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INTRODUCTION: Critically ill patients often endure pain, a distressing experience that can trigger diverse pathophysiological consequences. While remifentanil, with its rapid kinetics, is commonly used for analgesia in intensive care units (ICU), it frequently leads to opioid-related adverse effects. A promising alternative has emerged in oliceridine, a novel G protein-biased µ-opioid receptor agonist. This new drug offers the potential for effective pain relief with fewer side effects. However, its efficacy and safety profile in mechanically ventilated ICU patients remain to be fully elucidated. METHODS: This is a multicenter, prospective, randomized, single-blind, active-controlled trial conducted across 24 ICUs in China. A total of 292 mechanically ventilated patients requiring analgesia and sedation will be randomly assigned in a 1:1 ratio to either the oliceridine or remifentanil group. The oliceridine group will receive oliceridine (2-20 µg/kg/h), while the remifentanil group will receive remifentanil (1.5-12 µg/kg/h). Both groups will receive propofol for sedation if necessary. The target for analgesia is Critical-Care Pain Observation Tool (CPOT) < 3, and for sedation is Richmond Agitation-Sedation Scale (RASS) - 2 to 0. PLANNED OUTCOMES: The primary outcome will be the percentage of time within target analgesia during study drug administration. Secondary outcomes will include gastrointestinal dysfunction, respiratory depression, sedative usage, mechanical ventilation duration, ICU stay length, extubation failure rate, etc. TRIAL REGISTRATION: NCT06454292. Registered on June 11, 2024.
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BACKGROUND: Hepatocellular carcinoma (HCC) is a major health challenge with high incidence and poor survival rates in China. Systemic therapies, particularly tyrosine kinase inhibitors (TKIs), are the first-line treatment for advanced HCC, but resistance is common. The Rho GTPase family member Rho GTPase activating protein 12 (ARHGAP12), which regulates cell adhesion and invasion, is a potential therapeutic target for overcoming TKI resistance in HCC. However, no studies on the expression of ARHGAP12 in HCC and its role in resistance to TKIs have been reported. AIM: To unveil the expression of ARHGAP12 in HCC, its role in TKI resistance and its potential associated pathways. METHODS: This study used single-cell RNA sequencing (scRNA-seq) to evaluate ARHGAP12 mRNA levels and explored its mechanisms through enrichment analysis. CellChat was used to investigate focal adhesion (FA) pathway regulation. We integrated bulk RNA data (RNA-seq and microarray), immunohistochemistry and proteomics to analyze ARHGAP12 mRNA and protein levels, correlating with clinical outcomes. We assessed ARHGAP12 expression in TKI-resistant HCC, integrated conventional HCC to explore its mechanism, identified intersecting FA pathway genes with scRNA-seq data and evaluated its response to TKI and immunotherapy. RESULTS: ARHGAP12 mRNA was found to be highly expressed in malignant hepatocytes and to regulate FA. In malignant hepatocytes in high-score FA groups, MDK-[integrin alpha 6 (ITGA6) + integrin ß-1 (ITGB1)] showed specificity in ligand-receptor interactions. ARHGAP12 mRNA and protein were upregulated in bulk RNA, immunohistochemistry and proteomics, and higher expression was associated with a worse prognosis. ARHGAP12 was also found to be a TKI resistance gene that regulated the FA pathway. ITGB1 was identified as a crossover gene in the FA pathway in both scRNA-seq and bulk RNA. High expression of ARHGAP12 was associated with adverse reactions to sorafenib, cabozantinib and regorafenib, but not to immunotherapy. CONCLUSION: ARHGAP12 expression is elevated in HCC and TKI-resistant HCC, and its regulatory role in FA may underlie the TKI-resistant phenotype.
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Doping engineering is crucial for both fundamental science and emerging applications. While transition metal (TM) dopants exhibit considerable advantages in the tuning of magnetism and conductivity in bulk Ga2O3, investigations on TM-doped two-dimensional (2D) Ga2O3 are scarce, both theoretically and experimentally. In this study, the detailed variations in impurity levels within 3d TM-doped 2D Ga2O3 systems have been explored via first-principles calculations using the generalized gradient approximation (GGA) +U method. Our results show that the Co impurity tends to incorporate on the tetrahedral GaII site, while the other dopants favor square pyramidal GaI sites in 2D Ga2O3. Moreover, Sc3+, Ti4+, V4+, Cr3+, Mn3+, Fe3+, Co3+, Ni3+, Cu2+, and Zn2+ are the energetically favorable charge states. Importantly, a transition from n-type to p-type conductivity occurs at the threshold Cu element as determined by the defect formation energies and partial density of states (PDOS), which can be ascribed to the shift from electron doping to hole doping with respect to the increase in the atomic number in the 3d TM group. Moreover, the spin configurations in the presence of the square pyramidal and tetrahedral coordinated crystal field effects are investigated in detail, and a transition from high-spin to low-spin arrangement is observed. As the atomic number of the 3d TM dopant increases, the percentage contribution of O ions to the total magnetic moment significantly increases due to the electronegativity effect. Additionally, the formed 3d bands for most TM dopants are located near the Fermi level, which can be of significant benefit to the transformation of the absorbing region from ultraviolet to visible/infrared light. Our results provide theoretical guidance for designing 2D Ga2O3 towards optoelectronic and spintronic applications.
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Skeletal muscle development is a complex, regulated physiological process that involves myoblast proliferation and differentiation and the fusion of myotubes. In this study, phenotypic differences in the breast and leg muscles of 180-day-old Jingyuan chickens were investigated. Differentially methylated genes (DMG) that regulate muscle development were identified through differential expression analysis and weighted gene co-expression network analysis. Moreover, myoblasts were used as test material and treated with cycloleucine to investigate the effect of N6-methyladenosine (m6A) modification on their proliferation and differentiation. The results revealed that the myofiber diameter and cross-sectional area in the breast muscle of Jingyuan chickens were significantly smaller than those in the leg muscle, while myofiber density in the breast muscle was significantly higher. A total of 484 DMG were identified in both muscle types. Module gene association analysis with DMGs revealed multiple DMG associated with muscle development. In vitro cell model analysis revealed that cycloleucine treatment significantly downregulated the m6A modification level of myoblasts and inhibited their proliferation and differentiation. Additionally, stage-specific differences in LDHA, LDHB, and GAPDH expressions were observed during myoblast differentiation. Cycloleucine treatment significantly inhibited LDHA, LDHB, and GAPDH expression. These findings indicate that m6A methylation modifications play significant regulatory roles in muscle development, with LDHA, LDHB, and GAPDH being potential candidate genes for regulating muscle development. This study provides an essential theoretical basis for further study on the functional mechanisms of m6A modifications involved in muscle development.
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The global climate change has resulted in substantial modifications to the distribution patterns of narrowly distributed species across different time periods, leading to an imminent threat to the survival of some vulnerable species. Chimonobambusa tumidissinoda J. R. Xue & T. P. Yi ex Ohrnb., a bamboo species endemic to the transition zone from the Yunnan-Guizhou Plateau to the Sichuan Basin with high economic and ecological value, exhibits a limited range and rarity. Utilizing eight environmental variables and 56 occurrence records, we employed the MaxEnt model to predict the potential distribution range of C. tumidissinoda under current and future climate scenarios. The findings revealed that precipitation of the driest month (Bio14), elevation and isothermality (Bio3) were the crucial factors determining the species' distribution, accounting for 31.24%, 28.27% and 17.24% of data variability, respectively. The distribution centroid of C. tumidissinoda is anticipated to shift towards higher latitudes in response to future climate change, and the projected habitat suitability is expected to expand under ssp245 and ssp585 scenarios while remaining unchanged or contracting under the ssp126 scenario. Despite these expansions, the suitable habitats remain limited, with the largest being approximately 2.08 × 104 km2, indicating a significant threat to its survival. Our study provides insights into the adaptive responses of C. tumidissinoda to climate change, enriching scientific knowledge for developing effective conservation measurements as well as sustainable utilization.
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Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet-derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element-binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC-mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC-induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes.
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Carcinoma Ductal Pancreático , Metabolismo de los Lípidos , Neoplasias Pancreáticas , Factor de Crecimiento Derivado de Plaquetas , Proteína 1 de Unión a los Elementos Reguladores de Esteroles , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Humanos , Animales , Ratones , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Línea Celular Tumoral , Linfocinas/metabolismo , Linfocinas/genética , Modelos Animales de Enfermedad , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , MasculinoRESUMEN
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases. We categorize acute pancreatitis by etiology into acute biliary pancreatitis (ABP) and hypertriglyceridemia-induced acute pancreatitis (HTGP). AIM: To investigate the clinical significance of NLR and PLR in assessing persistent organ failure (POF) in HTGP and ABP. METHODS: A total of 1450 patients diagnosed with acute pancreatitis (AP) for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled. The patients were categorized into two groups according to the etiology of AP: ABP in 530 patients and HTGP in 241 patients. We collected and compared the clinical data of the patients, including NLR, PLR, and AP prognostic scoring systems, within 48 h of hospital admission. RESULTS: The NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In the HTGP group, both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score ≥ 3. Likewise, in the ABP group, NLR and PLR were significantly elevated in patients with severe AP, modified computed tomography severity index score ≥ 4, Japanese Severity Score ≥ 3, and modified Marshall score ≥ 2. Moreover, NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups. CONCLUSION: NLR and PLR vary between ABP and HTGP, are strongly associated with AP prognostic scoring systems, and have predictive potential for the occurrence of POF in both ABP and HTGP.
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Transcriptional regulation, involving the complex interplay between regulatory sequences and proteins, directs all biological processes. Computational models of transcription lack generalizability to accurately extrapolate in unseen cell types and conditions. Here, we introduce GET, an interpretable foundation model designed to uncover regulatory grammars across 213 human fetal and adult cell types. Relying exclusively on chromatin accessibility data and sequence information, GET achieves experimental-level accuracy in predicting gene expression even in previously unseen cell types. GET showcases remarkable adaptability across new sequencing platforms and assays, enabling regulatory inference across a broad range of cell types and conditions, and uncovering universal and cell type specific transcription factor interaction networks. We evaluated its performance on prediction of regulatory activity, inference of regulatory elements and regulators, and identification of physical interactions between transcription factors. Specifically, we show GET outperforms current models in predicting lentivirus-based massive parallel reporter assay readout with reduced input data. In fetal erythroblasts, we identify distal (>1Mbp) regulatory regions that were missed by previous models. In B cells, we identified a lymphocyte-specific transcription factor-transcription factor interaction that explains the functional significance of a leukemia-risk predisposing germline mutation. In sum, we provide a generalizable and accurate model for transcription together with catalogs of gene regulation and transcription factor interactions, all with cell type specificity.
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Contaminación del Aire , Asma , Negro o Afroamericano , Hispánicos o Latinos , Humanos , Asma/etnología , Asma/etiología , Hispánicos o Latinos/estadística & datos numéricos , Negro o Afroamericano/estadística & datos numéricos , Contaminación del Aire/efectos adversos , Estados Unidos/epidemiología , Disparidades en el Estado de Salud , Femenino , MasculinoRESUMEN
The rapid advancement of sequencing technologies has led to the identification of numerous mutations in cancer genomes, many of which are variants of unknown significance (VUS). Computational models are increasingly being used to predict the functional impact of these mutations, in both coding and noncoding regions. Integration of these models with emerging genomic datasets will refine our understanding of mutation effects and guide clinical decision making. Future advancements in modeling protein interactions and transcriptional regulation will further enhance our ability to interpret VUS. Periodic incorporation of these developments into VUS reclassification practice has the potential to significantly improve personalized cancer care.
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Neoplasias , Humanos , Neoplasias/genética , Mutación , Biología Computacional/métodos , Genómica/métodos , Variación GenéticaRESUMEN
Gemcitabine resistance is a major obstacle to the effectiveness of chemotherapy in pancreatic ductal adenocarcinoma (PDAC). Therefore, new strategies are needed to sensitize cancer cells to gemcitabine. Here, we constructed gemcitabine-resistant PDAC cells and analyzed them with RNA-sequence. Employing an integrated approach involving bioinformatic analyses from multiple databases, TGFB2 is identified as a crucial gene in gemcitabine-resistant PDAC and is significantly associated with poor gemcitabine therapeutic response. The patient-derived xenograft (PDX) model further substantiates the gradual upregulation of TGFB2 expression during gemcitabine-induced resistance. Silencing TGFB2 expression can enhance the chemosensitivity of gemcitabine against PDAC. Mechanistically, TGFB2, post-transcriptionally stabilized by METTL14-mediated m6A modification, can promote lipid accumulation and the enhanced triglyceride accumulation drives gemcitabine resistance by lipidomic profiling. TGFB2 upregulates the lipogenesis regulator sterol regulatory element binding factor 1 (SREBF1) and its downstream lipogenic enzymes via PI3K-AKT signaling. Moreover, SREBF1 is responsible for TGFB2-mediated lipogenesis to promote gemcitabine resistance in PDAC. Importantly, TGFB2 inhibitor imperatorin combined with gemcitabine shows synergistic effects in gemcitabine-resistant PDAC PDX model. This study sheds new light on an avenue to mitigate PDAC gemcitabine resistance by targeting TGFB2 and lipid metabolism and develops the potential of imperatorin as a promising chemosensitizer in clinical translation.
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Adenosina , Carcinoma Ductal Pancreático , Desoxicitidina , Resistencia a Antineoplásicos , Gemcitabina , Metabolismo de los Lípidos , Neoplasias Pancreáticas , Factor de Crecimiento Transformador beta2 , Humanos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/genética , Resistencia a Antineoplásicos/genética , Animales , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Ratones , Adenosina/análogos & derivados , Adenosina/farmacología , Adenosina/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Transducción de Señal/efectos de los fármacos , Reprogramación Metabólica , Proteína 1 de Unión a los Elementos Reguladores de EsterolesRESUMEN
Inosine monphosphate (IMP) is one of the important indicators for evaluating meat flavor, and long noncoding RNAs (lncRNAs) play an important role in its transcription and post-transcriptional regulation. Currently, there is little information about how lncRNA regulates the specific deposition of IMP in chicken muscle. In this study, we used transcriptome sequencing to analyze the lncRNAs of the breast and leg muscles of the Jingyuan chicken and identified a total of 357 differentially expressed lncRNAs (DELs), of which 158 were up-regulated and 199 were down-regulated. There were 2,203 and 7,377 cis- and trans-regulated target genes of lncRNAs, respectively, and we identified the lncRNA target genes that are involved in NEGF signaling pathway, glycolysis/glucoseogenesis, and biosynthesis of amino acids pathways. Meanwhile, 621 pairs of lncRNA-miRNA-mRNA interaction networks were constructed with target genes involved in purine metabolism, fatty acid metabolism, and biosynthesis of amino acids. Next, three interacting meso-networks gga-miR-1603-LNC_000324-PGM1, gga-miR-1768-LNC_000324-PGM1, and gga-miR-21-LNC_011339-AMPD1 were identified as closely associated with IMP-specific deposition. Both differentially expressed genes (DEGs) PGM1 and AMPD1 were significantly enriched in IMP synthesis and metabolism-related pathways, and participated in the anabolic process of IMP in the form of organic matter synthesis and energy metabolism. This study obtained lncRNAs and target genes affecting IMP-specific deposition in Jingyuan chickens based on transcriptome analysis, which deepened our insight into the role of lncRNAs in chicken meat quality.
Jingyuan chicken is an excellent local chicken breed listed in the Catalogue of Livestock and Poultry Genetic Resources of China. Its unique growing environment has enabled Jingyuan chicken to develop the characteristics of compact meat, unique flavor, and high nutritional value, which makes it the first choice for chicken food. Inosine monophosphate (IMP) is widely recognized as an important indicator for evaluating the flavor of livestock and poultry meat. To mine potential long noncoding RNAs (lncRNAs) and their regulatory IMP-specific deposition interaction networks, we used transcriptome sequencing to identify 357 lncRNAs that were differentially expressed in breast and leg muscles of 180-d-old Jingyuan hens. We screened the key lncRNAs affecting IMP and three lncRNA-miRNA-mRNA regulatory networks by bioinformatics methods. This provides a new approach to studying IMP-specific deposition, improvement of chicken meat flavor, and breed improvement in Jingyuan chickens.
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Pollos , Perfilación de la Expresión Génica , Inosina Monofosfato , ARN Largo no Codificante , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Pollos/genética , Pollos/metabolismo , Inosina Monofosfato/metabolismo , Transcriptoma , MicroARNs/genética , MicroARNs/metabolismo , Carne/análisis , Inosina/metabolismo , Inosina/genética , Músculo Esquelético/metabolismo , Regulación de la Expresión GénicaRESUMEN
Background: Previous studies have indicated beneficial outcomes of transcutaneous electrical acupoint stimulation (TEAS), but high-quality and comprehensive meta-analyses are lacking. The aim was to quantitatively analyze the efficacy and safety of perioperative TEAS on postoperative pain and recovery. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched through July 2022. Randomized controlled trials (RCTs) that examined the perioperative application of TEAS in adults compared with sham-TEAS and/or non-TEAS were eligible. Cumulative analgesic consumption within 24 h and rest pain scores at 2, 6, 12, and 24 h postoperatively were the two co-primary outcomes. Results: Seventy-six RCTs (n = 9,665 patients) were included. Patients treated with TEAS experienced a reduction in clinical importance in cumulative analgesic (morphine equivalent) consumption (WMD: -14.60 mg, 97.5% CI: -23.60 to -5.60; p < 0.001) and a reduction in statistical importance in rest pain scores at multiple time points within the first 24 postoperative hours. The secondary outcome analysis also identified clinically significant recovery benefits to TEAS during the first 24 h after surgery. Furthermore, TEAS could effectively reduce opioid-related side effects and did not increase serious side effects. Conclusion: This article describes current evidence about TEAS intervention on early postoperative pain and recovery. The results support the effectiveness of TEAS, but more high-quality evidence of clinical applicability is also needed. Systematic review registration: PROSPERO (CRD42021249814).
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By using first principles calculations, we theoretically investigate the electronic structures and the interfacial and optical properties of the two-dimensional tellurene (Te)-gallium arsenide (GaAs) van der Waals heterostructures (vdWHs), i.e., α-Te/GaAs and γ-Te/GaAs, formed using Te and GaAs monolayers. It has been demonstrated that, the semiconductor-semiconductor contacted α-Te/GaAs vdWH exhibits a type-II band alignment with a direct band gap of 0.28 eV while the metal-semiconductor contacted γ-Te/GaAs vdWH has a p-type Schottky contact with a Schottky barrier height (SBH) of 0.36 eV at the interface. The transition from type-II to type-III band alignment is observed firstly in the α-Te/GaAs vdWH when the in-plane biaxial strain is less than -5.2% and larger than 4.4%, meanwhile, the p-type Schottky contact to Ohmic contact transition may be realized in the γ-Te/GaAs vdWH when the in-plane biaxial strain is less than -2.4%. Finally, the maximum optical absorption coefficients of the α- and γ-Te/GaAs vdWHs have been found to be up to 31% and 29%, respectively, and may be modulated effectively by applying in-plane biaxial strain. The obtained results may be of importance in the design of nanoelectronic devices based on the proposed tellurene/GaAs vdWHs.
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Inosine monophosphate (IMP) is widely regarded as an important indicator for evaluating the flavour of poultry meat. However, little is known about the molecular mechanisms affecting the specific deposition of IMP. In this study, we functionally verified PKM2 (Pyruvate kinase M2), a candidate gene related to IMP synthesis, in order to reveal the important role of PKM2 in meat flavour and muscle development of Jingyuan chickens. The results showed that the IMP content in breast muscle of Jingyuan chickens was negatively correlated with PKM2 mRNA expression (r = -0.1710), while the IMP content in leg muscle was significantly positively correlated with PKM2 mRNA expression (r = 0.7350) (P < 0.05). During myogenesis, PKM2 promoted the proliferation rate of myoblasts and the expression of proliferation marker genes, inhibited the apoptosis rate and the expression of apoptosis marker genes, and decreased the expression of differentiation marker genes. Up-regulation of PKM2 enhanced the expression of key genes in the purine metabolic pathway and the de novo synthesis pathway of IMP, and suppressed the expression of key genes in the salvage pathway. ELISA assays showed that PKM2 decreased IMP and hypoxanthine (HX) contents, while adenosine triphosphate (ATP) and uric acid (UA) contents were clearly elevated. In summary, these studies revealed that PKM2 regulates myogenesis and specific deposition of IMP, which can be used to improve the quality of Jingyuan chicken meat.
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Pollos , Inosina Monofosfato , Mioblastos , Animales , Pollos/metabolismo , Pollos/crecimiento & desarrollo , Inosina Monofosfato/metabolismo , Mioblastos/metabolismo , Piruvato Quinasa/metabolismo , Piruvato Quinasa/genética , Carne/análisis , Desarrollo de Músculos , Músculo Esquelético/metabolismo , Músculo Esquelético/crecimiento & desarrollo , Proliferación CelularRESUMEN
BACKGROUND: Oral microbiota imbalance is associated with the progression of various lung diseases, including lung cancer. Pulmonary nodules (PNs) are often considered a critical stage for the early detection of lung cancer; however, the relationship between oral microbiota and PNs remains unknown. METHODS: We conducted a 'Microbiome with pulmonary nodule series study 1' (MCEPN-1) where we compared PN patients and healthy controls (HCs), aiming to identify differences in oral microbiota characteristics and discover potential microbiota biomarkers for non-invasive, radiation-free PNs diagnosis and warning in the future. We performed 16 S rRNA amplicon sequencing on saliva samples from 173 PN patients and 40 HCs to compare the characteristics and functional changes in oral microbiota between the two groups. The random forest algorithm was used to identify PN salivary microbial markers. Biological functions and potential mechanisms of differential genes in saliva samples were preliminarily explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of Orthologous Groups (COG) analyses. RESULTS: The diversity of salivary microorganisms was higher in the PN group than in the HC group. Significant differences were noted in community composition and abundance of oral microorganisms between the two groups. Neisseria, Prevotella, Haemophilus and Actinomyces, Porphyromonas, Fusobacterium, 7M7x, Granulicatella and Selenomonas were the main differential genera between the PN and HC groups. Fusobacterium, Porphyromonas, Parvimonas, Peptostreptococcus and Haemophilus constituted the optimal marker sets (area under curve, AUC = 0.80), which can distinguish between patients with PNs and HCs. Further, the salivary microbiota composition was significantly correlated with age, sex, and smoking history (P < 0.001), but not with personal history of cancer (P > 0.05). Bioinformatics analysis of differential genes showed that patients with PN showed significant enrichment in protein/molecular functions related to immune deficiency and energy metabolisms, such as the cytoskeleton protein RodZ, nicotinamide adenine dinucleotide phosphate dehydrogenase (NADPH) dehydrogenase, major facilitator superfamily transporters and AraC family transcription regulators. CONCLUSIONS: Our study provides the first evidence that the salivary microbiota can serve as potential biomarkers for identifying PN. We observed a significant association between changes in the oral microbiota and PNs, indicating the potential of salivary microbiota as a new non-invasive biomarker for PNs. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR2200062140; Date of registration: 07/25/2022.
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Neoplasias Pulmonares , Microbiota , Humanos , Saliva/microbiología , ARN Ribosómico 16S/genética , Microbiota/genética , Biomarcadores , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , OxidorreductasasRESUMEN
Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.
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Stroke, a critical health issue in the US, not only has physical repercussions but also potentially affects the health-related quality of life (HRQoL) through neuropsychiatric outcomes like depressive symptoms and suicidal thoughts. This study utilized a nationally representative sample of 1302 US stroke survivors (age ≥ 20) from the US National Health and Nutrition Examination Survey (2005-2018) to assessed relationships between QoL via the CDC HRQOL-4 and evaluated depressive symptoms and suicidal ideation using the Patient Health Questionnaire-9 (PHQ-9). Participants (mean age: 64.4; 56.0 % female) showed that 40.7 % had at least mild depressive symptoms, and 18.8 % exhibited major depressive symptoms. Suicidal ideation was reported by 8.1 %. After sociodemographic and health condition adjustments, mild and major depressive symptoms, along with suicidal ideation, were associated with poorer general health status and more physically and mentally unhealthy days and activity limitation days. A dose-response relationship between PHQ-9 scores and HRQoL outcomes was evident (All P for trend <0.001). Stroke survivors with suicidal ideation also experienced more physically and mentally unhealthy days and activity limitation days. Depressive symptoms and suicidal ideation are associated with reduced HRQoL among US stroke survivors, underscoring the importance of thorough neuropsychiatric evaluations and interventions to bolster stroke survivors' well-being.