Effects of isotropic stress on the band structure elastic, optical, thermal, and x-ray diffraction properties of TiSnO3.

BACKGROUND: Cubic perovskite titanium stannous oxide (TiSnO3) is a promising material for various applications due to its functional properties. However, understanding how these properties change under external stress is crucial for its development and optimization. METHOD: This study employed density functional theory calculations to investigate the structural, electronic, optical, thermal, and mechanical properties of TiSnO3 under varying degrees of external static isotropic stress (0-120 GPa). RESULTS: The study reveals a significant decrease in the bandgap of TiSnO3 with increasing stress due to lattice modifications and the formation of delocalized electrons. Partial density of states analysis indicates that Sn and O states play a key role in shaping the electronic band structure. TiSnO3 exhibits increased light absorption with stress, accompanied by a blue shift in absorption peaks, whereas, both polarizability and refractive index decrease with increasing stress. Mechanically, all elastic moduli (bulk, shear, and Young's) show an increase under stress, signifying a stiffening response of the material under stress. Similarly, the Pugh ratio suggests a transition from ductile to brittle behaviour at elevated stress levels. Phonon dispersion calculations indicate the instability of the cubic phase at 0 K. However, a phonon gap emerges at 30 GPa and widens with increasing stress. X-ray diffraction further supports these findings by demonstrating a shift in diffraction peaks towards higher angles with increasing stress, consistent with the applied stress. CONCLUSION: In conclusion, this computational study offers a thorough understanding of how external stress influences the properties of TiSnO3, providing valuable insights for potential applications in various fields.

Numerical study of diffusive fish farm system under time noise.

In the current study, the fish farm model perturbed with time white noise is numerically examined. This model contains fish and mussel populations with external food supplied. The main aim of this work is to develop time-efficient numerical schemes for such models that preserve the dynamical properties. The stochastic backward Euler (SBE) and stochastic Implicit finite difference (SIFD) schemes are designed for the computational results. In the mean square sense, both schemes are consistent with the underlying model and schemes are von Neumann stable. The underlying model has various equilibria points and all these points are successfully gained by the SIFD scheme. The SIFD scheme showed positive and convergent behavior for the given values of the parameter. As the underlying model is a population model and its solution can attain minimum value zero, so a solution that can attain value less than zero is not biologically possible. So, the numerical solution obtained by the stochastic backward Euler is negative and divergent solution and it is not a biological phenomenon that is useless in such dynamical systems. The graphical behaviors of the system show that external nutrient supply is the important factor that controls the dynamics of the given model. The three-dimensional results are drawn for the various choices of the parameters.

In Vitro and In Vivo Anti-Inflammatory Activity of a Combination of Extracts from Cinnamomum zeylanicum, Alpinia galanga, and Withania somnifera used in Unani Medicine.

Objectives: Continuous and excessive secretion of pro-inflammatory and anti-inflammatory chemicals and cytokines may further deteriorate inflammation. Anti-inflammatory drugs play an imperative role in inhibiting the evolution of inflammatory diseases. As per the Unani doctrine, a holistic treatment approach is used to treat illnesses. Therefore, drugs having different actions are used to achieve the synergic effect. Three drugs (Cinnamomum zeylanicum, Alpinia galanga, and Withania somnifera), which are frequently used in Unani medicine for joint disorders were selected to evaluate the anti-inflammatory activity of the extract derived from them. Methods: We used RAW 264.7 macrophage cells to see the expression of inflammatory markers IL-1ß, IL-6, and TNF-α. Cytotoxic activity was assessed with MTT assay and Nitric Oxide (NO) was evaluated using Griess reagent. Further, anti-inflammatory activity was evaluated in Wistar Albino rats using carrageenan-induced paw oedema and immunohistochemistry assays for Cyclooxygenase-2 (COX-2). All the data were analyzed using ANOVA and Dunnett t test for multiple comparisons. Results: This extract did not show any cytotoxic effect and the gene expression was significantly reduced for IL-1ß, IL-6, and TNF-α in a dose-dependent manner. Further, NO production was also significantly reduced in the test groups. Immunohistochemistry revealed that the test groups had less inflammation as compared to the control group. Conclusion: It may be inferred that the ethanolic extract of the three herbs has strong anti-inflammatory activity in the tested inflammatory models and the extract is safe as it did not show any cytotoxic effects in both in vitro and in vivo conditions.

Investigation of ultra wide bandgap Flouro-perovskite materials RBeF3 (R[bond, double bond]K and Li) for smart window applications: A DFT study.

The human body is affected by ultraviolet radiation because it can penetrate and harm bodily cells. Although skin cancer and early aging are consequences of prolonged exposure to ultraviolet (UV) rays, sun rays signify immediate excessive exposure. In this context, some structural, optical, electrical, and mechanical properties of the beryllium-based cubic fluoro-perovskite RBeF3 (R[bond, double bond]K and Li) compounds are examined through the use of density functional theory (DFT) within generalized gradient approximation (GGA) using the Perdew-Burke-Ernzerhof (PBE) approximations (GGA-PBE). The compounds KBeF3 and LiBeF3 have space group 221-pm3m, and their lattice constants and volumes are (3.765, 3.566) Å and (53.380, 45.379) Å3, respectively, based on their structural properties. Computed results indicate that the compounds' bandgaps are 7.35 eV and 7.12 eV, respectively, with an indirect nature for KBeF3 and LiBeF3. The properties of the band structure indicate that both compounds are insulators. The bonding properties of these compounds, RBeF3, are a combination of covalent and ionic. Optical properties of the compounds are examined which reflect the light-matter interaction like reflectivity, conductivity, and absorption. These materials were likely very hard but brittle, based on a higher bulk modulus B from elastic features, the B/G ratio, Pugh's ratio, and Vickers hardness. The compound RBeF3, as determined by the findings, is used as a UV protection and reflection layer for car and room windows.

D-Pinitol improves cognitive dysfunction and neuronal damage induced by isoproterenol via modulation of NF-κB/BDNF/GFAP signaling in Swiss albino mice.

Objectives: Neurological disorders are the world's most distressing problem. The adverse effects of current medications continue to compel scientists to seek safer, more effective, and economically affordable alternatives. In this vein, we explored the effect of D-Pinitol on isoproterenol-induced neurotoxicity in mice. Materials and Methods: Forty-two mice were randomly distributed into 7 groups each having 6 animals. Group I; received saline. Group II; received isoproterenol (ISO) 15 mg/kg/day, s.c. for 20 days. Group III, IV; received 50 and 100 mg/kg/day/oral of D-Pinitol, respectively along with ISO for 20 days. Group V; received D-Pinitol 100 mg/kg/day/oral for 20 days. Group VI; received propranolol 20 mg/kg/day/oral and ISO for 20 days. Group VII; received propranolol 20 mg/kg/day/oral for 20 days. On the 21st day after behavioral tests, blood was collected and mice were sacrificed for various biochemical, histopathological, and immunohistochemical analyses. Results: Chronic administration of isoproterenol caused neurotoxicity, cognitive dysfunction, and histopathological changes in the brain as evidenced by increase in GFAP, oxidative stress (via SOD, CAT, TBARS, and GSH), neuroinflammation (NF-kB, TNF-α, IL-6, and IL-10), and decrease in AchE and BDNF. Co-administration of D-Pinitol (100 mg/kg) significantly prevented these pathological alterations. The cognitive improvement was also observed through the forced swim test, elevated plus maze test, and rotarod test. Conclusion: Our findings on D-Pinitol thus clearly established its neuroprotective role in ISO-induced neurodegeneration in Swiss albino mice.

Exploring Oral Cavity Cancer in the United Arab Emirates (UAE).

Background This study delves into the demographics and clinical characteristics of oral cavity tumors in the context of the United Arab Emirates. It further investigates the efficacy of four different treatment modalities in impacting patient survival rates. It aims to understand if any treatments significantly improve survival compared to others. Methodology To assess the survival outcomes across the different treatment groups, the study employed the log-rank test, a non-parametric statistical test widely used in survival analysis. The sample consisted of patients from the electronic medical records assigned to one of the following four treatment groups: radiotherapy only (RT), radiotherapy with surgery and chemotherapy (RT+S+C), radiotherapy with surgery (RT+S), and, finally, radiotherapy with chemotherapy including immunotherapy (RT+C). Data collection involved tracking survival times from the initiation of treatment until the last follow-up period or the occurrence of an event (e.g., death). The statistical analysis was conducted using the chi-squared statistic to determine the distribution of survival times across the groups, providing a quantitative measure of the difference between the observed and expected survival. The Kaplan-Meier curve was plotted for the cohort divided into four groups. Results The log-rank test yielded a p-value of 0.321019, suggesting no statistically significant difference in survival among the treatment groups at the 5% significance level. The chi-squared statistic was 3.498018, within the 95% acceptance region, further corroborating the null hypothesis of no significant survival difference across the groups. Despite this, an observed medium effect size of 0.59 indicates a moderate difference in survival between the groups. Conclusions The findings illustrate that while there is no statistically significant difference in survival rates among the four treatment groups, the medium effect size observed suggests a moderate difference in survival. This emphasizes the need to consider the statistical significance and effect size in clinical research, as they provide different insights into treatment efficacy.

Understanding the Radiation Dose Variability in Nasopharyngeal Cancer: An Organs-at-Risk Approach.

Objective This study aims to thoroughly assess the radiation dose distribution to critical organs in patients with nasopharyngeal carcinoma, focusing on the correlation between the radiation dosages for the various organs at risk (OARs) in nasopharyngeal cancer patients. Methods We meticulously analysed a dataset comprising 38 nasopharyngeal carcinoma patients, focusing on radiation dosages measured in Gray (Gy) and volumetric data in cubic centimetres (cc) of critical organs, including the lens, brainstem, spinal cord, optic nerve, optic chiasm, and cochlea. A detailed exploratory data analysis approach encompassed univariate, bivariate, and multivariate techniques. Results Our analysis revealed several key findings. The mean and median values across various dose measurements were closely aligned, indicating symmetrical distributions with minimal skewness. The histograms further corroborated this, showing evenly distributed dose values across different anatomical regions. The correlation matrix highlighted varying degrees of interrelationships between the doses, with some showing strong correlations while others exhibited minimal or no correlation. The 3D scatter plot provided a view of the multi-dimensional dose relationships, with a specific focus on the spinal cord, lens, and brainstem doses. The bivariate scatter plots revealed symmetrical distributions between the right and left lens doses and more complex relationships involving the brainstem and spinal cord, illustrating the intricacies of dose distribution in radiation therapy. Conclusion Our findings reveal distinct radiation exposure patterns to OARs of nasopharyngeal carcinoma. This research emphasises the need for tailored radiation therapy planning to achieve optimal clinical outcomes while safeguarding vital organs.

Integrating Artificial Intelligence Into Radiation Oncology: Can Humans Spot AI?

Introduction Artificial intelligence (AI) is transforming healthcare, particularly in radiation oncology. AI-based contouring tools like Limbus are designed to delineate Organs at Risk (OAR) and Target Volumes quickly. This study evaluates the accuracy and efficiency of AI contouring compared to human radiation oncologists and the ability of professionals to differentiate between AI-generated and human-generated contours. Methods At a recent AI conference in Abu Dhabi, a blind comparative analysis was performed to assess AI's performance in radiation oncology. Participants included four human radiation oncologists and the Limbus® AI software. They contoured specific regions from CT scans of a breast cancer patient. The audience, consisting of healthcare professionals and AI experts, was challenged to identify the AI-generated contours. The exercise was repeated twice to observe any learning effects. Time taken for contouring and audience identification accuracy were recorded. Results Initially, only 28% of the audience correctly identified the AI contours, which slightly increased to 31% in the second attempt. This indicated a difficulty in distinguishing between AI and human expertise. The AI completed contouring in up to 60 seconds, significantly faster than the human average of 8 minutes. Discussion The results indicate that AI can perform radiation contouring comparably to human oncologists but much faster. The challenge faced by professionals in identifying AI versus human contours highlights AI's advanced capabilities in medical tasks. Conclusion AI shows promise in enhancing radiation oncology workflow by reducing contouring time without quality compromise. Further research is needed to confirm AI contouring's clinical efficacy and its integration into routine practice.

Analytical study of reaction diffusion Lengyel-Epstein system by generalized Riccati equation mapping method.

In this study, the Lengyel-Epstein system is under investigation analytically. This is the reaction-diffusion system leading to the concentration of the inhibitor chlorite and the activator iodide, respectively. These concentrations of the inhibitor chlorite and the activator iodide are shown in the form of wave solutions. This is a reaction†"diffusion model which considered for the first time analytically to explore the different abundant families of solitary wave structures. These exact solitary wave solutions are obtained by applying the generalized Riccati equation mapping method. The single and combined wave solutions are observed in shock, complex solitary-shock, shock singular, and periodic-singular forms. The rational solutions also emerged during the derivation. In the Lengyel-Epstein system, solitary waves can propagate at various rates. The harmony of the system's diffusive and reactive effects frequently governs the speed of a single wave. Solitary waves can move at a variety of speeds depending on the factors and reaction kinetics. To show their physical behavior, the 3D and their corresponding contour plots are drawn for the different values of constants.

Endometrial Carcinoma: A Comprehensive Analysis of Clinical Parameters, Treatment Modalities, and Prognostic Outcomes at a Tertiary Oncology Center in the UAE.

Background Endometrial carcinoma (EC) remains a pressing global health issue, with a discernible upsurge in incidence, especially in developed countries. Notably, the United Arab Emirates (UAE) has witnessed a surge in EC cases, demanding an in-depth, region-specific exploration into the disease's clinical, treatment, and prognostic facets against the backdrop of its unique socio-genetic and environmental contours. Aim This study aimed to profess a comprehensive understanding of EC by examining clinical parameters, treatment modalities, and prognostic outcomes in the UAE context, thereby seeking to delineate potential correlations between varied therapeutic combinations, patient demographics, and tumor characteristics in affecting prognostic outcomes. Materials and methods A retrospective cohort study involving 93 patients diagnosed with EC from January 2011 to March 2023 at a leading oncology center in the UAE was conducted. Data, including demographic information, clinical presentation, treatment modalities, and prognostic outcomes, were meticulously extracted and analyzed. The R software (version 4.2.2) facilitated exhaustive statistical analyses, involving descriptive statistics, correlation analyses with the polycor package, and survival analyses utilizing the Kaplan-Meier method and Cox regression analysis via the survival and survminer packages, respectively. Results Although the correlation matrix revealed a noticeable relationship between "Family history" and "Age," most parameters displayed independence, offering a robust platform for ensuing multivariate analyses. Kaplan-Meier survival curves, stratified by therapeutic modalities, exhibited no statistically significant survival differences across therapeutic cohorts (p-values: 0.44, 0.86, and 0.83). Conversely, the composite Cox regression model underscored "non-national" demographic, Diabetes Mellitus II, and stromal invasion as pivotal prognostic factors, indicating the multifactorial nature of survival in EC patients and emphasizing demographic and tumor characteristics over therapeutic modalities as influential prognostic determinants. Conclusion In conclusion, while therapy types were not directly correlated with survival, demographic and tumor traits prominently impacted prognostic outcomes, advocating for an intricate, multidimensional approach to managing EC in the UAE. This study hopes to sow seeds for subsequent research, shaping clinically and culturally apt practices and policies in the region's healthcare landscape.

Exploring the role of miR-200 family in regulating CX3CR1 and CXCR1 in lung adenocarcinoma tumor microenvironment: implications for therapeutic intervention.

Lung adenocarcinoma (LUAD) is the most common malignant subtype of lung cancer (LC). miR-200 family is one of the prime miR regulators of epithelial-mesenchymal transition (EMT) and worst overall survival (OS) in LC patients. The study aimed to identify and validate the key differentially expressed immune-related genes (DEIRGs) regulated by miR-200 family which may serve for therapeutic aspects in LUAD tumor microenvironment (TME) by affecting cancer progression, invasion, and metastasis. The study identified differentially expressed miRNAs (DEMs) in LUAD, consisting of hsa-miR-200a-3p and hsa-miR-141-5p, respectively. Two highest-degree subnetwork motifs identified from 3-node miRNA FFL were: (i) miR-200a-3p-CX3CR1-SPIB and (ii) miR-141-5p-CXCR1-TBX21. TIMER analysis showed that the expression levels of CX3CR1 and CXCR1 were significantly positively correlated with infiltrating levels of M0-M2 macrophages and natural killer T (NKT) cells. The OS of LUAD patients was significantly affected by lower expression levels of hsa-miR-200a-3p, CX3CR1 and SPIB. These DEIRGs were validated using the human protein atlas (HPA) web server. Further, we validated the regulatory role of hsa-miR-200a-3p in an in-vitro indirect co-culture model using conditioned media from M0, M1 and M2 polarized macrophages (THP-1) and LUAD cell lines (A549 and H1299 cells). The results pointed out the essential role of hsa-miR-200a-3p regulated CX3CL1 and CX3CR1 expression in progression of LC TME. Thus, the study augments a comprehensive understanding and new strategies for LUAD treatment where miR-200 family regulated immune-related genes, especially chemokine receptors, which regulate the metastasis and invasion of LUAD, leading to the worst associated OS.

Integrative multiomics and weighted network approach reveals the prognostic role of RPS7 in lung squamous cell carcinoma pathogenesis.

Lung cancer is one of the most commonly occurring malignant cancers with the highest rate of mortality globally. Difference between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) and their treatment strategies according to genetic markers may be helpful in reducing the cancer progression and increasing the overall survival (OS) in patients. LUSC is known for comparatively less typical onco-drivers, target therapy resistance, marked genomic complexity, and a reasonably higher mutation rate. The mRNA-seq data and clinical information of LUAD and LUSC cohorts from UCSC Xena comprising 437 and 379 patient samples were extracted. Differential expression and weighted network analyses revealed 47 and 18 hub differentially expressed genes (DEGs) corresponding to LUAD and LUSC cohorts. These hub DEGs were further subjected to protein-protein interaction network (PPIN) and OS analyses. Lower mRNA expression levels of both RPS15A and RPS7 worsened the OS of LUSC patients. Additionally, both these prognostic biomarkers were validated via external sources such as UALCAN, cBioPortal, TIMER, and HPA. RPS7 had higher mutation frequency compared to RPS15A and showed significant negative correlations with infiltrating levels of CD4+ T cells, CD8+ T cells, neutrophils, and macrophages. Our findings provided novel insights into biomarker discovery and the critical role of ribosomal biogenesis especially smaller ribosomal subunit in pathogenesis of LUSC.

Oral delivery of nerolidol alleviates cyclophosphamide-induced renal inflammation, apoptosis, and fibrosis via modulation of NF-κB/cleaved caspase-3/TGF-ß signaling molecules.

Cyclophosphamide (CP) is one of the most extensively used antineoplastic drug, but the nephrotoxicity caused by this drug is a major limiting factor for its use. Nerolidol (NERO) is a natural bioactive compound with diverse pharmacological actions. In Vitro and in vivo study was performed using HK-2 renal cells and Swiss Albino mice. Cell lines and animals were treated with NERO 25 and 50 µM + 30 µM CP (in vitro), 200 and 400 mg/kg, p.o. NERO from day 1 to day 15 + 200 mg/kg, i.p. CP on day 17 as single intraperitoneal injection (in vivo). The makers of oxidative stress, renal-specific injury markers, inflammation, apoptosis, fibrosis, and histopathological changes were studied. The study's outcome showed a significant reduction in the level of malonaldehyde and interleukin-6 (p < 0.01), tumor necrosis factor-α, IL-1ß (p < 0.001), and an increase in the superoxide dismutase, catalase, glutathione and interleukin-10 level (p < 0.01), in the in vivo study when treated with NERO 400 and compared with CP 200. In Vitro study showed reduced expression of nuclear factor kappa light chain enhancer of activated B cells, cleaved caspase-3, kidney injury molecule-1 and transforming growth factor-ß-1 (p < 0.001), when treated with NERO 50 µM whereas NERO 25 µM only reduced the level of cleaved caspase-3 (p < 0.05) when compared with 30 µM. NERO 400 also reduced uric acid (p < 0.05), urea (p < 0.01), blood urea nitrogen, and serum creatinine levels (p < 0.001) and increased the level of blood-urea-nitrogen/creatinine ratio (p < 0.001). Additionally, the level of fibrosis-specific markers such as transforming growth factor-ß1, hyaluronic acid (p < 0.01), 4-hydroxyproline, a collagen-rich area in Masson's' trichome stain, and Smad3 expression was also significantly reduced (p < 0.001). Furthermore, the outcome of multiple renal staining showed structural reversal aberrations, reduction of the thick basement membrane, and glycogen level toward normal when treated with NERO 400. Thus, the study showed a novel mechanistic modality of NERO against cyclophosphamide-induced renal toxicity. The outcome of this study can be considered a step closer to the development of an adjuvant to mitigate cyclophosphamide-induced renal toxicity among patients treated with cyclophosphamide.

Speech Emotion Recognition Using Convolution Neural Networks and Multi-Head Convolutional Transformer.

Speech emotion recognition (SER) is a challenging task in human-computer interaction (HCI) systems. One of the key challenges in speech emotion recognition is to extract the emotional features effectively from a speech utterance. Despite the promising results of recent studies, they generally do not leverage advanced fusion algorithms for the generation of effective representations of emotional features in speech utterances. To address this problem, we describe the fusion of spatial and temporal feature representations of speech emotion by parallelizing convolutional neural networks (CNNs) and a Transformer encoder for SER. We stack two parallel CNNs for spatial feature representation in parallel to a Transformer encoder for temporal feature representation, thereby simultaneously expanding the filter depth and reducing the feature map with an expressive hierarchical feature representation at a lower computational cost. We use the RAVDESS dataset to recognize eight different speech emotions. We augment and intensify the variations in the dataset to minimize model overfitting. Additive White Gaussian Noise (AWGN) is used to augment the RAVDESS dataset. With the spatial and sequential feature representations of CNNs and the Transformer, the SER model achieves 82.31% accuracy for eight emotions on a hold-out dataset. In addition, the SER system is evaluated with the IEMOCAP dataset and achieves 79.42% recognition accuracy for five emotions. Experimental results on the RAVDESS and IEMOCAP datasets show the success of the presented SER system and demonstrate an absolute performance improvement over the state-of-the-art (SOTA) models.

Comprehensive multiomics and in silico approach uncovers prognostic, immunological, and therapeutic roles of ANLN in lung adenocarcinoma.

The anillin actin-binding protein (ANLN) is immensely overexpressed in cancers, including lung cancer (LC). Phytocompounds have gained interest due to their broader potential and reduced unwanted effects. Screening numerous compounds presents a challenge, but in silico molecular docking is pragmatic. The present study aims to identify the role of ANLN in lung adenocarcinoma (LUAD), along with identification and interaction analysis of anticancer and ANLN inhibitory phytocompounds followed by molecular dynamics (MD) simulation. Using a systematic approach, we found that ANLN is significantly overexpressed in LUAD and mutated with a frequency of 3.73%. It is linked with advanced stages, clinicopathological parameters, worsening of relapse-free survival (RFS), and overall survival (OS), pinpointing its oncogenic and prognostic potential. High-throughput screening and molecular docking of phytocompounds revealed that kaempferol (flavonoid aglycone) interacts strongly with the active site of ANLN protein via hydrogen bonds, Vander Waals interactions, and acts as a potent inhibitor. Furthermore, we discovered that ANLN expression was found to be significantly higher (p) in LC cells compared to normal cells. This is a propitious and first study to demonstrate ANLN and kaempferol interactions, which might eventually lead to removal of rout from cell cycle regulation posed by ANLN overexpression and allow it to resume normal processes of proliferation. Overall, this approach suggested a plausible biomarker role of ANLN and the combination of molecular docking subsequently led to the identification of contemporary phytocompounds, bearing symbolic anticancer effects. The findings would be advantageous for pharmaceutics but require validation using in vitro and in vivo methods. HIGHLIGHTS: • ANLN is significantly overexpressed in LUAD. • ANLN is implicated in the infiltration of TAMs and altering plasticity of TME. • Kaempferol (potential ANLN inhibitor) shows important interactions with ANLN which could remove the alterations in cell cycle regulation, imposed by ANLN overexpression eventually leading to normal process of cell proliferation.

Investigating the link between miR-34a-5p and TLR6 signaling in sepsis-induced ARDS.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are lung complications diagnosed by impaired gaseous exchanges leading to mortality. From the diverse etiologies, sepsis is a prominent contributor to ALI/ARDS. In the present study, we retrieved sepsis-induced ARDS mRNA expression profile and identified 883 differentially expressed genes (DEGs). Next, we established an ARDS-specific weighted gene co-expression network (WGCN) and picked the blue module as our hub module based on highly correlated network properties. Later we subjected all hub module DEGs to form an ARDS-specific 3-node feed-forward loop (FFL) whose highest-order subnetwork motif revealed one TF (STAT6), one miRNA (miR-34a-5p), and one mRNA (TLR6). Thereafter, we screened a natural product library and identified three lead molecules that showed promising binding affinity against TLR6. We then performed molecular dynamics simulations to evaluate the stability and binding free energy of the TLR6-lead molecule complexes. Our results suggest these lead molecules may be potential therapeutic candidates for treating sepsis-induced ALI/ARDS. In-silico studies on clinical datasets for sepsis-induced ARDS indicate a possible positive interaction between miR-34a and TLR6 and an antagonizing effect on STAT6 to promote inflammation. Also, the translational study on septic mice lungs by IHC staining reveals a hike in the expression of TLR6. We report here that miR-34a actively augments the effect of sepsis on lung epithelial cell apoptosis. This study suggests that miR-34a promotes TLR6 to heighten inflammation in sepsis-induced ALI/ARDS. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03700-1.

Design, synthesis, and biological evaluation of morpholinopyrimidine derivatives as anti-inflammatory agents.

Here, we outline the synthesis of a few 2-methoxy-6-((4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)(phenyl)methyl)phenol derivatives and assess their anti-inflammatory activity in macrophage cells that have been stimulated by LPS. Among these newly synthesized morpholinopyrimidine derivatives, 2-methoxy-6-((4-methoxyphenyl)(4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)methyl)phenol (V4) and 2-((4-fluorophenyl)(4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)methyl)-6-methoxyphenol (V8) are two of the most active compounds which can inhibit the production of NO at non-cytotoxic concentrations. Our findings also showed that compounds V4 and V8 dramatically reduced iNOS and cyclooxygenase mRNA expression (COX-2) in LPS-stimulated RAW 264.7 macrophage cells; western blot analysis showed that the test compounds decreased the amount of iNOS and COX-2 protein expression, hence inhibiting the inflammatory response. We find through molecular docking studies that the chemicals had a strong affinity for the iNOS and COX-2 active sites and formed hydrophobic interactions with them. Therefore, use of these compounds could be suggested as a novel therapeutic strategy for inflammation-associated disorders.

Design of a Planar Sensor Based on Split-Ring Resonators for Non-Invasive Permittivity Measurement.

The permittivity of a material is an important parameter to characterize the degree of polarization of a material and identify components and impurities. This paper presents a non-invasive measurement technique to characterize materials in terms of their permittivity based on a modified metamaterial unit-cell sensor. The sensor consists of a complementary split-ring resonator (C-SRR), but its fringe electric field is contained with a conductive shield to intensify the normal component of the electric field. It is shown that by tightly electromagnetically coupling opposite sides of the unit-cell sensor to the input/output microstrip feedlines, two distinct resonant modes are excited. Perturbation of the fundamental mode is exploited here for determining the permittivity of materials. The sensitivity of the modified metamaterial unit-cell sensor is enhanced four-fold by using it to construct a tri-composite split-ring resonator (TC-SRR). The measured results confirm that the proposed technique provides an accurate and inexpensive solution to determine the permittivity of materials.

Integrative Genomic Analysis of m6a-SNPs Identifies Potential Functional Variants Associated with Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that affects 35 million people worldwide. However, no potential therapeutics currently are available for AD because of the multiple factors involved in it, such as regulatory factors with their candidate genes, factors associated with the expression levels of its corresponding genes, and many others. To date, 29 novel loci from GWAS have been reported for AD by the Psychiatric Genomics Consortium (PGC2). Nevertheless, the main challenge of the post-GWAS era, namely to detect significant variants of the target disease, has not been conducted for AD. N6-methyladenosine (m6a) is reported as the most prevalent mRNA modification that exists in eukaryotes and that influences mRNA nuclear export, translation, splicing, and the stability of mRNA. Furthermore, studies have also reported m6a's association with neurogenesis and brain development. We carried out an integrative genomic analysis of AD variants from GWAS and m6a-SNPs from m6AVAR to identify the effects of m6a-SNPs on AD and identified the significant variants using the statistically significance value (p-value <0.05). The cis-regularity variants with their corresponding genes and their influence on gene expression in the gene expression profiles of AD patients were determined, and showed 1458 potential m6a-SNPs (based on p-value <0.05) associated with AD. eQTL analysis showed that 258 m6a-SNPs had cis-eQTL signals that overlapped with six significant differentially expressed genes based on p-value <0.05 in two datasets of AD gene expression profiles. A follow-up study to elucidate the impact of our identified m6a-SNPs in the experimental study would validate our findings for AD, which would contribute to the etiology of AD.