Free Solution Research Articles

Investigating the Mechanisms Underlying U46619-Induced Contraction on Porcine Lower Esophageal Sphincter.

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES. To achieve this, contractions of the clasp and sling strips of the porcine LES, induced by U46619, were measured using isometric transducers. Furthermore, the contractile mechanism of U46619 in the porcine LES was investigated by pretreating the strips with atropine (a muscarinic receptor antagonist), tetrodotoxin (a neuronal sodium channel blocker), nifedipine (a calcium channel blocker), and Ca2+-free Krebs-Henseleit solution. Additionally, reverse transcription polymerase chain reaction (PCR) and immunohistochemistry (IHC) were performed to determine the presence of the TXA2 receptor in porcine LES. The results of this study demonstrated that U46619 caused marked concentration-dependent contractions in both porcine sling and clasp strips. The mechanism of U46619-induced contraction of the porcine LES was found to be related to calcium channels. Furthermore, the reverse transcription PCR analysis and IHC revealed that the TXA2 receptor was expressed in the clasp and sling fibers of porcine LES. Consequently, this study suggests that U46619 mediates the contraction of porcine LES through calcium channels and has potential as a therapeutic approach for treating GERD. SIGNIFICANCE STATEMENT: This study establishes that U46619 induces concentration-dependent contractions in porcine LES, primarily mediated by calcium channels. The presence of the TXA2 receptor in LES clasp and sling fibers is confirmed. These findings highlight U46619's potential as a GERD therapeutic by targeting calcium channels for LES contraction modulation.

DriveLEDs: software for synchronous control and video acquisition of fluorescent signals

Current research uses various fluorescent biosensors to measure ion concentrations, neuronal activity, or cellular components in biological preparations. Several free solutions are available to researchers for recording or analysing fluorescent signals. However, when using different software packages, there are great difficulties in converting data between them. Problems also arise with linking and coordination of individual hardware devices into a single measurement system. Our paper presents useful software that allows to avoid most of these problems. It enables the recording, online visualization and preliminary analysis of fluorescent signals in brain cells and other experimental models. We describe and test software optimized for ratiometric measurements. The program selects device operating modes that allow reliable changes in illumination wavelength, camera image capture, and online graphical visualization of fluorescent signal amplitudes or ratiometric data. The performance of the software was successfully tested on mouse brain using two experimental models; i) simultaneous monitoring of intracellular chloride and hydrogen in transgenic mice expressing genetically encoded biosensor; ii) recording changes in reactive oxygen species during synaptic stimulation of neurons in mouse hippocampal slices. This software allows to overcome the incompatibility of the devices used and reduce the cost of experimental measurements. The software is completely original, easy to use and may be of interest to many scientists involved in the analysis of light-controlled signals in a variety of experimental models, including drug screening, epilepsy models, and other applications. The software is open-source product and can be obtained via GitHub: https://github.com/AndreyZakharovExp/DriveLEDs.

In diabetic male Wistar rats, quercetin-conjugated superparamagnetic iron oxide nanoparticles have an effect on the SIRT1/p66Shc-mediated pathway related to cognitive impairment

BackgroundQuercetin (QC) possesses a variety of health-promoting effects in pure and in conjugation with nanoparticles. Since the mRNA-SIRT1/p66Shc pathway and microRNAs (miRNAs) are implicated in the oxidative process, we aimed to compare the effects of QC and QC-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on this pathway.MethodsThrough the use of the chemical coprecipitation technique (CPT), SPIONs were synthesized, coated with dextran, and conjugated with quercetin. Adult male Wistar rats were given intraperitoneal injections of streptozotocin to look for signs of type 1 diabetes (T1D). The animals were randomized into five groups: the control group got deionized water (DI), free QC solution (25 mg/kg), SPIONs (25 mg/kg), and QCSPIONs (25 mg/kg), and all groups received repeat doses administered orally over 35 days. Real-time quantitative PCR was used to assess the levels of miR-34a, let-7a-p5, SIRT1, p66Shc, CASP3, and PARP1 expression in the hippocampus of diabetic rats.ResultsIn silico investigations identified p66Shc, CASP3, and PARP1 as targets of let-7a-5p and miR-34a as possible regulators of SIRT1 genes. The outcomes demonstrated that diabetes elevated miR-34a, p66Shc, CASP3, and PARP1 and downregulated let-7a-5p and SIRT1 expression. In contrast to the diabetic group, QCSPIONs boosted let-7a-5p expression levels and consequently lowered p66Shc, CASP3, and PARP1 expression levels. QCSPIONs also reduced miR-34a expression, which led to an upsurge in SIRT1 expression.ConclusionOur results suggest that QCSPIONs can regulate the SIRT1/p66Shc-mediated signaling pathway and can be considered a promising candidate for ameliorating the complications of diabetes.

Ekonomia polityczna a demokracja w pismach klasyków liberalizmu – John Stuart Mill i Herbert Spencer

POLITICAL ECONOMY AND DEMOCRACY IN THE WRITINGS OF CLASSICAL LIBERALS – JOHN STUART MILL AND HERBERT SPENCER The main aim of this paper is showing mainstream economic theory as an important factor shaping the evolution of political liberalism. The role of the economic theory in this process seems underestimated. The paper analyses the writings of two classical liberal thinkers – John Stuart Mill and Herbert Spencer, the former a pioneer of egalitarian liberalism, the latter of laissez-faire liberalism. Both Mill and Spencer were the followers of the classical political economy accepting the classical theory of distribution. Both saw the distribution of wealth as a spontaneous process, seeing no possibility correcting it for the people’s sake without disturbances or damages. According to the classical theory of wage fund, workers would get higher incomes only through accumulation of capital by owners and repressing their own fertility. Such statement was fundamentally opposite to all postulates of the workers’ movement. Workers always claimed bigger share in social income and legislation favoring laborers. The inevitable result of this contradiction was a conflict between liberal and democratic ideas. Mill and Spencer proposed two different solutions. J. S. Mill found a specific compromise and proposed enlarging franchise on working class, but with a still dominant position of the educated classes. Mill was against equal franchise for the working class because he did not conceive them as liable, rational and sober people. This position results from the wage fund doctrine; according to it, abundant workers’ fertility is wasteful for them and only sexual restraint (or chastity) would make their wages higher. Spencer in his early writing was an enthusiast of democracy, supposing the working class’ affinity to free market solutions. His later disappointment with democracy turned him into a strong critic of democratic parliamentarism from the standpoint of laissez-faire individualism. The case of these two liberal thinkers shows fundamental difficulty in reconciliation between the ideas of democracy and free market. We could choose democracy accepting welfare state or choose free market solution and become unambiguous critics of democracy. Spencer was a forerunner of all later ‘neoliberal’ critics of welfare state. Mill’s opinion was halfway between laissez-faire liberalism and modern egalitarian liberalism. Democracy and equal voting rights became acceptable by mainstream economist only when they had abandoned the wage fund doctrine and other constructs of the classical political economy. Thus changes in the economic theory had a significant impact on the evolution of political liberalism.

A New Artificial Staggered-Grid Central Difference Solution for Checkerboard Problem in Incompressible, Steady, Inviscid, and Quasi-One-Dimensional Flow through Convergent Nozzle

In this paper, a novel artificial staggered grid points and under-relaxation free solution for a checkerboard pattern problem in a quasi-one-dimensional, incompressible, steady, and inviscid flow is introduced. The purpose of this numerical development is to obtain a new numerical solution, which is under-relaxation factor free scheme, more accurate, and easier to implement than a conventional staggered grid scheme. The proposed numerical solution can be described as the non-staggered grid/collocated grid central difference scheme which is free of pressure checkerboard pattern or spurious oscillation. The accuracy and convergence speed of the proposed numerical scheme is benchmarked against a conventional SIMPLE-based finite volume scheme and the exact solution for the flow problem in a convergent nozzle. The numerical analysis shows that the proposed numerical scheme outperforms the SIMPLE-based finite volume scheme in terms of accuracy, computational resource, and convergence speed. Also, the proposed numerical scheme has consistent numbers of iteration over the different grid sizes in contrast to the SIMPLE-based scheme which is iteration-grid size dependent. The proposed numerical scheme can be implemented with both uniform and non-uniform grid points and shows good agreement with the exact solution for every grid size. However, the uniform grid approach produces significantly more accurate results than the non-uniform grid approach. Hence, the choice of grid distribution is still an important factor affecting the accuracy of the proposed numerical solution. The proposed numerical technique can be further extended to solve incompressible flow problem in the complex 2D-3D domain with unstructural grids.

Injectable dexamethasone-loaded peptide hydrogel for therapy of radiation-induced ototoxicity by regulating the mTOR signaling pathway

Radiation-induced ototoxicity is associated with inflammation response and excessive reactive oxygen species in the cochlea. However, the effectiveness of many drugs in clinical settings is limited due to anatomical barriers in the inner ear and pharmacokinetic instability. To address this issue, we developed an injectable hydrogel called RADA32-HRN-dexamethasone (RHD). The RHD hydrogel possesses self-anti-inflammatory properties and can self-assemble into nanofibrous structures, ensuring controlled and sustained release of dexamethasone in the local region. Flow cytometry analysis revealed that the uptake of FITC-conjugated RHD gel by hair cells increased in a time-dependent manner. Compared to free dexamethasone solutions, dexamethasone-loaded RHD gel achieved a longer and more controlled release profile of dexamethasone. Additionally, RHD gel effectively protected against the inflammatory response, reduced excessive reactive oxygen species production, and reversed the decline in mitochondrial membrane potentials induced by ionizing radiation, leading to attenuation of apoptosis and DNA damage. Moreover, RHD gel promoted the recovery of outer hair cells and partially restored auditory function in mice exposed to ionizing radiation. These findings validated the protective effects of RHD gel against radiation-induced ototoxicity in both cell cultures and animal models. Furthermore, RHD gel enhanced the activity of the mammalian target of rapamycin (mTOR) signaling pathway, which was inhibited by ionizing radiation, thereby promoting the survival of hair cells. Importantly, intratympanic injections of RHD gel exhibited excellent biosafety and do not interfere with the anti-tumor effects of radiotherapy. In summary, our study demonstrates the therapeutic potential of injectable dexamethasone-loaded RHD hydrogel for the treatment of radiation-induced hearing loss by regulating the mTOR signaling pathway.

Flanking AT base pairs affect the localization of monovalent cations in DNA A-tracts.

Capillary electrophoresis has been used to measure the free solution mobilities of a series of 26-base pair (bp) DNA oligomers containing two phased A4T1in-tracts embedded in flanking sequences containing 0 to 11 additional AT bps. A random-sequence 26-bp oligomer with 12 isolated AT bps was used as the reference. Mobility ratios (A-tract/reference) were measured in background electrolytes (BGEs) containing mixtures of small monovalent cations and tetrabutylammonium (TBA+ ) or tetrapropylammonium (TPA+ ) ions. The mobility ratios observed in 0.3M TBA+ were >1.00, suggesting that the TBA+ ions had formed electrostatic contact pairs with the AT bp in the reference and in the A-tract flanking sequences, decreasing the mobilities of both oligomers. The TBA-AT pairing interactions could be eliminated by increasing the concentration of small monovalent cations in the BGE. In 0.3M TPA+ , electrostatic contact pairs were formed with the AT bps in the flanking sequences and in the A-tracts. Interestingly, the shapes of the mobility ratio profiles observed for the A4T1in-tract oligomers depended on the total number of A+T residues in the oligomer.

A novel ME2so free cryopreservation solution designed for advanced cell-based therapy applications

A novel ME2so free cryopreservation solution designed for advanced cell-based therapy applications

Ambroxol-Enhanced Frequency and Amplitude of Beating Cilia Controlled by a Voltage-Gated Ca2+ Channel, Cav1.2, via pHi Increase and [Cl-]i Decrease in the Lung Airway Epithelial Cells of Mice.

Ambroxol (ABX), a frequently prescribed secretolytic agent which enhances the ciliary beat frequency (CBF) and ciliary bend angle (CBA, an index of amplitude) by 30%, activates a voltage-dependent Ca2+ channel (CaV1.2) and a small transient Ca2+ release in the ciliated lung airway epithelial cells (c-LAECs) of mice. The activation of CaV1.2 alone enhanced the CBF and CBA by 20%, mediated by a pHi increasei and a [Cl-]i decrease in the c-LAECs. The increase in pHi, which was induced by the activation of the Na+-HCO3- cotransporter (NBC), enhanced the CBF (by 30%) and CBA (by 15-20%), and a decrease in [Cl-]i, which was induced by the Cl- release via anoctamine 1 (ANO1), enhanced the CBA (by 10-15%). While a Ca2+-free solution or nifedipine (an inhibitor of CaV1.2) inhibited 70% of the CBF and CBA enhancement using ABX, CaV1.2 enhanced most of the CBF and CBA increases using ABX. The activation of the CaV1.2 existing in the cilia stimulates the NBC to increase pHi and ANO1 to decrease the [Cl-]i in the c-LAECs. In conclusion, the pHi increase and the [Cl-]i decrease enhanced the CBF and CBA in the ABX-stimulated c-LAECs.

Asymmetric particle-antiparticle Dirac equation: first quantization

We derive a Dirac-like equation, the asymmetric Dirac equation, where particles and antiparticles sharing the same wave number have different energies and momenta. We show that this equation is Lorentz covariant under proper Lorentz transformations (boosts and spatial rotations) and also determine the corresponding transformation law for its wave function. We obtain a formal connection between the asymmetric Dirac equation and the standard Dirac equation and we show that by properly adjusting the free parameters of the present wave equation we can make it reproduce the predictions of the usual Dirac equation. We show that the rest mass of a particle in the theoretical framework of the asymmetric Dirac equation is a function of a set of four parameters, which are relativistic invariants under proper Lorentz transformations. These four parameters are the analog to the mass that appears in the standard Dirac equation. We prove that in order to guarantee the covariance of the asymmetric Dirac equation under parity and time reversal operations (improper Lorentz transformations) as well as under the charge conjugation operation, these four parameters change sign in exactly the same way as the four components of a four-vector. The mass, though, being a function of the square of those parameters remains an invariant. We also extensively study the free particle plane wave solutions to the asymmetric Dirac equation and derive its energy, helicity, and spin projection operators as well as several Gordon’s identities. The hydrogen atom is solved in the present context after applying the minimal coupling prescription to the asymmetric Dirac equation, which also allows us to appropriately obtain its non-relativistic limit.

Polycationic Ru(II) Luminophores: Syntheses, Photophysics, and Application in Electrostatically Driven Sensitization of Lanthanide Luminescence.

A series of photoluminescent Ru(II) polypyridine complexes have been synthesized in a manner that varies the extent of the cationic charge. Two ligand systems (L1 and L2), based upon 2,2'-bipyridine (bipy) mono- or difunctionalized at the 5- or 5,5'-positions using N-methylimidazolium groups, were utilized. The resulting Ru(II) species therefore carried +3, +4, +6, and +8 complex moieties based on a [Ru(bipy)3]2+ core. Tetra-cationic [Ru(bipy)2(L2)][PF6]4 was characterized using XRD, revealing H-bonding interactions between two of the counteranions and the cationic unit. The ground-state features of the complexes were found to closely resemble those of the parent unfunctionalized [Ru(bipy)3]2+ complex. In contrast, the excited state properties produce a variation in emission maxima, including a bathochromic 44 nm shift of the 3MLCT band for the tetra-cationic complex; interestingly, further increases in overall charge to +6 and +8 produced a hypsochromic shift in the 3MLCT band. Supporting DFT calculations suggest that the trend in emission behavior may, in part, be due to the precise nature of the LUMO and its localization. The utility of a photoactive polycationic Ru(II) complex was then demonstrated through the sensitization of a polyanionic Yb(III) complex in free solution. The study shows that electrostatically driven ion pairing is sufficient to facilitate energy transfer between the 3MLCT donor state of the Ru(II) complex and the accepting 2F5/2 excited state of Yb(III).

Optimizing large real-world data analysis with parquet files in R: A step-by-step tutorial.

The use of open-source programming languages can facilitate open science practices in real-world evidence (RWE) studies. Real-world studies often rely on using big data, which makes using such languages complicated. We demonstrate an efficient approach that enables RWE researchers to use R to undertake RWE analysis tasks from cohort building to reporting. Using the Merative Marketscan data (2017-2019), we developed an R function to transform the data into parquet format to be used in R. Then, we compared the differences in data size before and after transformation. We compared the performance of the transformed data in R to the original data in terms of numerical consistency and running times required to complete simple exploratory tasks. To show how the transformed databases can be used in practice, we conducted a simplified replication of an active comparator new user study from the literature. All codes are available on GitHub. Our approach exhibited high efficiency in data storage, as evidenced by the converted data size, which ranged from 10% to 43% of that of the original data files. The runtime of the exploratory tasks in R generally outperformed that of the original data with SAS. We showed, through example, how the converted data can be efficiently used to implement an RWE study. We demonstrate a free and efficient solution to facilitate the use of open-source programming languages with big real-world databases, which can facilitate the adoption of open science practices.

Linearly convergent adjoint free solution of least squares problems by random descent

We consider the problem of solving linear least squares problems in a framework where only evaluations of the linear map are possible. We derive randomized methods that do not need any other matrix operations than forward evaluations, especially no evaluation of the adjoint map is needed. Our method is motivated by the simple observation that one can get an unbiased estimate of the application of the adjoint. We show convergence of the method and then derive a more efficient method that uses an exact linesearch. This method, called random descent, resembles known methods in other context and has the randomized coordinate descent method as special case. We provide convergence analysis of the random descent method emphasizing the dependence on the underlying distribution of the random vectors. Furthermore we investigate the applicability of the method in the context of ill-posed inverse problems and show that the method can have beneficial properties when the unknown solution is rough. We illustrate the theoretical findings in numerical examples. One particular result is that the random descent method actually outperforms established transposed-free methods (TFQMR and CGS) in examples.

Effect of TiO<sub>2 </sub>on Photocatalytic Activity of NiZnFe<sub>2</sub>O<sub>4</sub>/TiO<sub>2</sub> Nanocrystalline for Methylene Blue Degradation

The photocatalytic activity of NiZnFe2O4/TiO2 core-shell gg nanocrystalline was carried out. The NiZnFe2O4/TiO2 core-shell was synthesized using co-precipitation method with various concentrations 1:0, 1:1, 1:2, 1:3, 1:4, and 1:5. X-ray diffraction spectra pattern showed crystallite size at various concentrations 1:0, 1:1, and 1:3, which of 5.00 nm, 4.90 nm, and 10.81 nm, respectively. The morphology of NiZnFe2O4 nanocrystalline was characterized by transmission electron microscopy which confirmed that the sample undergoes agglomeration with not uniform particle shape. The average particle size of the nanocrystalline was 10.26 nm. Fourier transform infra-red showed functional groups such as Ti-O-Ti, M-Otetra, and M-Oocta at 1473.62, 563 - 586, and 401- 424 cm-1. In addition, the presence of Ti-O-Ti and M-O functional groups indicates NiZnFe2O4/TiO2 core-shell has been formed. The absorbance spectrum of the NiZnFe2O4/TiO2 core-shell has an energy band gap in the range of 2.1 – 3.3 eV. The results of the Vibrating sample magnetometer showed saturation magnetization and coercivity values ​​in the range of 12.4 – 22.9 emu/gr and 47 - 55 Oe, which were correlated as soft magnetic properties. NiZnFe2O4/TiO2 was successfully degraded Methylene Blue that reach 99.8% under UV light irradiation. The addition of TiO2 increases degradation, TiO2 acts as a trapping state that inhibits electron-hole recombination which can prolong the reaction time between free electrons and MB solution molecules. This study revealed the high potential of NiZnFe2O4/TiO2 core-shell nanocrystalline in photocatalytic application.

Optimization, cellular uptake, and in vivo evaluation of Eudragit S100-coated bile salt-containing liposomes for oral colonic delivery of 5-aminosalicylic acid

Eudragit S100-coated bile salt-containing liposomes were prepared and optimized by experimenting with different variables, including bile salt type and concentration, and the method of incorporation into liposomes using a model hydrophilic compound, 5-aminosalicylic acid (5-ASA). After optimizing the formulation, cellular uptake, and animal pharmacokinetic experiments were performed. The inclusion of sodium glycocholate (SG) into liposomes decreased liposome particle size and entrapment efficiency significantly but had no effect on zeta potential. The method of incorporating SG into the lipid or aqueous phase of the liposome did not notably impact the characteristics of the liposomes but the hydration media had a substantial effect on the entrapment efficiency of 5-ASA. In vitro drug release in different fluids simulating distinct gastrointestinal tract sections, indicated pH-dependent disintegration of the coating layer of coated SG-containing liposomes. The majority of the drug was retained when subjected to simulated gastric fluid (SGF) and fed-state simulated intestinal fluid (FeSSIF) (≈ 37% release after 2 h in SGF pH 1.2, followed by 3 h in FeSSIF pH 5). The remaining drug was subsequently released in phosphate-buffered saline pH 7.4 (≈ 85% release within 24 h). Increasing SG concentration in the liposomes decreased the amount of drug released in FeSSIF. Similar results were observed when SG was replaced with sodium taurocholate. Cellular uptake studies in Caco-2 cells demonstrated that all liposomal formulations (conventional liposomes, bile salt-containing liposomes, and coated bile salt-containing liposomes) have shown to be equally effective at increasing the cellular uptake compared to free fluorescein solution. In the pharmacokinetic study, coated bile salt-containing liposomes showed a lower Cmax and prolonged residence in the gastrointestinal tract in comparison to conventional liposomes. Taken together, these findings suggest that the polymer-coated bile salt-containing liposomes have the potential to serve as a drug delivery system targeted at the colon.

Co-delivering irinotecan and imiquimod by pH-responsive micelle amplifies anti-tumor immunity against colorectal cancer

Irinotecan (IRT), a classic clinical chemotherapeutic agent for treating colorectal cancer, has been found to induce immunogenic cell death (ICD) while exerting cytotoxicity in tumor cells. This effect is likely to be amplified in combination with immune modulators. Unfortunately, free drugs without targeting capacity would receive poor outcomes and strong side effects. To address these issues, in this work, an acid-sensitive micelle based on an amphiphilic poly(β-amino ester) derivative was constructed to co-deliver IRT and the immune adjuvant imiquimod (IMQ), termed PII. PII kept stable under normal physiological conditions. After internalization by tumor cells, PII dissociated in acidic lysosomes and released IRT and IMQ rapidly. In the CT26 tumor mouse model, PII increased the intra-tumoral SN38 (the active metabolite of IRT) and IMQ concentrations by up to 9.39 and 3.44 times compared with the free drug solution. The tumor inhibition rate of PII achieved 87.29%. This might profit from that IRT induced ICD, which promoted dendritic cells (DCs) maturation and intra-tumoral infiltration of CD8+ T cells. In addition, IMQ enhanced the antigen presenting ability of DCs and stimulated tumor associated macrophages to secrete tumor-killing cytokines. PII provided an effective strategy to combat colorectal cancer by synergy of chemotherapy and immunoregulation.

Anti-CD4 antibody and dendrimeric peptide based targeted nano-liposomal dual drug formulation for the treatment of HIV infection

AimsDevelopment and characterization of LAM and DTG loaded liposomes conjugated anti-CD4 antibody and peptide dendrimer (PD2) to improve the therapeutic efficacy and to achieve targeted treatment for HIV infection. Main methodsA 2-level full factorial design was used to optimize the preparation of dual drug loaded liposomes. Optimized dual drug loaded ligand conjugated liposomes were assessed for their cytotoxicity and cell internalization on TZM-bl cells. Anti-HIV efficiency of the dual drug loaded liposomes were screened for their inhibitory potential in TZM-bl cells and the activities were confirmed using Peripheral Blood Mononuclear Cells (PBMCs). Key findingsThe particle size of the optimized dual drug-loaded liposomes was 133.7 ± 4.04 nm, and the spherical morphology of the liposomes was confirmed by TEM analysis. The entrapment efficiency was 34 ± 4.9 % and 54 ± 1.8 % for LAM and DTG, respectively, and a slower in vitro release of LAM and DTG was observed when entrapped into liposomes. The cytotoxicity of the dual drug loaded liposomes was similar to the cytotoxicity of free drug solutions. Conjugation of anti-CD4 antibody and PD2 did not significantly influence the cytotoxicity but it enhanced the uptake of liposomes into the cells. Conjugated dual drug loaded liposomes exhibited better HIV inhibition with lower IC50 values (0.0003 ± 0.0002 μg/mL) compared to their free drug solutions (0.002 ± 0.001 μg/mL). The liposomal formulations have shown similar activities in both screening and confirmatory cell-based assays. SignificanceThe results demonstrated the cell targeting ability of dual drug loaded liposomes conjugated with anti-CD4 antibody and peptide dendrimer. Conjugated liposomes also improved anti-HIV efficiency of LAM and DTG.

Obtaining of enriched di-tryptophan fractions by gamma irradiation of free tryptophan solutions

Obtaining of enriched di-tryptophan fractions by gamma irradiation of free tryptophan solutions

GE-DDRL: Graph Embedding and Deep Distributional Reinforcement Learning for Reliable Shortest Path: A Universal and Scale Free Solution

This paper studies the reliable shortest path (RSP) problem in stochastic transportation networks. State-of-the-art RSP solutions usually target one specific RSP problem; moreover, the corresponding algorithm’s computational complexity scales at least linearly with the size of the underlying transportation network. While in this paper, we propose a graph embedding and deep distributional reinforcement learning (GE-DDRL) method, which serves as a universal and scale-free solution to the RSP problem. GE-DDRL uses deep distributional reinforcement learning (DDRL) to estimate the full travel-time distribution of a given routing policy, and improves the given routing policy with the generalized policy iteration (GPI) scheme. Further, in order to achieve the generalization ability to new destination nodes, we employ one of the canonical graph embedding techniques (Skip-Gram) to compress the nodes’ representation into <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$d$</tex-math> </inline-formula> -dimensional real-valued vectors. With the properly compressed node features, GE-DDRL is able to generalize its estimation of the routing policy’s travel-time distribution to untrained destination nodes, and hence achieve the ‘all-to-all’ navigation functionality. To the best of our knowledge, GE-DDRL serves as the first RSP planner, which applies simultaneously to almost all RSP objectives and in the meanwhile, is scale free with the size of the transportation network in terms of the online decision-making time and memory complexity. Experimental results and comparisons with state of the arts show the efficacy and efficiency of GE-DDRL in a range of transportation networks.

Improvement of foaming properties of ovalbumin: Insights into the synergistic effect of preheating and high-intensity ultrasound on physicochemical properties and structure analysis

Ovalbumin (OVA), characterized by its high concentration in eggs, possesses remarkable foaming properties. Nevertheless, OVA is highly sensitive to thermal changes and acid-base conditions, substantially hampering its application potential for foaming purposes within the food industry. This experiment aimed to examine the effects of preheating and high-intensity ultrasound (HIU) treatment at different powers on OVA foaming properties and explore the underlying mechanisms. The results revealed that OVA exhibited the highest foaming capacity (31.5 %) and foaming stability (96.7 %) under the treatment condition of 200w + 60°C. Additionally, significant improvements were observed in the content of free sulfhydryl groups (37.27 μmg/g), solution viscosity (142.33 mPa·s), and surface hydrophobicity (37.27 μg BPB) under this condition. The absolute value of the zeta potential (-10.28 mV) was significantly increased in the 200w + 60°C treatment group. Moreover, the polymer dispersity index of OVA (0.6045) was significantly reduced, resulting in improved dispersion than the control group. The structural analysis revealed significant changes in the α-helix and β-sheet content of OVA after treatment at 200w + 60 °C. The X-ray diffraction pattern exhibited sharper peaks, indicating a crystal structure, and the fluorescence peak displayed a slight blue shift along with increased hydrophobicity. Moreover, the preheating and HIU treatment induced a continuous uneven and irregular pore structure in OVA, which ultimately enhanced its foaming properties. In conclusion, the preheating and HIU treatment offers a novel approach to enhance the foaming properties of OVA.