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Understanding molecular mechanisms that dictate B cell diversity is important for targeting B cells as anti-cancer treatment. Through the single-cell dissection of B cell heterogeneity in longitudinal samples of patients with breast cancer before and after neoadjuvant chemotherapy, we revealed that an ICOSL+ B cell subset emerges after chemotherapy. Using three immunocompetent mouse models, we recapitulated the subset switch of human tumor-infiltrating B cells during chemotherapy. By employing B-cell-specific deletion mice, we showed that ICOSL in B cells boosts anti-tumor immunity by enhancing the effector to regulatory T cell ratio. The signature of ICOSL+ B cells is imprinted by complement-CR2 signaling, which is triggered by immunogenic cell death. Moreover, we identified that CD55, a complement inhibitory protein, determines the opposite roles of B cells in chemotherapy. Collectively, we demonstrated a critical role of the B cell subset switch in chemotherapy response, which has implications in designing novel anti-cancer therapies. VIDEO ABSTRACT.
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Linfocitos B/inmunología , Neoplasias de la Mama/inmunología , Ligando Coestimulador de Linfocitos T Inducibles/metabolismo , Animales , Antineoplásicos/metabolismo , Linfocitos B/metabolismo , Antígenos CD55/inmunología , Antígenos CD55/metabolismo , Línea Celular Tumoral , Proteínas del Sistema Complemento/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Ligando Coestimulador de Linfocitos T Inducibles/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Ratones , Ratones Endogámicos C57BL , Receptores de Complemento 3d/inmunología , Receptores de Complemento 3d/metabolismo , Transducción de Señal/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
BACKGROUND: The Caridea, affiliated with Malacostraca, Decapoda, and Pleocyemata, constitute one of the most significant shrimp groups. They are widely distributed across diverse aquatic habitats worldwide, enriching their evolutionary history. In recent years, considerable attention has been focused on the classification and systematic evolution of Caridea, yet controversies still exist regarding the phylogenetic relationships among families. METHODS: Here, the complete mitochondrial genome (mitogenome) sequences of five caridean species, namely Heterocarpus sibogae, Procletes levicarina, Macrobrachium sp., Latreutes anoplonyx, and Atya gabonensis, were determined using second-generation high-throughput sequencing technology. The basic structural characteristics, nucleotide composition, amino acid content, and codon usage bias of their mitogenomes were analyzed. Selection pressure values of protein-coding genes (PCGs) in species within the families Pandalidae, Palaemonidae, and Atyidae were also computed. Phylogenetic trees based on the nucleotide and amino acid sequences of 13 PCGs from 103 caridean species were constructed, and divergence times for various families within Caridea were estimated. RESULTS: The mitogenome of these five caridean species vary in length from 15,782 to 16,420 base pairs, encoding a total of 37 or 38 genes, including 13 PCGs, 2 rRNA genes, and 22 or 23 tRNA genes. Specifically, L. anoplonyx encodes an additional tRNA gene, bringing its total gene count to 38. The base composition of the mitogenomes of these five species exhibited a higher proportion of adenine-thymine (AT) bases. Six start codons and four stop codons were identified across the five species. Analysis of amino acid content and codon usage revealed variations among the five species. Analysis of selective pressure in Pandalidae, Palaemonidae, and Atyidae showed that the Ka/Ks values of PCGs in all three families were less than 1, indicating that purifying selection is influencing on their evolution. Phylogenetic analysis revealed that each family within Caridea is monophyletic. The results of gene rearrangement and phylogenetic analysis demonstrated correlations between these two aspects. Divergence time estimation, supported by fossil records, indicated that the divergence of Caridea species occurred in the Triassic period of the Mesozoic era, with subsequent differentiation into two major lineages during the Jurassic period. CONCLUSIONS: This study explored the fundamental characteristics and phylogenetic relationships of mitogenomes within the infraorder Caridea, providing valuable insights into their classification, interspecific evolutionary patterns, and the evolutionary status of various Caridea families. The findings provide essential references for identifying shrimp species and detecting significant gene rearrangements within the Caridea infraorder.
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Decápodos , Evolución Molecular , Genoma Mitocondrial , Filogenia , Animales , Decápodos/genética , Decápodos/clasificación , Uso de Codones , ARN de Transferencia/genética , Composición de Base , Selección GenéticaRESUMEN
Enolase-1 (Eno1) plays a critical role in regulating glucose metabolism; however, its specific impact on pancreatic islet ß-cells remains elusive. This study aimed to provide a preliminary exploration of Eno1 function in pancreatic islet ß-cells. The findings revealed that the expression of ENO1 mRNA in type 2 diabetes donors was significantly increased and positively correlated with HbA1C and negatively correlated with insulin gene expression. A high level of Eno1 in human insulin-secreting rat INS-1832/13 cells with co-localization with intracellular insulin proteins was accordingly observed. Silencing of Eno1 using siRNA or inhibiting Eno1 protein activity with an Eno1 antagonist significantly reduced insulin secretion and insulin content in ß-cells, while the proinsulin/insulin content ratio remained unchanged. This reduction in ß-cells function was accompanied by a notable decrease in intracellular ATP and mitochondrial cytochrome C levels. Overall, our findings confirm that Eno1 regulates the insulin secretion process, particularly glucose metabolism and ATP production in the ß-cells. The mechanism primarily involves its influence on insulin production, suggesting that Eno1 represents a potential target for ß-cell protection and diabetes treatment.
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Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Humanos , Ratas , Animales , Insulina/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , Glucosa/metabolismo , Expresión Génica , Adenosina Trifosfato/metabolismoRESUMEN
Drug resistance to chemotherapy in cancers remains significant clinical challenges. CD44 modulates cellular adhesion, migration and growth, which plays a pivotal role in driving cancer resistance and even recurrence. Despite ongoing efforts, accurate, safe, and real-time dynamic monitoring techniques for CD44 expression remain inadequate in guiding the management of drug-resistant cancer treatment. In this study, we developed a nano-quenching and recovery detector of CD44 (Cy3-AptCD44@BPNSs) for visualizing cancer drug resistance. The fluorescence recovery of the detector is directly related to the CD44 expression level on cancer cells, which can be used to indicate the degree of drug resistance. It's confirmed that downregulating CD44 expression on cancer cells results in a corresponding decrease in the fluorescence intensity of the detector, which enables precise and dynamic monitoring of CD44. In addition, the Cy3-AptCD44@BPNSs also exhibited specificity in detecting CD44. This visualizing strategy may open up a wide range of possibilities for rapid recognition to cancer drug resistance, which is more efficient and flexible.
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Resistencia a Antineoplásicos , Receptores de Hialuranos , Receptores de Hialuranos/metabolismo , Humanos , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Fluorescencia , Antineoplásicos/farmacologíaRESUMEN
INTRODUCTION: To evaluate eye growth of children wearing spectacle lenses with highly aspherical lenslets (HAL), slightly aspherical lenslets (SAL) and single-vision lenses (SVL) compared to eye growth patterns in non-myopes in Wenzhou, China. METHODS: The randomised trial had 170 myopic children (aged 8-13 years) randomly assigned to the HAL, SAL or SVL group. Normal eye growth was examined using 700 non-myopic schoolchildren (aged 7-9 years) in the Wenzhou Medical University-Essilor Progression and Onset of Myopia (WEPrOM) cohort study using logistic function models. Slow, normal and fast eye growth was defined as range of values <25th, 25th-75th and >75th percentiles, respectively. RESULTS: The predicted upper limits of slow eye growth (25th percentile) among non-myopes aged 7-10 years and 11-13 years were 0.20-0.13 and 0.08-0.01 mm (after 2-year period; 0.37-0.33 and 0.29-0.14 mm), respectively, while the upper limits of normal eye growth (75th percentile) were 0.32-0.31 and 0.28-0.10 mm (after 2-year period; 0.58-0.55 and 0.50-0.24 mm), respectively. The 2-year trial had 157 children, 96 of whom wore their lenses full time (everyday ≥12 h/day). The mean 2-year axial length change for HAL, SAL and SVL was 0.34, 0.51 and 0.69 mm (0.28, 0.46 and 0.69 mm in full-time wear), respectively. Slow eye growth was found in 35%, 17% and 2% (44%, 29% and 3% in full-time wear); normal eye growth in 35%, 26% and 12% (44%, 32% and 9% in full-time wear) and fast eye growth in 30%, 57% and 86% (12%, 39% and 88% in full-time wear), respectively (p < 0.001). CONCLUSIONS: The eye growth pattern in approximately 90% wearing HAL full time (compared with about 10% wearing SVL full time) was similar or slower than that of non-myopic children both after 1- and 2-year periods.
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Anteojos , Miopía , Niño , Humanos , China , Estudios de Cohortes , Progresión de la Enfermedad , Miopía/terapia , Refracción Ocular , AdolescenteRESUMEN
The complete mitochondrial genome provides crucial information for comprehending gene rearrangement, molecular evolution, and phylogenetic analysis. Here, we have determined the complete mitogenome sequence of Gonatopsis borealis and Onychoteuthis compacta for the first time. Their genome sizes were 20,148 bp and 20,491 bp, respectively, including 18 protein-coding genes, COI-COIII, ATP6, and ATP8 are duplicated, 23 transfer RNA genes, and 2 ribosomal RNA (rRNA) genes (12S and 16S rRNA). Specifically, the overall A+T content is 70.69% and 72.67%. It shows a significant AT bias. The whole mitogenomes indicate positive AT skew (0.070 and 0.062). Furthermore, the gene order has been rearranged within Oegopsida. The tandem duplication random loss model was determined as most likely to explain the observed gene rearrangements. Phylogenetic analysis was performed, and the result tree was found to be consistent with the morphological identification classification. Estimation of divergence time for 35 species showed that the main differentiation of Oegopsida occurred in 140.70 Mya. These results will help to better understand the gene rearrangements and evolution of G. borealis and O. compacta and lay a foundation for further phylogeny genetic studies of Oegopsida.
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Childhood maltreatment has long-term negative effects on individuals' physical and mental well-being, and may increase the risk for suicidal ideation. However, how different patterns of childhood maltreatment affect subsequent suicidal ideation and the underlying mediating mechanisms remain unclear, particularly among Chinese adolescents. This study used latent profile analysis to identify patterns of childhood maltreatment among adolescents and explored how these patterns predicted subsequent suicidal ideation via depression, hope, and expressive suppression. This study used a two-wave, 1-year longitudinal design and included 2156 adolescents (Mage = 13.97 years, SDage = 1.61 years; 49.6% females). We identified three patterns of childhood maltreatment: low maltreatment, high psychological neglect, and high maltreatment. Compared with the low maltreatment group, the high maltreatment group indirectly predicted subsequent suicidal ideation 1 year later via depression through hope and expressive suppression, whereas the direct effect on suicidal ideation was not significant. Compared with the low maltreatment group, the high psychological neglect group had a significant direct effect on subsequent suicidal ideation and indirectly predicted suicidal ideation through depression or hope. Identifying patterns of childhood maltreatment among adolescents will assist mental health workers in developing targeted interventions to effectively alleviate suicidal ideation.
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Growth is a fundamental aspect of aquaculture breeding programs, pivotal for successful cultivation. Understanding the mechanisms that govern growth and development differences across various stages can significantly boost seedling production of economically valuable species, thereby enhancing aquaculture efficiency and advancing the aquaculture industry. Mytilus coruscus, a commercially vital marine bivalve, underscores this importance. To decipher the intricate molecular mechanisms dictating growth and developmental disparities in marine shellfish, we conducted transcriptome sequencing and meticulously analyzed gene expression variations and molecular pathways linked to growth traits in M. coruscus. This study delved into the molecular and gene expression variations across five larval development stages, with a specific focus on scrutinizing the differential expression patterns of growth-associated genes using RNA sequencing and quantitative real-time PCR analysis. A substantial number of genes-36,044 differentially expressed genes (DEGs)-exhibited significant differential expression between consecutive developmental stages. These DEGs were then categorized into multiple pathways (Q value < 0.05), including crucial pathways such as the spliceosome, vascular smooth muscle contraction, DNA replication, and apoptosis, among others. In addition, we identified two pivotal signaling pathways-the Hedgehog (Hh) signaling pathway and the TGF-beta (TGF-ß) signaling pathway-associated with the growth and development of M. coruscus larvae. Ten key growth-related genes were pinpointed, each playing crucial roles in molecular function and the regulation of growth traits in M. coruscus. These genes and pathways associated with growth provide deep insights into the molecular basis of physiological adaptation, metabolic processes, and growth variability in marine bivalves.
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Proteínas Hedgehog , Mytilus , Animales , Proteínas Hedgehog/genética , Mytilus/genética , Larva/genética , Fitomejoramiento , Perfilación de la Expresión Génica , Factor de Crecimiento Transformador beta/genéticaRESUMEN
The extant marine mussels which belong to the Mytiloidea are widespread species inhabiting mostly coastal waters, with some distributed in the deep sea. To clarify the classification systems and phylogenetic relationships range from genus to family level within Mytiloidea, new sequence was used in a phylogenetic analysis including all the available Mytiloidea mitochondrial genomes. In this study, the complete mitochondrial genome of Vignadula atrata is 15,624 bp in length and contains 12 protein-coding genes (PCGs, atp8 is absent), two ribosomal RNA genes, and 22 transfer RNA genes. Phylogenetic analysis based on 12 PCGs showed that it has a close relationship to Bathymodiolus. The analysis of gene rearrangements in the Pteriomorphia showed that the arrangements are highly variable across species, novel gene rearrangements were found within Mytiloidea. The V. atrata mitogenome was provided in detail, with notes on the sequence and a key to the species of Vignadula. This study provides a perspective on the taxonomic histories of the marine mussels and refines the unclear relationship between the origin and evolution of species in Mytiloidea within Bivalvia.
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Bivalvos , Genoma Mitocondrial , Animales , Filogenia , Bivalvos/genética , ARN de Transferencia/genética , Reordenamiento GénicoRESUMEN
This study assessed temporal associations between parent-child relationship, parenting behaviors (i.e., warmth, rejection, and overprotection), and adolescents' depressive symptoms after trauma, using random-intercept cross-lagged panel models to distinguish between- and within-adolescent differences. We surveyed Chinese adolescents 12 (Aug 2018; T1), 21 (May 2019; T2), 27 (Nov 2019; T3) months after the Jiuzhaigou earthquake that occurred in August 2017. Of the 585 adolescents who participated in at least two waves of the study, mean age at T1 was 15.50 years old (SD = 1.58 years) and 57.8% were girls. Controlling adolescents' gender, age, ethnicity, trauma exposure at T1, and parents' marital status, between-adolescent results showed that parent-child relationship and parenting behaviors, parent-child relationship and depressive symptoms were correlated across models of parental warmth, rejection, and overprotection, whereas depressive symptoms were only correlated with parental rejection and overprotection. Within-adolescent results indicated that parent-child relationship and adolescents' depressive symptoms had bidirectional associations via the mediation of parental warmth from T1 to T3. Over the longer term following the earthquake, we found that parental rejection was bidirectionally associated with adolescents' depressive symptoms, whereas parental overprotection was unidirectionally influenced by adolescents' depressive symptoms from T2 to T3. In addition, more depressive symptoms in adolescents were associated with worsening parent-child relationship from T2 to T3. In conclusion, shortly after trauma, interventions should focus on improving parent-child relationship and relieving adolescents' depressive symptoms. Over the longer term after trauma, relieving adolescents' depressive symptoms should be prioritized to avoid its eroding effects on parent-child relationship and parenting behaviors, and to break the "vicious cycle".
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The hard-shell mussel (Mytilus coruscus) is widespread in the temperate coastal areas of the northwest Pacific and holds a significant position in the shellfish aquaculture market in China. However, the natural resources of this species have been declining, and population genetic studies of M. coruscus are also lacking. In this study, we conducted whole-genome resequencing (WGR) of M. coruscus from eight different latitudes along the Chinese coast and identified a total of 25,859,986 single nucleotide polymorphism (SNP) markers. Our findings indicated that the genetic diversity of M. coruscus from the Zhoushan region was lower compared with populations from other regions. Furthermore, we observed that the evolutionary tree clustered into two primary branches, and the Zhangzhou (ZZ) population was in a separate branch. The ZZ population was partly isolated from populations in other regions, but the distribution of branches was not geographically homogeneous, and a nested pattern emerged, consistent with the population differentiation index (FST) results. To investigate the selection characteristics, we utilized the northern M. coruscus populations (Dalian and Qingdao) and the central populations (Zhoushan and Xiangshan) as reference populations and the southern ZZ population as the target population. Our selection scan analysis identified several genes associated with thermal responses, including Hsp70 and CYP450. These genes may play important roles in the adaptation of M. coruscus to different living environments. Overall, our study provides a comprehensive understanding of the genomic diversity of coastal M. coruscus in China and is a valuable resource for future studies on genetic breeding and the evolutionary adaptation of this species.
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Mytilus , Animales , Pueblo Asiatico , Variación Genética , Mytilus/genética , Secuenciación Completa del GenomaRESUMEN
The complexity and multivariate analysis of biological systems and environment are the drawbacks of the current high-throughput sensing method and multianalyte identification. Deep learning (DL) algorithms contribute a big advantage in analyzing the nonlinear and multidimensional data. However, most DL models are data-driven black boxes suffering from nontransparent inner workings. In this work, we developed an explainable DL-assisted visualized fluorometric array-based sensing method. Based on a data set of 8496 fluorometric images of various target molecule fingerprint patterns, two typical DL algorithms and eight machine learning algorithms were investigated for the efficient qualitative and quantitative analysis of six aminoglycoside antibiotics (AGs). The convolutional neural network (CNN) approached 100% prediction accuracy and 1.34 ppm limit of detection of six AG analysis in domestic, industrial, medical, consumption, or aquaculture water. The class activation mapping assessment explicates how the CNN model assesses the importance of sensor elements and makes the discrimination decision. The feedback mechanism guides the sensor array evolution for less material using a simplified operation or efficient data acquisition. The explainable DL-assisted analysis method establishes an "end-to-end" strategy to resolve the black box of the DL algorithm, promote hardware design or principle optimization, and contribute facile indicators for environment monitoring, disease diagnosis, and even new scientific discovery.
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Aprendizaje Profundo , Algoritmos , Aminoglicósidos , Antibacterianos , Fluorescencia , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in solid tumors, but its clinical utility in risk stratification and early prediction of relapse for diffuse large B cell lymphoma (DLBCL) has not been well explored. METHODS: Here, using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before, during, and after first-line therapy in 73 Chinese DLBCL patients. RESULTS: The pretreatment ctDNA level serving as an independent prognostic factor for both progression-free survival (PFS, adjusted HR 2.47; p = 0.004) and overall survival (OS, adjusted HR 2.49; p = 0.011) was confirmed in our cohort. Furthermore, the patients classified as molecular responders who presented a larger decrease in ctDNA levels after the initial two treatment cycles had more favorable PFS (unreached vs. 6.25 months; HR 5.348; p = 0.0015) and OS (unreached vs. 25.87; HR 4.0; p = 0.028) than non-responders. In addition, interim ctDNA clearance may be an alternative noninvasive method of positron emission tomography and computed tomography (PET-CT) for predicting better PFS (HR 3.65; p = 0.0033) and OS (HR 3.536; p = 0.016). We also demonstrated that posttreatment ctDNA was a sensitive indicator for detecting minimal residual disease (MRD) in patients with a high risk of recurrence (HR 6.471; p = 0.014), who were otherwise claimed to achieve radiographic CR (complete remission). CONCLUSIONS: CtDNA is a promising noninvasive tool for prognosis prediction, response assessment, and early relapse prediction of first-line treatment in DLBCL patients.
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ADN Tumoral Circulante , Linfoma de Células B Grandes Difuso , Humanos , ADN Tumoral Circulante/genética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Recurrencia Local de Neoplasia , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Pronóstico , Biomarcadores de Tumor/genéticaRESUMEN
Aberrant activity of histone deacetylases (HDACs) is frequently detected in B-cell lymphomas, which indicated the therapeutic implications of HDAC inhibitors for B-cell malignancies. We have discovered that lymphoma cells treated with HDAC inhibitor presented with activation of Bruton tyrosine kinase (BTK) which played an important role in the development of B-cell malignancies. Therefore, our study intended to explore whether the addition of ibrutinib (BTK inhibitor) to chidamide (HDAC inhibitor) could generate combined anti-tumor effects in B-cell lymphomas. Using cell viability assay, cell cycle and apoptosis kit, we demonstrated an evident synergistic action of ibrutinib and chidamide in inhibiting tumor cell proliferation and motility. Consistent with in vitro data, the synergistic anti-tumor effects were also observed in multiple tumor-bearing mice models. By performing RNA-seq and flow cytometry of tumor tissue, the enhancement of anti-tumor immunity was observed with the co-treatment of chidamide and ibrutinib. Together, these mechanistic insights indicated that simultaneously targeting BTK and HDAC could be a promising clinical therapy for B-cell lymphomas.
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Inhibidores de Histona Desacetilasas , Linfoma de Células B , Animales , Humanos , Ratones , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Histona Desacetilasas , Linfoma de Células B/tratamiento farmacológicoRESUMEN
CD47 expressed on cancer cells enables macrophage immune evasion. Blocking CD47 using anti-CD47 monoclonal antibodies (mAbs) is a promising strategy. The anti-CD47 mAb TJC4 has anti-tumor activity but lacks hematological toxicity. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor for B-cell malignancy, induces phosphatidylserine (PS) extracellular exposure, representing an "eat-me" signal for macrophages. The present study aimed to explore whether TJC4-Venetoclax combined therapy exerts synergistic anti-cancer properties in B-cell lymphoma. In vitro, flow cytometry and microscopy assessed whether TJC4 monotherapy or combination treatment could promote macrophage-mediated phagocytosis of tumor cells. Induced PS exposure on the cell membrane was measured using flow cytometry with Annexin V-FITC staining. In vivo, Venetoclax and TJC4's synergistic anti-tumor effects were evaluated. B cell lymphoma cell lines express high levels of CD47 and patients with diffuse large B cell lymphoma expressing CD47 have a worse clinical prognosis. TJC4 eliminates tumor cells via macrophage-mediated phagocytosis. In vitro and in vivo, the TJC4-Venetoclax combination increased phagocytosis significantly compared with either agent alone, showing synergistic phagocytosis, and displayed synergistic anti-cancer properties in B-cell lymphoma. Our results support the TJC4-Venetoclax combination as a promising therapy, and suppressing BCL-2 and CD47 simultaneously could represent a novel therapeutic paradigm for B-cell lymphoma.
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Antineoplásicos , Linfoma de Células B Grandes Difuso , Anticuerpos Monoclonales , Antineoplásicos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes , Línea Celular Tumoral , Humanos , Factores Inmunológicos , Inmunoterapia/métodos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Fosfatidilserinas , Proteínas Proto-Oncogénicas c-bcl-2 , SulfonamidasRESUMEN
INTRODUCTION: Mantle cell lymphoma (MCL) is an aggressive and incurable B-cell-derived malignant disease. MCL is treated using general chemotherapy; however, disease progression and relapse are common; thus, the development of novel therapeutic targets for treatment of MCL is urgently required. Serum- and glucocorticoid-inducible kinase 1 (SGK1) is involved in various cellular activities, and its dysregulation contributes to the pathogenesis of multiple types of cancer. However, little is known regarding its functional roles and associated molecular mechanisms in MCL. METHODS: SGK1 inhibition mediated by either shRNA or treatment with SGK1 inhibitor (GSK650394) was conducted in MCL cell lines. Western blotting analysis was performed to figure out the expression of related proteins. MCL-cell-derived xenograft models were constructed to evaluate the anti-tumor effects of SGK1 inhibition or/and Bruton's tyrosine kinase (BTK) inhibition in vivo. RESULTS: In this study, it was shown that inhibition of SGK1 significantly reduced cell proliferation, invasion and migration, increased apoptosis and blocked cell cycle progression in MCL cells. Furthermore, SGK1 inhibition significantly reduced the activation of ERK, AKT/mTOR, JAK2/STAT3 and the NF-κB signaling pathways. Using MCL-cell-derived xenograft mice models, SGK1 inhibition decreased tumor cell proliferation and tumor growth. Importantly, SGK1 overexpression significantly promoted xenograft tumor growth. Moreover, simultaneous inhibition of SGK1 and Bruton tyrosine kinase (BTK) resulted in synergistic anti-tumor effects on MCL both in vitro and in vivo. CONCLUSION: SGK1 may be a novel candidate therapeutic target and simultaneous inhibition of SGK1 and BTK may be a promising therapeutic strategy for MCL patients. Further pre-clinical and even clinical studies of SGK1 inhibitor or combination with BTK inhibitor are essential.
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Linfoma de Células del Manto , Humanos , Ratones , Adulto , Animales , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/patología , Glucocorticoides/uso terapéutico , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Pirimidinas/uso terapéutico , Pirazoles/farmacología , Pirazoles/uso terapéutico , Piperidinas/uso terapéuticoRESUMEN
In the present study, mitogenomes of the species Trachypenaeus curvirostris and Parapenaeus fissuroides (Decapoda: Dendrobranchiata: Penaeidae) were sequenced. The total lengths of the two species were 15,956 bp and 15,937 bp in length with A + T biases of 67.08% and 67.69%, respectively. Both two species showed positive AT skews (0.016, 0.058) and negative GC skews (-0.254, -0.310). Both mitogenomes contained 13 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes. Results of phylogenetic analyses support close relationships among Aristeidae, Benthesicymidae and Solenoceridae. The family Sicyoniidae was observed to be deeply nested within Penaeidae. Within Penaeidae, T. curvirostris and P. fissuroides were most closely related to the genus Parapenaeopsis and Metapenaeopsis, respectively, indicated that these two species belong to Penaeidae. These results will help to better understand the evolutionary position of Penaeidae and provide reference for further phylogenetic research on Penaeoidea species.
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Genoma Mitocondrial , Penaeidae/genética , Filogenia , Animales , Composición de Base , Anotación de Secuencia Molecular , Penaeidae/clasificaciónRESUMEN
Post-traumatic stress symptoms (PTSSs) have been a common negative psychological response during the COVID-19 pandemic. Previous theories emphasized the unique effects of cognitive and family factors on PTSSs and overlooked their combined role, which suggested that the mechanisms underlying PTSSs were not fully understood. To fill this gap, this study aimed to examine the associations between attention to negative information, blaming others, parent-child relationship and PTSSs, as well as the combined role of these factors on PTSSs. During the COVID-19 pandemic, 1153 college students completed self-report questionnaires. Results indicated that attention to negative information increased PTSSs, both directly and via blaming others. Moreover, parent-child relationship buffered both the exacerbating effect of attention to negative information on blaming others and the effect of blaming others on worsening PTSSs. The current study integrates existing theories, expands the field of trauma research through considering the effect of cognitive and family factors on PTSSs, and provides theoretical support for interventions to relieve PTSSs.
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The hard clam Meretrix lamarckii is ecologically and economically important in the coastal regions of China. In this study, we evaluated the genetic diversity and population structure of six M. lamarckii populations in the East China Sea and the South China Sea using mitochondrial cytochrome c oxidase subunit 1 (COI) and cytochrome b (Cytb) genes. We obtained 582 bp of partly sequences comprising 28 novel haplotypes of COI gene from 138 specimens and 1168 bp of partly sequences comprising 22 novel haplotypes of Cytb gene from 125 specimens. The haplotype diversity of COI and Cytb genes ranged from 0.606 to 0.862 and 0.562 to 0.863, respectively. The nucleotide diversity ranged from 0.0015 to 0.0038 in COI gene and ranged from 0.0007 to 0.0032 in Cytb gene. Thus, there is moderate-level genetic diversity in M. lamarckii in the China Sea. The F-statistics showed that the Zhoushan (ZS) and Xiangshan (XS) populations were significantly (P < 0.01) differed from the populations of Wenzhou (WZ), Zhangpu (ZP), Shantou (ST), and Zhanjiang (ZJ) in both COI and Cytb genes. Both haplotypes network and plot of STRUCTURE analysis suggested obviously genetic divergence between East China Sea and South China Sea regions. Knowledge on genetic variation and population structure of M. lamarckii populations along the Southeast China Sea obtained from this study will support the aquaculture management and conservation of M. lamarckii in China.
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Bivalvos/genética , ADN Mitocondrial/genética , Animales , Bivalvos/clasificación , China , Citocromos b/genética , Complejo IV de Transporte de Electrones/genética , Marcadores Genéticos/genética , Variación Genética/genética , Haplotipos/genéticaRESUMEN
Many Nerita species live in warm-water environments, and they are some of the few organisms from the intertidal zone that can live in both freshwater and seawater. Previous comparative studies of the mitogenomes of Nerita species suggest that the genome rearrangements are very conservative. Generally, the species possess a set of similar mitochondrial gene arrangements, but nucleotide sequences can be used to elucidate phylogenetic relationships at various levels of divergence. Here, the mitogenomes of Nerita undata and Nerita balteata were sequenced and found to be 15,583 bp and 15,571 bp, respectively. The mitogenomes of both species contain 13 protein-coding genes, 22 tRNA genes, and two rRNA genes. The nucleotides of the two mitogenomes are highly similar, with the same gene composition and genomic organization as those present in other Nerita species. The tRNA secondary structures were different from those of other gastropods: trnS2 is not folded into typical secondary structures, and the dihydrouridine (DHU) arm simply forms a loop. The phylogenetic analysis showed that Neritimorpha is a sister group of Vetigastropoda and Caenogastropoda. Nerita balteata is a sister group of Nerita versicolor and Nerita undata, and all three species belong to Neritimorpha. This study contributes towards the comparative mitogenomic analysis of Neritidae and phylogenetic considerations among Neritimorpha species. The estimation of divergence time revealed that the two Nerita species were differentiated in the late Paleogene of the Cenozoic Era, and their evolution may be related to environmental changes.