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Neuroendocrine differentiation is often found in colorectal cancer but its impact on prognosis remains controversial. This study explored the association between neuroendocrine differentiation and prognosis in stage II/III colorectal cancer patients. METHODS: Between 2012 and 2018, a total of 3,441 stage II/III colorectal cancer patients were included for analysis. To verify neuroendocrine differentiation, immunohistochemistry was performed to explore the expression of chromogranin A and synaptophysin in colorectal cancer. In addition, the difference in overall survival between groups was analyzed. A Kaplan-Meier analysis was used to determine the clinicopathological characteristics significantly correlated with survival, and a Cox proportional hazards analysis was used to identify factors independently affecting overall survival prognosis. Furthermore, the findings were validated by the Gene Expression Omnibus database. RESULTS: Among the 3441 stage II/III colorectal cancer patients, in comparison to patients with neuroendocrine differentiation (+), patients with neuroendocrine differentiation (+) had a poorer prognosis (P = 0.001). Furthermore, multivariate survival analysis of stage II cases revealed that tumor differentiation (P = 0.018), nerve invasion (P < 0.001) and neuroendocrine differentiation (+) (P = 0.002) were independent prognostic factors. Moreover, the prognosis of patients with neuroendocrine differentiation (+) was similar to that of patients with high-risk factors in stage II cases (P = 0.639). High chromogranin A expression was correlated with poor prognosis in stage II colorectal cancer patients in the Gene Expression Omnibus database (P < 0.001). CONCLUSION: The prognosis of colorectal cancer with neuroendocrine differentiation (+) was poor, especially in stage II colorectal cancer patients. neuroendocrine differentiation might be another high-risk factor for the prognosis of stage II colorectal cancer patients.
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We demonstrate an ultrasensitive optomechanical strain sensor based on a SiN membrane and a Fabry-Perot cavity, enabling the measurements of both static and dynamic strain by monitoring reflected light fluctuations using a single-frequency laser. The SiN membrane offers high-quality-factor mechanical resonances that are sensitive to minute strain fluctuations. The two-beam Fabry-Perot cavity is constructed to interrogate the motion state of the SiN membrane. A static strain resolution of 4.00 nÉ is achieved by measuring mechanical resonance frequency shifts of the SiN membrane. The best dynamic resolution is 4.47 pÉHz-1/2, which is close to that of the sensor using high-finesse cavity and optical frequency comb, overcoming the dependence of ultrasensitive strain sensors on narrow-linewidth laser and high-finesse cavity with frequency locking equipment. This work opens up a promising avenue for a new generation of ultrasensitive strain sensors.
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Malignant tumors and central nervous system (CNS) disorders are intricately linked to a process known as "aberrant cell cycle re-entry," which plays a critical role in the progression of these diseases. Addressing the dysregulation in cell cycles offers a promising therapeutic approach for cancers and CNS disorders. MicroRNAs (miRNAs) play a crucial role as regulators of gene expression in cell cycle transitions, presenting a promising therapeutic avenue for treating these disorders and their comorbidities. This review consolidates the progress made in the last three years regarding miRNA-based treatments for diseases associated with aberrant cell cycle re-entry. It encompasses exploring fundamental mechanisms and signaling pathways influenced by miRNAs in cancers and CNS disorders, particularly focusing on the therapeutic effects of exosome-derived miRNAs. The review also identifies specific miRNAs implicated in comorbidity of cancers and CNS disorders, discusses the future potential of miRNA reagents in managing cell cycle-related diseases.
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Ciclo Celular , Enfermedades del Sistema Nervioso Central , Comorbilidad , MicroARNs , Neoplasias , Humanos , MicroARNs/genética , Neoplasias/genética , Neoplasias/terapia , Neoplasias/patología , Animales , Ciclo Celular/genética , Enfermedades del Sistema Nervioso Central/genética , Enfermedades del Sistema Nervioso Central/terapia , Transducción de SeñalRESUMEN
We demonstrate a fiber-optic strain sensor with high and tunable sensitivity by constructing a Fabry-Perot interferometer with tunable stretching length. By improving the ratio of stretching length to interference length for the proposed sensor, the measured strain sensitivity is up to 1932 pm/µÎµ, which is an order of magnitude higher than the maximum value of reported fiber-optic strain sensors so far. The sensitivity for a prepared sensor could be also tuned conveniently by changing the stretching length, and experimental results show that the sensitivity could be tuned from 1932 to 978 pm/µÎµ by reducing the stretching length from 12 to 6 mm. Furthermore, the proposed device is economical, straightforward, robust, and reproducible. The advantages make the proposed device promising in practical applications.
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With a worldwide expansion of urbanization, the conservation of urban biodiversity is attracting growing attention; it is important to study the relationship between wildlife and urban green spaces. In this study, we selected 31 parks in the urban area of Fuyang City in the North China Plain. A total of 8795 individual birds from 69 species were recorded. The study found that (a) at the local level, tree diversity and heights are the most important factors contributing to each level of bird diversity, followed by the coverage of shrubs and herbs, and (b) at the landscape level, the proportion of woodland has a strong positive correlation with the multidimensional diversity of birds, followed by the patch diversity and percent of grassland. Our results showed that artificial greenland can effectively increase bird diversity. While considering urban planning and human well-being, the proportion of vegetation and landscape in urban parks should be properly planned, providing more habitats to enrich bird diversity.
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Monitoreo del Ambiente , Parques Recreativos , Animales , Humanos , Ciudades , Ecosistema , Biodiversidad , Urbanización , China , AvesRESUMEN
Extracellular vesicles (EVs) are small particles secreted by numerous cell types and circulate in almost all body fluids, acting as crucial messengers for cell-to-cell communication. EVs involves multiple physiological and pathological processes, including tumor progression, via their multiple cargoes. Therefore, EVs have become attractive candidates for the treatment of tumor, including melanoma. Notably, due to the crucial role of the tumor microenvironment (TME) in promoting tumor malignant phenotype, and the close intercellular communication in TME, EVs-based therapy by targeting TME has become a cutting-edge and prospective strategy for inhibiting melanoma progression and strengthening the anti-tumor immunity. In this review, we aimed to summarize and discuss the role of therapeutic EVs, which target the components of TME in melanoma, thereby providing insights into these promising clinical strategies for the treatment of melanoma patients.
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Vesículas Extracelulares , Melanoma , Humanos , Melanoma/patología , Vesículas Extracelulares/metabolismo , Comunicación Celular , Microambiente Tumoral/genéticaRESUMEN
In order to develop an N6-methyladenosine-related gene prognostic index (m6A-GPI) that can predict the prognosis in colorectal cancer (CRC), we obtained m6A-related differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) and m6Avar database, seven genes were screened by weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis. Then, m6A-GPI was constructed based on the risk score. Survival analysis indicated that patients in the lower m6A-GPI group have more prolonged disease-free survival (DFS), and different clinical characteristic groups (tumor site and stage) also showed differential risk scores. In the analysis of the molecular characteristics, the risk score is positively associated with homologous recombination defects (HRD), copy number alterations (CNA), and the mRNA expression-based stemness index (mRNAsi). In addition, m6A-GPI also plays an essential role in tumor immune cell infiltration. The immune cell infiltration in the low m6A-GPI group is significantly higher in CRC. Moreover, we found that CIITA, one of the genes in m6A-GPI was up-regulated in CRC tissues based on real-time RT-PCR and Western blot. m6A-GPI is a promising prognostic biomarker that can be used to distinguish the prognosis of CRC patients in CRC.
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We experimentally demonstrate a high-rate discretely modulated continuous-variable quantum key distribution over 80-km standard single-mode fiber with a 2.5 Gbaud, 16-symbol, two-ring constellation. With the help of well-designed digital signal processing algorithms, the excess noise of the system can be effectively suppressed. The achieved secret key rates are 49.02 Mbits/s, 11.86 Mbits/s, and 2.11 Mbits/s over 25-km, 50-km, and 80-km optical fiber, respectively, and achieve 67.4%, 70.0%, and 66.5% of the secret key rate performance of a Gaussian-modulated protocol. Our work shows that it is feasible to build a high-performance, long-distance continuous-variable quantum key distribution system with only a small constellation size.
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ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. However, its complex pathogenesis and lack of effective drugs for treating it present significant challenges. Si-Ni-San (SNS) is one of the representative formulas for treating patients with MAFLD in traditional Chinese medicine (TCM) clinics. According to our previous work, SNS reduces lipid droplet (LD) deposition in livers of mice with MAFLD. AIM OF THE STUDY: To elucidate the mechanism of SNS in reducing LD deposition in MAFLD. MATERIALS AND METHODS: First, LD areas were detected with Oil red O staining in HepG2 cells induced by oleic acid (OA). Cell Counting Kit-8 (CCK-8) assay was used to test cell viability after treatment with different concentrations of SNS serum. The expression of Yes-associated protein 1 (YAP1) was monitored by Western blot. Second, C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and gavaged with SNS decoction during the 11th and 12th weeks. Then, the weight of the body and the liver was examined. LD numbers and their locations in the liver were detected by triglyceride (TG) assay and hematoxylin and eosin staining (H&E). The expression levels of YAP1 and perilipin2 (PLIN2) were detected using Western blot and immunohistochemistry (IHC) in liver tissues. Finally, active ingredients of SNS decoction and SNS serum were identified by liquid chromatography-mass spectrometry (LC-MS). Finally, molecular docking was performed between the compounds in SNS and YAP1 to analyze their active interaction. RESULTS: Cellular experiments showed that SNS serum reduced LD vacuoles and YAP1 expression in OA-induced HepG2 cells. Animal experiments confirmed that LD vacuoles, PLIN2 expression (3.16-fold), and YAP1 expression (2.50-fold) were increased in the HFD group compared with the normal diet (ND) group. SNS reduced LD vacuoles, TG content (0.84-fold), PLIN2 expression (0.33-fold), and YAP1 expression (0.27-fold) compared with the normal saline (NS) group in Yap1Flox mice with MAFLD. In SNS, baicalein-6-glucuronide, desoxylimonin, galangin-7-glucoside, glycyrrhizic-acid, licoricesaponin-K2, and nobiletin showed a high binding effect with YAP1. Knockout of hepatocyte YAP1 reduced LD vacuoles, TG content (0.40-fold), and PLIN2 expression (0.62-fold) in mice. Meanwhile, SNS reduced LD vacuoles, TG content (0.70-fold), and PLIN2 expression (0.19-fold) in Yap1LKO mice with MAFLD. The effect of SNS in reducing TG and PLIN2 was diminished in Yap1LKO mice compared with Yap1Flox mice. CONCLUSION: SNS reduced LD deposition and YAP1 expression in MAFLD liver cells both in vivo and in vitro. YAP1 was highly expressed in livers with MAFLD, and knockout of hepatocellular YAP1 reduced LD deposition in mice. SNS reduced LD deposition associated with decreased YAP1 in MAFLD liver cells.
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Gotas Lipídicas , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Gotas Lipídicas/metabolismo , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Hígado , Triglicéridos/metabolismo , Dieta Alta en Grasa , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
In continuous-variable quantum key distribution (CV-QKD), the key information are encoded on quadratures of the optical field, which are measured via balanced homodyne detector (BHD). The bandwidth of the BHD is one of key parameters for precise characterization of quantum states. We establish a theoretical model to analyze the impact of the BHD bandwidth and signal modulation patterns on the channel parameters estimation of CV-QKD systems. Based on the proposed model, the secure key rate of a practical CV-QKD system under different BHD bandwidths and signal modulation patterns are investigated. Our results show that insufficient BHD bandwidth will result in wrong estimate of the transmission loss and excess noise, which significantly affects the performance of CV-QKD systems. Given the BHD bandwidth, there exists an optimal signal repetition rate that maximizes the secure key rate. The BHD bandwidth requirement of the QKD system increases with the transmission distance for large duty cycle pulse. Furthermore, the root raised-cosine pulse signal modulation performs better than the square pulse signal modulation in general.
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An in-fiber Michelson interferometric sensor was presented by fabricating a concavity on the end face of a single mode fiber using a single CO2 laser pulse. Reflected beams from the bottom and air-cladding boundary of the concavity are coupled into the fiber core and superimpose to generate a two-beam in-fiber Michelson interferometer. Compared with other laser-machining methods where multiple scanning cycles with precise manipulation are needed, the proposed method is more straightforward because only a single laser pulse is used to construct the sensor. The concavity constructed by the CO2 laser is very smooth, and its shape could be controlled flexibly by changing the position of the single mode fiber and the parameters of the CO2 laser pulse, so the fringe visibilities of the proposed sensors could be more than 15 dB, which is higher than that of the most reported laser-machining in-fiber Michelson interferometers. The proposed sensor was demonstrated by measuring the temperature with a sensitivity of 11.13 pm/°C. Furthermore, the proposed device is compact (<100 µm), economical, and robust. These advantages make it a promising candidate in practical applications.
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In order to explore the imaging manifestations and pathological characteristics of spine tumors, this article explores the clinical diagnosis and treatment methods through multi-sample case analysis with the support of imaging, and proposes a targeted treatment method that uses a special PVP needle with a beveled puncture surface for puncture. Moreover, this article uses the supporting PVP syringe for bone cement injection, develops a health status questionnaire, and adopts a scoring method for comprehensive assessment. The purpose of this article is to show that through the combination of preoperative radiotherapy and postoperative bracing, bone cement injection to treat vertebral tumors can immediately obtain satisfactory pain relief. Finally, through case analysis and image performance, we can see that the method proposed in this article has a certain effect.
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OBJECTIVE: EVA1B, a protein coding gene, is a critical paralog of EVA1A gene. Herein, our study was conducted to investigate the role of EVA1B in colorectal cancer (CRC) progression and prognosis. METHODS: Pan-cancer analysis was conducted to analyze expression, genetic and epigenetic alterations, and immunological characteristics of EVA1B. Especially, immunological characteristics and mutational landscape were compared between high and low EVA1B expression groups in the combined TCGA-COAD and TCGA-READ datasets. Through random survival forest analysis, an EVA1B-derived genomic model was developed, and its prognostic value was verified in the external datasets (GSE14333, GSE39582, and GSE87211). Drug sensitivity was compared between high- and low-risk subpopulations. A nomogram was conducted through integrating independent factors. RESULTS: EVA1B expression presented a remarkable upregulation in most cancer types, especially CRC. EVA1B expression was significantly correlated to DNA methyltransferases, DNA mismatch repair genes, m6A regulators, TMB, and MSI across pan-cancer. High EVA1B expression indicated an undesirable CRC patients' prognosis. Additionally, its upregulation was correlated to enhanced immune cell infiltration, increased stromal and immune activation, and elevated activities of cancer immunity cycle. Higher frequencies of amplification and deletion were investigated in high EVA1B expression subpopulation. Following verification, the EVA1B-derived genomic model reliably predicted patients' prognosis and drug responses. The nomogram (age, stage, EVA1B-derived risk score) was conducted to quantify an individual's survival probability. Furthermore, our experimental validation based on immunohistochemistry indicated that EVA1B overexpression is correlated with CRC tumorigenesis and poor outcomes in our CRC patients' cohort. CONCLUSION: Collectively, our findings provided valuable resource for guiding the mechanisms and therapeutic analysis of EVA1B in CRC.
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Neoplasias Colorrectales , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Farmacogenética , Microambiente TumoralRESUMEN
OBJECTIVE: To analyse the saliva microbial abundance and composition by 16s rRNA sequence during Helicobacter pylori (H.pylori) eradication. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Hebei University of Chinese Medicine, Hebei Provincial Hospital of Traditional Chinese Medicine, from March 2019 to January 2020. METHODOLOGY: The saliva microbial were analysed before and after the bismuth-containing quadruple therapy. A total of ten saliva samples (three groups) were enrolled in the study. The authors used the linear discriminant analysis effect size (LEfSe) method and Welch's t-test for comparative analysis to identify which taxa could be significantly affected in three groups. RESULTS: H.pylori 16S rRNA gene sequence was not detected in the ten saliva samples. The abundance of Prevotella_sp._oral_clone_P4PB_83_P2 from healthy adults was higher than H.pylori-positive patients. Moreover, after the bismuth-containing quadruple therapy, the diversity and richness of saliva bacteria reduced. Lautropia, Burkholderiales, uncultured bacterium, Burkholderiaceae, and Actinomyces were enriched in H.pylori-positive patient samples after the bismuth-containing quadruple therapy. CONCLUSION: The diversity and richness of salivary microbiome were reduced in H.pylori-positive patient, and bismuth-containing quadruple therapy affected oral microbiota. Key Words: Helicobacter pylori, Saliva, Microbiota, RNA, Bismuth.
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Infecciones por Helicobacter , Helicobacter pylori , Microbiota , Adulto , Amoxicilina , Antibacterianos/uso terapéutico , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/genética , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , ARN Ribosómico 16S/genéticaRESUMEN
We propose a multidimensional reconciliation encoding algorithm based on a field-programmable gate array (FPGA) with variable data throughput that enables quantum key distribution (QKD) systems to be adapted to different throughput requirements. Using the circulatory structure, data flow in the most complex pipeline operation in the same time interval, which enables the structural multiplexing of the algorithm. We handle the calculation and storage of eight-dimensional matrices cleverly to conserve resources and increase data processing speed. In order to obtain the syndrome more efficiently, we designed a simplified algorithm according to the characteristics of the FPGA and parity-check matrix, which omits the unnecessary operation of matrix multiplication. The simplified algorithm could adapt to different rates. We validated the feasibility and high speed of the algorithm by implementing the multidimensional reconciliation encoding algorithm on a Xilinx Virtex-7 FPGA. Our simulation results show that the maximum throughput could reach 4.88 M symbols/s.
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BACKGROUND: The tumor immune microenvironment of colorectal cancer (CRC) affects tumor development, prognosis and immunotherapy strategies. Recently, immune-related lncRNA were shown to play vital roles in the tumor immune microenvironment. The objective of this study was to identify lncRNAs involved in the immune response, tumorigenesis and progression of CRC and to establish an immune-related lncRNA signature for predicting the prognosis of CRC. METHODS: We used data retrieved from the cancer genome atlas (TCGA) dataset to construct a 10-gene immune-related lncRNA pair (IRLP) signature model using a method based on the ranking and comparison of paired gene expression in CRC. The clinical prognosis, immune checkpoints and lncRNA-protein networks were analyzed to evaluate the signature. RESULTS: The signature was closely associated with overall survival of CRC patients (p < 0.001 in both of the training and validating cohorts) and the 3-year AUC values for the training and validating cohorts were 0.884 and 0.739, respectively. And, there were positive correlations between the signature and age (p = 0.048), clinical stage (p < 0.01), T stage (p < 0.01), N stage (p < 0.001) and M stage (p < 0.01). In addition, the signature model appeared to be highly relevant to some checkpoints, including CD160, TNFSF15, HHLA2, IDO2 and KIR3DL1. Further, molecular functional analysis and lncRNA-protein networks were applied to understand the molecular mechanisms underlying the carcinogenic effect and progression. CONCLUSION: The 10-gene IRLP signature model is an independent prognostic factor for CRC patient and can be utilized for the development of immunotherapy.
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Neoplasias Colorrectales , ARN Largo no Codificante , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunoglobulinas , ARN Largo no Codificante/genética , Microambiente Tumoral , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis TumoralRESUMEN
Intramuscular fat, as one of the most important palatability attribute of beef carcase, is the primary determinant of beef quality. The research of adipogenesis mechanism would provide new insight into intramuscular fatty deposition. Here, the role of microRNA-378 was investigated during bovine adipogenic differentiation. It was revealed that miR-378 expression exists variably in bovine major tissue and organs by RT-qPCR. It was predicted that miR-378 targets CaMKK2, as an AMPKα kinase, by DIANA Tools. For better research, primary preadipocytes with stable transfection for up-/down-regulated expression of miR-378 were constructed by lentiviral vectors with GFP gene. The analyses of qPCR showed that PPARγ and adiponectin mRNA levels increased, but C/EBPß, pref-1 and CaMKK2 mRNA levels decreased during adipogenic differentiation. When miR-378 was overexpressed, preadipocytes proliferation became slower, there are more cellular lipid droplets, and PPARγ and C/EBPß mRNA levels were higher, but pref-1, adiponectin and CaMKK2 were lower than control groups. Luciferase assay and western blot analysis validated that miR-378 binds the nucleotide sites of the 3'- untranslated region of CaMKK2, which inhibits the mRNA and protein expression of CaMKK2. These findings suggest that miR-378 promotes adipogenic differentiation in bovine intramuscular preadipocytes by targeting CaMKK2 via AMPK signalling pathway.
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Adipogénesis , MicroARNs , Adipocitos , Adipogénesis/genética , Animales , Bovinos , Diferenciación Celular , MicroARNs/genética , PPAR gammaRESUMEN
Cartilage is a kind of connective tissue that buffers pressure and is essential to protect joint movement. It is difficult to self-recover once cartilage is damaged due to the lack of blood vessels, lymph, and nerve tissues. Repair of cartilage injury is mainly achieved by stimulating chondrocyte proliferation and extracellular matrix (ECM) synthesis. Cartilage homeostasis involves the regulation of multiple growth factors and the transduction of cellular signals. It is a very complicated process that has not been elucidated in detail. In this review, we summarized a variety of signaling molecules related to chondrocytes function. Especially, we described the correlation between chondrocyte-specific regulatory factors and cell signaling molecules. It has potential significance for guiding the treatment of cartilage injury.
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Matrix nanocomposites are high performance materials possessing unusual features along with unique design possibilities. Due to extraordinary thermophysical characteristic contained by these matrix nanocomposites materials they are useful in several areas ranging from packaging to biomedical applications. Being an environment friendly, utilization of nanocomposites offer new technological opportunities for several sectors of aerospace, automotive, electronics and biotechnology. In this regards, current pagination is devoted to analyze thermal features of viscous fluid flow between orthogonally rotating disks with inclusion of metallic matrix nanocomposite (MMNC) and ceramic matrix nanocomposites (CMNC) materials. Morphological aspects of these nanomaterials on flow and heat transfer characteristics has been investigated on hybrid viscous fluid flow. Mathematical structuring of problem along with empirical relations for nanocomposites materials are formulated in the form of partial differential equations and later on converted into ordinary differential expressions by using suitable variables. Solution of constructed coupled differential system is found by collaboration of Runge-Kutta and shooting methods. Variation in skin friction coefficient at lower and upper walls of disks along with measurement about heat transfer rate are calculated against governing physical parameters. Impact of flow concerning variables on axial, radial components of velocity and temperature distribution are also evaluated. Contour plots are also drawn to explore heat and thermal profiles. Comparison and critical analysis of MMNc and CMNc have been presented at lower and upper porous disks. Our computed analysis indicates that hybrid nanofluids show significant influence as compared to simple nanofluids with the permutation of the different shape factors.
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Entropy optimization in convective viscous fluids flow due to a rotating cone is explored. Heat expression with heat source/sink and dissipation is considered. Irreversibility with binary chemical reaction is also deliberated. Nonlinear system is reduced to ODEs by suitable variables. Newton built in shooting procedure is adopted for numerical solution. Salient features velocity filed, Bejan number, entropy rate, concentration and temperature are deliberated. Numerical outcomes for velocity gradient and mass and heat transfer rates are displayed through tables. Assessments between the current and previous published outcomes are in an excellent agreement. It is noted that velocity and temperature show contrasting behavior for larger variable viscosity parameter. Entropy rate and Bejan number have reverse effect against viscosity variable. For rising values of thermal conductivity variable both Bejan number and entropy optimization have similar effect.