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1.
Sci Rep ; 14(1): 16420, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013914

ABSTRACT

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.

2.
Heliyon ; 10(10): e31274, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813166

ABSTRACT

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.

3.
Nat Commun ; 15(1): 3996, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734693

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Amyloidosis , Proto-Oncogene Proteins , Trans-Activators , Transcriptome , Animals , Male , Mice , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Amyloidosis/genetics , Amyloidosis/metabolism , Amyloidosis/pathology , Disease Models, Animal , Gene Expression Profiling , Gene Knockdown Techniques , Mice, Inbred C57BL , Mice, Transgenic , Phenotype , Plaque, Amyloid/metabolism , Plaque, Amyloid/pathology , Plaque, Amyloid/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Trans-Activators/genetics , Trans-Activators/metabolism
4.
Heliyon ; 10(9): e30544, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38742051

ABSTRACT

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.

5.
Curr Oncol Rep ; 26(5): 562-572, 2024 05.
Article in English | MEDLINE | ID: mdl-38587598

ABSTRACT

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.


Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Neoplasms/drug therapy , Neoplasms/immunology , Aged , Aging/immunology , Geriatrics/methods , Medical Oncology/methods , Immunotherapy/methods
6.
Biomed Res Int ; 2024: 5554208, 2024.
Article in English | MEDLINE | ID: mdl-38595330

ABSTRACT

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.


Subject(s)
Dysentery, Bacillary , Shigella , Humans , Phylogeny , Drug Resistance, Bacterial/genetics , Microbial Sensitivity Tests , Shigella/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/genetics , Dysentery, Bacillary/microbiology , Shigella flexneri
7.
Heliyon ; 10(7): e28223, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596014

ABSTRACT

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.

8.
Mol Cell Biochem ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38568359

ABSTRACT

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.

9.
Commun Chem ; 7(1): 70, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561493

ABSTRACT

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.

10.
Heliyon ; 10(3): e25622, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38371994

ABSTRACT

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.

11.
J Exp Med ; 221(2)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38226975

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized , Microglia , Animals , Mice , Immunotherapy , Phagocytes , Plaque, Amyloid
12.
Anim Sci J ; 95(1): e13919, 2024.
Article in English | MEDLINE | ID: mdl-38287469

ABSTRACT

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.


Subject(s)
Chickens , Enterocytes , Male , Animals , Chickens/genetics , Proglucagon/genetics , Actins , Dietary Carbohydrates , Ileum , Glucagon-Like Peptide 2 , RNA, Messenger/genetics , Microvilli
13.
J Poult Sci ; 60: 2023029, 2023.
Article in English | MEDLINE | ID: mdl-38084127

ABSTRACT

The aim of this study was to identify the histological features of chicken enteroendocrine cells before and after hatching. Tissue samples from the duodenum, proximal and distal parts of the jejunum and ileum, cecum and colorectum were collected from the embryos at days 18, 19, 20, and 21 of incubation, and from 3-day-old chicks. The expression of glucagon-like peptide (GLP)-1, somatostatin (SST), and neurotensin (NT) in the enteroendocrine cells was detected using the streptavidin-biotin method, and the colocalization of these peptides was revealed using the double immunofluorescence method. All of assessed peptides were expressed in the enteroendocrine cells at day 18 of incubation. GLP-1-immunoreactive cells were only observed in the jejunum and ileum. The cell numbers gradually increased as incubation progressed. NT-immunoreactive cells were detected in all intestinal parts at all incubation days, and the highest expression was observed in the colorectum of 3-day-old chicks. SST-immunoreactive cells were observed from the duodenum to the ileum, excluding the colorectum. The double immunofluorescence method revealed that GLP-1 and NT colocalized in the same endocrine cells of the jejunum and ileum. The colocalization ratio of GLP-1 with NT was the highest in the distal ileum of 3-day-old chicks. However, neither GLP-1 nor NT colocalized with SST. These results indicate that chicken enteroendocrine cells markedly change their density and colocalization ratios before and after hatching.

14.
J Am Chem Soc ; 145(50): 27336-27347, 2023 12 20.
Article in English | MEDLINE | ID: mdl-38055928

ABSTRACT

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.


Subject(s)
Nanostructures , Nucleic Acids , Humans , Nucleic Acids/metabolism , DNA/chemistry , Nanostructures/chemistry , Nanotechnology , Cytosol/metabolism , Nucleic Acid Conformation , Disulfides/metabolism
15.
Cancer Med ; 12(24): 22407-22419, 2023 12.
Article in English | MEDLINE | ID: mdl-38037736

ABSTRACT

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.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Helicobacter pylori/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/therapeutic use , RNA, Small Interfering/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/therapy , Stomach Neoplasms/microbiology , Molecular Docking Simulation , Cytotoxins/metabolism , Helicobacter Infections/genetics , Helicobacter Infections/microbiology
16.
Cancers (Basel) ; 15(22)2023 Nov 07.
Article in English | MEDLINE | ID: mdl-38001572

ABSTRACT

Cancer is the leading cause of morbidity and mortality in people throughout the world. There are many signaling pathways associated with cancerous diseases, from which the Mitogen-activated protein kinase (MAPK) pathway performs a significant role in this regard. Apoptosis and proliferation are correlated with MAPK signaling pathways. Plenty of experimental investigations were carried out to assess the role of indole alkaloids in MAPK-mediated cancerous diseases. Previous reports established that indole alkaloids, such as vincristine and evodiamine are useful small molecules in cancer treatment via the MAPK signaling system. Indole alkaloids have the anticancer potential through different pathways. Vincristine and evodiamine are naturally occurring indole alkaloids that have strong anticancer properties. Additionally, much research is ongoing or completed with molecules belonging to this group. The current review aims to evaluate how indole alkaloids affect the MAPK signaling pathway in cancer treatment. Additionally, we focused on the advancement in the role of indole alkaloids, with the intention of modifying the MAPK signaling pathways to investigate potential new anticancer small molecules. Furthermore, clinical trials with indole alkaloids in cancer treatment are also highlighted.

17.
Front Chem ; 11: 1141182, 2023.
Article in English | MEDLINE | ID: mdl-37881243

ABSTRACT

Total oxidisable precursor (TOP) assay can oxidise some per- and polyfluoroalkyl substances (PFASs) and their precursors, most of which cannot be quantitatively detected so far, and convert them to detectable PFASs, such as perfluoroalkyl acids (PFAAs). However, the conversion is constrained by the complexity of the target samples, including co-existent organics, unknown PFAS precursors, and background. In this study, the TOP assay is modified to increase the oxidation and conversion efficiency by changing the initial concentration of target sample, increasing oxidising doses, time, temperature, etc. The modified TOP assay is applied to test several aqueous film-forming foams (AFFF) and a PFAS-contaminated soil extract. The sum concentrations of the detectable PFASs are increased by up to ∼534× in the AFFF samples and ∼7× in the PFAS-contaminated soil extract. The detectable fluorotelomer sulfonate (FTS, such as 6:2/8:2 FTS) is accounted as an oxidation indicator to monitor the oxidation and conversion progress of the oxidisable PFASs precursors to the detectable PFASs. Overall, the modified TOP assay could be an appropriate method for identifying missing PFASs mass in complex matrices by detecting the PFASs precursors effectively.

19.
Front Immunol ; 14: 1203073, 2023.
Article in English | MEDLINE | ID: mdl-37671162

ABSTRACT

Cancer is one of the deadliest diseases, causing million of deaths each year globally. Conventional anti-cancer therapies are non-targeted and have systemic toxicities limiting their versatile applications in many cancers. So, there is an unmet need for more specific therapeutic options that will be effective as well as free from toxicities. Antibody-drug conjugates (ADCs) are suitable alternatives with the right potential and improved therapeutic index for cancer therapy. The ADCs are highly precise new class of biopharmaceutical products that covalently linked a monoclonal antibody (mAb) (binds explicitly to a tumor-associated surface antigen) with a customized cytotoxic drug (kills cancer cells) and tied via a chemical linker (releases the drug). Due to its precise design, it brings about the target cell killing sparing the normal counterpart and free from the toxicities of conventional chemotherapy. It has never been so easy to develop potential ADCs for successful therapeutic usage. With relentless efforts, it took almost a century for scientists to advance the formula and design ADCs for its current clinical applications. Until now, several ADCs have passed successfully through preclinical and clinical trials and because of proven efficacy, a few are approved by the FDA to treat various cancer types. Even though ADCs posed some shortcomings like adverse effects and resistance at various stages of development, with continuous efforts most of these limitations are addressed and overcome to improve their efficacy. In this review, the basics of ADCs, physical and chemical properties, the evolution of design, limitations, and future potentials are discussed.


Subject(s)
Biological Products , Drug-Related Side Effects and Adverse Reactions , Immunoconjugates , Neoplasms , Humans , Antibodies, Monoclonal
20.
Sci Total Environ ; 904: 166568, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37633378

ABSTRACT

The adsorption and desorption of 9 PFAS, including 3 perfluoroalkyl sulphonic and 6 perfluoroalkyl carboxylic acids, in artificial groundwater was investigated using 3 commercial adsorbents that comprised a powdered activated carbon (PAC), a surface-modified organoclay (NMC+n), and a carbonaceous organic amendment (ROAC). Sorption kinetics and isotherms of PFAS, as well as the effects of adsorbent dose, pH, index ion and ionic strength on PFAS adsorption and desorption were investigated. Sorption of multicomponent PFAS in the adsorbents was rapid, especially for NMC+n and ROAC, regardless of PFAS chain length. The sorption and (and especially) desorption of PFAS in the adsorbents was impacted by the pH, index ion, and ionic strength of simulated groundwater, especially for the short chain PFAS, with only minimal impacts on NMC+n and PAC compared to ROAC. Although the potential mineral and charged constituents of the adsorbents contributed to the adsorption of short chain PFAS through electrostatic interactions, these interactions were susceptible to variable groundwater chemistry. Hydrophobic interactions also played a major role in facilitating and increasing PFAS sorption, especially in adsorbents with aliphatic functional groups. The desorption of PFAS from the adsorbents was below 8 % when the aqueous phase was deionised water, with no measurable desorption for NMC+n. In contrast, the desorption of short chain PFAS in simulated groundwater increased substantially (30-100 %) in the adsorbents, especially in ROAC and NMC+n, but more so with ROAC. In general, the three adsorbents exhibited strong stability for the long chain PFAS, especially the perfluoroalkyl sulphonic acids, with minimal to no sorption reversibility under different pH and ionic composition of simulated groundwater. This study highlights the importance of understanding not only the sorption of PFAS in groundwater using adsorbents, but also the desorption of PFAS, which may be useful for decision making during the ex-situ and in-situ treatment of PFAS-contaminated groundwater.

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