Predicting projectile residual velocities using an advanced artificial neural network model.

In this research, we delve into the fascinating dynamics of projectiles and their interactions with materials, with a keen focus on residual velocity - the speed a projectile retains after striking a target. This parameter is pivotal, especially when considering the design of protective barriers in various environments. Traditional methods of gauging residual velocity have been cumbersome, resource-intensive, and occasionally inconsistent. To address these challenges, we introduce an innovative approach using an Artificial Neural Network (ANN) model through MATLAB R2021a. This computerized tool, trained on a rich dataset from prior research, can predict residual velocities by considering multiple factors, including the initial speed of the projectile, its material and shape, and the thickness of the target. This paper meticulously details the development, training, and validation of the ANN model, highlighting its superior accuracy when compared to traditional methods like the Recht-Ipson model. The developed ANN model demonstrated remarkable performance compared to the Recht-Ipson model. During training, it exhibited a Mean Absolute Percentage Error (MAPE) of 0.0259 and a Root Mean Squared Error (RMSE) of 1.5993. For validation, MAPE was 0.0295, and RMSE was 2.2056. In contrast, the Recht-Ipson model displayed higher errors, with MAPE and RMSE values of 0.2349 and 14.1791, respectively. Furthermore, we discuss the potential of the ANN model in predicting not just residual velocities but also absorbed energy, showcasing its versatility. The practical implications of our findings are vast. From designing safer infrastructures in urban settings to enhancing armour systems in military applications, the ANN model's predictions can be a cornerstone for innovation.

Prognosis methods of stress corrosion cracking under harsh environmental conditions.

Stress corrosion cracking (SCC) under harsh environmental conditions still poses a significant challenge, despite extensive research efforts. The intricate interplay among mechanical, chemical, and electrochemical factors hinders the accurate prognosis of material degradation and remaining service life. Furthermore, the demand for real-time monitoring and early detection of SCC defects adds further complexity to the prognostication process. Therefore, there is an urgent need for comprehensive review papers that consolidate current knowledge and advancements in prognosis methods. Such reviews would facilitate a better understanding and resolution of the challenges associated with SCC under harsh environmental conditions. This work aims to provide a comprehensive overview of various prognosis methods utilized for the assessment and prediction of SCC in such environments. The paper will delve into the following sections: exacerbating harsh environmental conditions, non-destructive testing (NDT) techniques, electrochemical techniques, numerical modeling, and machine learning. This review is inclined to serve as a valuable resource for researchers and practitioners working in the field, facilitating the development of effective strategies to mitigate SCC and ensure the integrity and reliability of materials operating in challenging environments. Despite considerable research, stress corrosion cracking in harsh environments remains a critical issue, complicated by the interplay of mechanical, chemical, and electrochemical factors. This review aims to consolidate current prognosis methods, including non-destructive testing, electrochemical techniques, numerical modeling, and machine learning. Key findings indicate that while traditional methods offer limited reliability, emerging computational approaches show promise for real-time, accurate predictions. The paper also briefly discusses notable SCC failure cases to underscore the urgency for improved prognosis techniques. This work aspires to fill knowledge gaps and serve as a resource for developing effective SCC mitigation strategies, thereby ensuring material integrity in challenging operational conditions.

The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. The mechanism underlying opioid-induced dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine-treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine-naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine-dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin-degrading A. muciniphila in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota-gut-brain axis.

Low-Efficacy Mu Opioid Agonists as Candidate Analgesics: Effects of Novel C-9 Substituted Phenylmorphans on Pain-Depressed Behavior in Mice.

Low efficacy mu opioid receptor (MOR) agonists may serve as novel candidate analgesics with improved safety relative to high-efficacy opioids. This study used a recently validated assay of pain-depressed behavior in mice to evaluate a novel series of MOR-selective C9-substituted phenylmorphan opioids with graded MOR efficacies. Intraperitoneal injection of dilute lactic acid (IP acid) served as a noxious stimulus to depress locomotor activity by mice in an activity chamber composed of two compartments connected by an obstructed door. Behavioral measures included (1) crosses between compartments (vertical activity over the obstruction) and (2) movement counts quantified as photobeam breaks summed across compartments (horizontal activity). Each drug was tested alone and as a pretreatment to IP acid. A charcoal-meal test and whole-body-plethysmography assessment of breathing in 5% CO2 were also used to assess gastrointestinal (GI) inhibition and respiratory depression, respectively. IP acid produced a concentration-dependent depression in crosses and movement that was optimally alleviated by intermediate- to low-efficacy phenylmorphans with sufficient efficacy to produce analgesia with minimal locomotor disruption. Follow-up studies with two low-efficacy phenylmorphans (JL-2-39 and DC-1-76.1) indicated that both drugs produced naltrexone-reversible antinociception with a rapid onset and a duration of ~1hr. Potency of both drugs increased when behavior was depressed by a lower IP-acid concentration, and neither drug alleviated behavioral depression by a non-pain stimulus (IP lithium chloride). Both drugs produced weaker GI inhibition and respiratory depression than fentanyl and attenuated fentanyl-induced GI inhibition and respiratory depression. Results support further consideration of selective, low-efficacy MOR agonists as candidate analgesics. Significance Statement This study used a novel set of mu opioid receptor (MOR)-selective opioids with graded MOR efficacies to examine the lower boundary of MOR efficacy sufficient to relieve pain-related behavioral depression in mice. Two novel low-efficacy opioids (JL-2-39, DC-1-76.1) produced effective antinociception with improved safety relative to higher- or lower-efficacy opioids, and results support further consideration of these and other low-efficacy opioids as candidate analgesics.

Aloe vera/Chitosan-Based Edible Film with Enhanced Antioxidant, Antimicrobial, Thermal, and Barrier Properties for Sustainable Food Preservation.

Food bioactive packaging has received increasing attention from consumers and the food industry for its potential to reduce food waste and environmental issues. Several materials can be used to produce edible films/coats; however, bio-based, cost-effective, and sustainable coatings have gained a high reputation these days. For instance, Aloe vera gel (AV) is a promising bio-based material for edible coatings and films; therefore, the present study aimed to investigate the film-forming abilities of AV and Chitosan (CH) combination as a potential active food packaging material. The physicochemical and mechanical characteristics of formed films of various combinations were prepared at different concentrations, i.e., CH (0.5% w/v), AV (100%), CH:AV (75:25), and CH:AV (60:40). The results showed significant differences among all the prepared edible films wherein these differences were mainly on account of incorporating AV gel. The rheological and antioxidant properties of the formulations improved with the inclusion of AV gel. The films composed of CH:AV (60:40) positively affected the water solubility, thermal properties, and water vapour permeability of the edible films. The X-ray Diffraction (XRD) and Scanning electron microscopy (SEM) results showed that the films composed of CH:AV, (60:40) were amorphous and had smooth morphology. Further, the edible film solutions were applied to fresh figs (Ficus carica) to investigate their role in preserving fruits during storage. A significant reduction in microbial growth was found in coated fruits after 28 days of cold storage. The films composed of CH and AV showed overall improved results compared to the CH (0.5%, w/v). Therefore, the used formulations (CH:AV, 60:40) can form a sustainable film that has the potential to be utilized for fresh product preservation to maintain its quality and shelf life.

Endocannabinoid biosynthetic enzymes regulate pain response via LKB1-AMPK signaling.

Diacylglycerol lipase-beta (DAGLß) serves as a principal 2-arachidonoylglycerol (2-AG) biosynthetic enzyme regulating endocannabinoid and eicosanoid metabolism in immune cells including macrophages and dendritic cells. Genetic or pharmacological inactivation of DAGLß ameliorates inflammation and hyper-nociception in preclinical models of pathogenic pain. These beneficial effects have been assigned principally to reductions in downstream proinflammatory lipid signaling, leaving alternative mechanisms of regulation largely underexplored. Here, we apply quantitative chemical- and phospho-proteomics to find that disruption of DAGLß in primary macrophages leads to LKB1-AMPK signaling activation, resulting in reprogramming of the phosphoproteome and bioenergetics. Notably, AMPK inhibition reversed the antinociceptive effects of DAGLß blockade, thereby directly supporting DAGLß-AMPK crosstalk in vivo. Our findings uncover signaling between endocannabinoid biosynthetic enzymes and ancient energy-sensing kinases to mediate cell biological and pain responses.

Short-chain fatty acid, butyrate prevents morphine-and paclitaxel-induced nociceptive hypersensitivity.

Nociceptive hypersensitivity is a significant side effect with the chronic administration of opioids as well as chemotherapeutics. Both opioid-induced hypersensitivity (OIH) and chemotherapy-induced hypersensitivity (CIH) are characterized by an increased sensitivity to painful stimuli which can significantly reduce the quality of life for individuals on either drug(s). Here we demonstrate the nociceptive hypersensitivity associated with repeated administration of morphine (opioid) and paclitaxel (chemotherapeutic) treatment can be reversed by oral supplementation with the short-chain fatty acid (SCFA) sodium butyrate (NaBut). In two separate mouse behavioral models for nociceptive hypersensitivity, we found that thermal hyperalgesia (for OIH) and cold allodynia (for CIH) were prevented by treatment with oral butyrate (p.o, b.i.d). Electrophysiological recordings of small diameter dorsal root ganglia (DRG) neurons from morphine and paclitaxel treated mice showed an increase in neuronal hyperexcitability in both drug models which was likewise prevented by oral butyrate treatment. Using colonic conditioned media obtained from excised colon segments we found that gut mediators of morphine treated mice can induce hyperexcitability in naïve DRG neurons, but such enhanced excitability is not present when animals are co-treated with NaBut suggesting gut derived mediators modulate neuronal hyperexcitability. In-vitro NaBut treatment did not prevent morphine-induced excitability, suggesting an indirect role of butyrate in modulating neuronal hypersensitivity. These data taken together suggest that gut derived mediators affect opioid and chemotherapeutic-induced neuronal hypersensitivity that is prevented by the SCFA butyrate.

Role of mu opioid receptor (MOR) agonist efficacy as a determinant of opioid antinociception in a novel assay of pain-depressed behavior in female and male mice.

Introduction: Intermediate efficacy mu opioid receptor (MOR) agonists have potential to retain analgesic effectiveness while improving safety, but the optimal MOR efficacy for effective and safe opioid analgesia is unknown. Preclinical assays of pain-depressed behavior can assess effects of opioids and other candidate analgesics on pain-related behavioral depression, which is a common manifestation of clinically relevant pain and target of pain treatment. Accordingly, the present study goal was to validate a novel assay of pain-depressed locomotor behavior in mice and evaluate the role of MOR efficacy as a determinant of opioid analgesic effects and related safety measures. Methods: Male and female ICR mice were tested in a locomotor chamber consisting of 2 compartments connected by a doorway that contained a 1-inch-tall barrier. Dependent measures during 15-min behavioral sessions included crosses between compartments (which required vertical activity to surmount the barrier) and total movement counts (which required horizontal activity to break photobeams in each compartment). Results and Discussion: Intraperitoneal injection of lactic acid (IP acid) produced a concentration- and time-dependent depression of both endpoints. Optimal blockade of IP acid-induced behavioral depression with minimal motor impairment was achieved with intermediate-efficacy MOR treatments that also produced less gastrointestinal-transit inhibition and respiratory depression than the high-efficacy MOR agonist fentanyl. Sex differences in treatment effects were rare. Overall, these findings validate a novel procedure for evaluating opioids and other candidate analgesic effects on pain-related behavioral depression in mice and support continued research with intermediate-efficacy MOR agonists as a strategy to retain opioid analgesic effectiveness with improved safety.

Short-chain fatty acid, Butyrate prevents Morphine and Paclitaxel induced peripheral hypersensitivity.

Peripheral hypersensitivity is a significant side effect with the chronic administration of opioids as well as chemotherapeutics. Both opioid-induced hypersensitivity (OIH) and chemotherapy induced hypersensitivity (CIH) are characterized by an increased sensitivity to painful stimuli which can significantly reduce the quality of life for individuals on either drug(s). Here we demonstrate the peripheral hypersensitivity associated with chronic morphine (opioid) and paclitaxel (chemotherapeutic) treatment can be reversed by oral supplementation with the short-chain fatty acid (SCFA) sodium butyrate. In two separate mouse behavioral models for peripheral hypersensitivity, we found that thermal hyperalgesia (for OIH) and cold allodynia (for CIH) were prevented by co-treatment with oral butyrate. Electrophysiological recordings of small diameter dorsal root ganglia (DRG) neurons from morphine and paclitaxel treated mice showed an increase in neuronal hyperexcitability in both drug models which was likewise prevented by oral butyrate treatment. Using colonic conditioned media obtained from excised colon segments we found that gut mediators of morphine treated mice can induce hyperexcitability in naïve DRG neurons, but such enhanced excitability is not present when animals are co-treated with butyrate suggesting gut derived mediators modulate neuronal hyperexcitability. In-vitro butyrate treatment did not prevent morphine induced excitability, suggesting an indirect role of sodium butyrate in modulating neuronal hypersensitivity. These data taken together suggest that gut derived mediators affect opioid and chemotherapeutic induced neuronal hypersensitivity that is prevented by the SCFA butyrate.

Protective Efficacy of Inactivated H9N2 Vaccine in Turkey Poults under Both Experimental and Field Conditions.

Low pathogenic avian influenza (LPAI) H9N2 virus is one of the major poultry pathogens associated with severe economic losses in the poultry industry (broiler, layers, breeders, and grandparents' flocks), especially in endemic regions including the Middle East, North Africa, and Asian countries. This work is an attempt to evaluate the efficacy of whole inactivated H9N2 vaccine (MEFLUVACTM H9) in turkey poults kept under laboratory and commercial farm conditions. Here, 10,000 white turkey poults (1-day old) free from maternally derived immunity against H9N2 virus were divided into four groups; G1 involved 10 vaccinated birds kept under biosafety level-3 (BLS-3) as a laboratory vaccinated and challenged group, while G2 had 9970 vaccinated turkeys raised on a commercial farm. Ten of those birds were moved to BLS-3 for daily cloacal and tracheal swabbing to check for the absence of any life-threating disease, before conducting analyses. G3 (10 birds) served as a non-vaccinated challenged control under BSL-3 conditions, while G4 (10 birds) was used as a non-vaccinated and non-challenged control under BSL-3 conditions. Sera were collected on days 7-, 14-, 21-, and 28-post-vaccinations to monitor the humoral immune response using a hemagglutination-inhibition (HI) test. At these same intervals, cloacal and tracheal swabs were also checked for any viral infection. The challenge was conducted 28 days post-vaccination (PV) using AI-H9N2 in BSL-3 by intranasal inoculation of 6-log10 embryo infective dose50 (EID50). At 3-, 6-, and 10-days post-challenge, oropharyngeal swabs were taken from challenged birds to quantify viral shedding by quantitative polymerase chain reaction (qRT-PCR). The results of this study showed that vaccinated groups (G1/2) developed HI titers of 1.38, 4.38, 5.88, and 7.25 log2 in G1 vs. 1.2, 3.8, 4.9 and 6.2 log2 in G2 when measured at 7-, 14-, 21- and 28-days PV, respectively, while undetectable levels were recorded in non-vaccinated groups (G3/4). Birds in G3 showed 90% clinical sickness vs. 10% and 20% in G1/2, respectively, over a 10-day monitoring period following challenge. Vaccinated birds showed a significant reduction in virus shedding in terms of the number of shedders, amount of shed virus and shedding interval over the non-vaccinated challenged birds. Regarding mortality, all groups did not show any mortality, which confirms that the circulating H9N2 virus still has low pathogenicity and cannot cause mortality. However, the virus may cause up to 90% clinical sickness in non-vaccinated birds vs. 10% and 20% in laboratory- and farm-vaccinated birds, respectively, highlighting the role of the vaccine in limiting clinical sickness cases. In conclusion, under the current trial circumstances, MEFLUVACTM-H9 provided protective seroconversion titers, significant clinical sickness protection and significant reduction in virus shedding either in laboratory- or farm-vaccinated groups after a single vaccine dose.

Small extracellular vesicle-associated miR-6068 promotes aggressive phenotypes of prostate cancer through miR-6068/HIC2/SIRT1 axis.

Early diagnosis and treatment of patients with aggressive prostate cancer (PCa) remains a clinically unmet need. We aimed to determine the levels of small extracellular vesicle (sEV)-associated microRNAs (miRs); miR-4737, miR-6068, and miR-6076 in a large panel of PCa cells and delineate the biological significance of miR-6068 in promoting PCa cells. sEVs were isolated from the conditioned medium of PCa cells, followed by RNA extraction and quantitative Real-Time PCR analysis. Functional assays were performed, and the protein expression of hypermethylated in cancer 2 (HIC2), as a potential miR-6068 target gene, was evaluated in PCa tissues by immunohistochemistry. sEV-associated miR-6068, miR-4737, and miR-6076 levels displayed large and significant differences compared to normal cells. miR-6068 was explicitly upregulated in sEV of PC-3 and CWR-R1ca cells (P<0.010). Suppression of miR-6068 in CWR-R1ca cells decreased cell proliferation, colony formation, and cell migration. In contrast, upregulation of miR-6068 in RC77T/E cells decreased HIC2 levels and increased cell aggressive phenotypes. The overexpression of HIC2 in PCa tissues was primarily observed in the cytoplasm compared to benign prostatic hyperplasia (BPH) and normal tissues (P<0.0001). This study confirms the differential packaging of miR-4737, miR-6068, and miR-6076 in sEVs of PCa cells. MiR-6068 promotes PCa cells to acquire aggressive phenotypes by inhibiting the HIC2/Sirtuin 1 (SIRT1) axis.

Impact of Hybrid Fillers on the Properties of High Density Polyethylene Based Composites.

The main objective of this work is to develop a variety of hybrid high-density polyethylene (HDPE) micro- and nanocomposites and to investigate their thermal, mechanical, and morphological characteristics as a function of number of fillers and their contents percentage. In this study, 21 formulations of the composites were prepared using fillers with different sizes including micro fillers such as talc, calcium carbonate (CaCO3), as well as nano-filler (fumed silica (FS)) though the melt blending technique. The morphological, mechanical, and thermal properties of the composite samples were evaluated. The morphological study revealed negligible filler agglomerates, good matrix-filler interfacial bonding in case of combined both CaCO3 and FS into the composites. Sequentially, improvements in tensile, flexural and Izod impact strengths as a function of fillers loading in the HDPE matrix have been reported. The maximum enhancement (%) of tensile, flexural and impact strengths were 127%, 86% and 16.6%, respectively, for composites containing 25% CaCO3 and 1% FS without any inclusion of talc filler; this indicates that the types/nature, size, quantity and dispersion status of fillers are playing a major role in the mechanical properties of the prepared composites more than the number of the used fillers.

Chemotherapy induced gastrointestinal toxicities.

Chemotherapy-induced gastrointestinal dysfunction is a common occurrence associated with many different classes of chemotherapeutic agents. Gastrointestinal toxicity includes mucositis, diarrhea, and constipation, and can often be a dose-limiting complication, induce cessation of treatment and could be life threatening. The gastrointestinal epithelium is rich in rapidly dividing cells and hence is a prime target for chemotherapeutic drugs. The incidence of gastrointestinal toxicity, including diarrhea and mucositis, is extremely high for a wide array of chemotherapeutic and radiation regimens. In fact, 60%-100% of patients on high-dose chemotherapy suffer from gastrointestinal side effects. Unfortunately, treatment options are limited, and therapy is often restricted to palliative care. Therefore, there is a great unmet therapeutic need for preventing and treating chemotherapy-induced gastrointestinal toxicities in the clinic. In this review, we discuss our current understanding of the mechanisms underlying chemotherapy-induced diarrhea and mucositis, and emerging mechanisms involving the enteric nervous system, smooth muscle cells and enteric immune cells. Recent evidence has also implicated gut dysbiosis in the pathogenesis of not only chemotherapy-induced mucositis and diarrhea, but also chemotherapy-induced peripheral neuropathy. Oxidative stress induced by chemotherapeutic agents results in post-translational modification of ion channels altering neuronal excitability. Thus, investigating how chemotherapy-induced changes in the gut- microbiome axis may lead to gut-related toxicities will be critical in the discovery of new drug targets for mitigating adverse gastrointestinal effects associated with chemotherapy treatment.

Conversion of Sewage Water into H2 Gas Fuel Using Hexagonal Nanosheets of the Polyaniline-Assisted Deposition of PbI2 as a Nanocomposite Photocathode with the Theoretical Qualitative Ab-Initio Calculation of the H2O Splitting.

This study is very promising for providing a renewable enrgy (H2 gas fuel) under the elctrochemical splitting of the wastwater (sewage water). This study has double benefits: hydrogen generation and contaminations removel. This study is carried out on sewage water, third stage treated, from Beni-Suef city, Egypt. Antimony tin oxide (ATO)/polyaniline (PANI)/PbI2 photoelectrode is prepared through the in situ oxidative polymerization of PANI on ATO, then PANI is used as an assistant for PbI2 deposition using the ionic adsorption deposition method. The chemical structural, morphological, electrical, and optical properties of the composite are confirmed using different analytical tools such as X-ray diffreaction (XRD), scanning electron microscope (SEM), transmision electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV-Vis spectroscopy. The prepared PbI2 inside the composite has a crystal size of 33 nm (according to the peak at 12.8°) through the XRD analyses device. SEM and TEM confirm the hexagonal PbI2 sheets embedded on the PANI nanopores surface. Moreover, the bandgap values are enhanced very much after the composite formation, in which the bandgap values for PANI and PANI/PbI2 are 3 and 2.51 eV, respectively. The application of ATO/PANI/PbI2 nanocomposite electrode for sewage splitting and H2 generation is carried out through a three-electrode cell. The measurements carreid out using the electrocehical worksattion under th Xenon lamp (100 mW.cm-2). The produced current density (Jph) is 0.095 mA.cm-2 at 100 mW.cm-2 light illumination. The photoelectrode has high reproducibility and stability, in which and the number of H2 moles is 6 µmole.h-1.cm-1. The photoelectrode response to different monochromatic light, in which the produced Jph decreases from 0.077 to 0.072 mA.cm-2 with decreasing of the wavelengths from 390 to 636 nm, respectively. These values confirms the high response of the ATO/PANI/PbI2 nanocomposite electrode for the light illuminaton and hydrogen genration under broad light region. The thermodynamic parameters: activation energy (Ea), enthalpy (ΔH*), and entropy (ΔS*) values are 7.33 kJ/mol, -4.7 kJ/mol, and 203.3 J/mol.K, respectively. The small values of ΔS* relted to the high sesnivity of the prepared elctrode for the water splitting and then the hydrogen gneration. Finally, a theoretical study was mentioned for calculation geometry, electrochemical, and thermochemistry properties of the polyaniline/PbI2 nanocomposite as compared with that for the polyaniline.

Accelerated Discovery of the Polymer Blends for Cartilage Repair through Data-Mining Tools and Machine-Learning Algorithm.

In designing successful cartilage substitutes, the selection of scaffold materials plays a central role, among several other important factors. In an empirical approach, the selection of the most appropriate polymer(s) for cartilage repair is an expensive and time-consuming affair, as traditionally it requires numerous trials. Moreover, it is humanly impossible to go through the huge library of literature available on the potential polymer(s) and to correlate the physical, mechanical, and biological properties that might be suitable for cartilage tissue engineering. Hence, the objective of this study is to implement an inverse design approach to predict the best polymer(s)/blend(s) for cartilage repair by using a machine-learning algorithm (i.e., multinomial logistic regression (MNLR)). Initially, a systematic bibliometric analysis on cartilage repair has been performed by using the bibliometrix package in the R program. Then, the database was created by extracting the mechanical properties of the most frequently used polymers/blends from the PoLyInfo library by using data-mining tools. Then, an MNLR algorithm was run by using the mechanical properties of the polymers, which are similar to the cartilages, as the input and the polymer(s)/blends as the predicted output. The MNLR algorithm used in this study predicts polyethylene/polyethylene-graftpoly(maleic anhydride) blend as the best candidate for cartilage repair.

Effect of Au Plasmonic Material on Poly M-Toluidine for Photoelectrochemical Hydrogen Generation from Sewage Water.

This study provides H2 gas as a renewable energy source from sewage water splitting reaction using a PMT/Au photocathode. So, this study has a dual benefit for hydrogen generation; at the same time, it removes the contaminations of sewage water. The preparation of the PMT is carried out through the polymerization process from an acid medium. Then, the Au sputter was carried out using the sputter device under different times (1 and 2 min) for PMT/Au-1 min and PMT/Au-2min, respectively. The complete analyses confirm the chemical structure, such as XRD, FTIR, HNMR, SEM, and Vis-UV optical analyses. The prepared electrode PMT/Au is used for the hydrogen generation reaction using Na2S2O3 or sewage water as an electrolyte. The PMT crystalline size is 15 nm. The incident photon to current efficiency (IPCE) efficiency increases from 2.3 to 3.6% (at 390 nm), and the number of H2 moles increases from 8.4 to 33.1 mmol h-1 cm-2 for using Na2S2O3 and sewage water as electrolyte, respectively. Moreover, all the thermodynamic parameters, such as activation energy (Ea), enthalpy (ΔH*), and entropy (ΔS*), were calculated; additionally, a simple mechanism is mentioned for the water-splitting reaction.

Chronic Morphine Induces IL-18 in Ileum Myenteric Plexus Neurons Through Mu-opioid Receptor Activation in Cholinergic and VIPergic Neurons.

The gastrointestinal epithelium is critical for maintaining a symbiotic relationship with commensal microbiota. Chronic morphine exposure can compromise the gut epithelial barrier in mice and lead to dysbiosis. Recently, studies have implicated morphine-induced dysbiosis in the mechanism of antinociceptive tolerance and reward, suggesting the presence of a gut-brain axis in the pharmacological effects of morphine. However, the mechanism(s) underlying morphine-induced changes in the gut microbiome remains unclear. The pro-inflammatory cytokine, Interleukin-18 (IL-18), released by enteric neurons can modulate gut barrier function. Therefore, in the present study we investigated the effect of morphine on IL-18 expression in the mouse ileum. We observed that chronic morphine exposure in vivo induces IL-18 expression in the ileum myenteric plexus that is attenuated by naloxone. Given that mu-opioid receptors (MORs) are mainly expressed in enteric neurons, we also characterized morphine effects on the excitability of cholinergic (excitatory) and vasoactive intestinal peptide (VIP)-expressing (inhibitory) myenteric neurons. We found fundamental differences in the electrical properties of cholinergic and VIP neurons such that VIP neurons are more excitable than cholinergic neurons. Furthermore, MORs were primarily expressed in cholinergic neurons, although a subset of VIP neurons also expressed MORs and responded to morphine in electrophysiology experiments. In conclusion, these data show that morphine increases IL-18 in ileum myenteric plexus neurons via activation of MORs in a subset of cholinergic and VIP neurons. Thus, understanding the neurochemistry and electrophysiology of MOR-expressing enteric neurons can help to delineate mechanisms by which morphine perturbs the gut barrier.

Sex-specific role for serotonin 5-HT2A receptor in modulation of opioid-induced antinociception and reward in mice.

Opioids are among the most effective analgesics and the mainstay of pain management. However, concerns about safety and abuse liability have challenged their widespread use by the medical community. Opioid-sparing therapies include drugs that in combination with opioids have the ability to enhance analgesia while decreasing opioid requirement as well as their side effects. Sex differences in antinociceptive responses to opioids have received increasing attention in recent years. However, the molecular mechanisms underlying sex differences related to opioid-sparing adjuncts remain largely unexplored. Using warm water tail-withdrawal as a mouse model of acute thermal nociception, our data suggest that adjunctive administration of the serotonin 5-HT2A receptor (5-HT2AR) antagonist volinanserin dose-dependently enhanced potency of the opioid analgesic oxycodone in male, but not female, mice. This antinociceptive-like response induced by oxycodone was also augmented in 5-HT2AR knockout (5-HT2AR-/-) male, but not female mice; an effect that was reversed by Cre-loxP-mediated selective expression of 5-HT2AR in dorsal root ganglion (DRG) neurons of 5-HT2AR-/- littermates. Pharmacological inhibition with volinanserin or genetic deletion in 5-HT2AR-/- animals potentiated the ability of oxycodone to reduce DRG excitability in male mice. Adjunctive volinanserin did not affect oxycodone-induced conditioned place preference (CPP), whereas it reduced oxycodone-induced locomotor sensitization in male and female mice. Together, these results suggest that adjunctive volinanserin augments opioid-induced antinociception, but not abuse-related behavior, through a sex-specific signaling crosstalk mechanism that requires 5-HT2AR expression in mouse DRG neurons. Ultimately, our results may pave the way for the clinical evaluation of volinanserin as a potential sex-specific opioid adjuvant.

The Cannabinoid Receptor Type 1 Positive Allosteric Modulator ZCZ011 Attenuates Naloxone-Precipitated Diarrhea and Weight Loss in Oxycodone-Dependent Mice.

Opioid use disorder reflects a major public health crisis of morbidity and mortality in which opioid withdrawal often contributes to continued use. However, current medications that treat opioid withdrawal symptoms are limited by their abuse liability or lack of efficacy. Although cannabinoid 1 (CB1) receptor agonists, including Δ9-tetrahydrocannabinol, ameliorate opioid withdrawal in both clinical and preclinical studies of opioid dependence, this strategy elicits cannabimimetic side effects as well as tolerance and dependence after repeated administration. Alternatively, CB1 receptor positive allosteric modulators (PAMs) enhance CB1 receptor signaling and show efficacy in rodent models of pain and cannabinoid dependence but lack cannabimimetic side effects. We hypothesize that the CB1 receptor PAM ZCZ011 attenuates naloxone-precipitated withdrawal signs in opioid-dependent mice. Accordingly, male and female mice given an escalating dosing regimen of oxycodone, a widely prescribed opioid, and challenged with naloxone displayed withdrawal signs that included diarrhea, weight loss, jumping, paw flutters, and head shakes. ZCZ011 fully attenuated naloxone-precipitated withdrawal-induced diarrhea and weight loss and reduced paw flutters by approximately half, but its effects on head shakes were unreliable, and it did not affect jumping behavior. The antidiarrheal and anti-weight loss effects of ZCZ0111 were reversed by a CB1 not a cannabinoid receptor type 2 receptor antagonist and were absent in CB1 (-/-) mice, suggesting a necessary role of CB1 receptors. Collectively, these results indicate that ZCZ011 completely blocked naloxone-precipitated diarrhea and weight loss in oxycodone-dependent mice and suggest that CB1 receptor PAMs may offer a novel strategy to treat opioid dependence. SIGNIFICANCE STATEMENT: Opioid use disorder represents a serious public health crisis in which current medications used to treat withdrawal symptoms are limited by abuse liability and side effects. The CB1 receptor positive allosteric modulator (PAM) ZCZ011, which lacks overt cannabimimetic behavioral effects, ameliorated naloxone-precipitated withdrawal signs through a CB1 receptor mechanism of action in a mouse model of oxycodone dependence. These results suggest that CB1 receptor PAMs may represent a viable strategy to treat opioid withdrawal.

Effect of Processing Techniques on the Microstructure and Mechanical Performance of High-Density Polyethylene.

The versatility of high-density polyethylene (HDPE) makes it one of the most used polymers for vast applications ranging from food packaging to human implants. However, there still is confusion regarding the proper selection of processing techniques to produce HDPE specimens for high-end applications. Herein, we compare the processing of HDPE by two relevant techniques: compression and injection molding. The fabricated samples were studied using uniaxial tensile testing to determine their mechanical performance. Furthermore, the microstructure of samples was analyzed using different characterization techniques. Compression-molded specimens recorded a higher degree of crystallinity (DC) using two different characterization techniques such as differential scanning calorimetry (DSC) and X-ray diffraction (XRD). With this information, critical processing factors were determined, and a general structure-property relationship was established. It was demonstrated that having a higher DC resulted in higher yield strength and Young's modulus. Furthermore, premature failure was observed in the injection-molded specimens, resulting in lower mechanical performance. This premature failure was caused due to flow marks observed using scanning electron microscopy (SEM). Therefore, it is concluded that compression molding produces superior samples compared to injection molding.