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Bacterial testicular inflammation is one of the important causes of male infertility. Using plant-derived compounds to overcome the side effects of antibiotics is an alternative treatment strategy for many diseases. Schizandrin B (SchB) is a bioactive compound of herbal medicine Schisandra chinensis which has multiple pharmacological effects. However its effect and the mechanism against testicular inflammation are unknown. Here we tackled these questions using models of lipopolysaccharide (LPS)-induced mice and -Sertoli cells (SCs). Histologically, SchB ameliorated the LPS-induced damages of the seminiferous epithelium and blood-testicular barrier, and reduced the production of pro-inflammatory mediators in mouse testes. Furthermore, SchB decreased the levels of pro-inflammatory mediators and inhibited the nuclear factor kB (NF-κB) and MAPK (especially JNK) signaling pathway phosphorylation in LPS-induced mSCs. The bioinformatics analysis based on receptor prediction and the molecular docking was further conducted. We targeted androgen receptor (AR) and illustrated that AR might bind with SchB in its function. Further experiments indicate that the AR expression was upregulated by LPS stimulation, while SchB treatment reversed this phenomenon; similarly, the expression of the JNK-related proteins and apoptotic-related protein were also reversed after AR activator treatment. Together, SchB mitigates LPS-induced inflammation and apoptosis by inhibiting the AR-JNK pathway.
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Apoptosis , Ciclooctanos , Lignanos , Lipopolisacáridos , Compuestos Policíclicos , Células de Sertoli , Animales , Masculino , Ciclooctanos/farmacología , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/uso terapéutico , Lignanos/farmacología , Lignanos/uso terapéutico , Apoptosis/efectos de los fármacos , Ratones , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Receptores Androgénicos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Simulación del Acoplamiento Molecular , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , FN-kappa B/metabolismoRESUMEN
To obtain high-quality bovine oocytes, the effects of vitamin C (VC) on the IVM of bovine oocytes and early embryo development were investigated. The results showed the following. (1) The IVM medium containing 50 µg/mL VC improved the oocyte maturation rate but did not affect the parthenogenetic embryo development. (2) The IVC medium containing 20 µg/mL VC improved the cleavage rate of the IVF embryos and enhanced the mRNA transcriptions of pluripotency gene Oct4, Sox2, Cdx2, and Nanog in the blastocysts but had no effects on the blastocyst rate. (3) Combining supplementation of 50 µg/mL VC in IVM medium + 20 µg/mL VC in IVC medium (named as VC 50/20, similar hereinafter) elevated the cleavage rate of IVF embryos and enhanced the mRNA expressions of Oct4, Sox2, Cdx2, and Nanog in the blastocysts. (4) Combination of VC 0/20 and VC 50/20 enhanced the transcription of anti-apoptotic gene Bcl-2 and VC 50/0 weakened the transcription of pro-apoptotic gene Bax, while VC 0/40 and VC 0/60 increased Bax expression and diminished the Bcl-2/Bax ratio in blastocysts. Together, employing 50 µg/mL VC improves the IVM of bovine oocytes and combination of VC 50/20 potentially changes bovine embryo quality by enhancing the expressions of the pluripotency genes and regulating the expressions of apoptosis-related genes.
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Apolipoprotein-B (APOB)-containing lipoproteins cause atherosclerosis. Whether the vasculature is the initially responding site or if atherogenic dyslipidemia affects other organs simultaneously is unknown. Here we show that the liver responds to a dyslipidemic insult based on inducible models of familial hypercholesterolemia and APOB tracing. An acute transition to atherogenic APOB lipoprotein levels resulted in uptake by Kupffer cells and rapid accumulation of triglycerides and cholesterol in the liver. Bulk and single-cell RNA sequencing revealed a Kupffer-cell-specific transcriptional program that was not activated by a high-fat diet alone or detected in standard liver function or pathological assays, even in the presence of fulminant atherosclerosis. Depletion of Kupffer cells altered the dynamic of plasma and liver lipid concentrations, indicating that these liver macrophages help restrain and buffer atherogenic lipoproteins while simultaneously secreting atherosclerosis-modulating factors into plasma. Our results place Kupffer cells as key sentinels in organizing systemic responses to lipoproteins at the initiation of atherosclerosis.
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Aterosclerosis , Modelos Animales de Enfermedad , Macrófagos del Hígado , Hígado , Macrófagos del Hígado/metabolismo , Animales , Hígado/metabolismo , Hígado/patología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Masculino , Hiperlipoproteinemia Tipo II/metabolismo , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/patología , Dislipidemias/metabolismo , Ratones Endogámicos C57BL , Triglicéridos/sangre , Triglicéridos/metabolismo , Apolipoproteínas B/metabolismo , Apolipoproteínas B/sangre , Colesterol/metabolismo , Colesterol/sangre , Dieta Alta en Grasa/efectos adversos , Apolipoproteína B-100/metabolismo , FemeninoRESUMEN
While high-fat diet (HFD)-induced obesity is a major threat to global public health, the effect of HFD on cognition and insulin signaling during ageing remains controversial. The aim of this study was to characterize the dynamic alterations in cognition and cerebral insulin signaling during 6-month HFD consumption, and to investigate the potential therapeutic target and optimal timing to rescue obesity-related cognitive deficits. In the present study, impaired memory retention induced by 2-month HFD was recovered after 4 months on HFD. Prolonged (6-month) HFD did not further enhance tau hyperphosphorylation and ß-amyloid deposition, which was consistent with the alleviation of memory retention. In brain insulin signaling, 2-month HFD increased IRS-1 and p-IRS-1(Ser307)/IRS-1, while decreasing pAKT(Ser473)/AKT, PI3K and mTOR; 4-month HFD decreased IRS-1 and pAKT(Ser473)/AKT, while increasing AKT; 6-month HFD increased IRS-1, pAKT(Ser473)/AKT, and mTOR, while decreasing p-IRS-1(Ser307)/IRS-1, PI3K and AKT. Notably, bioinformatic analysis revealed a rhythmic process presented only in 4-month HFD group, with Srebf1 emerging as a link between circadian rhythms and insulin signaling pathway. These results suggest that prolonged HFD prevents further cognitive decline and the progression of Alzheimer's disease (AD)-related pathologies during ageing. Moreover, there may be a window for recovery, in which Srebf1 acts as a self-recovery switch to address obesity-related cognitive disorders in elders.
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Cognición , Dieta Alta en Grasa , Proteínas Sustrato del Receptor de Insulina , Insulina , Transducción de Señal , Dieta Alta en Grasa/efectos adversos , Animales , Insulina/metabolismo , Masculino , Cognición/fisiología , Proteínas Sustrato del Receptor de Insulina/metabolismo , Ratones , Obesidad/metabolismo , Proteínas tau/metabolismo , Encéfalo/metabolismo , Péptidos beta-Amiloides/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Ratones Endogámicos C57BLRESUMEN
OBJECTIVES: Artificial intelligence (AI) has been extensively used in the field of stomatology over the past several years. This study aimed to evaluate the effectiveness of AI-based models in the procedure, assessment, and treatment planning of surgical extraction. STUDY DESIGN: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a comprehensive search was conducted on the Web of Science, PubMed/MEDLINE, Embase, and Scopus databases, covering English publications up to September 2023. Two reviewers performed the study selection and data extraction independently. Only original research studies utilizing AI in surgical extraction of stomatology were included. The Cochrane risk of bias tool for randomized trials (RoB 2) was selected to perform the quality assessment of the selected literature. RESULTS: From 2,336 retrieved references, 35 studies were deemed eligible. Among them, 28 researchers reported the pioneering role of AI in segmentation, classification, and detection, aligning with clinical needs. In addition, another 7 studies suggested promising results in tooth extraction decision-making, but further model refinement and validation were required. CONCLUSIONS: Integration of AI in stomatology surgical extraction has significantly progressed, enhancing decision-making accuracy. Combining and comparing algorithmic outcomes across studies is essential for determining optimal clinical applications in the future.
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Inteligencia Artificial , Extracción Dental , Humanos , Planificación de Atención al PacienteRESUMEN
BACKGROUND: This multicenter, double-blinded, randomized controlled trial (RCT) aims to assess the impact of an artificial intelligence (AI)-based model on the efficacy of intracranial aneurysm detection in CT angiography (CTA) and its influence on patients' short-term and long-term outcomes. METHODS: Study design: Prospective, multicenter, double-blinded RCT. SETTINGS: The model was designed for the automatic detection of intracranial aneurysms from original CTA images. PARTICIPANTS: Adult inpatients and outpatients who are scheduled for head CTA scanning. Randomization groups: (1) Experimental Group: Head CTA interpreted by radiologists with the assistance of the True-AI-integrated intracranial aneurysm diagnosis strategy (True-AI arm). (2) Control Group: Head CTA interpreted by radiologists with the assistance of the Sham-AI-integrated intracranial aneurysm diagnosis strategy (Sham-AI arm). RANDOMIZATION: Block randomization, stratified by center, gender, and age group. PRIMARY OUTCOMES: Coprimary outcomes of superiority in patient-level sensitivity and noninferiority in specificity for the True-AI arm to the Sham-AI arm in intracranial aneurysms. SECONDARY OUTCOMES: Diagnostic performance for other intracranial lesions, detection rates, workload of CTA interpretation, resource utilization, treatment-related clinical events, aneurysm-related events, quality of life, and cost-effectiveness analysis. BLINDING: Study participants and participating radiologists will be blinded to the intervention. SAMPLE SIZE: Based on our pilot study, the patient-level sensitivity is assumed to be 0.65 for the Sham-AI arm and 0.75 for the True-AI arm, with specificities of 0.90 and 0.88, respectively. The prevalence of intracranial aneurysms for patients undergoing head CTA in the hospital is approximately 12%. To establish superiority in sensitivity and noninferiority in specificity with a margin of 5% using a one-sided α = 0.025 to ensure that the power of coprimary endpoint testing reached 0.80 and a 5% attrition rate, the sample size was determined to be 6450 in a 1:1 allocation to True-AI or Sham-AI arm. DISCUSSION: The study will determine the precise impact of the AI system on the detection performance for intracranial aneurysms in a double-blinded design and following the real-world effects on patients' short-term and long-term outcomes. TRIAL REGISTRATION: This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT06118840 . Registered 11 November 2023.
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Inteligencia Artificial , Angiografía por Tomografía Computarizada , Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Método Doble Ciego , Estudios Prospectivos , Valor Predictivo de las Pruebas , Estudios Multicéntricos como Asunto , Angiografía Cerebral/métodos , Masculino , Femenino , Factores de Tiempo , Ensayos Clínicos Controlados Aleatorios como Asunto , AdultoRESUMEN
Pancreatic adenocarcinoma (PAAD) is a fatal disease with poor survival. Increasing evidence show that hypoxia-induced exosomes are associated with cancer progression. Here, we aimed to investigate the function of hsa_circ_0007678 (circR3HCC1L) and hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD progression. Through the exoRBase 2.0 database, we screened for a circular RNA circR3HCC1L related to PAAD. Changes of circR3HCC1L in PAAD samples and cells were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration, invasion were analyzed by colony formation, cell counting, and transwell assays. Measurements of glucose uptake and lactate production were done using corresponding kits. Several protein levels were detected by western blotting. The regulation mechanism of circR3HCC1L was verified by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Exosomes were separated by differential ultracentrifugation. Animal experiments were used to verify the function of hypoxia-derived exosomal circR3HCC1L. CircR3HCC1L was upregulated in PAAD samples and hypoxic PAAD cells. Knockdown of circR3HCC1L decreased hypoxia-driven PAAD cell proliferation, migration, invasion, and glycolysis. Hypoxic PAAD cell-derived exosomes had higher levels of circR3HCC1L, hypoxic PAAD cell-derived exosomal circR3HCC1L promoted normoxic cancer cell malignant transformation and glycolysis in vitro and xenograft tumor growth in mouse models in vivo. Mechanistically, circR3HCC1L regulated pyruvate kinase M2 (PKM2) expression via sponging miR-873-5p. Also, PKM2 overexpression or miR-873-5p silencing offset circR3HCC1L knockdown-mediated effects on hypoxia-challenged PAAD cell malignant transformation and glycolysis. Hypoxic PAAD cell-derived exosomal circR3HCC1L facilitated PAAD progression through the miR-873-5p/PKM2 axis, highlighting the contribution of hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD.
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Pluripotent stem cells (PSCs) can differentiate into three germ layers and diverse autologous cell lines. Since cattle are the most commonly used large domesticated animals, an important food source, and bioreactors, great efforts have been made to establish bovine PSCs (bPSCs). bPSCs have great potential in bovine breeding and reproduction, modeling in vitro differentiation, imitating cancer development, and modeling diseases. Currently, bPSCs mainly include bovine embryonic stem cells (bESCs), bovine induced pluripotent stem cells (biPSCs), and bovine expanded potential stem cells (bEPSCs). Establishing stable bPSCs in vitro is a critical scientific challenge, and researchers have made numerous efforts to this end. In this review, the category of PSC pluripotency; the establishment of bESCs, biPSCs, and bEPSCs and its challenges; and the application outlook of bPSCs are discussed, aiming to provide references for future research.
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Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes , Bovinos , Animales , Células Madre Pluripotentes/metabolismo , Diferenciación Celular , Células Madre EmbrionariasRESUMEN
Recently, numerous studies have been conducted on renewable polymers derived from different natural sources, exploring their suitability for diverse biomedical applications. Lignin as one of the main components of lignocellulosic has garnered significant attention as a promising alternative to petroleum-based polymers. This interest is primarily due to its cost-effectiveness, biocompatibility, eco-friendly nature, as well as its antioxidant and antimicrobial properties. These characteristics could be more beneficial when incorporating lignin into the formulation of value-added products. Although lignin has a chemical structure that is suitable for various applications, these characteristics require modifications to guarantee that the resultant materials display the desired biological, chemical, and physical properties when applied in the creation of biodegradable hydrogels, particularly for biomedical purposes. This study delineates the recent modification approaches that have been employed in the creation of lignin-based hydrogels. These strategies encompass both chemical and physical interactions with other polymers. Additionally, this review encompasses an examination of the current applications of lignin hydrogels, spanning their use as scaffolds for tissue engineering, carriers for pharmaceuticals, materials for wound dressings and biosensors, and elements in flexible and wearable electronics. Finally, we delve into the challenges and constraints associated with these materials, discuss the necessary steps required to attain the appropriate properties for the development of innovative lignin-based hydrogels, and derive conclusions based on the presented findings.
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Hidrogeles , Lignina , Lignina/química , Hidrogeles/química , Polímeros , Ingeniería de Tejidos , ElectrónicaRESUMEN
Although multiple factors are known to concur with Alzheimer's disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed that IE2 upregulated immune and nervous system disease-related genes. Immunohistochemical analysis showed that the expressions of both amyloid precursor protein (APP) and p-Tau were significantly upregulated in the brains of IE2 mice and were markers of AD. Taken together, these findings provide useful insights into AD-like disease activated by HCMV IE2.
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Enfermedad de Alzheimer , Proteínas Inmediatas-Precoces , Humanos , Ratones , Animales , Ratones Transgénicos , Microglía/metabolismo , Enfermedad de Alzheimer/genética , Transactivadores/metabolismo , Citomegalovirus , Perfilación de la Expresión Génica , Análisis de Secuencia de ARNRESUMEN
Biomass-based fluorescent materials are an alternative to plastic-based materials for their multifunctional applications. Lignin, an inexpensive and easily available raw material, demonstrates outstanding environment-responsive properties such as pH, metal ions, dyes sensing, bioimaging and so on. To date, only a little work has been reported on the synthesis of lignin-based fluorescent materials. In this review report, synthetic approaches and light-responsive applications of lignin-based fluorescent carbon dots and other materials are summarized. The results reveal that lignin-based fluorescent carbon dots are prepared by hydrothermal method, exhibit small size <10 nm, reveal significant quantum yield, biocompatibility, non-toxicity, photostability and display substantial tunable emission and can be efficiently employed for sensing, bioimaging and energy storage applications. Finally, the forthcoming challenges, investigations, and options open for the chemical and/or physical modification of lignin into fluorescent materials for future applications are well-addressed. To our knowledge, this is the first comprehensive review report on lignin-based fluorescent materials and their light-responsive applications. In addition, this review will attract remarkable consideration and thrust for the researchers and biochemical technologists working with the preparation of lignin-based fluorescent materials for broad applications.
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Puntos Cuánticos , Puntos Cuánticos/química , Lignina/química , Colorantes Fluorescentes/química , Metales , Carbono/químicaRESUMEN
Introduction: Idiopathic pulmonary arterial hypertension (IPAH) is a rare and sporadic form of pulmonary arterial hypertension (PAH), characterized by elevated pulmonary arterial resistance leading to right heart failure. However, molecular mechanisms of PAH development are still not completely understood. Material and methods: In this study, we aimed to uncover key mRNAs and long non-coding RNA (lncRNAs), functional modules and pathways. Moreover, to detect the dysregulated pathway or biological function, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. PPI and co-expression networks were constructed to reveal the potential roles of PAH-related mRNAs and lncRNAs. Results: A total of 3,134 genes, including 945 up-regulated and 2,189 down-regulated genes, were identified to be differentially expressed in IPAH by differential expression analysis. We identified T cell differentiation and the T cell receptor signaling pathway as up-regulated in IPAH by using GO and KEGG analysis. Based on the PPI module analysis, we identified that the pro-inflammatory genes, such as OAS1, CXCL10, STAT1 and TLR4, were the hub genes in the PPI modules. To link the lncRNAs to the PPI modules, we calculated the Spearman correlation coefficient for lncRNA-DE-mRNA pairs to identify the modules with high correlation with each lncRNA. Conclusions: Notably, 6 of these lncRNAs were associated with modules characterized by the NOD-like receptor signaling pathway and chemokine signaling pathway, suggesting that these lncRNAs may promote the occurrence of IPAH via participating in the pro-inflammatory pathways. In conclusion, our systematic analysis not only improved our understanding of the molecular mechanism, but also provided potential lncRNA biomarkers for further research.
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High contents of internal ß-O-4 linkages in lignin are critical for high-yield production of high-value aromatic monomers by depolymerization. However, it remains great challenge due to lack of suitable protection strategy. In this work, a very effective lignin-first strategy was developed to produce ideal lignin with a super high content of ß-O-4 linkages (up to 72 %) from poplar, in which the pretreatment was undertaken at low temperatures of 90-130 °C with the use of AlCl3-catalyzed 1, 4-butanediol solution. 2D-HSQC NMR spectra revealed that lignin ß-O-4 linkages were protected from etherification of the OH group by 1, 4-butanediol at the α position of lignin aliphatic chains. Besides, the OH groups at the γ position of lignin was also etherified, leading the formation of a structure of Ph-CH=CHCH2O(CH2)4OH. Interestingly, structure protection facilitated the formation of lignin nanoparticles via self-assembly (<100 nm). In addition, it was observed from pyrolysis results that addition of 1, 4-butanediol remarkably protected the structure of lignin by avoiding condensation, promoting the production of aromatics. The cellulose-rich fraction possessed a high cellulose digestibility of 91.64 % by enzymatic hydrolysis at a cellulase dosage of 15 FPU/g cellulose, approximately 6-fold untreated poplar (15.91 %). This low-temperature lignin-first strategy was of great importance for multi-products biorefining lignocellulose because it leads to the production of both lignin with super high content of ß-O-4 linkages for depolymerization and highly digestible cellulose for sugar production.
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Celulosa , Lignina , Lignina/química , Temperatura , Celulosa/química , Butileno Glicoles , Hidrólisis , CatálisisRESUMEN
OBJECTIVES: This study aimed to develop a new patient-reported outcome measure (PROM) to systematically and scientifically evaluate patients' subjective feelings after orthognathic surgery. METHODS: A literature review and semi-structured interviews were conducted to construct a conceptual framework and an item pool, followed by expert and patient surveys for measure construction. We conducted a clinical investigation to test the feasibility, reliability, and content validity of this measure. RESULTS: The conceptual framework included four domains: psychological health, physiological health, social function, and satisfaction, and 33 items were included in the survey. Following the expert analysis, 31 items remained in the draft. The clinical investigation showed a 100% recovery and completion rate and good reliability, with Cronman-Brown formula coefficients of 0.893 and 0.944, respectively. CONCLUSIONS: A new outcome measure to evaluate patients' subjective feelings after orthognathic surgery was successfully developed, and the clinical investigation demonstrated that the PROM had satisfactory feasibility, reliability, and validity. Further studies are possible based on our PROM, and data on a larger scale may reveal more information on patients' subjective feelings about orthognathic surgery. CLINICAL SIGNIFICANCE: The novel PROM provides a systematic and scientific way to evaluate the patient's subjective feelings to help surgeons obtain complete patient-reported information after orthognathic surgery. Additionally, standardised multicentre research on patients' subjective feelings using our PROM is possible and could improve the effectiveness of the evaluation and help maintain treatment quality.
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Cirugía Ortognática , Humanos , Reproducibilidad de los Resultados , Medición de Resultados Informados por el Paciente , Encuestas y Cuestionarios , Satisfacción Personal , Calidad de Vida/psicologíaRESUMEN
Spermatogonial stem cells (SSCs) are the only primitive spermatogonial cells in males that can naturally transmit genetic information to their offspring and replicate throughout their lives. Phospholipase D family member 6 (PLD6) has recently been found to be a surface marker for SSCs in mice and boars; however, it has not been validated in cattle. The results of reversed transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qRT-PCR) found that the relative expression of the PLD6 gene in the testicular tissues of two-year-old Simmental calves was significantly higher than that of six-month-old calves. Immunofluorescent staining further verified the expression of PLD6 protein in bovine spermatogenic cells like germ cell marker DEAD box helicase 4 (DDX4, also known as VASA). Based on multiple bioinformatic databases, PLD6 is a conservative protein which has high homology with mouse Q5SWZ9 protein. It is closely involved in the normal functioning of the reproductive system. Molecular dynamics simulation analyzed the binding of PLD6 as a phospholipase to cardiolipin (CL), and the PLD6-CL complex showed high stability. The protein interaction network analysis showed that there is a significant relationship between PLD6 and piwi-interacting RNA (piRNA) binding protein. PLD6 acts as an endonuclease and participates in piRNA production. In addition, PLD6 in bovine and mouse testes has a similar expression pattern with the spermatogonium-related genes VASA and piwi like RNA-mediated gene silencing 2 (PIWIL2). In conclusion, these analyses imply that PLD6 has a relatively high expression in bovine testes and could be used as a biomarker for spermatogenic cells including SSCs.
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Circular RNA (circRNA) has been confirmed to play a vital role in pancreatic ductal adenocarcinoma (PDAC) progression. However, the function and regulatory mechanism of hsa_circ_0012634 in PDAC progression remain unclear. Quantitative real-time PCR was used to measure the expression of hsa_circ_0012634, microRNA (miR)-147b and homeodomain interacting protein kinase 2 (HIPK2). Cell function was assessed by cell counting kit 8 assay, EdU assay, colony formation assay and flow cytometry. Glucose uptake and lactate production were evaluated to determine cell glycolysis ability. Protein expression was examined by western blot analysis. RNA interaction was confirmed by RNA pull-down assay and dual-luciferase reporter assay. Exosomes were isolated from serums and cell culture supernatant using ultracentrifugation and identified by transmission electron microscopy. Animal experiments were conducted using nude mice. Hsa_circ_0012634 was downregulated in PDAC tissues and cells, and its overexpression suppressed PDAC cell proliferation, glycolysis and enhanced apoptosis. MiR-147b was targeted by hsa_circ_0012634, and its inhibitors repressed PDAC cell growth and glycolysis. HIPK2 could be targeted by miR-147b, and hsa_circ_0012634 regulated miR-147b/HIPK2 to suppress PDAC cell progression. Hsa_circ_0012634 was lowly expressed in serum exosomes of PDAC patients. Exosomal hsa_circ_0012634 inhibited PDAC cell growth and glycolysis in vitro, as well as tumorigenesis in vivo. Exosomal hsa_circ_0012634 restrained PDAC progression via the miR-147b/HIPK2 pathway, confirming that hsa_circ_0012634 might serve as a diagnosis and treatment biomarker for PDAC.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Exosomas , MicroARNs , Neoplasias Pancreáticas , Animales , Ratones , Exosomas/genética , Ratones Desnudos , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Proliferación Celular , MicroARNs/genética , Línea Celular Tumoral , Neoplasias PancreáticasRESUMEN
Due to the complexity of electromechanical equipment and the difficulties in obtaining large-scale health monitoring datasets, as well as the long-tailed distribution of data, existing methods ignore certain characteristics of health monitoring data. In order to solve these problems, this paper proposes a method for the fault diagnosis of rolling bearings in electromechanical equipment based on an improved prototypical network-the weight prototypical networks (WPorNet). The main contributions of this paper are as follows: (1) the prototypical networks, which perform well on small-sample classification tasks, were improved by calculating the different levels of influence of support sample distributions in order to achieve the prototypical calculation. The change in sample influence was calculated using the Kullback-Leibler divergence of the sample distribution. The influence change in a specific sample can be measured by assessing how much the distribution changes in the absence of that sample; and (2) The Gramian Angular Field (GAF) algorithm was used to transform one-dimensional time series into two-dimensional vibration images, which greatly improved the application effect of the 2D convolutional neural network (CNN). Through experiments on MAFAULDA and CWRU bearing datasets, it was shown that this network effectively solves the shortcomings of a small number of valid samples and a long-tail distribution in health monitoring data, it enhances the dependency between the samples and the global data, it improves the model's feature extraction ability, and it enhances the accuracy of model classification. Compared with the prototypical network, the improved network model increased the performance of the 2-way 10-shot, 2-way 20-shot, and 2-way 50-shot classification tasks by 5.23%, 5.74%, and 4.37%, respectively, and it increased the performance of the 4-way 10-shot, 4-way 20-shot, and 4-way 50-shot classification tasks by 12.02%, 10.47%, and 4.66%, respectively. Experimental results show that the improved prototypical network model has higher sample classification accuracy and stronger anti-interference ability compared with traditional small-sample classification models.
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A novel gel-based wearable sensor with environment resistance (anti-freezing and anti-drying), excellent strength, high sensitivity and self-adhesion was prepared by introducing biomass materials including both lignin and cellulose. The introduction of lignin decorated CNC (L-CNC) to the polymer network acted as nano-fillers to improve the gel's mechanical with high tensile strength (72 KPa at 25 °C, 77 KPa at -20 °C), excellent stretchability (803 % at 25 °C, 722 % at -20 °C). The abundant catechol groups formed in the process of dynamic redox reaction between lignin and ammonium persulfate endowed the gel with robust tissue adhesiveness. Impressively, the gel exhibited outstanding environment resistance, which could be stored for a long time (>60 days) in an open-air environment with a wide work temperature range (-36.5 °C-25 °C). Based on these significant properties, the integrated wearable gel sensor showed superior sensitivity (gauge factor = 3.11 at 25 °C and 2.01 at -20 °C) and could detect human activities with excellent accuracy and stability. It is expected that this work will provide a promising platform for fabricating and application of a high-sensitive strain conductive gel with long-term usage and stability.
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Lignina , Nanocompuestos , Humanos , Celulosa , Polímeros , Biomasa , Conductividad Eléctrica , HidrogelesRESUMEN
Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Fructosa/metabolismo , Hígado/metabolismo , Dieta , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Inflamación/metabolismo , Dieta Alta en Grasa , Ratones Endogámicos C57BLRESUMEN
Here, a Cu2+-doped lignin-based adsorbent (Cu-AL) was fabricated via the amination and Cu2+-doping of industrial alkali lignin for massive and selective adsorption of cationic dyes azure B (AB) and saffron T (ST). The Cu-N coordination structures endowed Cu-AL with stronger electronegativity and higher dispersity. Through the electrostatic attraction, π-π interaction, H-bonding, and Cu2+ coordination, the adsorption capacities of AB and ST reached up to 1168 and 1420 mg g-1, respectively. The pseudo-second-order model and Langmuir isotherm model were more relevant to the AB and ST adsorption on Cu-AL. Based on the thermodynamic study, the adsorption progresses were endothermic, spontaneous, and feasible. The Cu-AL maintained high removal efficiency to dyes after 4 reuses (>80%). Importantly, the Cu-AL could efficiently remove and separate AB and ST from dye mixtures even in real time. All the above characteristics demonstrated that Cu-AL was an excellent adsorbent for fast wastewater treatment.