Experimental Model Research Articles

Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function

Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.

Experimental and numerical studies on moisture adsorption/desorption characteristics across the circular fin tube desiccant coated heat exchanger

To improve the energy transfer abilities, enhance the quality of air, and curtail the growth of microorganisms, the desiccant coated heat exchangers are a capable substitute compared to conventional heat exchangers due to their capability of decoupling the sensible and latent loads and utilizing low-grade thermal energy. The concept of desiccant coated heat exchangers (DCHE) can be employed in various heat exchange/transport systems like heat pumps, atmospheric water harvesters, adsorption chillers, and air conditioners. Thus, in this research work, a circular fin tube desiccant coated heat exchanger (DCCHE) has been proposed and designed and a dynamic numerical model is established for simulating the combined heat and mass transport occurring across the adsorption/desorption process of a DCCHE employing finite element approach. The moisture and temperature distribution and flow of fluid are considered in the transient numerical model covering several domains such as water flow, air flow, and the coated desiccant. The desiccant material utilized in the current analysis is silica gel. The validation study showed good agreement, and the maximum error between the experimental result and simulated model for the humidity ratio of air and temperature of outlet air were observed to be ± 8 % and ± 7 %, respectively. A parametric analysis is carried out to assess the effect of varying the different input parameters on DCCHE’s performance. The field emission scanning electron microscopy results concluded that a uniform coating is formed on the circular fin surface. The experimental examination on the sorption kinetics of the silica gel showed that the moisture uptake capability was 0.34 g/g. Moreover, the proposed circular fin tube desiccant coated heat exchanger has been compared with the conventional plate type fin tube DCHE to assess its performance in terms of thermal coefficient of performance and specific dehumidification energy.

Deferiprone promoted remyelination and functional recovery through enhancement of oligodendrogenesis in experimental demyelination animal model.

Remyelination refers to myelin regeneration, which reestablishes metabolic supports to axons. However, remyelination often fails in multiple sclerosis (MS), leading to chronic demyelination and axonal degeneration. Therefore, pharmacological approaches toward enhanced remyelination are highly demanded. Recently, deferiprone (DFP) was reported to exert neuroprotective effects, besides its iron-chelating ability. Since DFP exerts protective effects through various mechanisms, which share several factors with myelin formation process, we aimed to investigate the effects of DFP treatment on remyelination. Focal demyelination was induced by injection of lysolecithin, into the optic nerve of male C57BL/6J mice. The animals were treated with DFP/vehicle, starting from day 7 and continued during the myelin repair period. Histopathological, electrophysiological, and behavioral studies were used to evaluate the outcomes. Results showed that DFP treatment enhanced remyelination, decreased g-ratio and increased myelin thickness. At the mechanistic level, DFP enhanced oligodendrogenesis and ameliorated gliosis during the remyelination period. Furthermore, our results indicated that enhanced remyelination led to functional recovery as evaluated by the electrophysiological and behavioral tests. Even though the exact molecular mechanisms by which DFP-enhanced myelin repair remain to be elucidated, these results raise the possibility of using deferiprone as a therapeutic agent for remyelination therapy in MS.

A comprehensive review of experimental models and induction protocols for avian necrotic enteritis over the past 2 decades

Necrotic enteritis (NE) is a severe gastrointestinal disease that poses a significant threat to the poultry industry. It leads to progressive damage to the small intestine, reduced performance, increased mortality rates, and substantial economic losses. With the removal of antimicrobial agents from chicken feed, there is an urgent need to find alternative approaches for NE control. Various approaches, including vaccination, prebiotics, probiotics, and plant-derived products, have been utilized to address NE in poultry management. To evaluate the efficacy of these preventive measures against NE, successful induction of NE is crucial to observe effects of these approaches in related studies. This study presents a comprehensive overview of the methods and approaches utilized for NE reproduction in related studies from 2004 to 2023. These considerations are the careful selection of a virulent Clostridium perfringens strain, preparation of challenge inoculum, choice of time and the route for challenge inoculum administration, and utilization of one or more predisposing factors to increase the rate of NE occurrence in birds under experiment. We also reviewed the different systems used for lesion scoring of NE-challenged birds. By gaining clarity on these fundamental parameters, researchers can make informed decisions regarding the selection of the most appropriate NE experimental design in their respective studies.

Experimental Protocols Used to Mimic Gastrointestinal Protein Digestion: A Systematic Review

Bioactive peptides derived from native proteins modulate physiological processes in the metabolic pathways. Given that multiple protocols in the literature mimic the digestion of dietary components, gathering studies that use such models directed at protein digestion processes is critical. This systematic review aimed to gather evidence that adopted adequate experimental models to simulate human protein digestion. The databases searched were PubMed, Web of Science, ScienceDirect, Embase, Virtual Health Library, and Scopus. A total of 1985 articles were found, resulting in 20 eligible in vitro studies. The Office of Health Assessment and Translation was used to evaluate methodological quality. Seven studies used plant-based protein sources, twelve used animal protein sources, and one used both. The duration of the oral phase varied, although 60% of the studies employed a protein digestion period of 120 min. Amylase, pepsin, and pancreatin enzymes were utilized in 40% of the studies, with pH levels of 7, 3, and 7, respectively, during the oral, gastric, and intestinal phases. The INFOGEST harmonized static model was adopted by 65% of the studies; INFOGEST is the most effective model for simulating gastrointestinal protein processes in humans and can be used to answer several research questions because it describes experimental conditions close to the human physiological situation.

EuroPED-NN: Uncertainty aware surrogate model

Abstract This work successfully generates an uncertainty-aware surrogate model of the EuroPED plasma pedestal model using the Bayesian neural network with noise contrastive prior (BNN-NCP) technique. This model is trained using data from the JET-ILW pedestal database and subsequent model evaluations, conforming to EuroPED-NN. The BNN-NCP technique has been proven to be a suitable method for generating uncertainty-aware surrogate models. It matches the output results of a regular neural network while providing confidence estimates for predictions as uncertainties. Additionally, it highlights out-of-distribution (OOD) regions using surrogate model uncertainties. This provides critical insights into model robustness and reliability. EuroPED-NN has been physically validated, first, analyzing electron density ne(ψpol = 0.94) with respect to increasing plasma current, Ip, and second, validating the ∆ − βp,ped relation associated with the EuroPED model. This affirms the robustness of the underlying physics learned by the surrogate model. On top of that, the method was used to develop a EuroPED-like model fed with experimental data, i.e. an uncertainty aware experimental model, which is functional in JET database. Both models have been also tested in ∼ 50 AUG shots.

Biochemical and histological changes in two nonalcoholic fatty liver disease models of different severity

Background. One of the priority areas of modern medicine, which unites the interests of various specialists (therapists, cardiologists, gastroenterologists, endocrinologists), is the study of the pathogenesis and clinical manifestations of nonalcoholic fatty liver disease (NAFLD), which is widespread and of unconditional social significance. The search for adequate experimental models of NAFLD that reflect the severity of liver damage is of paramount importance for studying its etiology and pathogenesis.The aim of the study. To compare biochemical and histological changes in experimental models of NAFLD of varying severity.Materials and methods. Two NAFLD model versions were used: a light one – nonalcoholic steatosis (NAS) and a severe variant – non-alcoholic steatohepatitis (NASH). The following biochemical parameters were measured: enzyme activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), plasma glucose concentration, total protein (TP), total bilirubin (TBil) and its conjugate fraction (CB), plasma concentrations of homocysteine (HC), total cholesterol (TC), triacylglycerides (TG), catalase (Cat), superoxide dismutase (SOD) and malondialdehyde (MDA).Results. When used in a model of steatohepatitis, liver function was impaired to a significantly greater extent than in the model of steatosis; this difference was manifested in a statistically significant increase in ALT, AST, AP, TC, Tbil, MDA (p < 0.001) and a decrease in Cat, SOD (p < 0.05). This is confirmed by the development of more pronounced symptoms of disorders of pigment and lipid metabolism, cytolytic and cholestatic syndromes, significant activation of lipid peroxidation and depression of the antioxidant system when modeling non-alcoholic steatohepatitis. Various degrees of severity of morphological changes in the experimental groups were revealed.Conclusion. The study showed the priority of determining biochemical markers, including the levels of ALT, AST, OBIL, TG, MDA and SOD to optimize laboratory methods for diagnosing the severity of liver dystrophy.The practical originality of the results lies in the optimization of the methodology for laboratory diagnosis of the severity of the pathological process in NAFLD.

Experimental modeling of the interaction of fluorine-containing granite melt and calcite marble

Experimental modeling of the interaction of fluorine-containing granite melt and calcite marble

Formulation and Evaluation of Diuretic Activity of Polyherbal Drug in Rats

An attempt was made in this study to investigate the diuretic activity of an ethanolic extract of a polyherbal formulation containing four drugs: seeds of Coriandrum sativum, buds of Syzigiumaromaticum, leaves of Ocimum sanctum, and curcumin (Curcuma longa), as well as leaves of Syzigiumaromaticum. According to the findings of this investigation, the extract of a polyherbal formulation (including seeds of Coriandrum sativum, buds and leaves of Syzigiumaromaticum& leaves of Ocimum sanctum, and Curcuma longa) possessed substantial activity. Various quantities of Polyherbal formulations (200 and 400 mg/kg), furosemide (10 mg/kg), and vehicle were given orally to rats (n = 6 animals per group), and the urine output was collected after 24 hours. All concentrations of Polyherbal formulation exhibited a dose-dependent relationship when compared to the control animals in the study. According to the findings of this study, the Polyherbal formulations have significant diuretic effect in rats when tested in the above-mentioned experimental model. That polyherbal formulation extract has such potent effect may be due to their ability to stimulate the excretion of Na+, K+, and Cl- concentrations in urine while also increasing the amount of urine excreted by the body. As diuretics, medicinal herbs are a key source of supply. When it comes to diuretics, both mono- and poly-herbal formulations have been employed successfully

The effects of baicalin in depression: preclinical evidence construction based on meta-analysis

BackgroundDepression manifests as a mental disorder characterized by a low mood, suicidal tendencies, disturbances in sleep-wake cycles, psychomotor agitation, and pronounced feelings of hopelessness and anhedonia. Baicalin, a natural flavonoid compound, shows significant promise in alleviating depressive symptoms in animals. This study aims to assess the impact of baicalin on experimental models of depression.MethodsA systematic search of electronic databases was conducted using the search terms “baicalin” AND “depression” OR “depressed” OR “anti-depression”. Preclinical animal models representing experimental depression were included in the analysis. The risk of bias in the included studies was evaluated using the CAMARADES tools.ResultsBaicalin significantly increased sucrose preference test (SPT) [SMD= 21.31, 95%CI (16.32, 26.31), P < 0.00001]. mThe tail suspension test (TST) duration significantly decreased in the baicalin group compared to the model group [SMD = −39.3, 95%CI (−49.71, −28.89), P < 0.0001]. Furthermore, baicalin reduced immobility time in rats subjected to the forced swim test (FST) [SMD = −39.73, 95%CI (−48.77, −30.69) P < 0.0001]. Compared to the model group, baicalin treatment also significantly increased the frequency of crossings in the open field test (OFT) [SMD = 32.44, 95%CI (17.74, 47.13), P < 0.00001].ConclusionBaicalin significantly improves the manifestations of depressive symptoms. The effect of baicalin against depression is exerted through its anti-inflammatory actions, inhibition of oxidative stress, regulation of the HPA axis, and restoration of neuroplasticity. Future studies will be needed to further explore how these promising preclinical findings can be translated into clinical treatment for depression.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472181.

Creating Fuzzy Models from Limited Data

The design of experiments is a methodological approach in which measurement experiments are carefully planned to obtain highly informative data. This paper addresses the challenge of constructing mathematical models for complex nonlinear processes when the available measurement data have low information content. This problem often arises when data are collected without the guidance of an experimental modeling expert. We examine two practical examples to illustrate this issue: a textile wastewater decolorization process and atmospheric corrosion of structural metal materials. In both cases, the measured data were insufficient to construct highly accurate models. It is, therefore, necessary to make a trade-off between model complexity and accuracy by adapting modeling techniques to work effectively with the limited data available. The main aim of the paper is, therefore, to focus on simple but effective techniques that allow as much information as possible to be extracted from low-quality measurements and to maximize the usefulness of the model for its intended purpose.

Sex similarities and divergences in systemic and muscle iron metabolism adaptations to extreme physical inactivity in rats.

Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI. Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (n=12/group). After 7days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot. Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, p<0.001), liver (LIC; +198%, P<0.001), spleen (SIC; +76.1%, P<0.001), and transferrin saturation (TS) in serum (+53.3%, P<0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% P<0.001) and SIC (+30.1%, P=0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; P<0.05) and a decrease of TFRC protein levels (-36%; -50%, respectively, P<0.05). HU males also exhibited an increase of splenic HO-1 and NRF2 mRNA levels, (p<0.001), as well as HU females (P<0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, P=0.004) while only a trend is observed in males (+17.5%, P=0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, P<0.001, +22%, P=0.011, respectively) and in females (+369%, P<0.001, +21.9%, P=0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (-68.9%, P<0.001, -76.8%, P<0.001, respectively) and females (-75.9%, P<0.001, -62.9%, P<0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (-39.9% for males P=0.010 and -49.1% for females P<0.001). Taken together, these data support that, in rats (1) extreme physical inactivity differently impacts the distribution of iron in both sexes, (2) splenic erythrophagocytosis could play a role in this iron misdistribution. The higher iron concentrations in atrophied soleus from both sexes are associated with a decoupling between the increase in iron storage proteins (i.e., ferritin and myoglobin) and the decrease in levels of iron export proteins (i.e., FPN and FLVCR1), thus supporting an iron sequestration in skeletal muscle under extreme physical inactivity.

Interaction between Intestinal Parasites and the Gut Microbiota: Implications for the Intestinal Immune Response and Host Defence

Intestinal parasites, including helminths and protozoa, account for a significant portion of the global health burden. The gastrointestinal (GI) tract not only serves as the stage for these parasitic infections but also as the residence for millions of microbes. As the intricacies of the GI microbial milieu continue to unfold, it is becoming increasingly apparent that the interactions between host, parasite, and resident microbes help dictate parasite survival and, ultimately, disease outcomes. Across both clinical and experimental models, intestinal parasites have been shown to impact microbial composition and diversity. Reciprocally, microbes can directly influence parasitic survival, colonization and expulsion. The gut microbiota can also indirectly impact parasites through the influence and manipulation of the host. Studying this host–parasite–microbiota axis may help bring about novel therapeutic strategies for intestinal parasitic infection as well as conditions such as inflammatory bowel disease (IBD). In this review, we explore the relationship between intestinal parasites, with a particular focus on common protozoa and helminths, and the gut microbiota, and how these interactions can influence the host defence and intestinal immune response. We will also explore the impact of this tripartite relationship in a clinical setting and its broader implications for human health.

A first-in-human phase I clinical study with MVX-ONCO-1, a personalized active immunotherapy, in patients with advanced solid tumors.

Purpose Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient's own tumor cells, providing the widest cancer-specific antigens repertoire and a standardized, sustained, local delivery over days of a potent adjuvant achieved by encapsulated cell technology. Experimental Design We conducted an open-label, single-arm, first-in-human, phase I study with MVX-ONCO-1 in advanced refractory solid cancer patients. MVX-ONCO-1 comprises irradiated autologous tumor cells co-implanted with two macrocapsules containing genetically engineered cells producing granulocyte macrophage stimulating factor (GM-CSF). Patients received six immunizations over nine weeks without maintenance therapy. Primary objectives were safety, tolerability, and feasibility, while secondary objectives focused on efficacy and immune monitoring. Results Data from 34 patients demonstrated safety and feasibility with minor issues. Adverse events included one serious event (SAE) possibly related to investigational medicinal product (IMP), and two moderate-related adverse events (AE). Over 50% of patients with advanced and mainly non-immunogenic tumors showed clinical benefits, including partial responses (PR), stable diseases (SD), and prolonged survival. In recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), one patient achieved a PR, while another survived for more than 7 years without anticancer therapy for over 5 years. Conclusion/Discussion MVX-ONCO-1 is safe, well-tolerated, and beneficial across several tumor types. Ongoing phase IIa trials target advanced R/M HNSCC patients post initial systemic therapy.

Cardioprotective role of long-term kefir and omega-3 fatty acid supplementation on myocardial apoptosis via oxidative stress-mediated lysosomal cathepsin release in isoproterenol-induced myocardial infarction rat model

Objective: The antiapoptotic and antioxidative role of long-term kefir and omega-3 fatty acids and their relationship with cysteine proteases on isoproterenol (ISO) induced myocardial infarction (MI) experimental model was investigated in our study. Material and Methods: Fifty male Sprague-Dawley rats were evenly divided into five distinct groups (n=10): Control, MI, kefir +MI, omega-3+MI, and kefir+omega 3+MI groups. Kefir 10% (with drinking water) and omega-3 fatty acid (30 mg/day per 100g body weight into the standard chow) were administrated during 30 days. ISO was subcutaneously injected into the rats (100 mg/ kg b.w.) on the 29th and 30th days. Myocardial tissue and blood samples were taken 12 hours after the last ISO dose. Creatine kinase MB (CK-MB) activities were measured in serum samples. Caspase-3, superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), DNA fragmentation, cathepsin B and L levels, were measured in myocardial tissue. Results: Serum CK-MB (p&lt;0.05) and cardiac tissue MDA (p&gt;0.05), NO (p&lt;0.01), caspase 3 (p&lt;0.01), DNA fragmentation (p&lt;0.001), cathepsin B (p&lt;0.05) and L (p&lt;0.05) activities were increased and SOD (p&lt;0.001) activities were decreased in MI group compared to control group. The preventive effects of long-term therapy with kefir and omega-3 fatty acids have been demonstrated on apoptosis, oxidative stress markers, and cysteine protease enzymes. Conclusion: Our results showed that long-term administration of kefir and omega-3 fatty acids might be effective in reducing myocardial apoptosis through oxidative stress-mediated release of cysteine proteases in myocardial infarction, especially in the kefir and combined therapy groups.

The Comparison of Catalytic Activity of Carbimazole and Methimazole on Electroreduction of Zinc (II) in Chlorates (VII): Experimental and Molecular Modelling Study

With the help of electrochemical methods, including CV and EIS, the influence of methimazole, carbimazole, and the concentration of the supporting electrolyte on the kinetics and mechanism of zinc electroreduction on a mercury electrode was compared and analyzed. Moreover, molecular dynamics simulations of zinc/carbimazole and zinc/methimazole solutions were carried out to determine the effect of drugs on the hydration sphere of Zn2+ ions. It was shown that the electroreduction of Zn2+ in the presence of methimazole and carbimazole occurs in two steps and the first one determines the kinetics of the entire process. The presence of both drugs in the solution and the increase in the concentration of the supporting electrolyte reduce the degree of hydration of the depolarizer ions and the hydration of the electrode surface, what is a factor favoring the rate of electroreduction. Based on theoretical studies, the formation of stable complexes between Zn2+ and the molecules of both drugs in a solution was considered unlikely. However, active complexes can be formed between depolarizer ions and molecules adsorbed at the electrode surface. They constitute a bridge facilitating charge exchange during the electrode reaction, revealing the catalytic abilities of methimazole and carbimazole. In the range of cdrug ≤ 1 × 10−3 mol dm−3, carbimazole is a better catalyst, whereas in the range of cdrug ≥ 5 × 10−3 mol dm−3, it is methimazole. The effectiveness of both compounds in catalyzing the first stage of the electrode reaction increases with the increase in the NaClO4 concentration.

Experimental and prediction model of axial compressive responses of corroded RC cylinders strengthened with CFRP

Currently, the capacity of corroded RC cylinders has been proven to significantly improve after being strengthened with carbon fiber reinforced polymer (CFRP). However, existing experimental data remains insufficient, resulting in few models available for predicting the post-strengthening capacity of corroded cylinder. The current understanding of the mechanism by which corrosion affects the mechanical properties of CFRP strengthened cylinders is also not yet clear. Against this background, this study conducted monotonic axial compression tests on CFRP-strengthened corroded RC cylinders. The experimental results indicate that while the CFRP layer predominantly controls the specimen's load-bearing capacity, the reduction in CFRP rupture strain due to increased corrosion rates should not be overlooked. When the corrosion rate reaches 35 %, the experimentally measured average rupture strain was only 65 % of the theoretical value, marking a 30 % decrease compared to non-corroded specimens. Subsequently, a predictive model for peak stress and strain of CFRP-confined corroded RC cylinders was proposed, which considers the confinement mechanisms of stirrups and CFRP as well as the degradation of CFRP rupture strain. Leveraging the existing test data, a dataset comprising 80 CFRP-strengthened corroded RC cylinder specimens was established to calibrate the key parameters in the proposed prediction model. Comparative analysis with existing models indicates that the peak stress and strain prediction model proposed in this study demonstrated the highest forecasting accuracy (the average errors for peak stress and strain were 14 % and 32.6 %, respectively), while existing other predictive models based on limited datasets suffer from a lack of universality. The experimental data and research conclusions of this article can provide reference for engineering practice and the establishment of models in subsequent research.

Spatial information allows inference of the prevalence of direct cell-to-cell viral infection.

The role of direct cell-to-cell spread in viral infections-where virions spread between host and susceptible cells without needing to be secreted into the extracellular environment-has come to be understood as essential to the dynamics of medically significant viruses like hepatitis C and influenza. Recent work in both the experimental and mathematical modelling literature has attempted to quantify the prevalence of cell-to-cell infection compared to the conventional free virus route using a variety of methods and experimental data. However, estimates are subject to significant uncertainty and moreover rely on data collected by inhibiting one mode of infection by either chemical or physical factors, which may influence the other mode of infection to an extent which is difficult to quantify. In this work, we conduct a simulation-estimation study to probe the practical identifiability of the proportion of cell-to-cell infection, using two standard mathematical models and synthetic data that would likely be realistic to obtain in the laboratory. We show that this quantity cannot be estimated using non-spatial data alone, and that the collection of a data which describes the spatial structure of the infection is necessary to infer the proportion of cell-to-cell infection. Our results provide guidance for the design of relevant experiments and mathematical tools for accurately inferring the prevalence of cell-to-cell infection in in vitro and in vivo contexts.

Microfluidic extensional flow device to study mass transfer dynamics in the polymer microparticle formation process.

Polymer microparticles are often used to encapsulate drugs for sustained drug-release treatments. One of the ways they are manufactured is by using a solvent extraction process, in which the polymer solution is emulsified into an aqueous bulk phase using a surfactant as a stabilizing agent, followed by the removal of the solvent. The radius of a polymer drop decreases as a function of time until the polymer reaches the gelling point, after which it is separated and dried. Among the various operating parameters, the rate of solvent extraction is a critical step that affects the morphology and porosity, and consequently, the kinetics of drug release. But a fundamental mechanistic understanding of the solvent extraction dynamics as a function of shear is still unexplored. In this study, we have developed an experimental mass transfer model to predict the extraction by using the microfluidic extensional flow device (MEFD) to probe the shear and extraction dynamics at the level of a single drop in a linear extensional flow field. We used a computer-controlled feedback algorithm to manipulate the flow field and hydrodynamically trap a Hele-Shaw drop and observe the extraction process. For the polymer solution, we used a biocompatible polymer, poly-lactic-co-glycolic acid (PLGA) with ethyl acetate (EtOAc) as the solvent. Our experiments were conducted by varying the extensional rate (G) in the channel from ∼0.1 s-1 to ∼10 s-1, and using an analytical solution of the flow field, we captured the dissolution process and measured the change in drop radius (R) with time (t). Interestingly, we initially observed a short-time asymptote R ∼ t, and later the long-time asymptote of R = constant; both trends were physically explained. The transport model developed in this work can be used to predict extraction rates and polymer microparticle composition for any polymer-solvent system. This work is also an important contribution to the literature on convective mass transfer in partially miscible emulsions.

Electrolytic synthesis of γ-Al2O3 nanoparticle from aluminum scrap for enhanced methylene blue adsorption: experimental and RSM modeling

The presence of methylene blue (MB) dye in wastewater has raised concern about human health and environmental ecology due to potential carcinogenic, and mutagenic effects. Therefore, this work aims to remove MB dye from wastewater using γ-Al2O3 nanoparticles synthesized from aluminum scrap via simple electrolytic method. The successful synthesis of the adsorbent was confirmed by a range of spectroscopy and microscopy techniques, including XRD, SEM, FTIR, and BET. The central composite design (CCD) of the response surface methodology (RSM) method was used to optimize the processing parameters such as solution pH, contact time, initial MB concentration, and adsorbent dose. The ANOVA results clearly shows that the quadratic model (p < 0.0001) was sufficient to the best predicting of the removal performance of MB dye (R2 = 0.9862). The optimum condition for the maximum MB dye removal (98.91%) was achieved at solution pH of 8.298, initial MB concentration of 31.657 mg/L, adsorbent dose of 0.387 g/L, and contact time of 46.728 min. Nano-γ-Al2O3 was shown to have a good surface area of 59 mg2/g by BET analysis. The adsorption kinetics follows the pseudo-second-order model (R2 = 0.997). With a maximum adsorption capacity of 137.17 mg/g, the Langmuir isotherm model (R2 = 984) provides the best fit to the adsorption isotherm data, indicating a monolayer adsorption process. Furthermore, thermodynamic analysis demonstrated that the adsorption of MB dye was an endothermic and spontaneous process. The reusability study showed that γ-Al2O3 nano-adsorbent retained 85.08% of its original removal efficiency after five cycles. According to the findings of the study, MB dye molecules were taken up by γ-Al2O3 nano-adsorbent via hydrogen bond formation, Van der Waals interaction, and electrostatic attraction. Therefore, γ-Al2O3 nanoparticles can be used as a potentially eco-friendly and low-cost adsorbent for the removal of MB dye from aqueous solutions.