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Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)+ metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD+ metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD+ precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD+ precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy.
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Background: Persistent human papillomavirus (HPV) infection remains a key risk factor for cervical cancer. HPV-based primary screening is widely recommended in clinical guidelines, and further longitudinal studies are needed to optimize strategies for detecting high-grade cervical lesions compared to cytology. Methods: From November 2015 to December 2023, 31,942 participants were included in the real-world observational study. Among those, 4,219 participants underwent at least two rounds of HPV tests, and 397 completed three rounds of HPV tests. All participants were tested for high-risk types of HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 (hrHPV) and low-risk types of HPV6/11 genotyping. Some participants also received cytology or colposcopy with pathology. Results: In the cross-sectional cohort, the prevalence of hrHPV and all HPV subtypes was 6.6% (2,108/31,942) and 6.8% (2,177/31,942), respectively. The three top hrHPV genotypes were HPV52 (1.9%), HPV58 (0.9%), and HPV16 (0.9%). Age distributions showed two peaks at 45-49 and 60-65 years. For the primary screening cohort, the hrHPV prevalence rate increased from 4.8% in 2015-2017 to 7.0% in 2020-2020 and finally reached 7.2% in 2023. For the longitudinal cohort study, the hrHPV prevalence rates in the repeated population (3.9, 5.3, and 6.0%) were lower than the primary hrHPV screening rates (6.6%), which indicated that repeated screening might decrease the prevalence rate. Methodologically, the hrHPV (89.5%) and the screening group of 16 subtypes (92.3%) demonstrated superior sensitivity than the cytology group (54.4%). Moreover, the longitudinal study indicated that the persistent hrHPV subgroup had a significantly higher (p = 0.04) incidence of high-grade squamous intraepithelial lesions and more histology progression events (7/17 vs. 0/5) than the reinfection group. Conclusion: The study indicates a rising high-risk HPV prevalence in Dongguan, with repeated screening reducing this trend. The findings support HPV-based primary screening and might guide HPV vaccination and cervical cancer prevention in South China.
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Virus del Papiloma Humano , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , China/epidemiología , Estudios Transversales , Detección Precoz del Cáncer , Genotipo , Virus del Papiloma Humano/genética , Virus del Papiloma Humano/aislamiento & purificación , Estudios Longitudinales , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Factores de Riesgo , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiologíaRESUMEN
BACKGROUND: The KCNQ1+KCNE1 (IKs) potassium channel plays a crucial role in cardiac adaptation to stress, in which ß-adrenergic stimulation phosphorylates the IKs channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death. However, the molecular connection between IKs channel phosphorylation and channel function, as well as why high-risk LQT1 mutations lose cAMP sensitivity, remain unclear. METHODS: Regular patch clamp and voltage clamp fluorometry techniques were utilized to record pore opening and voltage sensor movement of wild-type and mutant KCNQ1/IKs channels. The clinical phenotypic penetrance of each LQT1 mutation was analyzed as a metric for assessing their clinical risk. The patient-specific-induced pluripotent stem-cell model was used to test mechanistic findings in physiological conditions. RESULTS: By systematically elucidating mechanisms of a series of LQT1 variants that lack cAMP sensitivity, we identified molecular determinants of IKs channel regulation by phosphorylation. These key residues are distributed across the N-terminus of KCNQ1 extending to the central pore region of IKs. We refer to this pattern as the IKs channel PKA phosphorylation axis. Next, by examining LQT1 variants from clinical databases containing 10 579 LQT1 carriers, we found that the distribution of the most high-penetrance LQT1 variants extends across the IKs channel PKA phosphorylation axis, demonstrating its clinical relevance. Furthermore, we found that a small molecule, ML277, which binds at the center of the phosphorylation axis, rescues the defective cAMP effects of multiple high-risk LQT1 variants. This finding was then tested in high-risk patient-specific induced pluripotent stem cell-derived cardiomyocytes, where ML277 remarkably alleviates the beating abnormalities. CONCLUSIONS: Our findings not only elucidate the molecular mechanism of PKA-dependent IKs channel phosphorylation but also provide an effective antiarrhythmic strategy for patients with high-risk LQT1 variants.
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Proteínas Quinasas Dependientes de AMP Cíclico , Células Madre Pluripotentes Inducidas , Canal de Potasio KCNQ1 , Humanos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Fosforilación , Canal de Potasio KCNQ1/genética , Canal de Potasio KCNQ1/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Síndrome de Romano-Ward/genética , Síndrome de Romano-Ward/metabolismo , AMP Cíclico/metabolismo , Miocitos Cardíacos/metabolismo , Mutación , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/metabolismo , Células HEK293 , Canales de Potasio con Entrada de VoltajeRESUMEN
Hypomethylating agents (HMAs) are frontline therapies for Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). However, acquired resistance and treatment failure are commonplace. To address this, we perform a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and identify TOPORS as a loss-of-function target that synergizes with HMAs, reducing leukemic burden and improving survival in xenograft models. We demonstrate that depletion of TOPORS mediates sensitivity to HMAs by predisposing leukemic blasts to an impaired DNA damage response (DDR) accompanied by an accumulation of SUMOylated DNMT1 in HMA-treated TOPORS-depleted cells. The combination of HMAs with targeting of TOPORS does not impair healthy hematopoiesis. While inhibitors of TOPORS are unavailable, we show that inhibition of protein SUMOylation with TAK-981 partially phenocopies HMA-sensitivity and DDR impairment. Overall, our data suggest that the combination of HMAs with inhibition of SUMOylation or TOPORS is a rational treatment option for High-Risk MDS (HR-MDS) or AML.
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Sistemas CRISPR-Cas , Resistencia a Antineoplásicos , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/metabolismo , Animales , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Línea Celular Tumoral , Ratones , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/metabolismo , Sumoilación/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Daño del ADN/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética , ADN (Citosina-5-)-Metiltransferasa 1/antagonistas & inhibidores , FemeninoRESUMEN
Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a vital role in regulating redox homeostasis and reductive biosynthesis. However, if exogenous NADPH can be transported across the plasma membrane has remained elusive. In this study, we present evidence supporting that NADPH can traverse the plasma membranes of cells through a mechanism mediated by the P2X7 receptor (P2X7R). Notably, we observed an augmentation of intracellular NADPH levels in cultured microglia upon exogenous NADPH supplementation in the presence of ATP. The P2X7R-mediated transmembrane transportation of NADPH was validated with P2X7R antagonists, including OX-ATP, BBG, and A-438079, or through P2X7 knockdown, which impeded NADPH transportation into cells. Conversely, overexpression of P2X7 resulted in an enhanced capacity for NADPH transport. Furthermore, transfection of hP2X7 demonstrated the ability to complement NADPH uptake in native HEK293 cells. Our findings provide evidence for the first time that NADPH is transported across the plasma membrane via a P2X7R-mediated pathway. Additionally, we propose an innovative avenue for modulating intracellular NADPH levels. This discovery holds promise for advancing our understanding of the role of NADPH in redox homeostasis and neuroinflammation.
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Background: Exosomes contain abundant circular RNAs (circRNAs), playing an important role in intercellular communication. However, the function and underlying molecular mechanism of exosomal circRNAs in foot metastatic melanoma remain unclear. Methods: Twelve differentially expressed exosomal circRNAs between patients with metastatic and primary foot melanoma were screened through high-throughput sequencing, and their expression levels were detected by the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). CircRNA102927 silencing and overexpression A2058 cell line was constructed, and the effects of circRNA102927 on cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) were assessed using cell counting kit-8 (CCK-8), flow cytometry, wound healing, Transwell, and Western blot assays, respectively. Results: Twelve differentially expressed exosomal circRNAs were screened and ROC curve showed that six circRNAs could be used as the diagnostic biomarkers for metastatic melanoma. Melanoma-secreted exosomes induced the differentiation of CD4+ T cells into Treg cells. CircRNA102927 was highly expressed in metastatic melanomas. Functionally, circRNA102927 silencing inhibited proliferation, EMT, migration, and invasion in metastatic melanoma cells, while promoting apoptosis. Meanwhile, overexpression of circRNA102927 had the opposite effects. Conclusion: Our investigation suggests that silencing exosomal circRNA102927 may suppress foot melanoma metastasis by inhibiting invasiveness, EMT and promoting apoptosis.
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Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled proliferation of plasma cells in the bone marrow. MM patients with aggressive progression have poor survival, emphasizing the urgent need for identifying new therapeutic targets. Here, we show that the leukocyte immunoglobulin-like receptor B1 (LILRB1), a transmembrane receptor conducting negative immune response, is a top-ranked gene associated with poor prognosis in MM patients. LILRB1 deficiency inhibits MM progression in vivo by enhancing the ferroptosis of MM cells. Mechanistic studies reveal that LILRB1 forms a complex with the low-density lipoprotein receptor (LDLR) and LDLR adapter protein 1 (LDLRAP1) to facilitate LDL/cholesterol uptake. Loss of LILRB1 impairs cholesterol uptake but activates the de novo cholesterol synthesis pathway to maintain cellular cholesterol homeostasis, leading to the decrease of anti-ferroptotic metabolite squalene. Our study uncovers the function of LILRB1 in regulating cholesterol metabolism and protecting MM cells from ferroptosis, implicating LILRB1 as a promising therapeutic target for MM patients.
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Colesterol , Ferroptosis , Homeostasis , Receptor Leucocitario Tipo Inmunoglobulina B1 , Mieloma Múltiple , Receptores de LDL , Humanos , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Mieloma Múltiple/genética , Receptor Leucocitario Tipo Inmunoglobulina B1/metabolismo , Ferroptosis/genética , Colesterol/metabolismo , Receptores de LDL/metabolismo , Receptores de LDL/genética , Animales , Línea Celular Tumoral , Ratones , Antígenos CDRESUMEN
The cardiac KCNQ1+KCNE1 (I Ks ) channel regulates heart rhythm in both normal and stress conditions. Under stress, the ß-adrenergic stimulation elevates the intracellular cAMP level, leading to KCNQ1 phosphorylation by protein kinase A and increased I Ks , which shortens action potentials to adapt to accelerated heart rate. An impaired response to the ß-adrenergic stimulation due to KCNQ1 mutations is associated with the occurrence of a lethal congenital long QT syndrome (type 1, also known as LQT1). However, the underlying mechanism of ß-adrenergic stimulation of I Ks remains unclear, impeding the development of new therapeutics. Here we find that the unique properties of KCNQ1 channel gating with two distinct open states are key to this mechanism. KCNQ1's fully activated open (AO) state is more sensitive to cAMP than its' intermediate open (IO) state. By enhancing the AO state occupancy, the small molecules ML277 and C28 are found to effectively enhance the cAMP sensitivity of the KCNQ1 channel, independent of KCNE1 association. This finding of enhancing AO state occupancy leads to a potential novel strategy to rescue the response of I Ks to ß-adrenergic stimulation in LQT1 mutants. The success of this approach is demonstrated in cardiac myocytes and also in a high-risk LQT1 mutation. In conclusion the present study not only uncovers the key role of the AO state in I Ks channel phosphorylation, but also provides a new target for anti-arrhythmic strategy. Significance statement: The increase of I Ks potassium currents with adrenalin stimulation is important for "fight-or-flight" responses. Mutations of the IKs channel reducing adrenalin responses are associated with more lethal form of the type-1 long-QT syndrome (LQT). The alpha subunit of the IKs channel, KCNQ1 opens in two distinct open states, the intermediate-open (IO) and activated-open (AO) states, following a two-step voltage sensing domain (VSD) activation process. We found that the AO state, but not the IO state, is responsible for the adrenalin response. Modulators that specifically enhance the AO state occupancy can enhance adrenalin responses of the WT and LQT-associated mutant channels. These results reveal a mechanism of state dependent modulation of ion channels and provide an anti-arrhythmic strategy.
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INTRODUCTION: Approximately 40% of children with diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), which increases the risk of chronic kidney damage. At present, there is limited knowledge of racial or ethnic differences in diabetes-related kidney injury in children with diabetes. Understanding whether such differences exist will provide a foundation for addressing disparities in diabetes care that may continue into adulthood. Further, it is currently unclear which children are at risk to develop worsening or sustained DKA-related AKI. The primary aim is to determine whether race and ethnicity are associated with DKA-related AKI. The secondary aim is to determine factors associated with sustained AKI in children with DKA. METHODS AND ANALYSIS: This retrospective, multicentre, cross-sectional study of children with type 1 or type 2 diabetes with DKA will be conducted through the Paediatric Emergency Medicine Collaborative Research Committee. Children aged 2-18 years who were treated in a participating emergency department between 1 January 2020 and 31 December 2023 will be included. Children with non-ketotic hyperglycaemic-hyperosmolar state or who were transferred from an outside facility will be excluded. The relevant predictor is race and ethnicity. The primary outcome is the presence of AKI, defined by Kidney Disease: Improving Global Outcomes criteria. The secondary outcome is 'sustained' AKI, defined as having AKI ≥48 hours, unresolved AKI at last creatinine measurement or need for renal replacement therapy. Statistical inference of the associations between predictors (ie, race and ethnicity) and outcomes (ie, AKI and sustained AKI) will use random effects regression models, accounting for hospital variation and clustering. ETHICS AND DISSEMINATION: The Institutional Review Board of Children's Minnesota approved this study. 12 additional sites have obtained institutional review board approval, and all sites will obtain local approval prior to participation. Results will be presented at local or national conferences and for publication in peer-reviewed journals.
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Lesión Renal Aguda , Cetoacidosis Diabética , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Lesión Renal Aguda/etnología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/etnología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/etnología , Cetoacidosis Diabética/etnología , Cetoacidosis Diabética/complicaciones , Etnicidad/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Estudios Multicéntricos como AsuntoRESUMEN
Sheep and goat may become carriers of some zoonotic diseases. They are important livestock and experimental model animals for human beings. The fast and accurate identification of genetic materials originating from sheep and goat can prevent and inhibit the spread of some zoonotic diseases, monitor market product quality, and maintain the stability of animal husbandry and food industries. This study proposed a methodology for identifying sheep and goat common specific sites from a genome-wide perspective. A total of 150 specific sites were selected from three data sources, including the coding sequences of single copy genes from nine species (sheep, goat, cow, pig, dog, horse, human, mouse, and chicken), the dbSNPs for these species, and human 100-way alignment data. These 150 sites exhibited low intraspecific heterogeneity in the resequencing data of 1450 samples from five species (sheep, goat, cow, pig, and chicken) and high interspecific divergence in the human 100-way alignment data after quality control. The results were proven to be reliable at the data level. Using the process proposed in this study, specific sites of other species can be screened, and genome-level species identification can be performed using the screened sites.
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Cabras , Animales , Cabras/genética , Ovinos/genética , Humanos , Sitios Genéticos , Genoma/genética , Polimorfismo de Nucleótido Simple/genética , Bovinos/genética , Porcinos/genética , Especificidad de la Especie , RatonesRESUMEN
Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Glicoproteínas , Nanovacunas , Animales , Femenino , Humanos , Ratones , Adyuvantes Inmunológicos/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/prevención & control , Infecciones por Virus de Epstein-Barr/virología , Glicoproteínas/inmunología , Glicoproteínas/administración & dosificación , Herpesvirus Humano 4/inmunología , Linfoma/inmunología , Linfoma/virología , Nanovacunas/inmunologíaRESUMEN
Genome editing in non-model bacteria is important to understand gene-to-function links that may differ from those of model microorganisms. Although species of the Burkholderia cepacia complex (Bcc) have great biotechnological capacities, the limited genetic tools available to understand and mitigate their pathogenic potential hamper their utilization in industrial applications. To broaden the genetic tools available for Bcc species, we developed RhaCAST, a targeted DNA insertion platform based on a CRISPR-associated transposase driven by a rhamnose-inducible promoter. We demonstrated the utility of the system for targeted insertional mutagenesis in the Bcc strains B. cenocepacia K56-2 and Burkholderia multivorans ATCC17616. We showed that the RhaCAST system can be used for loss- and gain-of-function applications. Importantly, the selection marker could be excised and reused to allow iterative genetic manipulation. The RhaCAST system is faster, easier, and more adaptable than previous insertional mutagenesis tools available for Bcc species and may be used to disrupt pathogenicity elements and insert relevant genetic modules, enabling Bcc biotechnological applications. IMPORTANCE: Species of the Burkholderia cepacia complex (Bcc) have great biotechnological potential but are also opportunistic pathogens. Genetic manipulation of Bcc species is necessary to understand gene-to-function links. However, limited genetic tools are available to manipulate Bcc, hindering our understanding of their pathogenic traits and their potential in biotechnological applications. We developed a genetic tool based on CRISPR-associated transposase to increase the genetic tools available for Bcc species. The genetic tool we developed in this study can be used for loss and gain of function in Bcc species. The significance of our work is in expanding currently available tools to manipulate Bcc.
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Complejo Burkholderia cepacia , Sistemas CRISPR-Cas , Elementos Transponibles de ADN , Edición Génica , Mutagénesis Insercional , Complejo Burkholderia cepacia/genética , Edición Génica/métodos , Elementos Transponibles de ADN/genética , Genoma BacterianoRESUMEN
Meige syndrome is a rare neurological disease characterized by segmental dystonia, specifically blepharospasm and oromandibular dystonia. These symptoms are often accompanied by complex movements of the eyelids, lower facial muscles, mandible, and neck muscles. Bilateral blepharospasm is the most common feature of this disease. In this case report, we present the successful treatment of refractory blepharospasm in a 72-year-old woman with Meige syndrome via 2 incisions resulting from myectomy and in situ surgery.
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Salmonella enterica causes severe food-borne infections through contamination of the food supply chain. Its evolution has been associated with human activities, especially animal husbandry. Advances in intensive farming and global transportation have substantially reshaped the pig industry, but their impact on the evolution of associated zoonotic pathogens such as S. enterica remains unresolved. Here we investigated the population fluctuation, accumulation of antimicrobial resistance genes and international serovar Choleraesuis transmission of nine pig-enriched S. enterica populations comprising more than 9,000 genomes. Most changes were found to be attributable to the developments of the modern pig industry. All pig-enriched salmonellae experienced host transfers in pigs and/or population expansions over the past century, with pigs and pork having become the main sources of S. enterica transmissions to other hosts. Overall, our analysis revealed strong associations between the transmission of pig-enriched salmonellae and the global pork trade.
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Salmonella enterica , Animales , Salmonella enterica/genética , Salmonella enterica/aislamiento & purificación , Porcinos , Europa (Continente)/epidemiología , Humanos , Salmonelosis Animal/epidemiología , Salmonelosis Animal/transmisión , Salmonelosis Animal/microbiología , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/transmisión , Enfermedades de los Porcinos/epidemiología , Crianza de Animales Domésticos/métodos , Carne de Cerdo/microbiología , Américas/epidemiología , Microbiología de AlimentosRESUMEN
The marsupial specific RSX lncRNA is the functional analogue of the eutherian specific XIST, which coordinates X chromosome inactivation. We characterized the RSX interactome in a marsupial representative (the opossum Monodelphis domestica), identifying 135 proteins, of which 54 had orthologues in the XIST interactome. Both interactomes were enriched for biological pathways related to RNA processing, regulation of translation, and epigenetic transcriptional silencing. This represents a remarkable example showcasing the functional coherence of independently evolved lncRNAs in distantly related mammalian lineages.
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ARN Largo no Codificante , Inactivación del Cromosoma X , Animales , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , Monodelphis/genética , Monodelphis/metabolismoRESUMEN
Platostoma palustre (Mesona chinensis Benth or Hsian-tsao, also known as "Xiancao" in China), is an edible and medicinal plant native to India, Myanmar, and Indo-China. It is the main ingredient in the popular desserts Hsian-tsao tea, herbal jelly, and sweet herbal jelly soup. P. palustre is found abundantly in nutrient-rich substances and possesses unique aroma compounds. Variations in the contents of volatile compounds among different germplasms significantly affect the quality and flavor of P. palustre, causing contradiction in demand. This study investigates the variation in the volatile compound profiles of distinct ploidy germplasms of P. palustre by utilising headspace gas chromatography-mass spectrometry (HS-GC-MS) and an electronic nose (e-nose). The results showed significant differences in the aroma characteristics of stem and leaf samples in diverse P. palustre germplasms. A total of sixty-seven volatile compounds have been identified and divided into ten classes. Six volatile compounds (caryophyllene, α-bisabolol, benzaldehyde, ß-selinene, ß-elemene and acetic acid) were screened as potential marker volatile compounds to discriminate stems and leaves of P. palustre. In this study, leaves of P. palustre showed one odor pattern and stems showed two odor patterns under the influence of α-bisabolol, acetic acid, and butyrolactone. In addition, a correlation analysis was conducted on the main volatile compounds identified by HS-GC-MS and e-nose. This analysis provided additional insight into the variations among samples resulting from diverse germplasms. The present study provides a valuable volatilome, and flavor, and quality evaluation for P. palustre, as well as new insights and scientific basis for the development and use of P. palustre germplasm resources.
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Nariz Electrónica , Cromatografía de Gases y Espectrometría de Masas , Odorantes , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/análisis , Odorantes/análisis , Hojas de la Planta/química , Gusto , Tallos de la Planta/químicaRESUMEN
Long-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MSE technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD.
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Chenopodium quinoa , Dieta Occidental , Fermentación , Microbioma Gastrointestinal , Hordeum , Lactobacillus , Ratas Sprague-Dawley , Animales , Hordeum/química , Masculino , Lactobacillus/metabolismo , Chenopodium quinoa/química , Ratas , Hígado/metabolismo , Disbiosis , Metabolómica , Alimentos Fermentados , MultiómicaRESUMEN
The flow cytometry-based evaluation of TRBC1 expression has been demonstrated as a rapid and specific method for detecting T-cell clones in sCD3-positive TCRαß+ mature T-cell lymphoma. The aim of the study was to validate the utility of surface (s) TRBC1 and cytoplastic (cy) TRBC1 assessment in detecting clonality of sCD3-negative peripheral T-cell lymphomas (PTCLs), as well as exploring the existence and characteristics of sCD3-negative clonal T-cell populations with uncertain significance (T-CUS). Evaluation of sTRBC1 and cyTRBC1 were assessed on 61 samples from 37 patients with sCD3-negative PTCLs, including 26 angioimmunoblastic T-cell lymphoma (AITL) patients and 11 non-AITL patients. The sCD3-negative T-CUS were screened from 1602 patients without T-cell malignancy and 100 healthy individuals. Additionally, the clonality of cells was further detected through T-cell gene rearrangement analysis. We demonstrated the monotypic expression patterns of cyTRBC1 in all sCD3-negative PTCLs. Utilizing the cyTRBC1 evaluation assay, we identified a novel and rare subtype of sCD3-negative T-CUS for the first time among 13 out of 1602 (0.8%) patients without T-cell malignancy. The clonality of these cells was further confirmed through T-cell gene rearrangement analysis. This subset exhibited characteristics such as sCD3-cyCD3 + CD4 + CD45RO+, closely resembling AITL rather than non-AITL. Further analysis revealed that sCD3-negative T-CUS exhibited a smaller clone size in the lymph node and mass specimens compared to AITL patients. However, the clone size of sCD3-negative T-CUS was significantly lower than that of non-AITL patients in both specimen groups. In conclusion, we validated the diagnostic utility of cyTRBC1 in detecting sCD3-negative T-cell clonality, provided a comprehensive analysis of sCD3-negative T-CUS, and established a framework and provided valuable insights for distinguishing sCD3-negative T-CUS from sCD3-negative PTCLs based on their phenotypic properties and clone size.