiota , Vagina , Humanos , Feminino , Vagina/microbiologia , Ciclo Menstrual/fisiologia , Adulto , Adenomiose/microbiologia , Adenomiose/fisiopatologia , Adenomiose/complicações , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Estudos de Casos e Controles , RNA Ribossômico 16S/genética , Lactobacillus/isolamento & purificaçãoRESUMO
China has the largest pig herd in the world which accounts for more than 50% of the global pig population. Over the past three decades, the porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic loss to the Chinese swine industry. Currently, the prevalent PRRSV strains in the field are extremely complicated, and the NADC30-like strains, NADC34-like strains, and novel recombinant viruses have become a great concern to PRRS control in China. In this study, a novel NADC30-like PRRSV, named GS2022, was isolated from the lung of a dead pig collected from a farm that experienced a PRRS outbreak. The complete genome of GS2022 shares the highest identity with the NADC30 strain and contains a discontinuous deletion of 131 aa in nsp2. Novel deletion and insertion have been identified in ORF7 and 3'UTR. Recombination analysis revealed that the GS2022 is a potential recombinant of NADC30-like and JXA1-like strains. Both inter-lineage and intra-lineage recombination events were predicted to be involved in the generation of the GS2022. An infectious cDNA clone of GS2022 was assembled to generate the isogenic GS2022 (rGS2022). The growth kinetics of rGS2022 were almost identical to those of GS2022. The pathogenicity of the GS2022 and rGS2022 was evaluated using a nursery piglet model. In the infection groups, the piglets exhibited mild clinical symptoms, including short periods of fever and respiratory diseases. Both gross lesions and histopathological lesions were observed in the lungs and lymph nodes of the infected piglets. Therefore, we reported a novel recombinant NADC30-like PRRSV strain with moderate pathogenicity in piglets. These results provide new information on the genomic characteristics and pathogenicity of the NADC30-like PRRSV in China.
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Endometriosis diagnosis is usually delayed. The gold standard for diagnosing endometriosis is laparoscopy, which is invasive and accompanied by several risks. Currently, there are no effective non-invasive biomarkers for diagnosing endometriosis. Here, we investigated whether metabolites whose levels are altered in patients with endometriosis hold potential as diagnostic biomarkers for the disease. This case-control study involved 32 patients with endometriosis and 29 patients with other benign gynecological disease. The diagnosis of all patients was confirmed through postoperative histopathological examination, and the patients were divided into two groups: an endometriosis group (EM) and a control group. Fasting blood was collected and used for non-targeted metabolomic-based detection. The data were processed through principal component analysis, orthogonal partial least squares discriminant analysis, and significance analysis of microarrays. A univariate receiver operating characteristic curve was used to evaluate the diagnostic value of the metabolites. The metabolite profiles of patients with endometriosis were markedly different compared with those of the controls. In addition, several metabolic pathways, including biosynthesis of unsaturated fatty acids, arginine biosynthesis, and glutathione metabolism, were altered. Ornithine and medorinone showed better potential as biomarkers for endometriosis diagnosis than CA125. We analyzed the altered metabolic profiles in patients with endometriosis and found ornithine and medorinone as potential non-invasive biomarkers for endometriosis diagnosis, whereas the combined ornithine-medorinone diagnosis is more valuable. These findings may help advance research on non-invasive diagnostic biomarkers for endometriosis. Further research with an improved study design and a larger cohort should be performed to confirm the diagnostic potential and clinical application of these biomarkers.
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Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca2+.
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In this study, the novel polysaccharides named HSP-0 M and HSP-0.1 M were successfully purified from Huangshui (HS), and their structural properties and bioactivities were investigated. Structural analysis revealed that HSP-0 M had a molecular weight of 493.87 kDa and was composed of arabinose, galactose, glucose, xylose, and mannose in a molar ratio of 1.48:1.09:26.52:1.33:1.00. On the other hand, HSP-0.1 M was made up of fructose, arabinose, galactose, glucose, xylose, mannose, ribose, galacturonic acid and glucuronic acid in a ratio of 2.67:26.00:29.10:36.83:16.22:30.53:1.00:1.43:3.64 with a molecular weight of 157.6 kDa. Methylated and 2D NMR analyses indicated that T-Glcp-(1 â 4)-Glcp-(1 â 2)-Glcp-(1 â 3)-Glcp was the primary chain of HSP-0 M, and the backbone of HSP-0.1 M was made up of â3)-Galp-(1 â 6)-Manp-(1 â 3)-Glcp-(1 â 6)-Glcp-(1 â 2)-Manp-(1 â 6)-Glcp-(1 â 3)-Galp. Morphological research showed that both polysaccharides were homogeneous as well as exhibit a web-like structure and an irregular lamellar structure. Furthermore, HSP-0 M demonstrated the capacity to safeguard Lactococcus lactis from damage caused by low temperatures and freeze-drying, while HSP-0.1 M exhibited noteworthy antioxidant activity. These results established a theoretical foundation for the applications of HSPs in food products, cosmetics, and medicines.
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Antioxidantes , Peso Molecular , Polissacarídeos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Monossacarídeos/análise , Monossacarídeos/química , MetilaçãoRESUMO
Due to the extended generation cycle of trees, the breeding process for forest trees tends to be time-consuming. Genetic engineering has emerged as a viable approach to expedite the genetic breeding of forest trees. However, current genetic engineering techniques employed in forest trees often utilize continuous expression promoters such as CaMV 35S, which may result in unintended consequences by introducing genes into non-target tissues. Therefore, it is imperative to develop specific promoters for forest trees to facilitate targeted and precise design and breeding. In this study, we utilized single-cell RNA-Seq data and co-expression network analysis during wood formation to identify three vascular tissue-specific genes in poplar, PP2-A10, PXY, and VNS07, which are expressed in the phloem, cambium/expanding xylem, and mature xylem, respectively. Subsequently, we cloned the promoters of these three genes from '84K' poplar and constructed them into a vector containing the eyGFPuv visual selection marker, along with the 35S mini enhancer to drive GUS gene expression. Transgenic poplars expressing the ProPagPP2-A10::GUS, ProPagPXY::GUS, and ProPagVNS07::GUS constructs were obtained. To further elucidate the tissue specificity of these promoters, we employed qPCR, histochemical staining, and GUS enzyme activity. Our findings not only establish a solid foundation for the future utilization of these promoters to precisely express of specific functional genes in stems but also provide a novel perspective for the modular breeding of forest trees.
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Populus , Regiões Promotoras Genéticas , Populus/genética , Populus/metabolismo , Regiões Promotoras Genéticas/genética , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Xilema/genética , Xilema/metabolismo , Floema/genética , Floema/metabolismo , Genes de PlantasRESUMO
The growing concern about migratory birds potentially spreading ticks due to global warming has become a significant issue. The city of Nantong in this study is situated along the East Asia-Australasian Flyway (EAAF), with numerous wetlands serving as roosting sites for migratory birds. We conducted an investigation of hard ticks and determined the phylogenetic characteristics of tick species in this city. We utilized three different genes for our study: the mitochondrial cytochrome oxidase subunit 1 (COX1) gene, the second internal transcribed spacer (ITS2), and the mitochondrial small subunit rRNA (12 S rRNA) gene. The predominant tick species were Haemaphysalis flava (H. flava) and Haemaphysalis longicornis (H. longicornis). Additionally, specimens of Haemaphysalis campanulata (H. campanulata) and Rhipicephalus sanguineus (R. sanguineus) were collected. The H. flava specimens in this study showed a close genetic relationship with those from inland provinces of China, as well as South Korea and Japan. Furthermore, samples of H. longicornis exhibited a close genetic relationship with those from South Korea, Japan, Australia, and the USA, as well as specific provinces in China. Furthermore, R. sanguineus specimens captured in Nantong showed genetic similarities with specimens from Egypt, Nigeria, and Argentina.
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Migração Animal , Aves , Complexo IV da Cadeia de Transporte de Elétrons , Ixodidae , Filogenia , Animais , China , Ixodidae/genética , Ixodidae/classificação , Ixodidae/fisiologia , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/análise , RNA Ribossômico/genética , RNA Ribossômico/análise , Ninfa/crescimento & desenvolvimento , Ninfa/classificação , Ninfa/genética , Ninfa/fisiologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/análise , DNA Espaçador Ribossômico/análiseRESUMO
BACKGROUND: A series of signal detection methods have been developed to detect adverse drug reaction (ADR) signals in spontaneous reporting system. However, different signal detection methods yield quite different signal detection results, and we do not know which method has the best detection performance. How to choose the most suitable signal detection method is an urgent problem to be solved. In this study, we systematically reviewed the characteristics and application scopes of current signal detection methods, with the goal of providing references for the optimization selection of signal detection methods in spontaneous reporting system. METHODS: We searched six databases from inception to January 2023. The search strategy targeted literatures regarding signal detection methods in spontaneous reporting system. We used thematic analysis approach to summarize the advantages, disadvantages, and application scope of each signal detection method. RESULTS: A total of 93 literatures were included, including 27 reviews and 66 methodological studies. Moreover, 31 signal detection methods were identified in these literatures. Each signal detection method has its inherent advantages and disadvantages, resulting in different application scopes of these methods. CONCLUSION: Our systematic review finds that there are variabilities in the advantages, disadvantages, and application scopes of different signal detection methods. This finding indicates that the most suitable signal detection method varies across different drug safety scenarios. Moreover, when selecting signal detection method in a particular drug safety scenario, the following factors need to be considered: purpose of research, database size, drug characteristics, adverse event characteristics, and characteristics of the relations between drugs and adverse events.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Bases de Dados Factuais/estatística & dados numéricosRESUMO
PURPOSE: To examine the associations between use of statins and risks of various ovarian, uterine, and cervical diseases, including ovarian cancer, endometrial cancer, cervical cancer, ovarian cyst, polycystic ovarian syndrome, endometriosis, endometrial hyperplasia, endometrial polyp, and cervical polyp. METHODS: We conducted a cohort study among female participants in the UK Biobank. Information on the use of statins was collected through verbal interview. Outcome information was obtained by linking to national cancer registry data and hospital inpatient data. We used Cox proportional hazards regression to examine the associations. RESULTS: A total of 180,855 female participants (18,403 statin users and 162,452 non-users) were included. Use of statins was significantly associated with increased risks of cervical cancer (adjusted hazard ratio (HR), 1.55; 95% confidence interval (95% CI), 1.05-2.30) and polycystic ovarian syndrome (adjusted HR, 4.39; 95% CI, 1.68-11.49). However, we observed no significant association between use of statins and risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial hyperplasia, endometrial polyp, or cervical polyp. CONCLUSION: Our findings suggest that use of statins is associated with increased risks of cervical cancer and polycystic ovarian syndrome, but is not associated with increased or decreased risk of ovarian cancer, endometrial cancer, ovarian cyst, endometriosis, endometrial polyp, or cervical polyp.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Ovarianas , Humanos , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Estudos de Coortes , Adulto , Neoplasias Ovarianas/epidemiologia , Idoso , Bancos de Espécimes Biológicos , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/tratamento farmacológico , Doenças do Colo do Útero/epidemiologia , Doenças do Colo do Útero/induzido quimicamente , Doenças Uterinas/induzido quimicamente , Doenças Uterinas/epidemiologia , Fatores de Risco , Neoplasias do Colo do Útero/epidemiologia , Modelos de Riscos Proporcionais , Biobanco do Reino UnidoRESUMO
In this work, Rosa roxburghii Tratt fruit polysaccharides (RPs) were extracted by ultrasound-assisted enzymatic method. The highest extraction yield of RPs was 4.78⯱â¯0.10â¯% under the optimal extraction conditions. Two purified fractions named RP1 and RP3 were obtained and systematically characterized by a combination strategy of FT-IR, monosaccharide composition, molecular weight distribution, methylation and 2D NMR spectroscopy analyses. Structural analysis showed that the main chain of RP1 was composed of rhamnogalacturonan type I (RG-I), while the side chains were rich in arabinogalactan and galactose. RP3 was composed of long homogalacturonan (HG) backbone interspersed with alternating sequences of RG-I domains, with galactose and arabinose side chains. RP1 and RP3 induced apoptosis of MCF-7 cells in a dose dependent manner in vitro especially for RP1, and had no effect on L929 cells. Furthermore, the possible anticancer mechanisms were revealed, and results suggested that RP1 induced apoptosis through ROS-dependent pathway and mitochondrial pathway. The results of this work not only provided an efficient extraction method and theoretical basis for the application of RPs, but also may contribute to develop novel functional foods or pharmaceutical products for the prevention and treatment of human breast cancer disease.
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Rosa , Humanos , Rosa/química , Galactose/análise , Frutas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Polissacarídeos/químicaRESUMO
BACKGROUND: Yeast is often used to build cell factories to produce various chemicals or nutrient substances, which means the yeast has to encounter stressful environments. Previous research reported that unsaturated fatty acids were closely related to yeast stress resistance. Engineering unsaturated fatty acids may be a viable strategy for enhancing the stress resistance of cells. RESULTS: In this study, two desaturase genes, OLE1 and FAD2 from Z. rouxii, were overexpressed in S. cerevisiae to determine how unsaturated fatty acids affect cellular stress tolerance of cells. After cloning and plasmid recombination, the recombinant S. cerevisiae cells were constructed. Analysis of membrane fatty acid contents revealed that the recombinant S. cerevisiae with overexpression of OLE1 and FAD2 genes contained higher levels of fatty acids C16:1 (2.77 times), C18:1 (1.51 times) and C18:2 (4.15 times) than the wild-type S. cerevisiae pY15TEF1. In addition, recombinant S. cerevisiae cells were more resistant to multiple stresses, and exhibited improved membrane functionality, including membrane fluidity and integrity. CONCLUSION: These findings demonstrated that strengthening the expression of desaturases was beneficial to stress tolerance. Overall, this study may provide a suitable means to build a cell factory of industrial yeast cells with high tolerance during biological manufacturing. © 2023 Society of Chemical Industry.
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Ácidos Graxos Dessaturases , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos/metabolismoRESUMO
The development of single Chinese materia medica is an important direction of technological innovation in the field of Chinese materia medica at present, and the study of its comprehensive intellectual property protection system is of great significance to the intellectual property protection of the whole chain of innovative enterprises of single Chinese materia medica. Based on this, this paper takes the comprehensive protection system of intellectual property of Callicarpa nudiflora constructed by Jiuzhitang Pharmaceutical as a model to conduct empirical research, analyzes the protection forms applicable to intellectual property of Chinese materia medica, such as patents, administrative protection, trademarks, designs and intangible cultural heritages, and discusses the valuable and insufficient aspects of the protection system currently constructed by Jiuzhitang Pharmaceutical and puts forward the following suggestions:①paying attention to patent applications for planting/processing methods of raw medicinal materials, ②emphasizing the protection of geographical indications, authentic medicinal herbs, and new plant varieties, ③actively promoting product and technology upgrades, ④applying for data protection during product iteration, ⑤emphasizing the layout timing of patent and administrative protection, ⑥focusing on improving goodwill, ⑦enhancing awareness of intellectual property protection and promoting deep integration of industry, academia, and research. We hope that innovative enterprises engaged in the development of single Chinese materia medica can learn from the experience of the case, and optimize the strategy to better protect related products.
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Oocyte maturation is vital to attain full competence required for fertilization and embryogenesis. NLRP14 is preferentially expressed in mammalian oocytes and early embryos. Yet, the role and molecular mechanism of NLRP14 in oocyte maturation and early embryogenesis are poorly understood, and whether NLRP14 deficiency accounts for human infertility is unknown. Here, we found that maternal loss of Nlrp14 resulted in sterility with oocyte maturation defects and early embryonic arrest (EEA). Nlrp14 ablation compromised oocyte competence due to impaired cytoplasmic and nuclear maturation. Importantly, we revealed that NLRP14 maintained cytoplasmic UHRF1 abundance by protecting it from proteasome-dependent degradation and anchoring it from nuclear translocation in the oocyte. Furthermore, we identified compound heterozygous NLRP14 variants in women affected by infertility with EEA, which interrupted the NLRP14-UHRF1 interaction and decreased UHRF1 levels. Our data demonstrate NLRP14 as a cytoplasm-specific regulator of UHRF1 during oocyte maturation, providing insights into genetic diagnosis for female infertility.
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Infertilidade Feminina , Animais , Feminino , Humanos , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismo , Oócitos/metabolismo , Oogênese , Citoplasma , Desenvolvimento Embrionário/genética , Mamíferos , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Nucleosídeo-Trifosfatase/metabolismoRESUMO
Ferroptosis is an iron-dependent programmed cell death process characterized by the accumulation of lethal oxidative damage. Localized iron overload is a unique clinical phenomenon in ovarian endometriosis (EM). However, the role and mechanism of ferroptosis in the course of ovarian EM remain unclear. Traditionally, autophagy promotes cell survival. However, a growing body of research suggests that autophagy promotes ferroptosis under certain conditions. This study aimed to clarify the status of ferroptosis in ovarian EM and explore the mechanism(s) by which iron overload causes ferroptosis and ectopic endometrial resistance to ferroptosis in human. The results showed increased levels of iron and reactive oxygen species in ectopic endometrial stromal cells (ESCs). Some ferroptosis and autophagy proteins in the ectopic tissues differed from those in the eutopic endometrium. In vitro, iron overload caused decreased cellular activity, increased lipid peroxidation levels, and mitochondrial morphological changes, whereas ferroptosis inhibitors alleviated these phenomena, illustrating activated ferroptosis. Iron overload increased autophagy, and ferroptosis caused by iron overload was inhibited by autophagy inhibitors, indicating that ferroptosis caused by iron overload was autophagy-dependent. We also confirmed the effect of iron overload and autophagy on lesion growth in vivo by constructing a mouse EM model; the results were consistent with those of the in vitro experiments of human tissue and endometrial stomal cells. However, ectopic lesions in patients can resist ferroptosis caused by iron overload, which can promote cystine/glutamate transporter hyperexpression by highly expressing activating transcription factor 4 (ATF4). In summary, local iron overload in ovarian EM can activate autophagy-related ferroptosis in ESCs, and ectopic lesions grow in a high-iron environment via ATF4-xCT while resisting ferroptosis. The effects of iron overload on other cells in the EM environment require further study. This study deepens our understanding of the role of ferroptosis in ovarian EM.
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Endometriose , Ferroptose , Sobrecarga de Ferro , Feminino , Animais , Camundongos , Humanos , Fator 4 Ativador da Transcrição/metabolismo , Endometriose/metabolismo , Ferroptose/genética , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Ferro/metabolismo , Autofagia/genética , Células Estromais/metabolismoRESUMO
Perfluorocaproic acid (PFHxA) has received much attention as an emerging pollutant linked to neurological problems in humans and fish. However, the potential mechanism remains unknown. In this study, the pathological damage to tissue sections demonstrated that perfluorocaproic acid caused brain tissue damage, and the increased antioxidant index malondialdehyde (MDA) and decrease in superoxide Dismutase (SOD), acid phosphatase (ACP), alkaline phosphatase (AKP), glutathione peroxidase (GSH-Px), Catalase (CAT), and Lysozyme (LZM) that perfluorocaproic acid activated antioxidant stress and caused brain damage. Transcriptome sequencing discovered 1,532 divergent genes, 931 upregulated, and 601 down-regulated. Furthermore, according to GO enrichment analysis, the differently expressed genes were shown to be involved in biological processes, cellular components, and molecular functions. The MAPK, calcium, and Neuroactive ligand-receptor interaction were considerably enriched in the KEGG enrichment analysis. We then analyzed qRT-PCR and chose ten essential differentially expressed genes for validation. The qRT-PCR results followed the same pattern as the RNA-Seq results. In conclusion, our study shows that perfluorocaproic acid exposure causes oxidative stress in the brain. It establishes a theoretical foundation for future research into genes linked to perfluorocaproic acid toxicity.
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Lesões Encefálicas , Poluentes Químicos da Água , Animais , Humanos , Carpa Dourada/genética , Carpa Dourada/metabolismo , Antioxidantes/metabolismo , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Perfilação da Expressão Gênica , TranscriptomaRESUMO
This study aimed to enhance exopolysaccharide production by Tetragenococcus halophilus, and results showed that low temperature (20 °C) significantly improved exopolysaccharide production. Based on the analysis of batch fermentation kinetic parameters, a temperature-shift strategy was proposed, and the exopolysaccharide yield was increased by 28 %. Analysis of the structure of exopolysaccharide suggested that low temperature changed the molecular weight and monosaccharide composition. Transcriptomic analysis was performed to reveal mechanisms of low temperature improving exopolysaccharide production. Results suggested that T. halophilus regulated utilization of carbon sources through phosphotransferase system and increased the expression of key genes in exopolysaccharide biosynthesis to improve exopolysaccharide production. Meanwhile, metabolic pathways involved in glycolysis, amino acids synthesis, two-component system and ATP-binding cassette transporters were affected at low temperature. Results presented in this paper provided a theoretical basis for biosynthetic pathway of exopolysaccharide in T. halophilus and aided to strengthen its production and application in many areas.
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Perfilação da Expressão Gênica , Transcriptoma , Transcriptoma/genética , Temperatura , Enterococcaceae/genética , Enterococcaceae/metabolismoRESUMO
BACKGROUND: To determine whether there is a correlation between stiffness measured by strain elastography and the severity of dysmenorrhea and to determine the value of elastography in evaluating severe dysmenorrhea in patients with adenomyosis. METHODS: The correlation between tissue stiffness and dysmenorrhea was analyzed by performing elastography on premenopausal women diagnosed with adenomyosis. Expression levels of transforming growth factor-ß (TGF-ß), α-smooth muscle actin (α-SMA), and protein gene product 9.5 (PGP9.5) were detected by immunohistochemistry; the correlation of TGF-ß and α-SMA levels with the tissue stiffness and the degree of fibrosis was further analyzed. Also, the relationship of the PGP9.5 expression level with the tissue stiffness and degree of dysmenorrhea was determined. RESULTS: The degree of dysmenorrhea was significantly positively correlated with lesion stiffness in patients with adenomyosis but not with the uterine or lesion volume. The cutoff for the strain ratio was > 1.36 between the adenomyosis and control groups, with an area under the curve (AUC) of 0.987. For severe dysmenorrhea, the cutoff for the strain ratio was > 1.65 in patients with adenomyosis, with an AUC of 0.849. TGF-ß, α-SMA, and PGP9.5 expression levels were higher in adenomyotic lesions than in the endometrium of the adenomyosis and control groups. Both TGF-ß and α-SMA levels were positively correlated with the tissue stiffness and degree of fibrosis. Additionally, the expression level of PGP9.5 showed a positive correlation with the tissue stiffness and degree of dysmenorrhea. CONCLUSIONS: Elastography can be used to evaluate the degree of dysmenorrhea; the greater the tissue stiffness, the greater the degree of dysmenorrhea. In addition, elastography performed well in the diagnosis of adenomyosis and the evaluation of severe dysmenorrhea in patients with adenomyosis.