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As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its potential in fluorescence-guided surgery as well as photodynamic therapy (PDT). Moreover, 5-ALA-PDT has been suggested as a promising chemo-radio sensitization therapy for various cancers. However, insufficient 5-ALA-induced PpIX fluorescence and the induction of multiple resistance mechanisms may hinder the 5-ALA-PDT clinical outcome. Reduced efficacy and resistance to 5-ALA-PDT can result from genomic alterations, tumor heterogeneity, hypoxia, activation of pathways related to cell surveillance, production of nitric oxide, and most importantly, deregulated 5-ALA transporter proteins and heme biosynthesis enzymes. Understanding the resistance regulatory mechanisms of 5-ALA-PDT may allow the development of effective personalized cancer therapy. Here, we described the mechanisms underlying resistance to 5-ALA-PTD across various tumor types and explored potential strategies to overcome this resistance. Furthermore, we discussed future approaches that may enhance the efficacy of treatments using 5-ALA-PDT., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. All authors have been participated in the preparation of the manuscript, and have given their agreement to submit this manuscript in the present format., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Rhinoplasty can reduce nasal airways' resistance. This study evaluates the effects of rhinoplasty on sleep quality, daytime drowsiness, and obstructive sleep apnea (OSA)., Methods: In this prospective cohort study, 80 rhinoplasty candidates were examined before and six months after rhinoplasty to evaluate symptom changes. STOP-BANG, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) questionnaires, and nocturnal polysomnography were used, respectively, to screen for OSA, assess sleep quality, assess daytime drowsiness, and confirm results., Results: Seventeen men (21.2%) and 63 women (78.8%) were studied. PSQI results showed an increase only in post-operative sleep disturbance items ( p = 0.04). STOP-BANG showed an increase in apnea ( p = 0.06) and a decrease in snoring ( p = 0.06), which were both insignificant. The polysomnography tests confirmed the results of the questionnaires., Conclusion: Contrary to popular belief, rhinoplasty does not increase snoring, sleep disorders, or apnea.

Food systems impact different aspects of sustainability and human life, such as pollution, health, climate change, biodiversity loss, water shortage, and soil infertility. However, in many places, food systems are neither resilient nor sustainable. Integrated planning approaches can help to overcome fragmented strategies and policies in ways that improve the sustainability and resilience of food systems. This study explores such an approach by applying a climate-biodiversity-health (CBH) nexus to local and regional food systems in the Comox Valley region, British Columbia, Canada. The CBH nexus is used as an analytical lens to identify systems relationships among food systems, climate change, biodiversity and health issues and strategies in the region. The employs a place-based approach entailing semi-structured interviews with provincial, regional, and local stakeholders in order to develop a holistic understanding of planning challenges, strategies and their outcomes through the CBH lens. Outcomes of this work include a system map that can be used as a framework for elucidating how various strategies align or conflict with different CBH imperatives and can be used to support integrated community sustainability planning and policy-making efforts. The framework is developed within the Comox Valley context, but it can be adapted to other communities. This paper details the development of this framework, the interconnections between different components, and how this framework can be adopted in other communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Over the last decades, porous organic materials (POMs) have been extensively employed in various industrial approaches including gas separation, catalysis and energy production due to possessing indisputable advantages like great surface area, high permeability, controllable pore size, appropriate functionalization and excellent processability compared to traditional substances like zeolites, Alumina and polymers. This review presents the recent breakthroughs in the multifunctional POMs for potential use in the membrane-based CO 2 separation. Some examples of highly-selective membranes using multifunctional POMs are described. Moreover, various classifications of POMs following with their advantages and disadvantages in CO 2 separation processes are explained. Apart from reviewing the state-of-the-art POMs in CO 2 separation, the challenges/limitations of POMs with tailored structures for reasonable application are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Taghvaie Nakhjiri and Ghadiri.)

Triboelectrification is a ubiquitous and poorly understood phenomenon in powder processing, particularly for pharmaceutical powders. Charged particles can adhere to vessel walls, causing sheeting; they can also cause agglomeration, threatening the stability of powder formulations, and in extreme cases electrostatic discharges, which present a serious fire and explosion hazard. Triboelectrification is highly sensitive to environmental and material conditions, which makes it very difficult to compare experimental results from different publications. In this work, density functional theory (DFT) is used to investigate the charge transfer characteristics of several functional groups of paracetamol in order to better understand the mechanisms of charging at the nanoscale and the influence of the environmental and material properties on charge transfer. This is achieved by studying the structure and electronic properties at the molecule-substrate interface. Using this molecule-substrate approach, the charging contributions of individual functional groups are explored by examining the Hirschfeld charges, the charge density difference between the molecule and substrate, the density of states, and the location of the frontier orbitals (HOMO and LUMO) of a paracetamol molecule. Charge density difference calculations indicate a significant transfer of charge from the molecule to the surface. Observable regions of electron density enrichment and depletion are evident around the electron-donating and -withdrawing groups, respectively. The density of states for the paracetamol molecule evolves as it approaches the surface, and the band gap disappears upon contact with the substrate. Hirshfeld charge analysis reveals asymmetry in the charge redistribution around the molecule, highlighting the varying charging tendencies of different atoms.

Sweeping gas membrane distillation (SGMD) is considered a membrane distillation configuration. It uses an air stream to collect the water vapour. A 2D mathematical model is prepared in the current study to predict the effect of various operating parameters on the SGMD performance. Also, the temperature distribution in the SGMD was obtained. The effect of air inlet temperature, salt concentration, feed and air flowrate on air and salted solution outlet temperature and vapour flux through the membrane is investigated. There was good agreement between experimental data and modelling outputs. It was found that increase in air inlet temperature from 40 to 72 °C was increased the outlet temperature of air stream and cold solution from 37 to 63 °C and 38 to 65 °C respectively. Furthermore, increase in air inlet temperature led to the enhancement of vapour flux in the membrane distillation. Also, the salt concentration and feed flow rate did not have meaningful influence on the outlet temperatures, however, the flux was increased by increasing feed flowrate., (© 2024. The Author(s).)

Widespread alterations in the expression of various genes could contribute to the pathogenesis of epilepsy. The expression levels of various genes, including major inhibitory and excitatory receptors, ion channels, cell type-specific markers, and excitatory amino acid transporters, were assessed and compared between the human epileptic hippocampus and amygdala, and findings from autopsy controls. Moreover, the potential correlation between molecular alterations in epileptic brain tissues and the clinical characteristics of patients undergoing epilepsy surgery was evaluated. Our findings revealed significant and complex changes in the expression of several key regulatory genes in both the hippocampus and amygdala of patients with intractable epilepsy. The expression changes in various genes differed considerably between the epileptic hippocampus and amygdala. Different correlation patterns were observed between changes in gene expression and clinical characteristics, depending on whether the patients were considered as a whole or were subdivided. Altered molecular signatures in different groups of epileptic patients, defined within a given category, could be viewed as diagnostic biomarkers. Distinct patterns of molecular changes that distinguish these groups from each other appear to be associated with epilepsy-specific functional consequences., (© 2023. The Author(s).)

NAD(P)H Quinone Dehydrogenase 1 (NQO1) plays a pivotal role in the regulation of neuronal function and synaptic plasticity, cellular adaptation to oxidative stress, neuroinflammatory and degenerative processes, and tumorigenesis in the central nervous system (CNS). Impairment of the NQO1 activity in the CNS can result in abnormal neurotransmitter release and clearance, increased oxidative stress, and aggravated cellular injury/death. Furthermore, it can cause disturbances in neural circuit function and synaptic neurotransmission. The abnormalities of NQO1 enzyme activity have been linked to the pathophysiological mechanisms of multiple neurological disorders, including Parkinson's disease, Alzheimer's disease, epilepsy, multiple sclerosis, cerebrovascular disease, traumatic brain injury, and brain malignancy. NQO1 contributes to various dimensions of tumorigenesis and treatment response in various brain tumors. The precise mechanisms through which abnormalities in NQO1 function contribute to these neurological disorders continue to be a subject of ongoing research. Building upon the existing knowledge, the present study reviews current investigations describing the role of NQO1 dysregulations in various neurological disorders. This study emphasizes the potential of NQO1 as a biomarker in diagnostic and prognostic approaches, as well as its suitability as a target for drug development strategies in neurological disorders., (© 2023. The Author(s).)

Crystals of active pharmaceutical ingredients (API) are prone to triboelectric charging due to their dielectric nature. This characteristic, coupled with their typically low density and often large aspect ratio, poses significant challenges in the manufacturing process. The pharmaceutical industry frequently encounters issues during the secondary processing of APIs, such as particle adhesion to walls, clump formation, unreliable flow, and the need for careful handling to mitigate the risk of fire and explosions. These challenges are further intensified by the limited availability of powder quantities for testing, particularly in the early stages of drug development. Therefore, it is highly desirable to develop predictive tools that can assess the triboelectric propensity of APIs. In this study, Density Functional Theory calculations are employed to predict the effective work function of different facets of aspirin and paracetamol crystals, both in a vacuum and in the presence of water molecules on their surfaces. The calculations reveal significant variations in the work function across different facets and materials. Moreover, the adsorption of water molecules induces a shift in the work function. These findings underscore the considerable impact of distinct surface terminations and the presence of molecular water on the calculated effective work function of pharmaceuticals. Consequently, this approach offers a valuable predictive tool for determining the triboelectric propensity of APIs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: In this study, we aimed to illustrate the association between the Healthy Eating Index (HEI) and Dietary Quality Index (DQI) with bone mineral density (BMD) among postmenopausal Iranian women with osteoporosis compared to the healthy control., Methods: In the current case-control study, 131 postmenopausal women with osteoporosis and 131 healthy postmenopausal women participated. Dual-energy X-ray absorptiometry was used to assess the lumbar vertebrae and femoral neck BMD. The subjects completed a validated food frequency questionnaire (FFQ), and then HEI and DQI were calculated based on the FFQ data. Crude and adjusted multivariable logistic regression was used to assess the relation between HEI and DQI with the odds of the femoral and lumbar BMD., Results: According to the results, participants in the last tertile of HEI were more likely to have higher femoral and lumbar BMD in the crude model (odds ratio (OR) = 0.38; 95% confidence interval (CI): 0.20-0.71 and OR = 0.20; 95% CI: 0.10-0.40, respectively) and also in the adjusted model (OR = 0.40; 95% CI: 0.20-0.78 and OR = 0.20; 95% CI: 0.10-0.41, respectively). Also, in terms of DQI-I, participants in the last tertile were more likely to have higher femoral and lumbar BMD in the crude model (OR = 0.23; 95% CI: 0.12-0.45 and OR = 0.29; 95% CI: 0.15-0.55, respectively) and also in the adjusted model (OR = 0.29; 95% CI: 0.14-0.58 and OR = 0.34; 95% CI: 0.17-0.67, respectively)., Conclusions: The results of the current study supported the hypothesis that high-quality diets with healthy patterns can be clinically effective in maintaining bone health. Thus, recommendations regarding the consumption of nutrient-rich food groups in a healthy diet can serve as a practical non-pharmacological strategy against osteoporosis., (© 2023. The Author(s).)

Glioblastoma multiforme (GBM) is the most malignant type of cerebral neoplasm in adults with a poor prognosis. Currently, combination therapy with different anti-cancer agents is at the forefront of GBM research. Hence, this study aims to evaluate the potential anti-cancer synergy of a clinically approved neurokinin-1 receptor antagonist, aprepitant, and 5-aminolevulinic acid (5-ALA), a prodrug that elicits fluorescent porphyrins in gliomas on U-87 human GBM cells. We found that aprepitant and 5-ALA effectively inhibited GBM cell viability. The combinatorial treatment of these drugs exerted potent synergistic growth inhibitory effects on GBM cells. Moreover, aprepitant and 5-ALA induced apoptosis and altered the levels of apoptotic genes (up-regulation of Bax and P53 along with downregulation of Bcl-2). Furthermore, aprepitant and 5-ALA increased the accumulation of protoporphyrin IX, a highly pro-apoptotic and fluorescent photosensitizer. Aprepitant and 5-ALA significantly inhibited GBM cell migration and reduced matrix metalloproteinases (MMP-2 and MMP-9) activities. Importantly, all these effects were more prominent following aprepitant-5-ALA combination treatment than either drug alone. Collectively, the combination of aprepitant and 5-ALA leads to considerable synergistic anti-proliferative, pro-apoptotic, and anti-migratory effects on GBM cells and provides a firm basis for further evaluation of this combination as a novel therapeutic approach for GBM., (© 2023 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Objective: Idiopathic normal pressure hydrocephalus (NPH) is commonly accompanied by diverse comorbidities that impact the postoperative course and result in a distinction between shunt responders and shunt non-responders. This study aimed to enhance diagnostics by identifying prognostic differences between NPH patients, individuals with comorbidities, and those with other complications., Methods: The data of 119 patients with NPH coding at the University Clinic Münster from January 2009 to June 2017 were examined. The study primarily concentrated on examining symptoms, comorbidities, and radiological measurements, including callosal angle (CA) and Evans index (EI). To evaluate the progression of symptoms, a novel scoring system was developed to quantitatively assess the course at specific time points: 5-7 weeks, 1-1.5 years, and 2.5 years after the operation. This scoring system aimed to provide a standardized approach for measuring and tracking the development of symptoms over time. Logistic regression analyses were employed to identify predictor associated with 3 key outcomes: shunt implantation, surgical success, and the development of complications., Results: Among the comorbidities observed, hypertension was the most prevalent. Gait disturbance, in the absence of polyneuropathy, was identified as a predictor of a favorable surgical outcome. Hygroma development was associated with a combination of vascular factors and cognitive disorders. The presence of spinal/skeletal changes, diabetes, and vascular constellations were found to increase the likelihood of developing complications., Conclusions: The evaluation of comorbidities accompanied by NPH holds significant importance and necessitates meticulous observation, expertise, and multidisciplinary care., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Carbohydrates are the primary energy source in Asian countries, including Iran. An emerging method can be used to measure the quality of carbohydrates, including the carbohydrate quality index (CQI), which includes a variety of components. Low-carbohydrate diet score (LCDS) has been proposed as a new method of scoring micronutrient intake that could provide a reasonable explanation for the link between diet and the risk of chronic diseases., Objective: This study aimed to investigate the relationship between CQI, LCDS, glycemic index (GI), glycemic load (GL), insulin load (IL), and insulin index (II) with bone mass density (BMD) in postmenopausal women., Method: In this case-control study, 131 postmenopausal women with osteoporosis/osteopenia and 131 healthy postmenopausal women aged 45-65 participated. The dual-energy X-ray absorptiometry (DEXA) method measured the BMD of the lumbar vertebrae and femoral neck. A validated semi-quantitative food frequency questionnaire was used to assess dietary intake. Logistic regression were used to evaluate the relation between GI, GL, II, IL, CQI, and LCDS with BMD., Results: Diets with higher GI increased the risk of osteopenia and osteoporosis, but LCDS and CQI decreased the risk of osteopenia and osteoporosis., Conclusion: These findings suggest that a higher intake of fruits and vegetables and receiving various dietary vitamins, minerals, and antioxidant compounds may be a useful way to prevent osteopenia in Iranian women., (© 2023. The Author(s).)

In recent years, the emission of detrimental acidic pollutants to the atmosphere has raised the concerns of scientists. Sulphur dioxide (SO 2 ) is a harmful greenhouse gas, which its abnormal release to the atmosphere may cause far-ranging environmental and health effects like acid rain and respiratory problems. Therefore, finding promising techniques to alleviate the emission of this greenhouse gas may be of great urgency towards environmental protection. This paper aims to evaluate the potential of three novel absorbents (seawater (H 2 O), dimethyl aniline (DMA) and sodium hydroxide (NaOH) to separate SO 2 acidic pollutant from SO 2 /air gaseous stream inside the hollow fiber membrane contactor (HFMC). To reach this goal, a CFD-based simulation was developed to predict the results. Also, a mathematical model was applied to theoretically evaluate the transport equations in different compartments of contactor. Comparison of the results has implied seawater is the most efficient liquid absorbent for separating SO 2 . After seawater, NaOH and DMA are placed at the second and third rank (99.36% separation using seawater > 62% separation using NaOH > 55% separation using DMA). Additionally, the influence of operational parameters (i.e., gas and liquid flow rates) and also membrane/module parameters (i.e., length of membrane module, hollow fibers' number and porosity) on the SO 2 separation percentage is investigated as another highlight of this paper., (© 2023. The Author(s).)

Introduction: The association between plant-based diet indices and bone mineral density (BMD) of women with osteoporosis have not been studied in Iranian women. This study aimed to evaluate the association between plant-based diet indices and BMD in postmenopausal women with osteopenia/osteoporosis., Materials and Methods: The present research was a case-control study conducted on 131 postmenopausal women with osteoporosis/osteopenia and 131 healthy women. The BMD of the femoral neck and lumbar vertebrae was measured by the Dual-energy X-ray absorptiometry (DXEA) method. Participants were asked to complete a validated semi-quantitative food frequency questionnaire (FFQ). We used three versions of plant-based diet indices, including plant-based diet index (PDI), healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI). Two different multivariable logistic regression was used for the crude and adjusted model to assess the relationship between PDI, hPDI, and uPDI with odds of femoral and lumbar BMD., Results: There was a reverse association between last tertile of hPDI with femoral BMD abnormality in the both adjusted model [Model 1: odds ratio (OR): 0.33; 95% confidence interval (CI): 0.19-0.63 and Model 2: OR: 0.30; 95% CI: 0.15-0.58, respectively]. Furthermore, we found a reverse relationship between hPDI with lumbar BMD abnormality in the first adjusted model (OR: 0.36; 95% CI: 0.19-0.67). On the other hand, a negative association was observed in the second and last tertile of hPDI with lumbar BMD abnormality (OR: 0.47; 95% CI: 0.24-0.90 and OR: 0.34; 95% CI: 0.17-0.64, respectively). According to the results, the association of femoral BMD abnormality in the last tertile of uPDI compared to the first tertile in the both adjusted models (Model 1: OR: 2.85; 95% CI: 1.52-5.36 and Model 2: OR: 2.63; 95% CI: 1.37-5.06) were significant. Also, we observed a positive relationship between the last tertile of uPDI with lumbar BMD abnormality compared to the lowest tertile in the both adjusted models (Model 1; OR: 4.16; 95% CI: 2.20-7.85, Model 2; OR: 4.23; 95% CI: 2.19-8.19)., Conclusion: Overall, the findings indicated that in postmenopausal women with osteoporosis, a healthy plant-based diet could prevent bone loss, and an unhealthy plant-based diet might have detrimental effects on BMD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ghadiri, Cheshmazar, Shateri, Gerami, Nouri and Gargari.)

The dried flower bud of Syzygium aromaticum L. (S. aromaticum) (Myrtaceae), cloves, have been used for their analgesic and anti-inflammatory activities. Peritoneal adhesion (PA) is the most common complication of abdominal and pelvic surgeries, which causes significant adverse effects and severe economic burden. The present study aimed to evaluate the preventive effect of S. extract (SAE) on PA formation in a rat model. Male Wistar 8-week-old rats were randomly divided into sham, control (received vehicle), and treatment (0.25%, 0.5%, and 1% w/v of SAE) groups. The adhesion and related factors were examined using the Nair scoring system and immunological and biochemical kits for the levels of inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α], growth factors [transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF)], oxidative [nitric oxide (NO) and malondialdehyde (MDA)], and anti-oxidative [glutathione (GSH)] factors. Our results figured out that the adhesion score and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly increased, but the GSH level was decreased in the control group compared to the sham group (p < 0.001-0.05). On the other hand, the 0.25% SAE group had a lower adhesion score, and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly decreased compared with the vehicle group, and the level of GSH was increased (p < 0.001-0.05). SAE could efficiently reduce adhesion score and regulate inflammatory cytokines, oxidative and anti-oxidative factors, and biomarkers of fibrosis and angiogenesis. Therefore, clove extract can be considered a potential candidate for PA management., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Microbial populations play a crucial role in human health and the development of many diseases. These diseases often arise from the explosive proliferation of opportunistic bacteria, such as those in the nasal cavity. Recently, there have been increases in the prevalence of these opportunistic pathogens displaying antibiotic resistance. Thus, the study of the nasal microbiota and its bacterial diversity is critical in understanding pathogenesis and developing microbial-based therapies for well-known and emerging diseases. However, the isolation and analysis of these populations for clinical study complicates the already challenging task of identifying and profiling potentially harmful bacteria. Existing methods are limited by low sample throughput, expensive labeling, and low recovery of bacteria with ineffective removal of cells and debris. In this study, we propose a novel microfluidic channel with a zigzag configuration for enhanced isolation and detection of bacteria from human clinical nasal swabs. This microfluidic zigzag channel separates the bacteria from epithelial cells and debris by size differential focusing. As such, pure bacterial cell fractions devoid of large contaminating debris or epithelial cells are obtained. DNA sequencing performed on the separated bacteria defines the diversity and species present. This novel method of bacterial separation is simple, robust, rapid, and cost-effective and has the potential to be used for the rapid identification of bacterial cell populations from clinical samples.

Agitated filter bed dryer is often the equipment of choice in the pharmaceutical industry for the isolation of potent active pharmaceutical ingredients (API) from the mother liquor and subsequent drying through intermittent agitation. The use of an impeller to promote homogeneous drying could lead to undesirable size reduction of the crystal product due to shear deformation induced by the impeller blades during agitation, potentially causing off-specification product and further downstream processing issues. An evaluation of the breakage propensity of crystals during the initial development stage is therefore critical. A new versatile scale-down agitated filter bed dryer (AFBD) has been developed for this purpose. Carbamazepine dihydrate crystals that are prone to breakage have been used as model particles. The extent of particle breakage as a function of impeller rotational speed, size of clearance between the impeller and containing walls and base, and solvent content has been evaluated. A transition of breakage behaviour is observed, where carbamazepine dihydrate crystals undergo fragmentation first along the crystallographic plane [00l]. As the crystals become smaller and more equant, the breakage pattern switches to chipping. Unbound solvent content has a strong influence on the breakage, as particles break more readily at high solvent contents. The laboratory-scale instrument developed here provides a tool for comparative assessment of the propensity of particle attrition under agitated filter bed drying conditions., (© 2022. The Author(s).)

As COVID-19 waves continue to spread worldwide, demand for a portable, inexpensive and convenient biosensor to determine community immune/infection status is increasing. Here we describe an impedance-based affinity biosensor using Interdigitated Electrode (IDE) arrays to detect antibodies to SARS-CoV-2 in serum. We created the biosensor by functionalizing the IDEs' surface with abaculaovirus-expressed and purified Spike (S) protein to bind anti-SARS CoV-2antibodies. Gold nanoparticles (GNP) fused to protein G were used to probe for bound antibodies. An ELISA assay using horseradish peroxidase-protein G to probe for bound IgG confirmed that the purified S protein bound a commercial source of anti-SARS-CoV-2 antibodies specifically and bound anti-SARS-CoV-2 antibodies in COVID-19 positive serum. Then we demonstrated that our biosensor could detect anti-SARS-CoV-2 antibodies with 72% sensitivity in 2 h. Using GNP-protein G, the affinity biosensor had increased impedance changes with COVID-19positive serum and minimal or decreased impedance changes with negative serum. This demonstrated that our biosensor could discriminate between COVID-19 positive and negative sera, which were further improved using poly(vinyl alcohol)as a blocking agent., (© 2022. The Author(s).)

In the present study, a mathematical modelling was developed to investigate ibuprofen adsorption from pharmaceutical wastewater into activated carbon and sonicated activated carbon. The developed model was dissolved based on the finite element method. Effect of different operating parameters including particle porosity and diameter as well as ibuprofen diffusion coefficient in solution on the amount of ibuprofen adsorption at different time point and position in the particle were evaluated. It was found good agreement between experimental values and modelling results in terms of ibuprofen adsorption as a function time. The 84.5% and 92.5% of maximum adsorption was achieved for the AC and SAC at the centre of particle after 150 min. Increasing the particle porosity and ibuprofen diffusion coefficient was improved the ibuprofen adsorption into the adsorbent. However, the particle diameter had negative impact on the system performance. There was a decrease in solute adsorption from 84.10 to 7.30 mg/g and from 106 to 15.73 mg/g for the AC and SAC respectively with increasing the particle radius from 173 to 500 µm. Finally, it was concluded that the particle specifications play important role in the adsorption process as it was observed considerable change in the amount of adsorption at different positions in the particle with changing the particle specifications., (© 2021. The Author(s).)

Objective: The airway epithelium is a potential source of pathophysiology through activation of transient potential receptor vallinoid type 1 (TRPV1) channel. A positive feedback cycle caused by TRPV1 activity is hypothesized to induce upregulation and production of inflammatory cytokines, leading to exacerbations of chronic airway diseases. These cytokine and protein regulation effects were investigated in this study., Methods: Healthy (BEAS-2B) and cancer-derived (Calu-3) airway epithelial cell lines were assessed for changes to TRPV1 protein expression and mRNA expression following exposure to capsaicin (5-50 µM), and TRPV1 modulators including heat (43 °C), and hydrochloric acid (pH 3.4 to pH 6.4). Cytotoxicity was measured to determine the working concentration ranges of treatment. Subsequent bronchoconstriction by TRPV1 activation with capsaicin was measured on guinea pig airway tissue to confirm locally mediated activity without the action of known neuronal inputs., Results: TRPV1 protein expression was not different for all capsaicin, acidity, and heat exposures ( p  > 0.05), and was replicated in mRNA protein expression ( p  > 0.05). IL-6 and IL-8 expression were lower in BEAS-2B and Calu-3 cell lines exposed with acidity and heat ( p  < 0.05), but not consistently with capsaicin exposure, with potential cytotoxic effects possible., Conclusions: TRPV1 expression was present in airway epithelial cells but its expression was not changed after activation by TRPV1 activators. Thus, it was not apparent the reason for reported TRPV1 upregulation in patients with airway disease states. More complex mechanisms are likely involved and will require further investigation.

In this work, a novel strategy was addressed to fabricate new sensing probe (N-CDs@NaFZ) from nitrogen doped carbon dots (N-CDs) confined in Al-free ferrisilicates zeolite (NaFZ) by hydrothermal/solvothermal method. The probe was systematically characterized by HR-TEM, FTIR, energy dispersive X-ray (EDX), powder X-ray diffraction, and UV-Vis absorption and fluorescence spectrophotometers. Characterization of the designed nanocomposite template N-CDs@NaFZ by fluorescence spectrum demonstrates a variety of important conducts as stability improvements, reasonable dispersibility in water, highly emission intensity enhancement at 435 nm when excited at 340 nm, excitation independent fluorescence behaviors, great quantum yield percentage of 91.2%, and narrow size distribution 12 nm, as a nano-space confinement effect of zeolite effectively increase the rigidity of N-CDs. Based on the fluorescence quenching mechanism, the designed approach exhibits an excellent selectivity and good sensitive response to the presence of Hg(II) ions under ambient temperature, with a wide linear range of 0.1-1500 nM and lower detection limits of 5.5 pM. Influences of variables pH and incubation time were optimized. The N-CDs@NaFZ sensor was effectively applied for the detection of Hg(II) ions in the farmed and wild rainbow trout fishes, and the results are in reasonable agreement when compared with that obtained by the cold vapor atomic absorption method., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Crystal engineering has advanced the strategies for design and synthesis of organic solids with the main focus being on customising the properties of the materials. Research in this area has a significant impact on large-scale manufacturing, as industrial processes may lead to the deterioration of such properties due to stress-induced transformations and breakage. In this work, we investigate the mechanical properties of structurally related labile multicomponent solids of carbamazepine (CBZ), namely the dihydrate (CBZ·2H 2 O), a cocrystal of CBZ with 1,4-benzoquinone (2CBZ·BZQ) and the solvates with formamide and 1,4-dioxane (CBZ·FORM and 2CBZ·DIOX, respectively). The effect of factors that are external ( e.g. impact stressing) and/or internal ( e.g. phase transformations and thermal motion) to the crystals are evaluated. In comparison to the other CBZ multicomponent crystal forms, CBZ·2H 2 O crystals tolerate less stress and are more susceptible to breakage. It is shown that this poor resistance to fracture may be a consequence of the packing of CBZ molecules and the orientation of the principal molecular axes in the structure relative to the cleavage plane. It is concluded, however, that the CBZ lattice alone is not accountable for the formation of cracks in the crystals of CBZ·2H 2 O. The strength and the temperature-dependence of electrostatic interactions, such as hydrogen bonds between CBZ and coformer, appear to influence the levels of stress to which the crystals are subjected that lead to fracture. Our findings show that the appropriate selection of coformer in multicomponent crystal forms, targetting superior mechanical properties, needs to account for the intrinsic stress generated by molecular vibrations and not solely by crystal anisotropy. Structural defects within the crystal lattice, although highly influenced by the crystallisation conditions and which are especially difficult to control in organic solids, may also affect breakage., Competing Interests: The authors declare there were no conflicts of interest in this work., (This journal is © The Royal Society of Chemistry.)

Yoga is considered a widely-used approach for health conservation and can be adopted as a treatment modality for a plethora of medical conditions, including neurological and psychological disorders. Hence, we reviewed relevant articles entailing various neurological and psychological disorders and gathered data on how yoga exerts positive impacts on patients with a diverse range of disorders, including its modulatory effects on brain bioelectrical activities, neurotransmitters, and synaptic plasticity. The role of yoga practice as an element of the treatment of several neuropsychological diseases was evaluated based on these findings., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Non-disperse solvent extraction is an effective technique for the extraction of metal ions from aqueous solution. In this study, uranium extraction using n-dodecane solvent containing tributylphosphate extractant in a membrane contactor was investigated. A 2D mathematical model was developed for the fluid flow and mass transfer in the hollow fibre membrane extractor. The equations of the created model were solved using the finite element method. The uranium concentration distribution in the extractor at different extractant concentrations as well as feed acidity was studied. The results showed that there is reasonable good agreement between experimental uranium extraction and modelling outputs at different extractant concentrations. Increasing extractant concentration from 5 to 30% led to the enhancement of uranium extraction from 2.60 to 34.13%. Also, there was an increase in the uranium extraction with increasing feed acidity in the range of 1-3 M. Furthermore, based on the radial uranium concentration distribution, it was found that the main mass transfer resistance in the system was microporous membrane section. Finally, it was obtained that the uranium extraction efficiency could be improved significantly by increasing porosity-to-tortuosity ratio. It was concluded that the membrane specification plays the most important role as the dominant mass transfer resistant was in the membrane subdomain., (© 2021. The Author(s).)

Glidants and lubricants are often used to modify interparticle friction and adhesion in order to improve powder characteristics, such as flowability and compactability. Magnesium stearate (MgSt) powder is widely used as a lubricant. Shear straining causes MgSt particles to break, delaminate, and adhere to the surfaces of the host particles. In this work, a comparison is made of the effect of three mixer types on the lubricating role of MgSt particles. The flow behaviour of α-lactose monohydrate, coated with MgSt at different mass percentages of 0.2, 0.5, 1, and 5 is characterised. The mixing and coating process is carried out by dry blending using Turbula, ProCepT, and Mechanofusion. Measures have been taken to operate under equivalent mixing conditions, as reported in the literature. The flow resistance of the coated samples is measured using the FT4 rheometer. The results indicate that the flow characteristics of the processed powders are remarkably similar in the cases of samples treated by Turbula and Mechanofusion, despite extreme conditions of shear strain rate. The least flow resistance of samples is observed in the case of samples treated by the ProCepT mixer. High-velocity collisions of particles round off the sharp corners and edges, making them less resistant to flow. The optimal percentage of magnesium stearate is found to be approximately 1% by weight for all mixer types, as the addition of higher amounts of lubricant does not further improve the flowability of the material.

Spiral jet mills are ubiquitous in the pharmaceutical industry. Breakage and classification in spiral jet mills occur due to complex interactions between the fluid and the solid phases. The study of these interactions requires the use of computational fluid dynamics (CFD) for the fluid phase coupled with discrete element models (DEM) for the particle phase. In this study, we investigate particle dynamics in a 50-mm spiral jet mill through coupled CFD-DEM simulations. The simulations showed that the fluid was significantly decelerated by the presence of the particles in the milling chamber. Furthermore, we study the particle dynamics and collision statistics at two different operating conditions and three different particle loadings. As expected, the particle velocity was affected by both the particle loading and operating pressure. The particles moved slower at low pressures and high loadings. We also found that particle-particle collisions outnumbered particle-wall collisions.

Toll-like receptors (TLRs), a class of pattern recognition proteins, play an integral role in the modulation of systemic inflammatory responses. Cerebrovascular diseases (CVDs) are a group of pathological conditions that temporarily or permanently affect the brain tissue mostly via the decrease of oxygen and glucose supply. TLRs have a critical role in the activation of inflammatory cascades following hypoxic-ischemic events and subsequently contribute to neuroprotective or detrimental effects of CVD-induced neuroinflammation. The TLR signaling pathway and downstream cascades trigger immune responses via the production and release of various inflammatory mediators. The present review describes the modulatory role of the TLR signaling pathway in the inflammatory responses developed following various CVDs and discusses the potential benefits of the modulation of different TLRs in the improvement of functional outcomes after brain ischemia.

Peritoneal adhesion represents a severe complication following surgery. Punica granatum (pomegranate) possesses several anti-oxidative and anti-inflammatory properties. Pomegranate peel extract (PPEx) can alleviate the production of various inflammatory factors and cytokines. Thus, we sought to evaluate the anti-adhesion effects of pomegranate in rats. Thirty male Wistar rats (6-week-old, 220 ± 20 g) were divided into five groups (n = 6): normal group without any surgical procedures, control group, and experimental groups receiving 2 ml of 1%, 2%, and 4% w/v PPEx, respectively. Peritoneal adhesions were examined macroscopically. Furthermore, we evaluated inflammatory cytokines levels [interleukin 6 (IL-6), and tumour necrosis factor-α (TNF-α)], growth factors [transforming growth factor- β1 (TGF-β1), and vascular endothelial growth factor (VEGF)], and oxidative stress parameters [nitric oxide metabolites (NO), and malondialdehyde (MDA), and glutathione (GSH)] using biochemical methods. Our results showed that the adhesion score and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were increased in the control group. In contrast, the GSH level was diminished in the control group compared with the normal group (P < 0.001). PPEx (1 and 2% w/v) markedly reduced all measured parameters compared with the control group (P < 0.001-0.05). PPEx may reduce peritoneal adhesion by alleviating adhesion formation, IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA, and stimulating anti-oxidative factors. Therefore, PPEx may be considered an appropriate candidate for the treatment of postoperative peritoneal adhesion.

Spinal cord injury (SCI) is a disabling neurological disorder that causes neural circuit dysfunction. Although various therapies have been applied to improve the neurological outcomes of SCI, little clinical progress has been achieved. Stem cell-based therapy aimed at restoring the lost cells and supporting micromilieu at the site of the injury has become a conceptually attractive option for tissue repair following SCI. Adult human neural stem/progenitor cells (hNS/PCs) were obtained from the epileptic human brain specimens. Induction of SCI was followed by the application of lentiviral vector-mediated green fluorescent protein-labeled hNS/PCs seeded in PuraMatrix peptide hydrogel (PM). The co-application of hNS/PCs and PM at the SCI injury site significantly enhanced cell survival and differentiation, reduced the lesion volume, and improved neurological functions compared to the control groups. Besides, the transplanted hNS/PCs seeded in PM revealed significantly higher migration abilities into the lesion site and the healthy host tissue as well as a greater differentiation into astrocytes and neurons in the vicinity of the lesion as well as in the host tissue. Our data suggest that the transplantation of hNS/PCs seeded in PM could be a promising approach to restore the damaged tissues and improve neurological functions after SCI.

5-Aminolevulinic acid (5-ALA) is a naturally occurring non-proteinogenic amino acid, which contributes to the diagnosis and therapeutic approaches of various cancers, including glioblastoma (GBM). In the present study, we aimed to investigate whether 5-ALA exerted cytotoxic effects on GBM cells. We assessed cell viability, apoptosis rate, mRNA expressions of various apoptosis-related genes, generation of reactive oxygen species (ROS), and migration ability of the human U-87 malignant GBM cell line (U87MG) treated with 5-ALA at different doses. The half-maximal inhibitory concentration of 5-ALA on U87MG cells was 500 μg/mL after 7 days; 5-ALA was not toxic for human optic cells and NIH-3T3 cells at this concentration. The application of 5-ALA led to a significant increase in apoptotic cells, enhancement of Bax and p53 expressions, reduction in Bcl-2 expression, and an increase in ROS generation. Furthermore, the application of 5-ALA increased the accumulation of U87MG cells in the SUB-G1 population, decreased the expression of cyclin D1, and reduced the migration ability of U87MG cells. Our data indicate the potential cytotoxic effects of 5-ALA on U87MG cells. Further studies are required to determine the spectrum of the antitumor activity of 5-ALA on GBM.

Despite the ubiquity of physical systems evolving on time-dependent spatial domains, understanding their regular and chaotic dynamics is still in a rudimentary state. While chaos implies that the system's behavior can be altered by small perturbations, this sensitivity proves to be useful for control purposes. Here we report on the experimental discovery of a novel mechanism to control chaos by time-variation of the system (spatial domain) size: depending upon the rate of the latter, the chaotic state may be completely prevented. Our experimental observations are disentangled with theoretical insights and numerical modeling, which also reveals the ability to control spatio-temporal chaos, thus making the findings relevant to a wide range of natural phenomena.

Obstructive sleep apnea (OSA) is a chronic disorder that involves a decrease or complete cessation of airflow during sleep. It occurs when the muscles supporting the soft tissues in the throat relax during sleep, causing narrowing or closure of the upper airway. Sleep apnea is a serious medical condition with an increased risk of cardiovascular complications and impaired quality of life. Continuous positive airway pressure (CPAP) is the most effective treatment for moderate to severe cases of OSA and is effective in mild sleep apnea. However, CPAP therapy is associated with the development of several nasal side effects and is inconvenient for the user, leading to low compliance rates. The effects of CPAP treatment on the upper respiratory system, as well as the pathogenesis of side effects, are incompletely understood and not adequately researched. To better understand the effects of CPAP treatment on the upper respiratory system, we developed an in vitro 3D-printed microfluidic platform. A nasal epithelial cell line, RPMI 2650, was then exposed to certain conditions to mimic the in vivo environment. To create these conditions, the microfluidic device was utilized to expose nasal epithelial cells grown and differentiated at the air-liquid interface. The airflow was similar to what is experienced with CPAP, with pressure ranging between 0 and 20 cm of H 2 O. Cells exposed to pressure showed decreased barrier integrity, change in cellular shape, and increased cell death (lactate dehydrogenase release into media) compared to unstressed cells. Stressed cells also showed increased secretions of inflammatory markers IL-6 and IL-8 and had increased production of ATP. Our results suggest that stress induced by airflow leads to structural, metabolic, and inflammatory changes in the nasal epithelium, which may be responsible for developing nasal side-effects following CPAP treatment., (© 2021 IOP Publishing Ltd.)

Milling is widely used in various industries to tailor the particle size distribution for desired attributes. The ability to predict milling behaviour by testing the breakability of a small quantity of material is of great interest. In this paper, a widely available aerodynamic dispersion method, i.e. the Aero S disperser of Malvern Mastersizer 3000 has been evaluated for this purpose. This device is commonly used for dispersion of fine and cohesive powders, as the particles are accelerated and impacted at a bend, but here its use for assessing particle breakability is explored. The fluid flow field is modelled using one-way coupled Computational Fluid Dynamics approach, as the particle concentration is low, following which the particle impact velocity is calculated by Lagrangian tracking and used in the analysis of particle breakage. Experimental work on the breakability is carried out using aspirin, paracetamol, sucrose and α-lactose monohydrate particles. The relative shift in the specific surface area is determined and together with the calculated particle impact velocity and physical properties, they are used to calculate the breakability index. A good agreement is obtained with the single particle impact testing and aerodynamic dispersion by Scirocco disperser, indicating the breakability could also be inferred from this method., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, single-bubble electro-hydrodynamic effects on the two-phase laminar flow of water under electric field stress are investigated using numerical modeling. A 2D axisymmetric model is also developed to study the growth and departure of a single bubble. The phase-field method is applied to track the interphase between liquid and gas. The growth of the attached vapor bubble nucleus to a superheat at 7.0 °C and 8.5 °C are evaluated with 50° and 90° contact angles. The results show that the enhancement of the contact angle changes the velocity and temperature fields around the bubble. It is observed that the growing size and base of the bubble is increased with increasing the wall superheat, but the bubble departure diameter and time are decreased. The electric field results in raising the number of detached bubbles from the superheat at a certain time interval but decreasing the bubbles departure size. Additionally, the formation of stretched bubbles enhances the rate of heat flux and there is a non-linear relationship between the applied voltage and heat flux.

Collector type and pulp pH play an important role in the lead-zinc ore flotation process. In the current study, the effect of pulp pH and the collector type parameters on the galena and sphalerite flotation from a complex lead-zinc-iron ore was investigated. The ethyl xanthate and Aero 3418 collectors were used for lead flotation and Aero 3477 and amyl xanthate for zinc flotation. It was found that maximum lead grade could be achieved by using Aero 3418 as collector at pH 8. Also, iron and zinc recoveries and grades were increased in the lead concentrate at lower pH which caused zinc recovery reduction in the zinc concentrate and decrease the lead grade concentrate. Furthermore, the results showed that the maximum zinc grade and recovery of 42.9% and 76.7% were achieved at pH 6 in the presence of Aero 3477 as collector. For both collectors at pH 5, Zinc recovery was increased around 2-3%; however, the iron recovery was also increased at this pH which reduced the zinc concentrate quality. Finally, pH 8 and pH 6 were selected as optimum pH values for lead and zinc flotation circuits, respectively.

Preliminary studies indicate that a robust immune response across different cell types is crucial in recovery from coronavirus disease 2019 (COVID-19). An enormous number of investigations point to the vital importance of various micronutrients in the interactions between the host immune system and viruses, including COVID-19. There are complex and multifaceted links among micronutrient status, the host immune response, and the virulence of pathogenic viruses. Micronutrients play a critical role in the coordinated recruitment of innate and adaptive immune responses to viral infections, particularly in the regulation of pro- and anti-inflammatory host responses. Furthermore, inadequate amounts of micronutrients not only weaken the immune system in combating viral infections, but also contribute to the emergence of more virulent strains via alterations of the genetic makeup of the viral genome. The aim of this study was to evaluate the evidence that suggests the contribution of micronutrients in the spread as well as the morbidity and mortality of COVID-19. Both the presence of micronutrient deficiencies among infected individuals and the effect of micronutrient supplementation on the immune responses and overall outcome of the disease could be of great interest when weighing the use of micronutrients in the prevention and treatment of COVID-19 infection. These investigations could be of great value in dealing with future viral epidemics., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Porous hollow fibres made of polyvinylidene fluoride were employed as membrane contactor for carbon dioxide (CO 2 ) absorption in a gas-liquid mode with methyldiethanolamine (MDEA) based nanofluid absorbent. Both theoretical and experimental works were carried out in which a mechanistic model was developed that considers the mass transfer of components in all subdomains of the contactor module. Also, the model considers convectional mass transfer in shell and tube subdomains with the chemical reaction as well as Grazing and Brownian motion of nanoparticles effects. The predicted outputs of the developed model and simulations showed that the dispersion of CNT nanoparticles to MDEA-based solvent improves CO 2 capture percentage compared to the pure solvent. In addition, the efficiency of CO 2 capture for MDEA-based nanofluid was increased with rising MDEA content, liquid flow rate and membrane porosity. On the other hand, the enhancement of gas velocity and the membrane tortuosity led to reduced CO 2 capture efficiency in the module. Moreover, it was revealed that the CNT nanoparticles effect on CO 2 removal is higher in the presence of lower MDEA concentration (5%) in the solvent. The model was validated by comparing with the experimental data, and great agreement was obtained.

An integrated hydrometallurgical process was used for the zinc leaching and purification from a zinc ore containing 9.75 wt% zinc. The zinc minerals in the ore were hemimorphite, willemite, and calcophanite. Main gangue minerals were quartz, goethite, hematite, and calcite. Central composite design (CCD) method was used to design leaching experiments and the optimum conditions were found as follows: 30% of solid fraction, 22.05% sulphuric acid concentration, and the leaching temperature of 45 °C. The PLS containing 35.07 g/L zinc, 3.16 g/L iron, and 4.58 g/L manganese impurities was produced. A special purification process including Fe precipitation and Zn solvent extraction was implemented. The results showed that after precipitation of iron, Zn extraction of 88.5% was obtained with the 2 stages extraction system composed of 30 vol% D2EHPA as extractant. The overall Zn recovery from the ore was 71.44%. Therefore, an appropriate solution containing 16.6 g/L Zn, 0.05 g/L Fe, and 0.11 g/L Mn was prepared for the electro-winning unit without using the roasting and calcination steps (conventional method), which result in environmental pollution.

Here, electro-chemical properties of BN and BP nanocages as anodes in metal-ion batteries are examined. The effect of halogens adoption of BN and BP-NCs on electro-chemical properties of M-IBs are investigated. Results showed that the BP nanocages as anode electrode in M-IBs has higher efficiency than BN nanocages and the K-IB has higher cell voltage than N-IBs. Results indicated that the halogens adoption of BN and BP-NCs are improved the cell voltage of M-IBs. Results proved that the F-doped M-IBs have higher cell voltage than M-IBs. Finally, F-B 17 P 18 as anodes in K-IB is proposed as suitable electrodes.

Continuous membrane separation of pharmaceuticals from an aqueous feed was studied theoretically by development of high-performance mechanistic model. The model was developed based on mass and momentum transfer to predict separation and removal of ibuprofen (IP) and its metabolite compound, i.e. 4-isobutylacetophenone (4-IBAP) from aqueous solution. The modeling study was carried out for a membrane contactor considering mass transport of solute from feed to organic solvent (octanol solution). The solute experiences different mass transfer resistances during the removal in membrane system which were all taken into account in the modeling. The model's equations were solved using computational fluid dynamic technique, and the simulations were carried out to understand the effect of process parameters, flow pattern, and membrane properties on the removal of both solutes. The simulation results indicated that IP and 4-IBAP can be effectively removed from aqueous feed by adjusting the process parameters and flow pattern. More removal was obtained when the feed flows in the shell side of membrane system due to improving mass transfer. Also, feed flow rate was indicated to be the most affecting process parameter, and the highest solute removal was obtained at the lowest feed flow rate.

Wastewater effluent from alkaloid processing plants has the potential adverse environmental influences. Mathematical modelling and simulations were carried out using computational fluid dynamics of mass and momentum transfer in a hollow fibre membrane extractor. Conservation equations were derived for tyramine extraction in the membrane extractor and solved based on the finite element method. Model findings based on the computational fluid dynamics validated well with the experimental data. The results showed that increase in organic-phase flow rate, as well as the fibre length and its porosity, has a positive impact on the performance of the extractor, whereas the enhancement of aqueous-phase flow rate led to the reduction of tyramine extraction.

The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr -/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.

Purpose: The aim of this study was to develop a nasal powder formulation of the antifibrinolytic drug, tranexamic acid (TXA), in combination with the wound-healing agent hyaluronic acid (HA) for the local treatment of epistaxis (nose bleeding)., Methods: Formulations of TXA alone and with different concentrations of HA were freeze-dried and characterised according to their physicochemical properties. Aerosol performance was assessed to ensure nasal deposition with minimal lung deposition. Nasal epithelial cells were used to assess cytotoxicity, transport across the nasal epithelium, antioxidant, wound-healing and anti-inflammatory properties of all formulations., Results: Formulations containing TXA and HA were produced and found to be mostly deposited in the nasal cavity (more than 90%). Formulation of TXA + 0.3%HA showed wound reduction of 29.3% when assessed in ALI culture. At this concentration, formulations also reduced ROS production in RPMI 2650, and IL-8 production in primary nasal epithelial cells. Furthermore, for formulations containing HA, the higher viscosity may lead to larger residence time in the nasal cavity., Conclusions: Combination of TXA with HA shows promising results for the treatment of nasal epistaxis.