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A digital workflow is presented for multiple transfers of targeted jaw relation and restorative spaces from interim to definitive restorations in patients with severe tooth wear. Following analysis of the targeted restorative space, segmented arch stereolithographic templates were digitally created and fabricated for precise control of reduction depth. Then, the jaw relation was transferred from the initially determined stabilization splint to the temporary fixed restoration and definitive restoration by using a digital articulator. This digital approach yielded a stabilized jaw relationship and restorative spaces transferring effect throughout successive stages of occlusal reconstruction resulting in satisfactory prosthetic outcomes.
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Straw return is regarded as a widely used field management strategy for improving soil health, but its comprehensive effect on crop grain yield and quality remains elusive. Herein, a meta-analysis containing 1822 pairs of observations from 78 studies was conducted to quantify the effect of straw return on grain yield and quality of three main crops (maize, rice, and wheat). On average, compared with no straw return, straw return significantly (p< 0.05) increased grain yield (+4.3%), protein content (+2.5%), total amino acids concentration (+1.2%), and grain phosphorus content (+3.6%), respectively. Meanwhile, straw return significantly (p< 0.05) decreased rice chalky grain rate (-14.4%), overall grain hardness (-1.9%), and water absorption of maize and wheat (-0.5%), respectively. Moreover, straw return effects on grain yield and quality traits were infected by cultivated crop types, straw return amounts, straw return methods, and straw return duration. Our findings illustrated that direct straw return increased three main crop grain yields and improved various quality traits among different agricultural production areas. Although improper straw return may increase plant disease risk and affect seed germination, our results suggest that full straw return with covered or plough mode is a more suitable way to enhance grain yield and quality. Our study also highlights that compared with direct straw return, straw burning or composting before application may also be beneficial to farmland productivity and sustainability, but comparative studies in this area are still lacking.
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Unwanted icing on exposed surfaces poses significant risks, driving the quest for effective anti-icing mechanisms. While fracture mechanics concepts have been developed for designing coatings that weaken the ice-solid interface on soft surfaces, the factors that dictate ice adhesion strength and its counterpart, ice removal force, on hard surfaces remain poorly understood. In this study, we employ molecular dynamics simulations to investigate the interface rupture between ice and a hard solid substrate. The results indicate that the ice adhesion strength is contingent on the length of the ice cube. By examining the shearing behavior, we reveal a nanoscale critical force-bearing length. The shear force required to detach the ice scales proportionally with the length of the ice cube when it is smaller than the critical length. Once the ice cube length exceeds the critical length, the shear force stabilizes at a constant maximum value, revealing the existence of a maximum ice-removal force. The results align with the so-called strength versus toughness-controlled deicing regimes and are in agreement with cohesive zone modeling at the continuum length scale and recent experimental results. Our results extend this understanding to the nanoscale, confirming consistency between macro and micro scales. This consistency suggests that the toughness of the ice-solid interface is intrinsically governed by ice-surface interactions. By unraveling key intrinsic factors and their scale-dependent effects on the interface rupture of ice on surfaces, this study lays a solid theoretical foundation for the design and fabrication of next-generation anti-icing surfaces.
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The primary purpose of present study was to explore the effects of arsenic exposure on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear transcription factor-κB (NF-κB) signaling pathway in the hippocampus of offspring mice at different developmental stages. Sodium arsenite (NaAsO2) at doses of 0, 15, 30 or 60â¯mg/L administered to female mice and their pups. The nuclear translocation levels of NF-κB were assessed by EMSA. Real-time RT-PCR was used to measure Akt, NF-κB and PI3K mRNA levels. Protein expressions of PI3K, p-Akt, inhibitor kappa B kinase (IKK), p-NF-κB, protein kinase A (PKA), inhibitor kappa B (IκB), and cAMP response element-binding protein (CREB) were measured by Western blot. Results disclosed that exposure to 60â¯mg/L NaAsO2 could suppress NF-κB levels of nuclear translocation of postnatal day (PND) 20 and PND 40 mice. Arsenic downregulated the transcriptional and translational levels of PI3K, Akt and NF-κB. Additionally, protein expressions of p-IKK, p-IκB, PKA and p-CREB also reduced. Taken together, results of present study indicated that arsenic could downregulate the PI3K/Akt/NF-κB signaling pathway, particularly on PND 40, which might be involved in the cognitive impairments.
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Background: The clinical presentation of Community-acquired pneumonia (CAP) in hospitalized patients exhibits heterogeneity. Inflammation and immune responses play significant roles in CAP development. However, research on immunophenotypes in CAP patients is limited, with few machine learning (ML) models analyzing immune indicators. Methods: A retrospective cohort study was conducted at Xinhua Hospital, affiliated with Shanghai Jiaotong University. Patients meeting predefined criteria were included and unsupervised clustering was used to identify phenotypes. Patients with distinct phenotypes were also compared in different outcomes. By machine learning methods, we comprehensively assess the disease severity of CAP patients. Results: A total of 1156 CAP patients were included in this research. In the training cohort (n=809), we identified three immune phenotypes among patients: Phenotype A (42.0%), Phenotype B (40.2%), and Phenotype C (17.8%), with Phenotype C corresponding to more severe disease. Similar results can be observed in the validation cohort. The optimal prognostic model, SuperPC, achieved the highest average C-index of 0.859. For predicting CAP severity, the random forest model was highly accurate, with C-index of 0.998 and 0.794 in training and validation cohorts, respectively. Conclusion: CAP patients can be categorized into three distinct immune phenotypes, each with prognostic relevance. Machine learning exhibits potential in predicting mortality and disease severity in CAP patients by leveraging clinical immunological data. Further external validation studies are crucial to confirm applicability.
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Infecciones Comunitarias Adquiridas , Aprendizaje Automático , Fenotipo , Neumonía , Humanos , Infecciones Comunitarias Adquiridas/inmunología , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/mortalidad , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Neumonía/inmunología , Neumonía/diagnóstico , Neumonía/mortalidad , Anciano , Medición de Riesgo , Índice de Severidad de la Enfermedad , Adulto , InmunofenotipificaciónRESUMEN
BACKGROUND: Poor neurological recovery in patients after anterior cervical discectomy and fusion has been frequently reported; however, no study has analyzed the preoperative imaging characteristics of patients to investigate the factors affecting surgical prognosis. The purpose of this study was to investigate the factors that affect the preoperative imaging characteristics of patients and their influence on poor neurologic recovery after anterior cervical discectomy and fusion. METHODS: We retrospectively analyzed the clinical data of 89 patients who met the criteria for anterior cervical discectomy and fusion for the treatment of single-level cervical spondylotic myelopathy and evaluated the patients' neurological recovery based on the recovery rate of the Japanese Orthopaedic Association (JOA) scores at the time of the final follow-up visit. Patients were categorized into the "good" and "poor" groups based on the JOA recovery rates of ≥ 50% and < 50%, respectively. Clinical information (age, gender, body mass index, duration of symptoms, preoperative JOA score, and JOA score at the final follow-up) and imaging characteristics (cervical kyphosis, cervical instability, ossification of the posterior longitudinal ligament (OPLL), calcification of herniated intervertebral discs, increased signal intensity (ISI) of the spinal cord on T2-weighted imaging (T2WI), and degree of degeneration of the discs adjacent to the fused levels (cranial and caudal) were collected from the patients. Univariate and binary logistic regression analyses were performed to identify risk factors for poor neurologic recovery. RESULTS: The mean age of the patients was 52.56 ± 11.18 years, and the mean follow-up was 26.89 ± 11.14 months. Twenty patients (22.5%) had poor neurological recovery. Univariate analysis showed that significant predictors of poor neurological recovery were age (p = 0.019), concomitant OPLL (p = 0.019), concomitant calcification of herniated intervertebral discs (p = 0.019), ISI of the spinal cord on T2WI (p <0.05), a high grade of degeneration of the discs of the cranial neighboring levels (p <0.05), and a high grade of discs of the caudal neighboring levels (p <0.05). Binary logistic regression analysis showed that ISI of the spinal cord on T2WI (p = 0.001 OR = 24.947) and high degree of degeneration of adjacent discs on the cranial side (p = 0.040 OR = 6.260) were independent risk factors for poor neurological prognosis. CONCLUSION: ISI of the spinal cord on T2WI and high degree of cranial adjacent disc degeneration are independent risk factors for poor neurological recovery after anterior cervical discectomy and fusion. A comprehensive analysis of the patients' preoperative imaging characteristics can help in the development of surgical protocols and the management of patients' surgical expectations.
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Vértebras Cervicales , Discectomía , Recuperación de la Función , Fusión Vertebral , Humanos , Discectomía/métodos , Discectomía/efectos adversos , Fusión Vertebral/métodos , Fusión Vertebral/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Vértebras Cervicales/cirugía , Vértebras Cervicales/diagnóstico por imagen , Estudios Retrospectivos , Factores de Riesgo , Anciano , Adulto , Espondilosis/cirugía , Espondilosis/diagnóstico por imagen , Imagen por Resonancia Magnética , Estudios de Seguimiento , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Colorectal cancer (CRC) ranks second in mortality worldwide and requires effective and affordable remedies. Cyclovirobuxine D (CVB-D) is the main effective component of Huangyangning tablet, an approved traditional patent medicine, which is mainly used for cardiovascular treatment. As a multibioactive natural compound, CVB-D possesses underlying anticancer activities. EXPERIMENTAL APPROACH: Cell viability and clone-forming ability were determined in human CRC lines. Western blot, immunofluorescence assay, transmission electron microscopy and senescence-associated ß-galactosidase (SA-ß-Gal) staining were utilized to investigate cell autophagy and senescence. The molecular mechanisms were explored by virtual prediction and experimental validation. Patient-derived xenograft (PDX), dextran sulfate sodium salt (DSS), and azomethane (AOM)/DSS mouse models were employed for in vivo studies. KEY RESULTS: CVB-D inhibited the growth and development of advanced CRC cells / mice by inducing autophagic and senescent activities through the chaperonin containing TCP1 subunit 3 (CCT3)/yes-associated protein (YAP) axis. CVB-D acted as a promising inhibitor of CCT3 by interacting with its ATP site. In PDX tumours, CVB-D showed potential therapeutic effects by targeting CCT3. Treatment with CVB-D alleviated the mouse model of colitis induced by DSS and attenuated AOM/DSS-induced formation of adenomatous polyps by its action on CCT3. CONCLUSIONS AND IMPLICATIONS: Our study has provided a scientific basis for the suggestion that CVB-D may be recognized as a prospective drug candidate for the therapy of CRC in patients.
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Aiming to automatically monitor and improve stereoscopic image and video processing systems, stereoscopic image quality assessment approaches are becoming more and more important as 3D technology gains popularity. We propose a full-reference stereoscopic image quality assessment method that incorporate monocular and binocular features based on binocular competition and binocular integration. To start, we create a three-channel RGB fused view by fusing Gabor filter bank responses and disparity maps. Then, using the monocular view and the RGB fusion view, respectively, we extract monocular and binocular features. To alter the local features in the binocular features, we simultaneously estimate the saliency of the RGB fusion image. Finally, the monocular and binocular quality scores are calculated based on the monocular and binocular features, and the quality scores of the stereo image prediction are obtained by fusion. Performance testing in the LIVE 3D IQA database Phase I and Phase II. The results of the proposed method are compared with newer methods. The experimental results show good consistency and robustness.
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Breast cancer (BRCA) has become the most common type of cancer in women. Improving the therapeutic response remains a challenge. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a classic tumour suppressor with emerging new functions discovered in recent years, and myeloid PTEN loss has been reported to impair antitumour immunity. In this study, we revealed a novel mechanism by which myeloid PTEN potentially affects antitumour immunity in BRCA. We detected accelerated stress granule (SG) assembly under oxidative stress in PTEN-deficient bone marrow-derived macrophages (BMDMs) through the EGR1-promoted upregulation of TIAL1 transcription. PI3K/AKT/mTOR (PAM) pathway activation also promoted SG formation. ATP consumption during SG assembly in BMDMs impaired the phagocytic ability of 4T1 cells, potentially contributing to the disruption of antitumour immunity. In a BRCA neoadjuvant cohort, we observed a poorer response in myeloid PTENlow patients with G3BP1 aggregating as SGs in CD68+ cells, a finding that was consistent with the observation in our study that PTEN-deficient macrophages tended to more readily assemble SGs with impaired phagocytosis. Our results revealed the unconventional impact of SGs on BMDMs and might provide new perspectives on drug resistance and therapeutic strategies for the treatment of BRCA patients.
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The accurate instance segmentation of individual crop plants is crucial for achieving a high-throughput phenotypic analysis of seedlings and smart field management in agriculture. Current crop monitoring techniques employing remote sensing predominantly focus on population analysis, thereby lacking precise estimations for individual plants. This study concentrates on maize, a critical staple crop, and leverages multispectral remote sensing data sourced from unmanned aerial vehicles (UAVs). A large-scale SAM image segmentation model is employed to efficiently annotate maize plant instances, thereby constructing a dataset for maize seedling instance segmentation. The study evaluates the experimental accuracy of six instance segmentation algorithms: Mask R-CNN, Cascade Mask R-CNN, PointRend, YOLOv5, Mask Scoring R-CNN, and YOLOv8, employing various combinations of multispectral bands for a comparative analysis. The experimental findings indicate that the YOLOv8 model exhibits exceptional segmentation accuracy, notably in the NRG band, with bbox_mAP50 and segm_mAP50 accuracies reaching 95.2% and 94%, respectively, surpassing other models. Furthermore, YOLOv8 demonstrates robust performance in generalization experiments, indicating its adaptability across diverse environments and conditions. Additionally, this study simulates and analyzes the impact of different resolutions on the model's segmentation accuracy. The findings reveal that the YOLOv8 model sustains high segmentation accuracy even at reduced resolutions (1.333 cm/px), meeting the phenotypic analysis and field management criteria.
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ETHNOPHARMACOLOGICAL RELEVANCE: Babaodan (BBD) is a unique Chinese medication utilized in traditional Chinese medicine. It can eliminate toxins, induce diuresis, and eliminate yellowish hue. In addition to treating acute and chronic viral hepatitis, cholecystitis, cholangitis, and urinary tract infections, BBD has garnered popularity as a substitution treatment for several malignant cancers, particularly hepatocellular carcinoma (HCC). AIM OF THE STUDY: To elucidate the efficacy and mechanism of BBD alone and combined with camrelizumab (CLM) for treating HCC. METHODS: We investigated the effects of BBD on the HCC tumor microenvironment in vivo. Furthermore, we evaluated its effects on tumor growth and metastasis induced by M2 macrophages in vitro. RESULTS: In a mouse model of orthotopic HCC, BBD decreased tumor growth. Furthermore, it increased the M1/M2 macrophage ratio and CD8+ T-cell abundance in mice. In addition, BBD reversed HCC cell proliferation and metastasis induced by M2 macrophages, increased the anti-HCC effect of low-dose CLM, and attenuated organ damage induced by high-dose CLM. Lastly, BBD enhanced the efficacy of CLM via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: BBD increases the antitumor effect of CLM by modulating the tumor immune microenvironment and attenuating its the toxic side effects of CLM.
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Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Proliferación Celular , Neoplasias Hepáticas , Macrófagos , Microambiente Tumoral , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Proliferación Celular/efectos de los fármacos , Macrófagos/efectos de los fármacos , Ratones , Anticuerpos Monoclonales Humanizados/farmacología , Microambiente Tumoral/efectos de los fármacos , Masculino , Línea Celular Tumoral , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Ratones Endogámicos C57BL , Ratones Endogámicos BALB C , Sinergismo Farmacológico , Metástasis de la NeoplasiaRESUMEN
As an emerging contaminant, microplastics (MPs) have received considerable attention for their potential threat to the soil environment. However, the response of soil bacterial and fungal communities to MPs exposure remains unclear. In this study, we conducted a global meta-analysis of 95 publications and 2317 observations to assess the effects of nonbiodegradable MP properties and exposure conditions on soil microbial biomass, alpha and beta diversity, and community structure. Our results indicate that MPs increased (p < 0.05) soil active microbial biomass by 42%, with the effect varying with MPs type, exposure concentration, exposure time and soil pH. MPs concentration was identified as the most important factor controlling the response of soil microbial biomass to MPs. MPs addition decreased (p < 0.05) the soil bacterial Shannon and Chao1 indices by 2% and 3%, respectively, but had limited effects (p > 0.05) on soil fungal Shannon and Chao1 indices. The type of MPs and exposure time determined the effects of MPs on bacterial Shannon and Chao1 indices, while the type of MPs and soil pH controlled the response ratios of fungal Shannon and Chao1 indices to MPs. Specifically, soil organic carbon (SOC) was the major factor regulating the response ratio of bacterial alpha diversity index to MPs. The presence of MPs did not affect soil bacterial community structure and beta diversity. Our results highlight that MPs reduced bacterial diversity and richness but increased the soil active microbial biomass, suggesting that MPs could disrupt biogeochemical cycles by promoting the growth of specific microorganisms.
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Anterior diastema is a common esthetic defect in China. The general treatment for a patient with diastemata, including orthodontics and direct and indirect restorations, is a multidisciplinary clinical procedure covering the orthodontics, operative dentistry, general dentistry, and prosthodontics department. Given the diversity of departments and the complex etiology of this defect, decision-making regarding the closing methods and time selection is undefined and unintegrated, which makes the long-term stability of closure unpredictable. This article proposed an etiology-based decision tree with actual measurement of diastemata width for diastemata closure. The decisional steps include classifying the etiological factors based on patients' medical history and clinical manifestation to evaluate the stability of diastemata. After maintaining the stability of diastemata, contemporary and multidisciplinary treatment plans were selected in accordance with the measured width of diastemata and patients' cosmetic psychology, economics, and available time. These decision trees focus on the challenges of collaboration among dental departments, propose an objective and efficient ways for connections, and promote efficient and effective diastemata closure.
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Toma de Decisiones Clínicas , Diastema , Humanos , Grupo de Atención al Paciente , Estética Dental , Árboles de DecisiónRESUMEN
Acute lung injury (ALI) is characterized by an unregulated inflammatory reaction, often leading to severe morbidity and ultimately death. Excessive inflammation caused by M1 macrophage polarization and pyroptosis has been revealed to have a critical role in ALI. Recent study suggests that glycolytic reprogramming is important in the regulation of macrophage polarization and pyroptosis. However, the particular processes underlying ALI have yet to be identified. In this study, we established a Lipopolysaccharide(LPS)-induced ALI model and demonstrated that blocking glycolysis by using 2-Deoxy-D-glucose(2-DG) significantly downregulated the expression of M1 macrophage markers and pyroptosis-related genes, which was consistent with the in vitro results. Furthermore, our research has revealed that Phosphoglycerate Kinase 1(PGK1), an essential enzyme in the glycolysis pathway, interacts with NOD-, LRR- and pyrin domain-containing protein 3(NLRP3). We discovered that LPS stimulation improves the combination of PGK1 and NLRP3 both in vivo and in vitro. Interestingly, the absence of PGK1 reduces the phosphorylation level of NLRP3. Based on in vitro studies with mice bone marrow-derived macrophages (BMDMs), we further confirmed that siPGK1 plays a protective role by inhibiting macrophage pyroptosis and M1 macrophage polarization. The PGK1 inhibitor NG52 suppresses the occurrence of excessive inflammation in ALI. In general, it is plausible to consider a therapeutic strategy that focuses on modulating the relationship between PGK1 and NLRP3 as a means to mitigate the activation of inflammatory macrophages in ALI.
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Lesión Pulmonar Aguda , Macrófagos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Fosfoglicerato Quinasa , Piroptosis , Piroptosis/fisiología , Piroptosis/efectos de los fármacos , Animales , Fosfoglicerato Quinasa/metabolismo , Fosfoglicerato Quinasa/genética , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/enzimología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ratones , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Glucólisis/fisiología , Glucólisis/efectos de los fármacos , Masculino , Lipopolisacáridos/toxicidad , Ratones Noqueados , Células CultivadasRESUMEN
The use of stem cells capable of multilineage differentiation in treating Pelvic Floor Dysfunction (PFD) holds great promise since they are susceptible to entering connective tissue of various cell types and repairing damaged tissues. This research investigated the effect of microRNA-181a-5p (miR-181a-5p) on Bone Marrow Mesenchymal Stem Cells (BMSCs) in rats with PFD. BMSCs were transfected and analyzed for their fibroblast differentiation ability. miR-181a-5p, MFN1, and fibroblast-related genes were quantitatively analyzed. Whether MFN1 is a target gene of miR-181a-5p was predicted and confirmed. The efficacy of BMSCs in vivo rats with PFD was evaluated by measuring Leak Point Pressure (LPP), Conscious Cystometry (CMG), hematoxylin and eosin staining, and Masson staining. The present results discovered that miR-181a-5p was up-regulated and MFN1 was down-regulated during the differentiation of BMSCs into fibroblasts. Fibroblast differentiation of BMSCs was promoted after miR-181a-5p was induced or MFN1 was suppressed, but it was suppressed after miR-181a-5p was silenced. miR-181a-5p improved LPP and conscious CMG outcomes in PDF rats by targeting MFN1 expression, thereby accelerating fibroblast differentiation of BMSCs. In brief, miR-181a-5p induces fibroblast differentiation of BMSCs in PDF rats by MFN1, potentially targeting PDF therapeutics.
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Diferenciación Celular , Fibroblastos , Células Madre Mesenquimatosas , MicroARNs , Animales , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Femenino , Ratas Sprague-Dawley , Trastornos del Suelo Pélvico/genética , Trastornos del Suelo Pélvico/terapia , Ratas , Regulación hacia Arriba , Modelos Animales de Enfermedad , Regulación hacia Abajo , Células CultivadasRESUMEN
BACKGROUND: Cystatin is a protease inhibitor that also regulates genes expression linked to inflammation and plays a role in defense and regulation. METHODS AND RESULTS: Cystatin 10 (Smcys10) was cloned from Scophthalmus maximus and encodes a 145 amino acid polypeptide. The results of qRT-PCR showed that Smcys10 exhibited tissue-specific expression patterns, and its expression was significantly higher in the skin than in other tissues. The expression level of Smcys10 was significantly different in the skin, gill, head kidney, spleen and macrophages after Vibrio anguillarum infection, indicating that Smcys10 may play an important role in resistance to V. anguillarum infection. The recombinant Smcys10 protein showed binding and agglutinating activity in a Ca2+-dependent manner against bacteria. rSmcys10 treatment upregulated the expression of IL-10, TNF-α and TGF-ß in macrophages of turbot and hindered the release of lactate dehydrogenase (LDH) from macrophages after V. anguillarum infection, which confirmed that rSmcys10 reduced the damage to macrophages by V. anguillarum. The NF-κB pathway was suppressed by Smcys10, as demonstrated by dual-luciferase analysis. CONCLUSIONS: These results indicated that Smcys10 is involved in the host antibacterial immune response.
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Cistatinas , Enfermedades de los Peces , Proteínas de Peces , Peces Planos , Macrófagos , Vibrio , Animales , Peces Planos/inmunología , Peces Planos/genética , Peces Planos/metabolismo , Vibrio/patogenicidad , Cistatinas/genética , Cistatinas/metabolismo , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Proteínas de Peces/inmunología , Macrófagos/metabolismo , Macrófagos/inmunología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/genética , Enfermedades de los Peces/microbiología , Vibriosis/inmunología , Vibriosis/veterinaria , Vibriosis/genética , FN-kappa B/metabolismo , Clonación Molecular/métodos , Regulación de la Expresión GénicaRESUMEN
The alterations in DNA methylation and transcriptome in trophoblast cells under conditions of low oxygen and oxidative stress have major implications for pregnancy-related disorders. However, the exact mechanism is still not fully understood. In this study, we established models of hypoxia (H group) and oxidative stress (HR group) using HTR-8/SVneo trophoblast cells and performed combined analysis of genome-wide DNA methylation changes using reduced representation bisulphite sequencing and transcriptome expression changes using RNA sequencing. Our findings revealed that the H group exhibited a higher number of differentially methylated genes and differentially expressed genes than the HR group. In the H group, only 0.90% of all differentially expressed genes displayed simultaneous changes in DNA methylation and transcriptome expression. After the threshold was expanded, this number increased to 6.29% in the HR group. Notably, both the H group and HR group exhibited concurrent alterations in DNA methylation and transcriptome expression within Axon guidance and MAPK signalling pathway. Among the top 25 differentially methylated KEGG pathways in the promoter region, 11 pathways were commonly enriched in H group and HR group, accounting for 44.00%. Among the top 25 KEGG pathways in transcriptome with significant differences between the H group and HR group, 10 pathways were consistent, accounting for 40.00%. By integrating our previous data on DNA methylation from preeclamptic placental tissues, we identified that the ANKRD37 and PFKFB3 genes may contribute to the pathogenesis of preeclampsia through DNA methylation-mediated transcriptome expression under hypoxic conditions.
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Hipoxia de la Célula , Metilación de ADN , Estrés Oxidativo , Transcriptoma , Trofoblastos , Humanos , Trofoblastos/metabolismo , Estrés Oxidativo/genética , Transcriptoma/genética , Hipoxia de la Célula/genética , Línea Celular , Femenino , Embarazo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Fosfofructoquinasa-2/genética , Fosfofructoquinasa-2/metabolismoRESUMEN
BACKGROUND: Cancer stem cells (CSCs) are a distinct subpopulation of cancer cells with the capacity to constantly self-renew and differentiate, and they are the main driver in the progression of cancer resistance and relapse. The tumor microenvironment (TME) constructed by CSCs is the "soil" adapted to tumor growth, helping CSCs evade immune killing, enhance their chemical resistance, and promote cancer progression. AIM OF REVIEW: We aim to elaborate the tight connection between CSCs and immunosuppressive components of the TME. We attempt to summarize and provide a therapeutic strategy to eradicate CSCs based on the destruction of the tumor ecological niche. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review is focused on three main key concepts. First, we highlight that CSCs recruit and transform normal cells to construct the TME, which further provides ecological niche support for CSCs. Second, we describe the main characteristics of the immunosuppressive components of the TME, targeting strategies and summarize the progress of corresponding drugs in clinical trials. Third, we explore the multilevel insights of the TME to serve as an ecological niche for CSCs.
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Many solid tumors frequently overexpress Non-SMC Condensin I Complex Subunit H (NCAPH), and new studies suggest that NCAPH may be a target gene for clinical cancer therapy. Numerous investigations have shown that a variety of transcription factors, including as MYBL2, FOXP3, GATA3, and OTC1, can stimulate the transcription of NCAPH. Additionally, NCAPH stimulates many oncogenic signaling pathways, such as ß-Catenin/PD-L1, PI3K/AKT/SGK3, MEK/ERK, AURKB/AKT/mTOR, PI3K/PDK1/AKT, and Chk1/Chk2. Tumor immune microenvironment modification and tumor growth, apoptosis, metastasis, stemness, and treatment resistance all depend on these signals. NCAPH has the ability to form complexes with other proteins that are involved in glycolysis, DNA damage repair, and chromatin remodeling. This review indicates that NCAPH expression in most malignant tumors is associated with poor prognosis and low recurrence-free survival.
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Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias/patología , Transducción de Señal , Proteínas de Ciclo Celular/metabolismo , Animales , Microambiente TumoralRESUMEN
The scavenger receptors (SRs) gene family is considered as the membrane-associated pattern recognition receptors that plays important roles in the immune responses of organisms. However, there is currently limited research on the systematic identification of the SRs gene family in teleost and their role in the innate immunity of S. schegelii. In this study, we identified and annotated 15 SRs genes in S. schegelii. Through phylogenetic analysis, analysis of conserved domains, gene structure, and motif composition, we found that SRs gene family within different classes were relatively conserved. Additionally, we used qRT-PCR to analyze the expression patterns of SRs genes in immune-related tissues from healthy and Acinetobacter johnsonii-infected S. schegelii. The results showed that SRs genes exhibited different tissue expression patterns and the expression of SRs genes significantly changed after A. johnsonii infection. These results provided a valuable basis for further understanding of the functions of SRs in the innate immune response of S. schegelii.