A novel approach for the modification of eggshell powder and its application for lead and methylene blue removal.

Water pollution is one of the major concerns due to rapid industrialization and urbanization. Wastewater treatment has been an area of great interest for the researchers and among many technologies developed for water treatment, adsorption is the most preferred due to its efficiency and ability of been economical method. In this research, eggshell powder (ESP) is converted into modified eggshell powder (MESP) through chemical and thermal treatment (at 550 °C for 2 h) to use it as an adsorbent to remediate Pb2+ and Methylene blue (MB) from water, then it is transferred into modified eggshell powder magnetic composite (MESPMC) with iron coating to resolve the separation challenges and to boost the MESP's adsorption efficiency. FTIR analysis identified the functional groups of ESP, MESP, and MESPMC. XRD analysis reveals a hexagonal crystal structure of calcite in MESP and a combination of the hexagonal crystal structure of calcite and the cubic crystal structure of iron in MESPMC. The Scherrer equation is used to determine the average crystallite sizes of MESP and MESPMC, which are 22.59 nm and 12.15 nm, respectively. The SEM image shows the irregular shape of the MESP and MESPMC particles, as well as the active coating layer in MESPMC. EDX analysis reveals that Ca (20.92 %), O (56.83 %), and Fe (41.03 %), O (48.83 %) are the most abundant elements in MESP and MESPMC respectively. TGA analysis points out that MESPMC outperforms MESP in terms of thermal stability between 600 and 750 °C. MESP and MESPMC were found to be very efficient adsorbent for lead and methylene blue in aqueous medium. At 40 mg/mL adsorbent dosage, ESP, MESP, and MESPMC had the highest yields of Pb2+ removal, with 46.996 %, 99.27 %, and 99.78 % respectively at 200 rpm for 60 min with 25 °C. Furthermore, at the 0.5 mg/mL adsorbent dosage, ESP, MESP, and MESPMC have the maximum removal efficiency of methylene blue, with 47.19 %, 90.1 %, and 92 %, respectively at 200 rpm for 30 min with 25 °C. In both cases, the removal efficiency of MESPMC is slightly higher than that of MESP and much higher than that of ESP. Additionally, the results confirm that MESP and MESPMC are potential environment-friendly bio sources to remediate heavy metal (Pb2+) and methylene blue dye from water.

Monoterpenoid synergy: a new frontier in biological applications.

Monoterpenoids, compounds found in various organisms, have diverse applications in various industries. Their effectiveness is influenced by the oil's chemical composition, which in turn is influenced by plant genotype, environmental conditions, cultivation practices, and plant development stage. They are used in various industries due to their distinctive odor and taste, serving as ingredients, additives, insecticides, and repellents. These compounds have synergistic properties, resulting in superior combined effects over discrete ones, potentially beneficial for various health purposes. Many experimental studies have investigated their interactions with other ingredients and their antibacterial, insecticidal, antifungal, anticancer, anti-inflammatory, and antioxidant properties. This review discusses potential synergistic interactions between monoterpenoids and other compounds, their sources, and biological functions. It also emphasizes the urgent need for more research on their bioavailability and toxicity, underlining the importance and relevance of this comprehensive study in the current scientific landscape.

Enriching Wheat Bread With Banana Peel Powder: Impact on Nutritional Attributes, Bioactive Compounds, and Antioxidant Activity.

This research investigated the impact of enriching bread with banana peel powder (BPP) on nutritional attributes, bioactive components, antioxidant activity, and sensory characteristics. Four bread samples were prepared and evaluated: S1 (control), S2 (5% BPP), S3 (7% BPP), and S4 (10% BPP). The addition of BPP resulted in a reduction in moisture content and an increase in ash, fat, protein, and fibre levels, while reducing overall carbohydrate content. Furthermore, BPP-enriched bread exhibited an increase in total phenolic content (TPC) (ranging from 28.46 to 42.38 mg GAE/100 g) and total flavonoid content (TFC) (ranging from 6.63 to 9.46 QE mg/g), indicating enhanced antioxidant properties. The DPPH assay demonstrated the antioxidant potential of BPP-incorporated bread, with the radical scavenging activity (RSA) increasing from 18.84% to 53.03% with increasing BPP enrichment. Color assessment revealed changes in both crust and crumb, with a decrease from 78.46 to 40.53 in the lightness (L∗) value of the crust and from 61.21 to 41.10 in the lightness (L∗) value of the crumb. Additionally, changes in a∗ and b∗ values were observed. The a∗ values varied between 17.59 and 12.42 for the crust and between 6.96 and 5.89 for the crumb. The b∗ values varied between 31.61 and 23.65 for the crust and between 19.63 and 16.58 for the crumb. Sensory evaluation suggested that up to 5% BPP inclusion in bread mirrored the texture, taste, appearance, and overall acceptability of control bread, but enrichment beyond 5% resulted in lower sensory scores. In summary, the incorporation of BPP significantly influenced various aspects of bread, highlighting its potential for applications in the food and industry sectors.

Soliton structures of fractional coupled Drinfel'd-Sokolov-Wilson equation arising in water wave mechanics.

This article delves into the dynamic constructions of distinctive traveling wave solutions for wave circulation in shallow water mechanics, specifically addressing the time-fractional couple Drinfel'd-Sokolov-Wilson (DSW) equation. Introducing the previously untapped e x p ( - ϕ ( ξ ) ) -expansion method, we successfully generate a diverse set of analytic solutions expressed in hyperbolic, trigonometric, and rational functions, each with permitted parameters. Visualization through three-dimensional (3D) as well two-dimensional (2D) plots, including contour plots, reveals inherent wave phenomena in the DSW equation. These newly obtained wave solutions serve as a catalyst for refining theories in applied science, offering a means to validate mathematical simulations for the proliferation of waves in shallow water as well as other nonlinear scenarios. Obtained wave solutions demonstrate the bright soliton, periodic, multiple soliton, and kink soliton shape. The simplicity and efficacy of the implemented methods are demonstrated, providing a valuable tool for approximating the considered equation. All figures are devoted to demonstrate the complete wave futures of the attained solutions to the studied equation with the collaboration of specific selections of the chosen parameters. Moreover, it may have summarized that the attained wave solutions and their physical phenomena might be useful to comprehend the various kind of wave propagation in mathematical physics and engineering.

Alkaloid-based modulators of the PI3K/Akt/mTOR pathway for cancer therapy: Understandings from pharmacological point of view.

This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.

From farm to function: Exploring new possibilities with jute nanocellulose applications.

Recent scientific interest has surged in the application of bioresources within nanotechnology, primarily because of their eco-friendly nature, wide availability, and cost-effectiveness. Jute is globally recognized as the second most prevalent source of natural cellulose fibers, and it produces a significant quantity of jute sticks as a byproduct. Nanocellulose (NC), which includes cellulose nanofibrils (CNF) and cellulose nanocrystals (CNC), exhibits exceptional properties such as high strength, toughness, crystallinity, thermal stability, and stiffness. These attributes enable its versatile use across various sectors. The extensive surface areas and abundant hydroxyl groups of nanocellulose allow for diverse surface modifications, facilitating the design of advanced functional materials. This comprehensive review provides an overview of recent advancements in the synthesis, characterization, and potential applications of nanocellulose derived from jute. As a versatile natural fiber, jute holds immense potential across various research domains, including nanocellulose synthesis, scaffold fabrication, nanocarbon material preparation, life sciences, electronics and energy storage devices, drug delivery systems, nanomaterial synthesis, food packaging and paper industries. Additionally, its use extends to polymeric nanocomposites, sensors, and coatings. This study summarizes the extensive utilization of jute, emphasizing its versatility and potential across diverse research fields.

On simulations of 3D fractional WBBM model through mathematical and graphical analysis with the assists of fractionality and unrestricted parameters.

This study retrieves some novel exact solutions to the family of 3D space-time fractional Wazwaz-Benjamin-Bona-Mahony (WBBM) equations in the context of diverse nonlinear physical phenomena resulting from water wave mechanics. The family of WBBM equations is transformed for this purpose using a space and time fractional transformation into an ordinary differential equation (ODE). The ODE then uses a strong method, namely the Unified Method. Consequently, lump solutions, dark-bright soliton, singular and multiple soliton solutions, and periodic solutions are investigated. The disparities between the current study's conclusions and previously acquired solutions via other approaches are examined. All wave solutions produced are determined to be novel in terms of fractionality, unrestricted parameters, and implemented technique sense. The impact of unrestricted parameters and fractionality on the obtained solutions are visually presented, along with physical explanations. It is observed that the wave portents are varied with the increase of unrestricted parameters as well as fractionality. We dynamically showed that the appropriate transformation and the applied Unified approach more proficient in the study of water wave dynamics and might be used in future researches to clarify the many physical phenomena. The novelty of this work validate that the proposed method seem simple and useful tools for obtaining the solutions in PDEs and it is expected to use in mathematical physics and optical engineering.

Effects of SPI1-mediated transcriptome remodeling on Alzheimer's disease-related phenotypes in mouse models of Aß amyloidosis.

SPI1 was recently reported as a genetic risk factor for Alzheimer's disease (AD) in large-scale genome-wide association studies. However, it is unknown whether SPI1 should be downregulated or increased to have therapeutic benefits. To investigate the effect of modulating SPI1 levels on AD pathogenesis, we performed extensive biochemical, histological, and transcriptomic analyses using both Spi1-knockdown and Spi1-overexpression mouse models. Here, we show that the knockdown of Spi1 expression significantly exacerbates insoluble amyloid-ß (Aß) levels, amyloid plaque deposition, and gliosis. Conversely, overexpression of Spi1 significantly ameliorates these phenotypes and dystrophic neurites. Further mechanistic studies using targeted and single-cell transcriptomics approaches demonstrate that altered Spi1 expression modulates several pathways, such as immune response pathways and complement system. Our data suggest that transcriptional reprogramming by targeting transcription factors, like Spi1, might hold promise as a therapeutic strategy. This approach could potentially expand the current landscape of druggable targets for AD.

Morphostructural studies of pure and mixed metal oxide nanoparticles of Cu with Ni and Zn.

Nano-scale interactions between pure metal or metal-oxide components within an oxide matrix can improve functional performance over basic metal oxides. This study reports on the synthesis of monometallic (CuO), bimetallic (CuO-NiO) and trimetallic (CuO-NiO-ZnO) oxide nanoparticles (NPs) via the co-precipitation method and investigation of morphostructural properties. All of the synthesized metal oxide NPs were calcined at 550 °C temperature and annealed under vacuum. In this work, we applied Scherrer formula, modified Scherrer equation, Williamson-Hall plots, and Halder-Wagner plots to calculate the average crystallite size. The XRD data analysis showed that average crystallite sizes of the as-synthesized metal oxide phases were between 4 nm and 76 nm and average diameters calculated from SEM image were between 15 nm and 83 nm. The XRD studies also disclosed that average crystallite size and lattice microstrain of the CuO phases remain almost same (43 nm-46 nm and 2.074×10-3 to 2.665×10-3) for pure CuO and mixed CuO-NiO; but in case of mixed CuO-NiO-ZnO it is found to decrease in size to 11 nm where lattice microstrain increases to 9.653×10-3. Line broadening of diffraction peaks from microstrain contribution was between 0.02 and 0.01. Degree of crystallinity (%) of CuO phases found to decrease from 81 to 71. Dislocation density of CuO phases found to increase from 6.63×10-4nm-2 to 12.68×10-3nm-2. X-ray density of CuO phases increased from 6.48 to 6.53 g/cm3. Where this calculated small dislocation density well agreed with the high crystallinity. Crystal structure and specific surface area were determined from lattice constants and X-ray density. These synthesized nanopowders showed the existence of monoclinic, cubic, and hexagonal phases. The obtained NPs of multi-metal oxide explained more than one phases with different size, shape, and morphology at nano scale.

Enhancing resilience in transnational E-commerce supply chains: Critical factors, perspectives and strategic action plan.

This study develops a hybrid model to investigate the factors affecting transnational e-commerce supply chain resilience (TNSCRE) by integrating the Entropy Weight Method (EWM), Simple Additive Weighting (SAW), and Interpretive Structural Modeling (ISM). The study identifies 36 critical factors categorized under supply chain adaptability, supply chain efficiency, and supply chain evolution, and five criteria are used to rank these factors. The EWM is used to calculate the relative weights of the criteria, and the SAW method is used to rank the factors based on their weighted scores. The ISM is then used to evaluate the interrelationships among the key factors. The research highlights the significance of several factors, such as the speed of supply chain disruption recovery, interactive collaboration, and response time to supply chain disruption. Sensitivity analysis was performed to assess the robustness of the findings. Finally, a SWOT analysis is conducted to develop a strategic action plan for addressing these significant factors. The study provides a comprehensive understanding of the factors that impact TNSCRE from the perspective of multiple stakeholders. The findings can help e-commerce business owners improve their existing supply chain resilience and achieve sustainable growth in the context of globalization.

Immune Checkpoint Inhibitors in Geriatric Oncology.

PURPOSE OF REVIEW: This manuscript will update prior reviews of immune checkpoint inhibitors (ICIs) in light of basic science, translational, and clinical discoveries in the field of cancer immunology and aging. RECENT FINDINGS: ICIs have led to significant advancements in the treatment of cancer. Landmark trials of ICIs have cited the efficacy and toxicity experienced by older patients, but most trials are not specifically designed to address outcomes in older patients. Underlying mechanisms of aging, like cellular senescence, affect the immune system and may ultimately alter the host's response to ICIs. Validated tools are currently used to identify older adults who may be at greater risk of developing complications from their cancer treatment. We review changes in the aging immune system that may alter responses to ICIs, report outcomes and toxicities in older adults from recent ICI clinical trials, and discuss clinical tools specific to older patients with cancer.

Genome-Wide Investigation Reveals Potential Therapeutic Targets in Shigella spp.

Shigella stands as a major contributor to bacterial dysentery worldwide scale, particularly in developing countries with inadequate sanitation and hygiene. The emergence of multidrug-resistant strains exacerbates the challenge of treating Shigella infections, particularly in regions where access to healthcare and alternative antibiotics is limited. Therefore, investigations on how bacteria evade antibiotics and eventually develop resistance could open new avenues for research to develop novel therapeutics. The aim of this study was to analyze whole genome sequence (WGS) of human pathogenic Shigella spp. to elucidate the antibiotic resistance genes (ARGs) and their mechanism of resistance, gene-drug interactions, protein-protein interactions, and functional pathways to screen potential therapeutic candidate(s). We comprehensively analyzed 45 WGS of Shigella, including S. flexneri (n = 17), S. dysenteriae (n = 14), S. boydii (n = 11), and S. sonnei (n = 13), through different bioinformatics tools. Evolutionary phylogenetic analysis showed three distinct clades among the circulating strains of Shigella worldwide, with less genomic diversity. In this study, 2,146 ARGs were predicted in 45 genomes (average 47.69 ARGs/genome), of which only 91 ARGs were found to be shared across the genomes. Majority of these ARGs conferred their resistance through antibiotic efflux pump (51.0%) followed by antibiotic target alteration (23%) and antibiotic target replacement (18%). We identified 13 hub proteins, of which four proteins (e.g., tolC, acrR, mdtA, and gyrA) were detected as potential hub proteins to be associated with antibiotic efflux pump and target alteration mechanisms. These hub proteins were significantly (p < 0.05) enriched in biological process, molecular function, and cellular components. Therefore, the finding of this study suggests that human pathogenic Shigella strains harbored a wide range of ARGs that confer resistance through antibiotic efflux pumps and antibiotic target modification mechanisms, which must be taken into account to devise and formulate treatment strategy against this pathogen. Moreover, the identified hub proteins could be exploited to design and develop novel therapeutics against MDR pathogens like Shigella.

Computational approach for identifying immunogenic epitopes and optimizing peptide vaccine through in-silico cloning against Mycoplasma genitalium.

Mycoplasma genitalium is a pathogenic microorganism linked to a variety of severe health conditions including ovarian cancer, prostate cancer, HIV transmission, and sexually transmitted diseases. A more effective approach to address the challenges posed by this pathogen, given its high antibiotic resistance rates, could be the development of a peptide vaccine. In this study, we used experimentally validated 13 membrane proteins and their immunogenicity to identify suitable vaccine candidates. Thus, based on immunogenic properties and high conservation among other Mycoplasma genitalium sub-strains, the P110 surface protein is considered for further investigation. Later on, we identified T-cell epitopes and B-cell epitopes from the P110 protein to construct a multiepitope-based vaccine. As a result, the 'NIAPISFSFTPFTAA' T-cell epitope and 'KVKYESSGSNNISFDS' B-cell epitope have shown 99.53% and 87.50% population coverage along with 100% conservancy among the subspecies, and both epitopes were found to be non-allergenic. Furthermore, focusing on molecular docking analysis showed the lowest binding energy for MHC-I (-137.5 kcal/mol) and MHC-II (-183.3 kcal/mol), leading to a satisfactory binding strength between the T-cell epitopes and the MHC molecules. However, the constructed multiepitope vaccine (MEV) consisting of 54 amino acids demonstrates favorable characteristics for a vaccine candidate, including a theoretical pI of 4.25 with a scaled solubility of 0.812 and high antigenicity probabilities. Additionally, structural analyses reveal that the MEV displays substantial alpha helices and extended strands, vital for its immunogenicity. Molecular docking with the human Toll-like receptors TLR1/2 heterodimer shows strong binding affinity, reinforcing its potential to elicit an immune response. Our immune simulation analysis demonstrates immune memory development and robust immunity, while codon adaptation suggests optimal expression in E. coli using the pET-28a(+) vector. These findings collectively highlight the MEV's potential as a valuable vaccine candidate against M. genitalium.

Flavonoids and Alzheimer's disease: reviewing the evidence for neuroprotective potential.

Neurodegeneration, which manifests as several chronic and incurable diseases, is an age-related condition that affects the central nervous system (CNS) and poses a significant threat to the public's health for the elderly. Recent decades have experienced an alarming increase in the incidence of neurodegenerative disorders (NDDs), a severe public health issue due to the ongoing development of people living in modern civilizations. Alzheimer's disease (AD) is a leading trigger of age-related dementia. Currently, there are no efficient therapeutics to delay, stop, or reverse the disease's course development. Several studies found that dietary bioactive phytochemicals, primarily flavonoids, influence the pathophysiological processes underlying AD. Flavonoids work well as a supplement to manufactured therapies for NDDs. Flavonoids are effective in complementing synthetic approaches to treat NDDs. They are biologically active phytochemicals with promising pharmacological activities, for instance, antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, anti-apoptotic, and antioxidant effects. The production of nitric oxide (NO), tumor necrosis factor (TNF-α), and oxidative stress (OS) are downregulated by flavonoids, which slow the course of AD. Hence, this research turned from preclinical evidence to feasible clinical applications to develop newer therapeutics, focusing on the therapeutic potential of flavonoids against AD.

Quantification and description of photothermal heating effects in plasmon-assisted electrochemistry.

A growing number of reports have demonstrated plasmon-assisted electrochemical reactions, though debate exists around the mechanisms underlying the enhanced activity. Here we address the impact of plasmonic photothermal heating with cyclic voltammetry measurements and finite-element simulations. We find that plasmonic photothermal heating causes a reduction in the hysteresis of the anodic and cathodic waves of the voltammograms along with an increase in mass-transport limiting current density due to convection induced by a temperature gradient. At slow scan rates, a temperature difference as low as 1 K between the electrode surface and bulk electrolytic solution enhances the current density greater than 100%. Direct interband excitation of Au exclusively enhances current density by photothermal heating, while plasmon excitation leads to photothermal and nonthermal enhancements. Our study reveals the role of temperature gradients in plasmon-assisted electrochemistry and details a simple control experiment to account for photothermal heating.

Evaluation of THz wave transmission performance in TOPAS-based heptagonal photonic crystal fiber (He-PCF).

PCF denotes photonic crystal fiber which is utilized for terahertz (THz) waveguides and cladding in the shape of a hexagon with two elliptical air apertures (AHs), which are discussed. Such differentiation is made: When the frequency is 1 THz, effective material loss (EML) to a minimum of 0.028 cm-1 has been achieved. Making use of the heptagonal photonic crystal fiber (He-PCF) architecture, every simulation result utilizing COMSOL Multiphysics software implements the perfectly match layer (PML) and finite element method (FEM) boundary conditions. The He-PCF fiber demonstrates an effective mode loss (EML) of 0.028 cm-1 that is negligible, a substantial effective area (EA) measuring 7.31 × 10-8 m2 and an 80 % power concentration encompassing the central area at 1 THz frequency. Furthermore, regarding crucial optical guiding aspects like confinement loss, dispersion, and modality, a small study with respect to power fraction along with effective mode area (EMA) has again been conducted. Here, He-PCF THz waveguide is anticipated to provide a notable improvement in the current design for the communication field. Moreover, our suggested the PCF demonstrates perception by a solitary mode, as indicated through the utilization of the V-parameter, across a range in frequency spanning among 0.80 and 3 THz. Thus, it is anticipated that the layout of He-PCF fibers will facilitate efficient transmission of terahertz (THz) signals in a variety of communication applications.

Aducanumab anti-amyloid immunotherapy induces sustained microglial and immune alterations.

Aducanumab, an anti-amyloid immunotherapy for Alzheimer's disease, efficiently reduces Aß, though its plaque clearance mechanisms, long-term effects, and effects of discontinuation are not fully understood. We assessed the effect of aducanumab treatment and withdrawal on Aß, neuritic dystrophy, astrocytes, and microglia in the APP/PS1 amyloid mouse model. We found that reductions in amyloid and neuritic dystrophy during acute treatment were accompanied by microglial and astrocytic activation, and microglial recruitment to plaques and adoption of an aducanumab-specific pro-phagocytic and pro-degradation transcriptomic signature, indicating a role for microglia in aducanumab-mediated Aß clearance. Reductions in Aß and dystrophy were sustained 15 but not 30 wk after discontinuation, and reaccumulation of plaques coincided with loss of the microglial aducanumab signature and failure of microglia to reactivate. This suggests that despite the initial benefit from treatment, microglia are unable to respond later to restrain plaque reaccumulation, making further studies on the effect of amyloid-directed immunotherapy withdrawal crucial for assessing long-term safety and efficacy.

Low dietary carbohydrate induces structural alterations in enterocytes of the chicken ileum.

We investigated the role of dietary carbohydrates in the maintenance of the enterocyte microvillar structure in the chicken ileum. Male chickens were divided into the control and three experimental groups, and the experimental groups were fed diets containing 50%, 25%, and 0% carbohydrates of the control diet. The structural alterations in enterocytes were examined using transmission electron microscopy and immunofluorescent techniques for ß-actin and villin. Glucagon-like peptide (GLP)-2 and proglucagon mRNA were detected by immunohistochemistry and in situ hybridization, respectively. Fragmentation and wide gap spaces were frequently observed in the microvilli of the 25% and 0% groups. The length, width, and density of microvilli were also decreased in the experimental groups. The experimental groups had shorter terminal web extensions, and there were substantial changes in the mitochondrial density between the control and experimental groups. Intensities of ß-actin and villin immunofluorescence observed on the apical surface of enterocytes were lower in the 0% group. The frequency of GLP-2-immunoreactive and proglucagon mRNA-expressing cells decreased with declining dietary carbohydrate levels. This study revealed that dietary carbohydrates contribute to the structural maintenance of enterocyte microvilli in the chicken ileum. The data from immunohistochemistry and in situ hybridization assays suggest the participation of GLP-2 in this maintenance system.

Gene silencing of Helicobacter pylori through newly designed siRNA convenes the treatment of gastric cancer.

BACKGROUND: Helicobacter pylori is a gastric pathogen that is responsible for causing chronic inflammation and increasing the risk of gastric cancer development. It is capable of persisting for decades in the harsh gastric environment because of the inability of the host to eradicate the infection. Several treatment strategies have been developed against this bacterium using different antibiotics. But the effectiveness of treating H. pylori has significantly decreased due to widespread antibiotic resistance, including an increased risk of gastric cancer. The small interfering RNAs (siRNA), which is capable of sequence-specific gene-silencing can be used as a new therapeutic approach for the treatment of a variety of such malignancies. In the current study, we rationally designed two siRNA molecules to silence the cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) genes of H. pylori for their significant involvement in developing cancer. METHODS: We selected a common region of all the available transcripts from different countries of CagA and VacA to design the siRNA molecules. The final siRNA candidate was selected based on the results from machine learning algorithms, off-target similarity, and various thermodynamic properties. RESULT: Further, we utilized molecular docking and all atom molecular dynamics (MD) simulations to assess the binding interactions of the designed siRNAs with the major components of the RNA-induced silencing complex (RISC) and results revealed the ability of the designed siRNAs to interact with the proteins of RISC complex in comparable to those of the experimentally reported siRNAs. CONCLUSION: These designed siRNAs should effectively silence the CagA and VacA genes of H. pylori during siRNA mediated treatment in gastric cancer.

CytoDirect: A Nucleic Acid Nanodevice for Specific and Efficient Delivery of Functional Payloads to the Cytoplasm.

Direct and efficient delivery of functional payloads such as chemotherapy drugs, siRNA, or small-molecule inhibitors into the cytoplasm, bypassing the endo/lysosomal trapping, is a challenging task for intracellular medicine. Here, we take advantage of the programmability of DNA nanotechnology to develop a DNA nanodevice called CytoDirect, which incorporates disulfide units and human epidermal growth factor receptor 2 (HER2) affibodies into a DNA origami nanostructure, enabling rapid cytosolic uptake into targeted cancer cells and deep tissue penetration. We further demonstrated that therapeutic oligonucleotides and small-molecule chemotherapy drugs can be easily delivered by CytoDirect and showed notable effects on gene knockdown and cell apoptosis, respectively. This study demonstrates the synergistic effect of disulfide and HER2 affibody modifications on the rapid cytosolic delivery of DNA origami and its payloads to targeted cells and deep tissues, thereby expanding the delivery capabilities of DNA nanostructures in a new direction for disease treatment.