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Closely related species often use the same genes to adapt to similar environments. However, we know little about why such genes possess increased adaptive potential and whether this is conserved across deeper evolutionary lineages. Adaptation to climate presents a natural laboratory to test these ideas, as even distantly related species must contend with similar stresses. Here, we re-analyse genomic data from thousands of individuals from 25 plant species as diverged as lodgepole pine and Arabidopsis (~300 Myr). We test for genetic repeatability based on within-species associations between allele frequencies in genes and variation in 21 climate variables. Our results demonstrate significant statistical evidence for genetic repeatability across deep time that is not expected under randomness, identifying a suite of 108 gene families (orthogroups) and gene functions that repeatedly drive local adaptation to climate. This set includes many orthogroups with well-known functions in abiotic stress response. Using gene co-expression networks to quantify pleiotropy, we find that orthogroups with stronger evidence for repeatability exhibit greater network centrality and broader expression across tissues (higher pleiotropy), contrary to the 'cost of complexity' theory. These gene families may be important in helping wild and crop species cope with future climate change, representing important candidates for future study.
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Background: Mitochondrial dysfunction has been shown to play a critical role in cancer biology. However, its involvement in intrahepatic cholangiocarcinoma (iCCA) remains significantly understudied. Methods: RNA sequencing data of 30 pairs of iCCA and paracancerous tissues were collected from the First Affiliated Hospital of Wenzhou Medical University (WMU). The WMU cohort (n = 30) was integrated with public TCGA (n = 30) and GSE107943 (n = 30) datasets to establish a multi-center iCCA cohort. We merged the TCGA and GSE107943 cohorts into an exploration cohort to develop a mitochondria signature for prognosis assessment, and utilized the WMU cohort for external validation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Hallmarker analyses were used for functional interpretation of iCCA associated mitochondria-related genes (MRGs). In addition, unsupervised clustering was performed to identify mitochondria-based iCCA subtypes with the data of three institutions. Further investigations were conducted to examine the impact of mitochondrial dysfunction on drug responses, alteration of the tumor immune microenvironment, and immune responses. Results: Two hundred and sixty-three iCCA-related MRGs were identified to be related to fatty acid metabolism, oxidative phosphorylation, and apoptosis. Through univariate and multivariate Cox, and LASSO analyses, a mitochondria signature with five optimal MRGs was established to evaluate the prognosis of iCCA patients with the AUC values ranged from 0.785 to 0.928 in the exploration cohort. The signature also exhibited satisfactory performance in the WMU cohort with AUC values of 0.817-0.871, and was identified as an independent risk predictor in both cohorts. Additionally, we found that patients with higher mitochondria score with poor prognosis presented lower infiltration levels of CD4+ T-cell, NK cells, and monocytes, and demonstrated higher sensitivity to targeted therapies, including sorafenib. Furthermore, two distant mitochondria-based subtypes were determined, and subtype 2 was associated with shorter survival time and immunosuppressive tumor microenvironment. Finally, the differential protein expression of five key MRGs was verified by Immunohistochemistry. Conclusion: We found mitochondrial dysfunction modulates aberrant metabolism, oxidative stress, immune responses, apoptosis, and drug sensitivity in iCCA. A mitochondria signature and two mitochondria-based iCCA subtypes were identified for clinical risk stratification and immunophenotyping.
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Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and Rhabdocline needle cast (RNC) epidemics are responsible for major damage of forest ecosystems in North America. Here we investigate the genetic architecture of tolerance and resistance to needle cast diseases in Douglas-fir (Pseudotsuga menziesii) caused by two fungal pathogens: SNC caused by Nothophaeocryptopus gaeumannii, and RNC caused by Rhabdocline pseudotsugae. We performed case-control genome-wide association analyses and found disease resistance and tolerance in Douglas-fir to be polygenic and under strong selection. We show that stomatal regulation as well as ethylene and jasmonic acid pathways are important for resisting SNC infection, and secondary metabolite pathways play a role in tolerating SNC once the plant is infected. We identify a major transcriptional regulator of plant defense, ERF1, as the top candidate for RNC resistance. Our findings shed light on the highly polygenic architectures underlying fungal disease resistance and tolerance and have important implications for forestry and conservation as the climate changes.
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Ascomicetos , Resistência à Doença , Estudo de Associação Genômica Ampla , Doenças das Plantas , Pseudotsuga , Resistência à Doença/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Pseudotsuga/genética , Pseudotsuga/microbiologia , Pseudotsuga/fisiologia , Ascomicetos/fisiologia , Ascomicetos/patogenicidade , Árvores/genética , Adaptação Fisiológica/genética , Herança Multifatorial , Regulação da Expressão Gênica de Plantas , Genes de PlantasRESUMO
Plum (Prunus salicina Lindl.) is commercially cultivated worldwide for the high levels of nutrients in the fruit. In recent years, anthracnose has been severe in some plum planting areas in China, resulting in a large number of necrotic leaves, blight and pre-mature leaf fall. In this study, anthracnose samples of plum leaves were collected from Hezhou, Guilin and Lipu, Guangxi Province, and Meishan city, Abe Tibetan and Qiang autonomous prefecture of Sichuan Province. Characteristics of mycelia on PDA, morphology of appressoria and conidia, and analysis of sequences of several marker regions (internal transcribed spacer [ITS] region, glyceraldehyde-3-phosphate dehydrogenase [GAPDH], chitin synthase [CHS-1], histone H3 [HIS3], actin [ACT], ß-tubulin [TUB2], and the intergenic region between apn2 and MAT1-2-1 [ApMat]). The resulting 101 Colletotrichum isolates obtained were identified as eight species: C. fructicola (50.5%), C. siamense (24.8%), C. karsti (8.9%), C. plurivorum (7.9%), C. aeschynomenes (3.9%), C. gloeosporioides (2%), C. celtidis (1%) and C. phyllanthi (1%). Representatives of all eight Colletotrichum species were found to cause disease on wounded leaves of plum seedlings in pathogenicity assays. As far as we are aware, this is the first report of anthracnose of plum caused by C. celtidis and C. phyllanthi in China.
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Addressing fracture-related infections (FRI) and impaired bone healing remains a significant challenge in orthopedics and stomatology. Researchers aim to address this issue by utilizing biodegradable biomaterials, such as magnesium/poly lactic acid (Mg/PLA) composites, to offer antibacterial properties during the degradation of biodegradable implants. Existing Mg/PLA composites often lack sufficient Mg content, hindering their ability to achieve the desired antibacterial effect. Additionally, research on the anti-inflammatory effects of these composites during late-stage degradation is limited. To strengthen mechanical properties, bolster antibacterial efficacy, and enhance anti-inflammatory capabilities during degradation, we incorporated elevated Mg content into PLA to yield Mg/PLA composites. These composites underwent in vitro degradation studies, cellular assays, bacterial tests, and simulation of the PLA degradation microenvironment. 20 wt% and 40 wt% Mg/PLA composites displayed significant antibacterial properties, with three composites exhibiting notable anti-inflammatory effects. In contrast, elevated Mg content detrimentally impacted mechanical properties. The findings suggest that Mg/PLA composites hold promise in augmenting antibacterial and anti-inflammatory attributes within polymers, potentially serving as temporary regenerative materials for treating bone tissue defects complicated by infections.
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Implantes Absorvíveis , Antibacterianos , Anti-Inflamatórios , Magnésio , Poliésteres , Magnésio/química , Antibacterianos/farmacologia , Antibacterianos/química , Poliésteres/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Teste de Materiais , Camundongos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Methods using genomic information to forecast potential population maladaptation to climate change or new environments are becoming increasingly common, yet the lack of model validation poses serious hurdles toward their incorporation into management and policy. Here, we compare the validation of maladaptation estimates derived from two methods-Gradient Forests (GFoffset) and the risk of non-adaptedness (RONA)-using exome capture pool-seq data from 35 to 39 populations across three conifer taxa: two Douglas-fir varieties and jack pine. We evaluate sensitivity of these algorithms to the source of input loci (markers selected from genotype-environment associations [GEA] or those selected at random). We validate these methods against 2- and 52-year growth and mortality measured in independent transplant experiments. Overall, we find that both methods often better predict transplant performance than climatic or geographic distances. We also find that GFoffset and RONA models are surprisingly not improved using GEA candidates. Even with promising validation results, variation in model projections to future climates makes it difficult to identify the most maladapted populations using either method. Our work advances understanding of the sensitivity and applicability of these approaches, and we discuss recommendations for their future use.
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Florestas , Pseudotsuga , Adaptação Fisiológica/genética , Genômica , Mudança ClimáticaRESUMO
Background: According to statistics, ovarian cancer (OV) is the most prevalent type of gynecologic malignancy and has the highest mortality rate of all gynecologic tumors. Although several studies have shown that oxidative stress (OS) contributes significantly to the onset and progression of cancer, the role of OS in OV needs to be investigated further. Thus, it is critical to comprehend the function of OS-related genes in OV. Methods: In this study, all data related to the transcriptome and clinical status of the patients were retrieved from "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) databases. Using the unsupervised cluster analysis technique, all patients with OV were classified into two different subtypes (categories) based on the OS gene. All hub genes were screened using the weighted gene co-expression network analysis (WGCNA). Since the hub genes and the differentially expressed genes (DEGs) in both categories were found to intersect, the univariate Cox regression analysis was implemented. A multivariate Cox analysis was also performed to construct a novel clinical prognosis model, which was validated using data from the GEO cohort. In addition, the relationship between risk score and immune cell infiltration level was evaluated using CIBERSORT. Finally, qRT-PCR was used to confirm the expression of the genes used to construct the model. Results: Two subtypes of OS were obtained. The findings indicated that OS-C1 had a better survival outcome than OS-C2. The results of WGCNA yielded 112 hub genes. For univariate COX regression analyses, 49 OS-related trait genes were obtained. Finally, a clinical prognostic model containing two genes was constructed. This model could differentiate between patients with OV having varying years of survival in the TCGA and GEO cohorts. The model risk score was verified as an independent prognostic indicator. According to the results of CIBERSORT, many tumor-infiltrating immune cells were found to be significantly related to the risk score. Furthermore, the results revealed that patients with low-risk OV in the CTLA4 treatment group had a high likelihood of benefiting from immunotherapy. qRT-PCR results also showed that the expression of MARVELD1 and VSIG4 was high in the OV samples. Conclusions: Analysis of the results suggested that the newly developed model, which contained two characteristic OS-related genes, could successfully predict the survival outcomes of all patients with OV. The findings of this study could offer valuable information and insights into the refinement of personalized therapy and immunotherapy for OV in the future.
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BACKGROUND: Bone metastases are rare in oral squamous cell carcinoma (OSCC). It has not been defined on the risk and prognosis of OSCC patients with bone metastases. The purpose of this study was to assess the factors associated with the development and prognosis of bone metastases among OSCC patients. METHODS: Demographic and clinicopathological characteristics of OSCC patients diagnosed between 2010 and 2019 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. To explore risk factors for developing bone metastases and prognosis, the univariate and multivariate logistic and Cox regression analysis were performed, further the predictive nomogram models were constructed. RESULTS: The incidence rate of bone metastases in newly diagnosed OSCC patients was 0.91 % (95 %CI 0.81% -1.02 %). Ultimately, 137 OSCC patients with bone metastases and 19,469 OSCC patients without bone metastases were included in the present study. Pathological grade, primary site, T/N stage and distant organ metastases (liver/lung/brain) were independently associated with the risk of developing bone metastases among OSCC patients. The C-index of a constructed risk-predicting nomogram was 0.86 (95 %CI 0.83-0.89). Multivariate Cox regression analysis indicated that lung metastases, the use of surgery as well as chemotherapy were three independent prognostic factors. The C-indexes of constructed risk-predicting nomograms were 0.70 (95 %CI 0.65-0.75), 0.68 (95 %CI 0.63-0.73) for OS and CSS, respectively. Calibration plots demonstrated an agreementbetween the established nomogram's predicted survival and actual survival. In addition, decision curve analysis (DCA) indicated these established nomograms had considerable net benefits and clinical utilities. CONCLUSION: This study defined the risk and prognostic factors for bone metastases among OSCC patients and the established nomograms were well calibrated for discrimination to predict bone metastasis development and prognosis.
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Neoplasias Ósseas , Carcinoma de Células Escamosas , Neoplasias Bucais , Nomogramas , Programa de SEER , Humanos , Masculino , Neoplasias Ósseas/secundário , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/diagnóstico , Feminino , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/diagnóstico , Fatores de Risco , Prognóstico , Idoso , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/diagnóstico , Adulto , Incidência , Estadiamento de NeoplasiasRESUMO
Theoretical and experimental investigations have shown that biochar, following KOH activation, enhances the efficiency of NO removal. Similarly, NaOH activation also improves NO removal efficiency, although the underlying mechanism remains unclear. In this study, zigzag configurations were employed as biochar models. Density functional theory (DFT) was utilized to examine how Li and Na single adsorption and OH co-adsorption affect the reaction pathways of NO reduction on the biochar surface. The rate constants for all reaction-determining steps (RDSs) within a temperature range of 200 to 1000 K were calculated using conventional transition state theory (TST). The results indicate a decrease in the activation energy for NO reduction reactions on biochar when activated by Li and Na adsorption, thus highlighting their beneficial role in NO reduction. Compared to the case with Na activation, Li-activated biochar exhibited superior performance in terms of the NO elimination rate. Furthermore, upon the adsorption of the OH functional group onto the Li-decorated and Na-decorated biochar models (LiOH-decorated and NaOH-decorated chars), the RDS energy barriers were higher than those of Li and Na single adsorption but easily overcome, suggesting effective NO reduction. In conclusion, Li-decorated biochar showed the highest reactivity due to its low RDS barrier and exothermic reaction on the surface.
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Commercially available guided bone regeneration (GBR) membranes often exhibit limited mechanical properties or bioactivity, leading to poor performance in repairing bone defects. To surmount this limitation, we developed a Janus structural composite membrane (Mg-MgO/PCL) reinforced by dual Mg (Mg sheets and MgO NPs) by using a combined processing technique involving casting and electrospinning. Results showed that the addition of Mg sheets and MgO NPs enhanced the mechanical properties of the composite membrane for osteogenic space maintenance, specifically tensile strength (from 10.2 ± 1.2 to 50.3 ± 4.5 MPa) and compression force (from 0 to 0.94 ± 0.09 N mm-1), through Mg sheet reinforcement and improved crystallization. The dense cast side of the Janus structure membrane displayed better fibroblast barrier capacity than a single fiber structure; meanwhile, the PCL matrix protected the Mg sheet from severe corrosion due to predeformation. The porous microfibers side supported preosteoblast cell adhesion, enhanced osteogenesis, and angiogenesis in vitro, through the biomimetic extracellular matrix and sustainable Mg2+ release. Furthermore, the Mg-MgO/PCL membrane incorporating 2 wt % MgO NPs exhibited remarkable antimicrobial properties, inducing over 88.75% apoptosis in Staphylococcus aureus. An in vivo experiment using the rat skull defect model (Φ = 5 mm) confirmed that the Mg-MgO/PCL membrane significantly improved new bone formation postsurgery. Collectively, our investigation provides valuable insights into the design of multifunctional membranes for clinical oral GBR application.
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Óxido de Magnésio , Poliésteres , Ratos , Animais , Óxido de Magnésio/farmacologia , Poliésteres/farmacologia , Poliésteres/química , Regeneração Óssea , Osteogênese , Adesão CelularRESUMO
Backgrounds and aims: Immunotherapies have formed an entirely new treatment paradigm for hepatocellular carcinoma (HCC). Tertiary lymphoid structure (TLS) has been associated with good response to immunotherapy in most solid tumors. Nonetheless, the role of TLS in human HCC remains controversial, and recent studies suggest that their functional heterogeneity may relate to different locations within the tumor. Exploring factors that influence the formation of TLS in HCC may provide more useful insights. However, factors affecting the presence of TLSs are still unclear. The human gut microbiota can regulate the host immune system and is associated with the efficacy of immunotherapy but, in HCC, whether the gut microbiota is related to the presence of TLS still lacks sufficient evidence. Methods: We performed pathological examinations of tumor and para-tumor tissue sections. Based on the location of TLS in tissues, all patients were divided into intratumoral TLS (It-TLS) group and desertic TLS (De-TLS) group. According to the grouping results, we statistically analyzed the clinical, biological, and pathological features; preoperative gut microbiota data; and postoperative pathological features of patients. Results: In a retrospective study cohort of 60 cases from a single center, differential microbiota analysis showed that compared with the De-TLS group, the abundance of Lachnoclostridium, Hungatella, Blautia, Fusobacterium, and Clostridium was increased in the It-TLS group. Among them, the enrichment of Lachnoclostridium was the most significant and was unrelated to the clinical, biological, and pathological features of the patients. It can be seen that the difference in abundance levels of microbiota is related to the presence of TLS. Conclusion: Our findings prove the enrichment of Lachnoclostridium-dominated gut microbiota is associated with the presence of It-TLS in HCC patients.
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Carcinoma Hepatocelular , Microbioma Gastrointestinal , Neoplasias Hepáticas , Estruturas Linfoides Terciárias , Humanos , Carcinoma Hepatocelular/terapia , Estudos Retrospectivos , Neoplasias Hepáticas/terapia , ClostridialesRESUMO
BACKGROUND: Even after curative resection, the prognosis for patients with intrahepatic cholangiocarcinoma (iCCA) remains disappointing due to the extremely high incidence of postoperative recurrence. METHODS: A total of 280 iCCA patients following curative hepatectomy from three independent institutions were recruited to establish the retrospective multicenter cohort study. The very early recurrence (VER) of iCCA was defined as the appearance of recurrence within 6 months. The 3D tumor region of interest (ROI) derived from contrast-enhanced CT (CECT) was used for radiomics analysis. The independent clinical predictors for VER were histological stage, AJCC stage, and CA199 levels. We implemented K-means clustering algorithm to investigate novel radiomics-based subtypes of iCCA. Six types of machine learning (ML) algorithms were performed for VER prediction, including logistic, random forest (RF), neural network, bayes, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost). Additionally, six clinical ML (CML) models and six radiomics-clinical ML (RCML) models were developed to predict VER. Predictive performance was internally validated by 10-fold cross-validation in the training cohort, and further evaluated in the external validation cohort. RESULTS: Approximately 30 % of patients with iCCA experienced VER with extremely discouraging outcome (Hazard ratio (HR) = 5.77, 95 % Confidence Interval (CI) = 3.73-8.93, P < 0.001). Two distinct iCCA subtypes based on radiomics features were identified, and subtype 2 harbored a higher proportion of VER (47.62 % Vs 25.53 %) and significant shorter survival time than subtype 1. The average AUC values of the CML and RCML models were 0.744 ± 0.018, and 0.900 ± 0.014 in the training cohort, and 0.769 ± 0.065 and 0.929 ± 0.027 in the external validation cohort, respectively. CONCLUSION: Two radiomics-based iCCA subtypes were identified, and six RCML models were developed to predict VER of iCCA, which can be used as valid tools to guide individualized management in clinical practice.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Hepatectomia , Teorema de Bayes , Estudos de Coortes , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Aprendizado de Máquina , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Estudos RetrospectivosRESUMO
The assessment of early atherosclerosis (AS) is of great significance for the early diagnosis and mechanism research. Herein, a novel nanoprobe PCN@FL is developed to realize the simultaneous detection and imaging of phosphorylation and hypochlorous acid (HClO). The selective recognition of HClO is achieved through the specific interaction between DMTC and HClO, while the levels of phosphorylation are detected via the specific interaction between Zr (IV) and phosphates. The nanoprobe can be utilized to monitor the fluctuations in HClO and phosphate in early atherosclerosis. It is observed that the levels of HClO and phosphate in the serum of early AS mice are higher than those of the normal mice. Ultimately, the levels of hypochlorous acid and phosphorylation in the inner wall of aortic vessels are imaged by two-photon microscope. The results show that the levels of HClO and phosphorylation in the early atherosclerotic mice are significantly higher than those of in normal mice. The nanoprobe provides a suitable fluorescent tool for simultaneous detection and imaging of HClO and phosphorylation, which holds promise for early atherosclerotic disease assessment.
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Corantes Fluorescentes , Ácido Hipocloroso , Camundongos , Animais , Fosforilação , Imagem Óptica/métodos , FosfatosRESUMO
Forest trees provide critical ecosystem services for humanity that are under threat due to ongoing global change. Measuring and characterizing genetic diversity are key to understanding adaptive potential and developing strategies to mitigate negative consequences arising from climate change. In the area of forest genetic diversity, genetic divergence caused by large-scale changes at the chromosomal level has been largely understudied. In this study, we used the RNA-seq data of 20 co-occurring forest trees species from genera including Acer, Alnus, Amelanchier, Betula, Cornus, Corylus, Dirca, Fraxinus, Ostrya, Populus, Prunus, Quercus, Ribes, Tilia, and Ulmus sampled from Upper Peninsula of Michigan. These data were used to infer the origin and maintenance of gene family variation, species divergence time, as well as gene family expansion and contraction. We identified a signal of common whole genome duplication events shared by core eudicots. We also found rapid evolution, namely fast expansion or fast contraction of gene families, in plant-pathogen interaction genes amongst the studied diploid species. Finally, the results lay the foundation for further research on the genetic diversity and adaptive capacity of forest trees, which will inform forest management and conservation policies.
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Ecossistema , Árvores , Árvores/genética , Florestas , Perfilação da Expressão GênicaRESUMO
The topography of the Tibetan Plateau (TP) has shaped the paleoclimatic evolution of the Asian monsoon. However, the influence of the TP on the global climate, beyond the domain of the Asian monsoon, remains unclear. Here we show that the Pacific and Atlantic Oceans act as efficient repeaters that boost the global climatic impact of the TP. The simulations demonstrate that oceanic repeaters enable TP heating to induce a wide-ranging climate response across the globe. A 1 °C TP warming can result in a 0.73 °C temperature increase over North America. Oceanic repeaters exert their influence by enhancing the air-sea interaction-mediated horizontal heat and moisture transport, as well as relevant atmospheric circulation pathways including westerlies, stationary waves, and zonal-vertical cells. Air-sea interactions were further tied to local feedbacks, mainly the decreased air-sea latent heat flux from the weakening air-sea humidity difference and the increased shortwave radiation from sinking motion-induced cloud reduction over the North Pacific and Atlantic Oceans. Our findings highlight the crucial influence of TP heating variation on the current climate under a quasi-fixed topography, in contrast to topography change previously studied in paleoclimate evolution. Therefore, TP heating should be considered in research on global climate change.
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The regulation of protein kinase B (AKT) phosphorylation by Tripartite motif-containing protein 31 (TRIM31) is implicated as an essential mechanism in the progression of many malignant tumors. Nevertheless, the function of the TRIM31/AKT pathway in oral squamous cell carcinoma (OSCC) remains elusive. Here, immunohistochemistry analysis of human OSCC tissue microarrays indicated significantly higher levels of TRIM31 and phosphorylated AKT (p-AKT) in OSCC tumors than in adjacent tissue samples. Also, we detected a positive association between TRIM31 expression and clinical OSCC development. In in vitro studies, TRIM31 knockdown severely impaired OSCC cell growth, invasion, and migration. By contrast, TRIM31 overexpression improved these cell behaviors, while subsequent AKT inhibition abrogated the effect. In vivo tumorigenesis experiments using nude mice also validated the effects of TRIM31/AKT signaling in tumor growth. Furthermore, TRIM31 upregulation facilitated glucose uptake, as well as lactate and adenosine triphosphate production of OSCC cells, while such positive effects on glycolysis and malignant cell phenotypes were reversed by treatment with AKT or glycolysis inhibitors. In conclusion, TRIM31 may improve OSCC progression by enhancing AKT phosphorylation and subsequent glycolysis. Hence, TRIM31 has the potential as a treatment target in OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Glicólise , Camundongos Nus , Neoplasias Bucais/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genéticaRESUMO
Changes in human lifestyles have led to a dramatic increase in the incidence of Crohn's disease worldwide. Predicting the activity and remission of Crohn's disease has become an urgent research problem. In addition, the influence of each attribute in the test sample on the prediction results and the interpretability of the model still deserves further investigation. Therefore, in this paper, we proposed a wrapper feature selection classification model based on a combination of the improved ant colony optimization algorithm and the kernel extreme learning machine, called bIACOR-KELM-FS. IACOR introduces an evasive strategy and astrophysics strategy to balance the exploration and exploitation phases of the algorithm and enhance its optimization capabilities. The optimization capability of the proposed IACOR was validated on the IEEE CEC2017 benchmark test function. And the prediction was performed on Crohn's disease dataset. The results of the quantitative analysis showed that the prediction accuracy of bIACOR-KELM-FS for predicting the activity and remission of Crohn's disease reached 98.98%. The analysis of important attributes improved the interpretability of the model and provided a reference for the diagnosis of Crohn's disease. Therefore, the proposed model is considered a promising adjunctive diagnostic method for Crohn's disease.
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Doença de Crohn , Humanos , Algoritmos , Aprendizado de Máquina , BenchmarkingRESUMO
Developing composite materials with optimized mechanics, degradation, and bioactivity for bone regeneration has long been a crucial mission. Herein, a multifunctional Mg/Poly-l-lactic acid (Mg/PLLA) composite membrane based on the "materials plain" concept through the accumulative rolling (AR) method is proposed. Results show that at a rolling ratio of 75%, the comprehensive mechanical properties of the membrane in the rolling direction are self-reinforced significantly (elongation at break ≈53.2%, tensile strength ≈104.0 MPa, Young's modulus ≈2.13 GPa). This enhancement is attributed to the directional arrangement and increased crystallization of PLLA molecular chains, as demonstrated by SAXS and DSC results. Furthermore, the AR composite membrane presents a lamellar heterostructure, which not only avoids the accumulation of Mg microparticles (MgMPs) but also regulates the degradation rate. Through the contribution of bioactive MgMPs and their photothermal effect synergistically, the membrane effectively eliminates bacterial infection and accelerates vascularized bone regeneration both in vitro and in vivo. Notably, the membrane exhibits outstanding rat skull bone regeneration performance in only 4 weeks, surpassing most literature reports. In short, this work develops a composite membrane with a "one stone, four birds" effect, opening an efficient avenue toward high-performance orthopedic materials.
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Regeneração Óssea , Poliésteres , Ratos , Animais , Espalhamento a Baixo Ângulo , Difração de Raios X , Poliésteres/química , BactériasRESUMO
The strong dependency of almost all malignant tumors on methionine potentially offers a pathway for cancer treatment. We engineer an attenuated strain of Salmonella typhimurium to overexpress an L-methioninase with the aim of specifically depriving tumor tissues of methionine. The engineered microbes target solid tumors and induce a sharp regression in several very divergent animal models of human carcinomas, cause a significant decrease in tumor cell invasion, and essentially eliminate the growth and metastasis of these tumors. RNA sequencing analyses reveal that the engineered Salmonella reduce the expression of a series of genes promoting cell growth, cell migration, and invasion. These findings point to a potential treatment modality for many metastatic solid tumors, which warrants further tests in clinical trials.
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Metionina , Neoplasias , Animais , Humanos , Metionina/metabolismo , Metionina/uso terapêutico , Neoplasias/tratamento farmacológico , Racemetionina/metabolismo , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo , Modelos AnimaisRESUMO
Ovarian serous cystadenocarcinoma (OV) is a fatal gynecologic cancer with a five-year survival rate of only 46%. Resistance to platinum-based chemotherapy is a prevalent factor in OV patients, leading to increased mortality. The platinum resistance in OV is driven by transcriptome heterogeneity and tumor heterogeneity. Studies have indicated that ovarian cancer stem cells (OCSCs), which are chemoresistant and help in disease recurrence, are enriched by platinum-based chemotherapy. Stem cells have a significant influence on the OV progression and prognosis of OV patients and are key pathology mediators of OV. However, the molecular mechanisms and targets of OV have not yet been fully understood. In this study, systematic research based on the TCGA-OV dataset was conducted for the identification and construction of key stem cell-related diagnostic and prognostic models for the development of multigene markers of OV. A six-gene diagnostic and prognostic model (C19orf33, CBX2, CSMD1, INSRR, PRLR, and SLC38A4) was developed based on the differentially expressed stem cell-related gene model, which can act as a potent diagnostic biomarker and can characterize the clinicopathological properties of OV. The key genes related to stem cells were identified by screening the genes differentially expressed in OV and control samples. The mRNA-miRNA-TF molecular network for the six-gene model was constructed, and the potential biological significance of this molecular model and its impact on the infiltration of immune cells in the OV tumor microenvironment were elucidated. The differences in immune infiltration and stem cell-related biological processes were determined using gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) for the selection of molecular treatment options and providing a reference for elucidating the posttranscriptional regulatory mechanisms in OV.