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Anguimorpha, within the order Squamata, represents a group with distinct morphological and behavioral characteristics in different ecological niches among lizards. Within Anguimorpha, there is a group characterized by limb loss, occupying lower ecological niches, concentrated within the subfamily Anguinae. Lizards with limbs and those without exhibit distinct locomotor abilities when adapting to their habitats, which in turn necessitate varying degrees of energy expenditure. Mitochondria, known as the metabolic powerhouses of cells, play a crucial role in providing approximately 95% of an organism's energy. Functionally, mitogenomes (mitochondrial genomes) can serve as a valuable tool for investigating potential adaptive evolutionary selection behind limb loss in reptiles. Due to the variation of mitogenome structures among each species, as well as its simple genetic structure, maternal inheritance, and high evolutionary rate, the mitogenome is increasingly utilized to reconstruct phylogenetic relationships of squamate animals. In this study, we sequenced the mitogenomes of two species within Anguimorpha as well as the mitogenomes of two species in Gekkota and four species in Scincoidea. We compared these data with the mitogenome content and evolutionary history of related species. Within Anguimorpha, between the mitogenomes of limbless and limbed lizards, a branch-site model analysis supported the presence of 10 positively selected sites: Cytb protein (at sites 183 and 187), ND2 protein (at sites 90, 155, and 198), ND3 protein (at site 21), ND5 protein (at sites 12 and 267), and ND6 protein (at sites 72 and 119). These findings suggested that positive selection of mitogenome in limbless lizards may be associated with the energy requirements for their locomotion. Additionally, we acquired data from 205 mitogenomes from the NCBI database. Bayesian inference (BI) and Maximum Likelihood (ML) trees were constructed using the 13 mitochondrial protein-coding genes (PCGs) and two rRNAs (12S rRNA and 16S rRNA) from 213 mitogenomes. Our phylogenetic tree and the divergence time estimates for Squamata based on mitogenome data are consistent with results from previous studies. Gekkota was placed at the root of Squamata in both BI and ML trees. However, within the Toxicofera clade, due to long-branch attraction, Anguimorpha and (Pleurodonta + (Serpentes + Acrodonta)) were closely related groupings, which might indicate errors and also demonstrate that mitogenome-based phylogenetic trees may not effectively resolve long-branch attraction issues. Additionally, we reviewed the origin and diversification of Squamata throughout the Mesozoic era, suggesting that Squamata originated in the Late Triassic (206.05 Mya), with the diversification of various superfamilies occurring during the Cretaceous period. Future improvements in constructing squamate phylogenetic relationships using mitogenomes will rely on identifying snake and acrodont species with slower evolutionary rates, ensuring comprehensive taxonomic coverage of squamate diversity, and increasing the number of genes analyzed.
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Genoma Mitocondrial , Lagartos , Filogenia , Selección Genética , Animales , Lagartos/genética , Lagartos/clasificación , Genoma Mitocondrial/genética , Evolución MolecularRESUMEN
OBJECTIVES: Exposure to benzo[α]pyrene (BaP) increases the incidence and severity of allergic rhinitis (AR), but the underlying mechanisms remain unclear. Thus, we investigated the in vivo effects of BaP exposure on mucus hypersecretion and tissue remodeling in a rat model of AR. METHODS: Female Sprague-Dawley rats were randomly divided into 4 groups: a negative control group, a group of healthy rats exposed to BaP, a group of rats with ovalbumin (OVA)-induced AR, and a group of AR model rats exposed to BaP. Nasal symptoms and levels of OVA-specific serum immunoglobulin E (IgE) were measured in each individual rat. Moreover, examination of goblet cell hyperplasia and collagen deposition was carried out with periodic acid-Schiff (PAS) staining and Masson trichrome (MT) staining. Mucin 5AC (MUC5AC) expression was assessed by immunohistochemistry. RESULTS: BaP significantly increased the number of sneezes, the number of nasal rubs and the levels of OVA-specific serum IgE in rats with AR. Statistically significant differences in goblet cell hyperplasia and collagen deposition were observed between the BaP-exposed AR model group and the AR model group. Immunohistochemical results showed that the nasal mucosa of AR model rats displayed markedly elevated MUC5AC expression after BaP exposure. CONCLUSION: Our data indicate that mucus hypersecretion and the development of nasal remodeling might be pathophysiologic mechanisms underlying increased susceptibility to AR after exposure to BaP.
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Here, we developed an efficient method for the synthesis of s-alkyl or aryl thiocarbamates catalyzed by Na2CO3 under mild conditions using alkyl or aryl isocyanates and thiophenols or thiols. In situ reaction with deuterated tetrahydrofuran (d8-THF) was carried out to investigate the reaction mechanism. This method has the advantages of high yield, good functional group tolerance and high atom economy.
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This study was conducted during October 2021 (autumn) and April 2022 (spring) to explore the phytoplankton community structure, their distribution characteristics, and the influence of environmental factors in the coastal waters of the Southern Beibu Gulf. The 15 sampling sites were grouped based on the difference in offshore distance to analyze the temporal and spatial differences in community structure and environmental driving in the investigated sea area of the coastal waters of the Southern Beibu Gulf. Permutational multivariate analysis of variance was conducted on the sample data in time and space, revealing that there is no significant difference in space (p > 0.05), but there is significant difference in time (p < 0.05). Notably, water pressure, pH, chemical oxygen demand, nitrite, and labile phosphate were higher in autumn, while total ammonia nitrogen, dissolved oxygen, and suspended solids were significantly higher in spring. Additionally, the study identified 87 phytoplankton species belonging to 6 phyla, dominating by Bacillariophyta, followed by Dinophyta and Cyanophyta. The phytoplankton density, Shannon Weiner's diversity index (H'), Pielou's evenness index (J), and Margalef's richness index (D) ranged from 84.88 to 4675.33 cells L-1, 0.56 to 2.58, 0.26 to 0.89, and 1.21 to 3.64, respectively. Permutational multivariate analysis of variance showed non-significant spatial differences in phytoplankton composition (p > 0.05) but seasonal differences (p < 0.05). Furthermore, canonical correspondence analysis (CCA) identified pH, dissolved oxygen, suspended solids, chemical oxygen demand, nitrite, and labile phosphate as key environmental factors influencing the phytoplankton community structure (p < 0.05). In this study, the dynamic changes of phytoplankton community structure and environmental factors in the southern coastal waters of Beibu Gulf were analyzed in detail from two aspects of time and space. The key environmental factors to protect the ecological environment in the southern coastal area of Beibu Gulf were found out. It provides a reference method and theoretical basis for the management and protection of Beibu Gulf and other tropical marine environment.
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Monitoreo del Ambiente , Fitoplancton , Estaciones del Año , Agua de Mar , Fitoplancton/crecimiento & desarrollo , Agua de Mar/química , Biodiversidad , Análisis Espacio-Temporal , ChinaRESUMEN
NTRK gene fusion leads to the activation of downstream signaling pathways, which is a oncogenic driver in various cancers. NTRK fusion-positive cancers can be treated with the first-generation TRK inhibitors, larotrectinib and entrectinib. Unfortunately, the patients eventually face the dilemma of no drugs available as the emergence of certain resistance mutations. The development of efficient and broad-spectrum second-generation TRK inhibitors is still of great significance. Here, we analyzed the binding modes of compounds 6, 10 with TRKA protein, respectively, a series of novel indazole TRK inhibitors were designed and synthesized using molecular hybridization strategy. Among them, the optimal compound B31 showed strong antiproliferative activities against Km-12, Ba/F3-TRKAG595R, and Ba/F3-TRKAG667C cell lines with IC50 values of 0.3, 4.7, and 9.9 nM, respectively. And the inhibitory effect against TRKAG667C (IC50 = 9.9 nM) was better than that of selitrectinib (IC50 = 113.1 nM). Further, compound B31 exhibited moderate kinase selectivity and excellent plasma stability (t1/2 > 480 min). In vivo pharmacokinetic studies in Sprague-Dawley rats showed that B31 had acceptable pharmacokinetic properties.
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Antineoplásicos , Proliferación Celular , Descubrimiento de Drogas , Indazoles , Inhibidores de Proteínas Quinasas , Ratas Sprague-Dawley , Receptor trkA , Indazoles/farmacología , Indazoles/química , Indazoles/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Humanos , Animales , Relación Estructura-Actividad , Receptor trkA/antagonistas & inhibidores , Receptor trkA/metabolismo , Proliferación Celular/efectos de los fármacos , Ratas , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Estructura Molecular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral , MasculinoRESUMEN
Developing multifunctional engineered adsorbents is an effective strategy for decontaminating the environment from various pollutants. In this study, a polyfunctionalized carbon-framework composite, MSC-CFM, was synthesized. The composite comprises an aromatic carbon framework enriched with various functional groups, including magnetic nanoparticles, hydroxyl, and amino groups. MSC-CFM was used to decontaminate Cr(VI) and polycyclic aromatic nitrides (p-dimethylaminoazobenzene sulfonate (DAS) and diphenyl-4, 4 '-di [sodium (azo-2 -) -1-amino-naphthalene-4-sulfonate] (DANS)) from acidic wastewater. The adsorption capacities of MSC-CFM for Cr(VI), DAS and DANS, quantified using the Langmuir isotherm model, were 161.28, 310.83, and 1566.09 mg/g, respectively. Cr(VI) and PAHs (DAS and DANS) were monolayer adsorbed controlled by chemisorption. MSC-CFM could maintain good adsorption efficiency after up to 6 adsorption and desorption cycles. The presence of polycyclic aromatic nitrides promoted the adsorption of Cr(VI) in the Cr(VI)-DAS/DANS binary systems. Removal of pollutants by MSC-CFM involved a variety of unreported reaction mechanisms, such as electrostatic attraction, redox reaction, anion exchange, intermolecular hydrogen bonding, complexation reaction, π-π interaction, and anion-π interaction. MSC-CFM, enriched with a variety of functional groups, is a promising new material for environmental protection. It has good potential for practical application in treating polluted wastewater.
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Carbono , Cromo , Aguas Residuales , Contaminantes Químicos del Agua , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Adsorción , Cromo/química , Carbono/química , Hidrocarburos Policíclicos Aromáticos/químicaRESUMEN
In the context of global warming, the frequency of severe weather occurrences, such as unexpected cold spells and heat waves, will grow, as well as the intensity of these natural disasters. Lizards, as a large group of reptiles, are ectothermic. Their body temperatures are predominantly regulated by their environment and temperature variations directly impact their behavior and physiological activities. Frequent cold periods and heat waves can affect their biochemistry and physiology, and often their ability to maintain their body temperature. Mitochondria, as the center of energy metabolism, are crucial for maintaining body temperature, regulating metabolic rate, and preventing cellular oxidative damage. Here, we used RT-qPCR technology to investigate the expression patterns and their differences for the 13 mitochondrial PCGs in Sphenomorphus incognitus (Squamata:Scincidae), also known as the brown forest skink, under extreme temperature stress at 4 °C, 8 °C, 34 °C, and 38 °C for 24 h, compared to the control group at 25 °C. In southern China, for lizards, 4 °C is close to lethal, and 8 °C induces hibernation, while 34/38 °C is considered hot and environmentally realistic. Results showed that at a low temperature of 4 °C for 24 h, transcript levels of ATP8, ND1, ND4, COI, and ND4L significantly decreased, to values of 0.52 ± 0.08, 0.65 ± 0.04, 0.68 ± 0.10, 0.28 ± 0.02, and 0.35 ± 0.02, respectively, compared with controls. By contrast, transcript levels of COIII exhibited a significant increase, with a mean value of 1.86 ± 0.21. However, exposure to 8 °C for 24 h did not lead to an increase in transcript levels. Indeed, transcript levels of ATP6, ATP8, ND1, ND3, and ND4 were significantly downregulated, to 0.48 ± 0.11, 0.68 ± 0.07, 0.41 ± 0.08, 0.54 ± 0.10, and 0.52 ± 0.07, respectively, as compared with controls. Exposure to a hot environment of 34 °C for 24 h led to an increase in transcript levels of COI, COII, COIII, ND3, ND5, CYTB, and ATP6, with values that were 3.3 ± 0.24, 2.0 ± 0.2, 2.70 ± 1.06, 1.57 ± 0,08, 1.47 ± 0.13, 1.39 ± 0.56, and 1.86 ± 0.12, respectively, over controls. By contrast, ND4L exhibited a significant decrease (to 0.31 ± 0.01) compared with controls. When exposed to 38 °C, the transcript levels of the 13 PCGs significantly increased, ranging from a 2.04 ± 0.23 increase in ND1 to a 6.30 ± 0.96 rise in ND6. Under two different levels of cold and heat stress, the expression patterns of mitochondrial genes in S. incognitus vary, possibly associated with different strategies employed by this species in response to low and high temperatures, allowing for rapid compensatory adjustments in mitochondrial electron transport chain proteins in response to temperature changes. Furthermore, this underscores once again the significant role of mitochondrial function in determining thermal plasticity in reptiles.
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An efficient and CO2-promoted dehydroxylative coupling of benzylic alcohols catalyzed by ligand-free cuprous chloride has been achieved. The discovered catalytic reductive coupling reaction is a newly C-C bond-forming transformation of alcohols. Mechanistic insight is gained through control reactions.
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Potamanthidae belongs to the superfamily Ephemeroidea but has no complete mt genome released in the NCBI (except for two unchecked and one partial mt genome). Since the sister clade to Potamanthidae has always been controversial, we sequenced seven mt genomes of Potamanthidae (two species from Rhoenanthus and five species from Potamanthus) in order to rebuild the phylogenetic relationships of Potamanthidae in this study. The divergence time of Potamanthidae was also investigated by utilizing five fossil calibration points because of the indeterminate origin time. In addition, because Rhoenanthus coreanus and Potamanthus luteus are always in low-temperature environments, we aimed to explore whether these two species were under positive selection at the mt genome level. Amongst the 13 PCGs, CGA was used as the start codon in COX1, whereas other genes conformed to initiating with an ATN start codon. From this analysis, UUA (L), AUU (I), and UUU (F) had the highest usage. Furthermore, the DHU arm was absent in the secondary structure of S1 in all species. By combining the 13 PCGs and 2 rRNAs, we reconstructed the phylogenetic relationship of Potamanthidae within Ephemeroptera. The monophyly of Potamanthidae and the monophyly of Rhoenanthus and Potamanthus were supported in the results. The phylogenetic relationship of Potamanthidae + (Ephemeridae + Polymitarcyidae) was also recovered with a high prior probability. The divergence times of Potamanthidae were traced to be 90.44 Mya (95% HPD, 62.80-121.74 Mya), and the divergence times of Rhoenanthus and Potamanthus originated at approximately 64.77 Mya (95% HPD, 43.82-88.68 Mya), thus belonging to the late Pliocene Epoch or early Miocene Epoch. In addition, the data indicated that R. coreanus was under negative selection and that ATP8 and ND2 in Potamanthidae had a high evolutionary rate.
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Disulfidptosis, an innovative type of controlled cellular death linked to metabolic dysfunction, has garnered attention. However, there is limited knowledge regarding the involvement of disulfidptosisrelated lnRNAs (DRlncRNAs) in laryngeal squamous cell carcinoma (LSCC). The objective of our team in this study seeks to establish a DRlncRNAs signature, investigate their prognostic value in LSCC, and explore their associations with immune cell subpopulations, biological signaling pathways, and exploring implications for drug sensitivity. We accessed LSCC patients' RNA-seq data and pertinent clinical data for subsequent further analysis from The Cancer Genome Atlas (TCGA) portal. A literature search was conducted focusing on disulfidptosis-related genes. Pearson correlation coefficients were calculated to identify DRlncRNAs. Differential expression analysis of lncRNAs was performed. Utilizing univariate Cox regression analysis, we identified disulfidptosis-associated prognostic lncRNAs. The LASSO-Cox regression analysis was employed to refine this set of lncRNAs and construct a disulfidptosis-related lncRNAs signature. Various statistical techniques were employed to appraise model predictive performance. Subsequently, risk groups were stratified based on the risk score derived from the DRlncRNAs signature. The superiority of the risk score in prognostication over traditional clinicopathological features in LSCC patients was demonstrated. Evident distinctions emerged between risk groups, particularly in immune cell subpopulations like activated mast cells, eosinophils, and activated NK cells. Finally, the low-risk group demonstrated reduced IC50 values for specific chemotherapeutics like cisplatin and gemcitabine. The in vitro experiments indicated differential behavior of our DRlncRNAs. The DRlncRNAs signature can serve as a robust biomarker with the ability to predict both prognosis and therapeutic responses among patients with LSCC.
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It is well-known that water quality has great significance on microbial community composition in aquatic environments. In this study, we detected water column indicates the microbial community composition of nine sampling sites over two seasons using Illumina TruSeq sequencing in Songtao Reservoir, Hainan Province, Southmost China. The study indicated that the dominant phylum was Actinobacteria, Proteobacteria, Bacteroidetes, and Cyanobacteria. The diversity parameters showed that the microbial community composition had significant spatiotemporal variations, including the significantly higher Shannon index and Simpson index upstream than those midstream and downstream. Besides, there were significantly higher Chao1 index, Shannon index, and Simpson index in winter than in summer. Principal coordinates analysis (PCoA) showed the microbial structural composition had significant seasonal differences. The results of microbial community composition further revealed that the eutrophication level upstream was higher than that of midstream and downstream. The redundancy analysis (RDA) diagram indicated that the abundance of microbiology species significantly correlated with temperature, total phosphorus, Se, and Ni. Furthermore, the mantel's test showed that the temperature and total phosphorus significantly affected the community composition of archaea and bacteria. Overall, our finding here partially validated our hypothesis that the spatiotemporal variations of microbial community composition are significantly related to nutrients, physicochemical factors and metals, which has been unknown previously in tropical drinking waterbodies. This study substantially contributed to understanding of the composition of microbial community in tropical drinking water reservoirs and the main environmental driving factors in tropical zones. It also provided a reference for the management of reservoir operation to ensure drinking water safe.
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Kiwifruit soft rot is highly contagious and causes serious economic loss. Therefore, early detection and elimination of soft rot are important for postharvest treatment and storage of kiwifruit. This study aims to accurately detect kiwifruit soft rot based on hyperspectral images by using a deep learning approach for image classification. A dual-branch selective attention capsule network (DBSACaps) was proposed to improve the classification accuracy. The network uses two branches to separately extract the spectral and spatial features so as to reduce their mutual interference, followed by fusion of the two features through the attention mechanism. Capsule network was used instead of convolutional neural networks to extract the features and complete the classification. Compared with existing methods, the proposed method exhibited the best classification performance on the kiwifruit soft rot dataset, with an overall accuracy of 97.08% and a 97.83% accuracy for soft rot. Our results confirm that potential soft rot of kiwifruit can be detected using hyperspectral images, which may contribute to the construction of smart agriculture.
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Actinidia , Redes Neurales de la Computación , Enfermedades de las Plantas , Actinidia/microbiología , Enfermedades de las Plantas/microbiología , Aprendizaje Profundo , Imágenes Hiperespectrales/métodos , Frutas/microbiología , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the rabbit hemorrhagic disease virus (RHDV). Since the first outbreaks of type 2 RHDV (RHDV2) in April 2020 in China, the persistence of this virus in the rabbit population has caused substantial economic losses in rabbit husbandry. Previous failures in preventing RHDV2 prompted us to further investigate the immune mechanisms underlying the virus's pathogenicity, particularly concerning the spleen, a vital component of the mononuclear phagocyte system (MPS). For this, a previous RHDV2 isolate, CHN/SC2020, was utilized to challenge naive adult rabbits. Then, the splenic transcriptome was determined by RNA-Seq. This study showed that the infected adult rabbits had 3148 differentially expressed genes (DEGs), which were associated with disease, signal transduction, cellular processes, and cytokine signaling categories. Of these, 100 upregulated DEGs were involved in inflammatory factors such as IL1α, IL-6, and IL-8. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were significantly enriched in the cytokine-cytokine receptor interaction signaling pathway, which may play a vital role in CHN/SC2020 infection. At the same time, proinflammatory cytokines and chemokines were significantly increased in the spleen at the late stages of infection. These findings suggested that RHDV2 (CHN/SC2020) might induce dysregulation of the cytokine network and compromise splenic immunity against viral infection, which expanded our understanding of RHDV2 pathogenicity.
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Infecciones por Caliciviridae , Citocinas , Virus de la Enfermedad Hemorrágica del Conejo , Bazo , Transcriptoma , Animales , Virus de la Enfermedad Hemorrágica del Conejo/genética , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Bazo/virología , Bazo/inmunología , Conejos , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/genética , Citocinas/metabolismo , Citocinas/genética , Perfilación de la Expresión Génica , Inflamación/virología , Inflamación/genéticaRESUMEN
This study aims to investigate the potential regulatory network responsible for the meat quality using multi-omics to help developing better varieties. Slaughter performance and meat quality of Shuxing No.1 rabbit outperformed IRA rabbit according to the tested rabbit parameters. Differentially expressed genes (DEGs) and differentially abundance proteins (DAPs) were involved in meat quality-related pathways, such as PI3K - Akt and MAPK signaling pathways. Only SMTNL1 and PM20D2 shared between DEGs and DAPs. Olfactory-sensitive undecanal, a differentially abundant metabolite (DAM) in volatilomics (vDAMs), correlated with all of the remaining 11 vDAMs, and most of 12 vDAMs were associated with amino acid metabolism. Integration revealed that 829 DEGs/DAPs were associated with 15 DAMs in four KEGG pathways, such as melatonin (a DAM in widely targeted metabolomics) was significantly positively correlated with ALDH and negatively correlated with RAB3D and CAT in the tryptophan metabolism pathway. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor. SIGNIFICANCE: Shuxing No.1 rabbit is a new breed of meat rabbit in the Chinese market. In meat marketing, meat quality usually determines the purchase intention of consumers. Determining the biological and molecular mechanisms of meat quality in meat rabbit is essential for developing strategies to improve meat quality. According to the tested rabbit parameters, this study ascertained that the slaughter performance and meat quality of Shuxing No.1 rabbit surpasses that of IRA rabbit. The present study profiled the transcriptome, proteome, widely targeted metabolome, and volatilome of longissimus dorsi from Shuxing No.1 rabbit and IRA rabbit. The study found that meat quality and flavor-related tryptophan metabolism pathway is enriched with many DEGs/DAPs (including ALDH, RAB3D, and CAT), as well as a DAM, melatonin. This study sheds light on the potential mechanisms that contribute to the improved meat quality and flavor.
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Carne , Proteómica , Transcriptoma , Animales , Conejos , Proteómica/métodos , Carne/análisis , Metabolómica , Redes Reguladoras de Genes , Proteoma/metabolismo , Proteoma/análisis , Músculo Esquelético/metabolismoRESUMEN
Breast cancer, particularly triple-negative breast cancer (TNBC), poses a global health challenge. Emerging evidence has established a positive association between elevated levels of stearoyl-CoA desaturase 1 (SCD1) and its product oleate (OA) with cancer development and metastasis. SCD1/OA leads to alterations in migration speed, direction, and cell morphology in TNBC cells, yet the underlying molecular mechanisms remain elusive. To address this gap, we aim to investigate the impact of OA on remodeling the actin structure in TNBC cell lines, and the underlying signaling. Using TNBC cell lines and bioinformatics tools, we show that OA stimulation induces rapid cell membrane ruffling and enhances filopodia formation. OA treatment triggers the subcellular translocation of Arp2/3 complex and Cdc42. Inhibiting Cdc42, not the Arp2/3 complex, effectively abolishes OA-induced filopodia formation and cell migration. Additionally, our findings suggest that phospholipase D is involved in Cdc42-dependent filopodia formation and cell migration. Lastly, the elevated expression of Cdc42 in breast tumor tissues is associated with a lower survival rate in TNBC patients. Our study outlines a new signaling pathway in the OA-induced migration of TNBC cells, via the promotion of Cdc42-dependent filopodia formation, providing a novel insight for therapeutic strategies in TNBC treatment.
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Ácido Oléico , Neoplasias de la Mama Triple Negativas , Humanos , Seudópodos , Movimiento Celular , Actinas , Complejo 2-3 Proteico Relacionado con la ActinaRESUMEN
Sorghum aphid (Melanaphis sacchari) and head smut fungi (Sporisorium reilianum) infesting sorghum cause delayed growth and development, and reduce yield and quality. This study use bioinformatics and molecular biological approaches to profile the gene expression pattern during sorghum development and under pest infestation, and analyzed the natural allelic DNA variation of sorghum MYC gene family. The findings provide insights for potential application in breeding the stress resistant and high productivity sorghum varieties. The results indicated that there are 28 MYC genes identified in sorghum genome, distributed on 10 chromosomes. The bHLH_MYC_N and HLH domains are the conserved domains of the MYC gene in sorghum. Gene expression analysis showed that SbbHLH35.7g exhibited high expression levels in leaves, SbAbaIn showed strong expression in early grains, and SbMYC2.1g showed high expression levels in mature pollen. In anti-aphid strains at the 5-leaf stage, SbAbaIn, SbLHW.4g and SbLHW.2g were significantly induced in leaves, while SbbHLH35.7g displayed the highest expression level in panicle tissue, which was significantly induced by the infection of head smut. Promoter cis-element analysis identified methyl jasmonate (MJ), abscisic acid (ABA), salicylic acid (SA) and MYB-binding sites related to drought-stress inducibility. Furthermore, genomic resequencing data analysis revealed natural allelic DNA variations such as single nucleotide polymorphism (SNP) and insertion-deletion (INDEL) for the key SbMYCs. Protein interaction network analysis using STRING indicated that SbAbaIn interacts with TIFYdomain protein, and SbbHLH35.7g interacts with MDR and imporin. SbMYCs exhibited temporal and spatial expression patterns and played vital roles during the sorghum development. Infestation by sugarcane aphids and head smut fungi induced the expression of SbAbaIn and SbbHLH35.7g, respectively. SbAbaIn modulated the jasmonic acid (JA) pathway to regulate the expression of defensive genes, conferring resistance to insects. On the other hand, SbbHLH35.7g participated in detoxification reactions to defend against pathogens.
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Acetatos , Alelos , Áfidos , Ciclopentanos , Sorghum , Sorghum/genética , Ciclopentanos/metabolismo , Ciclopentanos/farmacología , Áfidos/genética , Oxilipinas/farmacología , Oxilipinas/metabolismo , Perfilación de la Expresión Génica , Animales , Regulación de la Expresión Génica de las Plantas , Variación Genética , Genes myc/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/parasitologíaRESUMEN
ABSTRACT: Graft-versus-host disease (GVHD) occurs in about 10% to 33% of patients receiving "allogeneic" or "autologous" chimeric antigen receptor T (CAR-T) cells after preceding allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the substantial presence of alloreactive T cells. Extracorporeal photopheresis (ECP) shows promising clinical outcomes in the treatment of GVHD after allo-HSCT without hampering antitumor and antiviral effects. This raises an interesting question: whether ECP might constitute a new way to treat patients with GVHD after CAR T-cell therapy without compromising CAR-T cells significantly. Third-generation CD19-specific CAR-T cells were generated and an in vitro ECP protocol was established. The impact of ECP on CAR-T cells was comprehensively investigated in 2 models: the nondilution model reflects days after CAR T-cell infusion and the dilution model weeks after infusion. The therapeutic effect of ECP on GVHD was examined in an in vitro mixed lymphocyte reaction (MLR) assay. We found, ECP-treated CAR-T cells demonstrated reduced potency in inducing alloreaction compared with that of the group without ECP treatment in MLR assay. ECP could selectively induce apoptosis, thereby enriching the naive and central memory CAR-T cells with a reduced alloreactivity. The cytokine milieu of CAR-T cells could be switched from immune stimulation to immune tolerance in both models. Moreover, ECP could modulate the proliferative capacity of CAR-T cells without hampering their long-term functionality in the dilution model. In conclusion, ECP constitutes a promising treatment strategy for GVHD after allo-HSCT and CAR T-cell transfusion, as ECP reduces the alloreactivity without hampering CAR T-cell functionality.
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Enfermedad Injerto contra Huésped , Inmunoterapia Adoptiva , Fotoféresis , Enfermedad Injerto contra Huésped/terapia , Enfermedad Injerto contra Huésped/etiología , Fotoféresis/métodos , Humanos , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Receptores Quiméricos de Antígenos , Linfocitos T/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
Independent predictors of mortality and transfusion therapy in polytrauma patients from the Chinese population remain unknown. Here, we aimed to identify these predictors by retrospectively collecting and analyzing vital signs and laboratory results for 408 critically ill patients suffering from polytrauma who were treated in Affiliated Kunshan Hospital of Jiangsu University, Jiangsu Province, China from January 2020 to December 2021. We identified risk factors for mortality and transfusion therapy using logistic regression analysis. As a results, we enrolled a total of 408 polytrauma patients, with a male-to-female ratio of 2:1, a mean age of 49.02 ± 16.84 years, a mortality rate of 15.9 %, and a blood transfusion rate of 45.8 %. The multivariate logistic regression showed that decreased Glasgow Coma Scale (GCS) score (Odds ratio (OR) = 0.72, 95 % confidence interval (95%CI): 0.63-0.83, P < 0.001), decreased base excess (BE) (OR = 0.77, 95%CI: 0.67-0.87, P < 0.001), and increased Injury Severity Score (ISS) (OR = 1.12, 95%CI: 1.06-1.17, P < 0.001) were independent risk factors for the mortality. In addition, increased GCS score (OR = 1.17, 95%CI: 1.03-1.35, P = 0.020), increased heart rate (OR = 1.05, 95%CI: 1.04-1.07, P < 0.001), decreased systolic blood pressure (SBP) (OR = 0.97, 95%CI: 0.96-0.99, P < 0.001), increased peripheral oxygen saturation (SpO2) (OR = 1.10, 95%CI: 1.04-1.16, P = 0.002), decreased serum lactate (OR = 0.58, 95%CI: 0.42-0.79, P = 0.001), decreased BE (OR = 0.49, 95%CI: 0.39-0.62, P < 0.001), and increased ISS (OR = 1.25, 95%CI: 1.18-1.33, P < 0.001) were independent risk factors for blood transfusion. The area under receiver operating characteristic curves (AUROCs) of the model to predict mortality and blood transfusion were 0.976 (95%CI: 0.960-0.992, P < 0.001) and 0.973 (95%CI: 0.958-0.987, P < 0.001). In conclusion, decreased BE level was significantly associated with all-cause mortality in polytrauma patients. BE, ISS, and GCS might be independent important predictors for mortality and blood transfusion of polytrauma patients.
RESUMEN
Salting pretreatment is an effective method to improve the quality of frozen fish. This study investigated the quality changes and proteomic profile differences of frozen yellowfin tuna fillets pretreated with ultrasound-assisted salting (UAS) and static salting (SS). This study was centered on three aspects: physicochemical indicators' determination, histological observation, and proteomic analysis. The results showed that UAS significantly increased yield, salt content, and water-holding capacity (WHC), decreased total volatile base nitrogen (TVBN) compared to SS (p < 0.05), and significantly increased water in the protein matrix within myofibrils. Histological observations showed that the tissue cells in the UAS group were less affected by frozen damage, with a more swollen structure and rougher surface of myofibrils observed. Furthermore, 4D label-free proteomics revealed 56 differentially abundant proteins (DAPs) in UAS vs. NT comparison, mainly structural proteins, metabolic enzymes, proteasomes, and their subunits, which are associated with metabolic pathways such as calcium signaling pathway, gap junction, actin cytoskeletal regulation, and necroptosis, which are intimately associated with quality changes in freeze-stored tuna fillets. In brief, UAS enhances the potential for the application of salting pretreatment to improve frozen meat quality, and 4D label-free proteomics provides knowledge to reveal the potential links between quality and molecular changes in processed frozen meat to optimize future UAS meat processing.
RESUMEN
Neuromorphic light sensors with analogue-domain image processing capability hold promise for overcoming the energy efficiency limitations and latency of von Neumann architecture-based vision chips. Recently, metal halide perovskites, with strong light-matter interaction, long carrier diffusion length, and exceptional photoelectric conversion efficiencies, exhibit reconfigurable photoresponsivity due to their intrinsic ion migration effect, which is expected to advance the development of visual sensors. However, suffering from a large bandgap, it is challenging to achieve highly tunable responsivity simultaneously with a wide-spectrum response in perovskites, which will significantly enhance the image recognition accuracy through the machine learning algorithm. Herein, we demonstrate a broadband neuromorphic visual sensor from visible (Vis) to near-infrared (NIR) by coupling all-inorganic metal halide perovskites (CsPbBr3) with narrow-bandgap lead sulfide (PbS). The PbS/CsPbBr3 heterostructure is composed of high-quality single crystals of PbS and CsPbBr3. Interestingly, the ion migration of CsPbBr3 with the implementation of an electric field induces the energy band dynamic bending at the interface of the PbS/CsPbBr3 heterojunction, leading to reversible, multilevel, and linearly tunable photoresponsivity. Furthermore, the reconfigurable and broadband photoresponse in the PbS/CsPbBr3 heterojunction allows convolutional neuronal network processing for pattern recognition and edge enhancements from the Vis to the NIR waveband, suggesting the great potential of the PbS/CsPbBr3 heterostructure in artificial intelligent vision sensing.