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Background: Darunavir is an anti-HIV protease inhibitor repurposed for SARS-CoV-2 treatment. Objective: The aim of this study was to assess the population pharmacokinetics of darunavir in SARS-CoV-2 patients compared with HIV patients. Methods: Two separate models were created by means of a nonlinear mixed-effect approach. The influence of clinical covariates on each basic model was tested and the association of significant covariates with darunavir parameters was assessed at multivariate regression and classification and regression tree (CART) analyses. Monte Carlo simulation assessed the influence of covariates on the darunavir concentration versus time profile. Results: A one-compartment model well-described darunavir concentrations in both groups. In SARS-CoV-2 patients (n = 30), interleukin (IL)-6 and body surface area were covariates associated with darunavir oral clearance (CL/F) and volume of distribution (Vd), respectively; no covariates were identified in HIV patients (n = 25). Darunavir CL/F was significantly lower in SARS-CoV-2 patients compared with HIV patients (4.1 vs. 10.3 L/h; p < 0.001). CART analysis found that an IL-6 level of 18 pg/mL may split the SARS-CoV-2 population in patients with low versus high darunavir CL/F (mean ± standard deviation 3.47 ± 1.90 vs. 8.03 ± 3.24 L/h; proportion of reduction in error = 0.46). Median (interquartile range) darunavir CL/F was significantly lower in SARS-CoV-2 patients with IL-6 levels ≥ 18 pg/mL than in SARS-CoV-2 patients with IL-6 levels < 18 pg/mL or HIV patients (2.78 [2.16–4.47] vs. 7.24 [5.88–10.38] vs. 9.75 [8.45–13.79] L/h, respectively; p < 0.0001). Increasing IL-6 levels affected darunavir concentration versus time simulated profiles. We hypothesized that increases in IL-6 levels associated with severe SARS-CoV-2 disease may downregulate the cytochrome P450 (CYP) 3A4-mediated metabolism of darunavir. Conclusions: This is a proof-of-concept of SARS-CoV-2 disease–drug interactions, and may support the need for optimal dose selection of sensitive CYP3A4 substrates in severe SARS-CoV-2 patients. [ABSTRACT FROM AUTHOR]

Background: Retinol (ROH) is an essential micronutrient required for normal fetal development and an essential molecule for antioxidant processes. Objective: To investigate the putative role of ROH as a marker of preeclampsia in early second trimester amniotic fluid (AF). Materials and methods: Case-control study comparing the concentration of ROH and other antioxidants such as uric acid, vitamin E and malondialdehyde (MDA) in second trimester AF in patients that later developed preeclampsia with normal pregnancies. Results: The concentration of ROH in amniotic fluids of women that later developed preeclampsia was significantly higher than those of uncomplicated pregnancies (66.72 µg/l (49.00-70.56) vs. 44.4 µg/l (31.9-51.17), p < 0.05). No statistical significant difference was found in uric acid, vitamin E and MDA concentration. In the multivariate logistic regression, concentrations of ROH in amniotic fluids directly correlate with the risk of developing preeclampsia (OR 1.13, IC 0.01-1.26, p < 0.05). Conclusions: Second trimester AF ROH concentration was significantly higher in pregnancies that developed preeclampsia compared to normal pregnancies. [ABSTRACT FROM AUTHOR]

The paper deals with the Neuro-fuzzy model-based control and its application. Various types of the fuzzy logic and neural-net-based nonlinear autoregressive models with exogenous variables are reviewed with respect to the model error. Two types of model-based neuro-fuzzy control – a cancellation controller and a predictive controller are reviewed – and the robustness issues of such control are discussed. Finally, the application of the proposed design method to a laboratory scale heat exchanger is given. [ABSTRACT FROM AUTHOR]

The authors report the cases of two patients with CT-documented paramedian mesencephalo-thalamic infarcts, showing language disturbances. The first patient showed a non fluent, transcortical motor-like language disorder. The CT study disclosed that it was the dorso-median thalamic nucleus that was mostly involved in both cases. These findings agree with a few previous pathological studies suggesting that the paramedian thalamic nuclei, particularly the dorso-median nucleus may play some role in language disturbances. However the anatomical basis for thalamic aphasia remains speculative, taking into account the importance of cortical connections in the origin of subcortical neuropsychological disturbances. [ABSTRACT FROM AUTHOR]

Abstract  A security extension for IEEE Std 1149.1 is proposed. It provides a locking mechanism which prevents unauthorised users to interfere via test bus with the system normal operation. The security extension requires small hardware overhead and allows full conformance with IEEE Std 1149.1. [ABSTRACT FROM AUTHOR]

Beyond its clinical diversity and severity, acute myeloid leukemia (AML) is known for its complex molecular background and for rewiring biological processes to aid disease onset and maintenance. FLT3 mutations are among the most recurring molecular entities that cooperatively drive AML, and their inhibition is a critical molecularly oriented therapeutic strategy. Despite being a promising avenue, it still faces challenges such as intrinsic and acquired drug resistance, which led us to investigate whether and how autophagy and inflammasome interact and whether this interaction could be leveraged to enhance FLT3 inhibition as a therapeutic strategy. We observed a strong and positive correlation between the expression of key genes associated with autophagy and the inflammasome. Gene set enrichment analysis of the FLT3-ITD samples and their ex vivo response to five different FLT3 inhibitors revealed a common molecular signature compatible with autophagy and inflammasome activation across all poor responders. Inflammasome activation was also shown to strongly increase the likelihood of a poor ex vivo response to the FLT3 inhibitors quizartinib and sorafenib. These findings reveal a distinct molecular pattern within FLT3-ITD AML samples that underscores the necessity for further exploration into how approaching these supportive parallel yet altered pathways could improve therapeutic strategies. [ABSTRACT FROM AUTHOR]

Gaucher Disease (GD) is an autosomal recessive, lysosomal storage disease caused by pathogenic variants in the glucocerebrosidase gene, leading to the loss of β-glucocerebrosidase (GCase) enzymatic activity. Enzyme replacement therapy (ERT) with recombinant GCase is the standard of care in GD patients. Our study investigates the combined use of in silico molecular evolution, synthetic biology and gene therapy approaches to develop a new synthetic recombinant enzyme. We engineered four GCases containing missense mutations in the signal peptide (SP) from four selected mammalian species, and compared them with human GCase without missense mutations in the SP. We investigated transcriptional regulation with CMV and hEF1a promoters alongside a GFP control construct in 293-FT human cells. One hEF1a-driven mutant GCase shows a 5.2-fold higher level of transcription than control GCase. In addition, this mutant exhibits up to a sixfold higher activity compared with the mock-control, and the predicted tertiary structure of this mutant GCase aligns with human GCase. We also evaluated conserved and coevolved residues mapped to functionally important positions. Further studies are needed to assess its functionality in a GD animal model. Altogether, our findings provide in vitro evidence of the potential of this engineered enzyme for improved therapeutic effects for GD. Article highlights. Conservation and coevolution analysis of amino acid frequencies in GBA1 homologs of pathogenic variants associated with Gaucher disease, Parkinson’ disease risk or Dementia with Lewy bodies risk.Article Highlights: A novel synthetic recombinant GCase enzyme engineered with missense mutations in the signal peptide from selected mammalian species Correlation between transfection efficiency and catalytic activity indicates possible intrinsic sequence features influencing DNA uptake and gene expression [ABSTRACT FROM AUTHOR]

Western diets are the underlying cause of metabolic and liver diseases. Recent trend to limit the consumption of protein-rich animal products has become more prominent. This dietary change entails decreased protein consumption; however, it is still unknown how this affects innate immunity. Here, we studied the influence of a low protein diet (LPD) on the liver response to bacterial infection in mice. We found that LPD protects from Salmonella enterica serovar Typhimurium (S. Typhimurium)-induced liver damage. Bulk and single-cell RNA sequencing of murine liver cells showed reduced inflammation and upregulation of autophagy-related genes in myeloid cells in mice fed with LPD after S. Typhimurium infection. Mechanistically, we found reduced activation of the mammalian target of rapamycin (mTOR) pathway, whilst increased phagocytosis and activation of autophagy in LPD-programmed macrophages. We confirmed these observations in phagocytosis and mTOR activation in metabolically programmed human peripheral blood monocyte-derived macrophages. Together, our results support the causal role of dietary components on the fitness of the immune system. Low protein diet protects against Salmonella Typhimurium-mediated liver injury in mice corresponding to reduced mTOR activation and increased autophagy in macrophages. mTOR pathway activation with amino acid supplementation reverses this protection. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a well-known risk factor for the development of cardiovascular diseases and atherosclerosis. The effects of combined pretreatment with atorvastatin and fenofibrate (Tricor) were studied in a mouse model of acute lipemia induced by a general lipase inhibitor, poloxamer 407 (P-407, 250 mg/kg). This lipemia is characterized by significantly increased serum levels of triglycerides (TG), low-density lipoprotein (LDL) cholesterol, together with decreased concentration of high-density lipoprotein (HDL) cholesterol. Atorvastatin pretreatment had a hypolipidemic effect, decreasing concentrations of LDL cholesterol and increasing HDL cholesterol. Pretreatment of mice with fenofibrate decreased TG level, increasing HDL cholesterol. Combined pretreatment with atorvastatin and fenofibrate decreased TG and total cholesterol. Elevation of the serum cystatin C level was found in control and lipemic mice pretreated with atorvastatin, fenofibrate, or both. Liver expression of lysosomal acid lipase increased in atorvastatin- or/and fenofibrate-pretreated groups of lipemic mice. It was concluded that increased expression of lysosomal acid lipase is related to the removal of lipid droplets from hepatocytes, thus preventing acute lipemia. Lastly, cystatin C may be a "theranostic" biomarker for hypolipidemic drugs. [ABSTRACT FROM AUTHOR]

Intravenously admistered iodinated contrast media have been demostrated, since early experience with computed tomography of the brain, to improve clinical value of the procedure for detecting intracranial lesions. There is no universal agreement about the amount and the method of administration of the contrast medium. Many authors maintain that the use of large doses gives better results for the diagnosis of tumors and metastases. The purpose of this paper is to evaluate the tolerance of iopamidol administered by rapid intravenous infusion in a large number of patients undergoing contrast enhanced computed tomography to detect brain metastases. The authors examined 969 consecutive adult patients suffering from lung cancer, brain metastases have been detected in 17% of cases. Adverse reactions to contrast media occurred in 3 patients. Non ionic contrast media are recommended in this diagnostic procedure. [ABSTRACT FROM AUTHOR]

Background: Dextran Sulfate Sodium (DSS) induces ulcerative colitis (UC), a type of inflammatory bowel disease (IBD) that leads to inflammation, swelling, and ulcers in the large intestine. The aim of this experimental study is to examine how sinomenine, a plant-derived alkaloid, can prevent or reduce the damage caused by DSS in the colon and rectum of rats. Material and methods: Induction of ulcerative colitis (UC) in rats was achieved by orally administering a 2% Dextran Sulfate Sodium (DSS) solution, while the rats concurrently received oral administrations of sinomenine and sulfasalazine. The food, water intake was estimated. The body weight, disease activity index (DAI), colon length and spleen index estimated. Antioxidant, cytokines, inflammatory parameters and mRNA expression were estimated. The composition of gut microbiota was analyzed at both the phylum and genus levels in the fecal samples obtained from all groups of rats. Results: Sinomenine treatment enhanced the body weight, colon length and reduced the DAI, spleen index. Sinomenine treatment remarkably suppressed the level of NO, MPO, ICAM-1, and VCAM-1 along with alteration of antioxidant parameters such as SOD, CAT, GPx, GR and MDA. Sinomenine treatment also decreased the cytokines like TNF-α, IL-1, IL-1β, IL-6, IL-10, IL-17, IL-18 in the serum and colon tissue; inflammatory parameters viz., PAF, COX-2, PGE2, iNOS, NF-κB; matrix metalloproteinases level such as MMP-1 and MMP-2. Sinomenine significantly (P < 0.001) enhanced the level of HO-1 and Nrf2. Sinomenine altered the mRNA expression of RIP1, RIP3, DRP3, NLRP3, IL-1β, caspase-1 and IL-18. Sinomenine remarkably altered the relative abundance of gut microbiota like firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia, and Actinobacteria. Conclusion: The results clearly indicate that sinomenine demonstrated a protective effect against DSS-induced inflammation, potentially through the modulation of inflammatory pathways and gut microbiota. [ABSTRACT FROM AUTHOR]

PPMG-based composite electrolytes were fabricated via the solution method using the polyvinyl alcohol and polyvinylpyrrolidone blend reinforced with various contents of sulfonated inorganic filler. Sulfuric acid was employed as the sulfonating agent to functionalize the external surface of the inorganic filler, i.e., graphene oxide. The proton conductivities of the newly prepared proton exchange membranes (PEMs) were increased by increasing the temperature and content of sulfonated graphene oxide (SGO), i.e., ranging from 0.025 S/cm to 0.060 S/cm. The induction of the optimum level of SGO is determined to be an excellent route to enhance ionic conductivity. The single-cell performance test was conducted by sandwiching the newly prepared PEMs between an anode (0.2 mg/cm2 Pt/Ru) and a cathode (0.2 mg/cm2 Pt) to prepare membrane electrode assemblies, followed by hot pressing under a pressure of approximately 100 kg/cm2 at 60 °C for 5–10 min. The highest power densities achieved with PPMG PEMs were 14.9 and 35.60 mW/cm2 at 25 °C and 70 °C, respectively, at ambient pressure with 100% relative humidity. Results showed that the newly prepared PEMs exhibit good electrochemical performance. The results indicated that the prepared composite membrane with 6 wt% filler can be used as an alternative membrane for applications of high-performance proton exchange membrane fuel cell. [ABSTRACT FROM AUTHOR]

Background: Malaria infection during pregnancy presents a substantial health threat, adversely impacting both the mother and fetus. Its pathogenesis and clinical consequences further complicate diagnosis, treatment, and prevention, particularly in endemic regions. The precise impact of malaria infection on hematological profiles needs to be clearly elucidated, and the occurrence of malaria in expectant mothers still needs to be explored. Consequently, this study aims to assess the prevalence of malaria infection among pregnant women as well as to investigate and correlate the effects of this infection on the hematological parameters of pregnant women in Yola, Nigeria. Methods: A structured hybrid questionnaire was used to gather socio-demographic, clinical, and obstetric data from 100 pregnant women aged 15–45 years. Malaria parasitemia was determined and confirmed using a light microscope, blood smear-staining techniques, and rapid diagnostic tests (RDT). At the same time, the packed cell volume (PCV) was measured using a microhematocrit reader. Also, the complete blood count was determined using Turk’s solution and Neubauer’s counting chamber (hemocytometer). Results: Out of the 100 participants in the study, 76 tested positive for malaria, resulting in a prevalence rate of 76%. The age group between 30 and 34 years and multigravida recorded high values of malaria-infected women, accounting for 18 (23.7%) and 49%, respectively. Also, the study’s findings indicate that malaria-infected pregnant women had a significantly higher occurrence of anemia than those not infected (P =.045). In addition, eosinophil counts, total white blood cells (WBC), and neutrophil count were notably higher in pregnant women infected by malaria compared to those not infected (P <.05). Conversely, lymphocyte count, basophil count, and monocyte count were significantly lower in pregnant women infected by malaria compared to uninfected pregnant women. Conclusion: Pregnant women participating in prenatal care at the Specialist Hospital in Yola, Nigeria, exhibited a relatively high occurrence of malaria parasite infection, and these infected pregnant women displayed a notable change in specific hematological parameters. The findings of this study offer valuable insights into the pathogenesis of malaria during pregnancy and contribute to improved diagnostic and management strategies for pregnant women at risk of malaria infection. [ABSTRACT FROM AUTHOR]

Background: Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood. Methods: A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5′-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM. Results: Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iβ and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages. Conclusion: The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway. [ABSTRACT FROM AUTHOR]

This research article proposes a solution for efficient hardware implementation of deep neural networks (DNNs) in Edge-AI applications. An effective Hybrid ADDer (HADD) block for accumulation in fixed-point multiply-accumulate (MAC) operation is developed to overcome area and power limitations. The proposed HADD design offers a considerable reduction in area and power consumption, with a tolerable accuracy loss and reduced latency. The inference results show an accuracy of 96.97 and 96.64% for MNIST and A-Z Handwritten Alphabet datasets, respectively, using the LeNet-5 DNN model. Compared to the conventional adder implementation, the proposed HADD design reduces area utilization by 44% and power consumption by 51%, with a reduction in delay of 19% for 8-bit precision at 180 nm. For the same bit precision, the proposed design reduces area by 31%, power consumption by 34%, and delay by 8.1% at 45 nm. The proposed design further investigates edge detection applications, and the results for different standard images were promising. Overall, the proposed accumulator arithmetic block is a viable solution for error-tolerant AI applications, including DNN for image classification, object recognition, and other image-processing applications. [ABSTRACT FROM AUTHOR]

Histone deacetylases (HDACs) has been implicated in cardiac diseases, while the role of HDAC6 in dilated cardiomyopathy (DCM) remains obscure. The in silico analyses predicted potential association of HDAC6 with autophagy-related genes and DCM. Thus, we evaluated the functional relevance of HDAC6 in DCM in vivo and in vitro. We developed a rat model in vivo and a cell model in vitro by doxorubicin (DOX) induction to simulate DCM. HDAC6 expression was determined in myocardial tissues of DCM rats. DCM rats exhibited elevated HDAC6 mRNA and protein expression as compared to sham-operated rats. We knocked HDAC6 down and/or overexpressed NLRP3 in vivo and in vitro to characterize their roles in cardiomyocyte autophagy. It was established that shRNA-mediated HDAC6 silencing augmented cardiomyocyte autophagy and suppressed NLRP3 inflammasome activation, thus ameliorating cardiac injury in myocardial tissues of DCM rats. Besides, in DOX-injured cardiomyocytes, HDAC6 silencing also diminished NLRP3 inflammasome activation and cell apoptosis but enhanced cell autophagy, whereas ectopic NLRP3 expression negated the effects of HDAC6 silencing. Since HDAC6 knockdown correlates with enhanced cardiomyocyte autophagy and suppressed NLRP3 inflammasome activation through an interplay with NLRP3, it is expected to be a potential biomarker and therapeutic target for DCM. 1. HDAC6 was up-regulated in DCM rats. 2. HDAC6 knockdown promoted cardiomyocyte autophagy to relieve cardiac dysfunction. 3. HDAC6 knockdown inhibited NLRP3 inflammasome and promoted cardiomyocyte autophagy. 4. Silencing HDAC6 promoted autophagy and repressed apoptosis in cardiomyocytes. 5. This study provides novel therapeutic targets for DCM. [ABSTRACT FROM AUTHOR]

In order to improve the performance of deep neural network (DNN) accelerators, it is necessary to optimize compute efficiency and operating frequency. However, the implementation of contemporary DNNs often requires excessive resources due to the heavy multiply-and-accumulate (MAC) computations. In this work proposes a MAC unit designed with a Co-ordinate Rotation DIgital Computer (CORDIC)-based architecture, which is both power and area-efficient for 8-bit and higher-bit precision. The CORDIC-based designs are typically associated with low throughput. To address this issue, a performance-centric pipelined architecture is investigated that increases throughput. The study conducts a detailed Pareto analysis of accuracy variation at different precision levels and required pipeline stages to achieve high performance. The proposed MAC unit's post-synthesis results at the 45nm technology node are provided, and performance is evaluated on a deep neural network using Vertex-7 FPGA board. The proposed fixed-point MAC architecture is scalable for all bit-precision and flexible for the decimal point implication. The study finds that the proposed Fixed Q 3.5 precision with five pipeline stage-based MAC shows better performance metrics compared to the recursive CORDIC-based MAC design. The proposed MAC design has a lower area-delay-product (ADP) which is 1.13 × , and higher throughput of 2.73 × compared to the recursive CORDIC-based MAC. The study evaluated the performance of the proposed MAC unit using the fully connected NN for the MNIST dataset and found that the throughput 1.89 × better compared to the conventional MAC-based design. [ABSTRACT FROM AUTHOR]

Background: Alterations in time awareness have been reported in dementia, particularly in Alzheimer's disease (AD) and frontotemporal dementia (FTD). However, the neurophysiological correlates underlying these alterations remain largely unexplored. This study aimed to investigate the neurophysiological correlates of altered time awareness in AD and FTD patients. Methods: A total of 150 participants (50 AD patients, 50 FTD patients, and 50 healthy controls [HC]) underwent a standardized neuropsychological assessment, an altered time awareness survey, and transcranial magnetic stimulation (TMS) to assess cholinergic (short latency afferent inhibition—SAI), GABAergic (short interval intracortical inhibition—SICI), and glutamatergic (intracortical facilitation—ICF) circuits. Results: In AD patients, the most frequent symptom was difficulty in ordering past events (52.0%), while FTD patients primarily struggled with estimating temporal intervals between events (40.0%). Significant differences were observed between HC and both patient groups, as well as between AD and FTD patients in their tendency to re-live past events. Binomial logistic regression analysis revealed that impairments in glutamatergic and cholinergic circuits significantly predicted the likelihood of participants manifesting altered time awareness symptoms. Conclusions: This study provides novel insights into the neurophysiological correlates of altered time awareness in AD and FTD patients, highlighting the involvement of specific neurotransmitter circuits, particularly glutamatergic and cholinergic circuits. Further research is needed to explore the potential clinical implications and therapeutic targets arising from these findings. [ABSTRACT FROM AUTHOR]

Naloxone is a well-known opioid antagonist and has been suggested to have neuroprotective effects in cerebral ischemia. We investigated whether naloxone exhibits anti-inflammatory and neuroprotective effects in neural stem cells (NSCs) injured by oxygen-glucose deprivation (OGD), whether it affects the NOD-like receptor protein 3 (NLRP3) inflammasome activation/assembly, and whether the role of the phosphatidylinositol 3-kinase (PI3K) pathway is important in the control of NLRP3 inflammasome activation/assembly by naloxone. Primary cultured NSCs were subjected to OGD and treated with different concentrations of naloxone. Cell viability, proliferation, and the intracellular signaling proteins associated with the PI3K pathway and NLRP3 inflammasome activation/assembly were evaluated in OGD-injured NSCs. OGD significantly reduced survival, proliferation, and migration and increased apoptosis of NSCs. However, treatment with naloxone significantly restored survival, proliferation, and migration and decreased apoptosis of NSCs. Moreover, OGD markedly increased NLRP3 inflammasome activation/assembly and cleaved caspase-1 and interleukin-1β levels in NSCs, but naloxone significantly attenuated these effects. These neuroprotective and anti-inflammatory effects of naloxone were eliminated when cells were treated with PI3K inhibitors. Our results suggest that NLRP3 inflammasome is a potential therapeutic target and that naloxone reduces ischemic injury in NSCs by inhibiting NLRP3 inflammasome activation/assembly mediated by the activation of the PI3K signaling pathway. [ABSTRACT FROM AUTHOR]

Environmental challenges, specifically chronic stress, have long been associated with neuropsychiatric disorders, including anxiety and depression. Sirtuin-1 (SIRT1) is a NAD+-dependent deacetylase that is widely distributed in the cortex and is involved in stress responses and neuropsychiatric disorders. Nevertheless, how chronic stress modulates the SIRT1 pathway and associated signaling remains unclear. In this study, we first explored the impact of chronic unpredictable mild stress (CUMS) on the SIRT1/PGC1α/SIRT3 pathway, on GABAergic mechanisms, and on mitophagy, autophagy and apoptosis in mice. We also asked whether activation of SIRT1 by resveratrol (RSV) can attenuate CUMS-induced molecular and behavioral alterations. Two-month-old C57/BL6J mice were subjected to three weeks of CUMS and one week of RSV treatment (30 mg/kg; i.p.) during the third week of CUMS. CUMS caused downregulation of the SIRT1/PGC1α/SIRT3 pathway leading to impaired mitochondrial morphology and function. CUMS also resulted in a reduction in numbers of parvalbumin-positive interneurons and increased oxidative stress leading to reduced expression of autophagy- and mitophagy-related proteins. Strikingly, activation of SIRT1 by RSV ameliorated expression of SIRT1/PGC1α/SIRT3, and also improved mitochondrial function, GABAergic mechanisms, mitophagy, autophagy and apoptosis. RSV also rescued CUMS-induced anxiety-like and depressive-like behavior in mice. Our results raise the compelling possibility that RSV treatment might be a viable therapeutic method of blocking stress-induced behavioral alterations. [ABSTRACT FROM AUTHOR]

Despite the ability of combination antiretroviral therapy (cART) to suppress viremia, there is persistence low levels of HIV proteins such as Transactivator of transcription (Tat) in the central nervous system (CNS), contributing to glial activation and neuroinflammation. Accumulating evidence also implicates the role of drugs of abuse in exacerbating neurological complications associated with HIV-1. The combined effects of HIV Tat, drugs of abuse, and cART can thus create a toxic milieu in the CNS. The present study investigated the combinatorial effects of HIV-Tat, cocaine, and cART on autophagy and NLRP3 inflammasome activation. We selected a combination of three commonly used cART regimens: tenofovir, emtricitabine, and dolutegravir. Our results demonstrated that exposure of mouse primary microglia (MPMs) to these agents—HIV Tat (25 ng/ml), cocaine (1 μM), and cART (1 μM each) resulted in upregulation of autophagy markers: Beclin1, LC3B-II, and SQSTM1 with impaired lysosomal functioning involving increased lysosomal pH, decreased LAMP2 and cathepsin D, ultimately leading to dysregulated autophagy. Our findings also demonstrated activation of the NLRP3 signaling in microglia exposed to these agents. We further demonstrated that gene silencing of key autophagy protein BECN1 significantly blocked NLRP3-mediated activation of microglia. Silencing of NLRP3, however, failed to block HIV Tat, cocaine, and cART-mediated dysregulation of the autophagy-lysosomal axis; these in vitro phenomena were also validated in vivo using iTat mice administered cocaine and cART. This study thus underscores the cooperative effects of HIV Tat, cocaine, and cART in exacerbating microglial activation involving dysregulated autophagy and activation of the NLRP3 inflammasome signaling. [ABSTRACT FROM AUTHOR]

Background and objective: The life expectancy of people living with HIV (PLWHIV) has significantly improved in recent decades, mostly due to antiretroviral (ARV) therapy. Aging can affect the pharmacokinetics of drugs and, as a consequence, increase the risk of drug interactions and toxicity that may impact treatment. The aim of this study was to carry out a systematic review of the literature on the effect of aging on ARV pharmacokinetics. Methods: Searches were performed in the BVS, EMBASE and PUBMED databases until November 2022. All studies available in English, Spanish and Portuguese investigating the pharmacokinetics of ARV approved by the US Food and Drug Administration (FDA) from 2005 to 2020 were selected. Peer-reviewed publications were included if they met all criteria: adults (≥ 18 years of age) living with or without HIV; report any pharmacokinetic parameter or plasma concentration of at least one of the following ARVs: tenofovir alafenamide fumarate (TAF); doravirine (DOR), rilpivirine (RIL) and etravirine (ETR); darunavir (DRV), tipranavir (TPV) and fostemsavir (FTR); dolutegravir (DTG), raltegravir (RAL), bictegravir (BIC) and elvitegravir (EVG); maraviroc (MVC); ibalizumab (IBA); cobicistat (COBI). Pharmacokinetic parameters were reported stratified per age group: young adults (aged 18–49 years) or older (age ≥ 50 years) and all studies were evaluated for quality. The review protocol was registered in the PROSPERO database (registration number CRD42021236432). Results: Among 97 studies included, 20 reported pharmacokinetic evaluation in older individuals (age ≥ 50 years). Twenty five percent of the articles were phase I randomized clinical trials with HIV-negative participants and non-compartmental pharmacokinetic analysis presenting the parameters area under the curve (AUC) and peak drug concentration (Cmax). Seven age-stratified studies evaluated BIC, ETR, DRV, DTG, DOR and RAL. We found publications with discordant results for ETR and DTG pharmacokinetics in different age groups. DRV exposure was highly variable but modestly increased in aging PLWHIV. In contrast, no influence of age on BIC, DOR and RAL exposure was observed. A variability in pharmacokinetic parameters could be observed for the other ARVs (TAF and MVC) in different age groups. Conclusion: Exposure to DRV increases modestly with age, while exposure to BIC, DOR and RAL appears to be unaffected by age. As the available evidence to confirm a potential effect of aging on ARV pharmacokinetics is limited, further studies are necessary. [ABSTRACT FROM AUTHOR]

Chronic pain is not only one of the most common health problems, it is often challenging to treat adequately. Chronic pain has a high prevalence globally, affecting approximately 20% of the adult population. Chronic inflammatory pain and neuropathic (nerve) pain conditions are areas of large unmet medical need because analgesic/adjuvant agents recommended for alleviation of these types of chronic pain often lack efficacy and/or they produce dose-limiting side effects. Recent work has implicated the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome in the pathobiology of chronic pain, especially neuropathic and inflammatory pain conditions. NLRP3 is activated by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). This in turn leads to recruitment and activation of caspase-1 an enzyme that cleaves the inactive IL-1β and IL-18 precursors to their respective mature pro-inflammatory cytokines (IL-1β and IL-18) for release into the cellular milieu. Caspase-1 also cleaves the pyroptosis-inducing factor, gasdermin D, that leads to oligomerization of its N-terminal fragment to form pores in the host cell membrane. This then results in cellular swelling, lysis and release of cytoplasmic contents in an inflammatory form of cell death, termed pyroptosis. The ultimate outcome may lead to the development of neuropathic pain and/or chronic inflammatory pain. In this review, we address a role for NLRP3 inflammasome activation in the pathogenesis of various chronic pain conditions. [ABSTRACT FROM AUTHOR]

Background: Sodium butyrate (NaB) is a short-chain fatty acid produced by intestinal microbial fermentation of dietary fiber, and has been shown to be effective in inhibiting ulcerative colitis (UC). However, how NaB regulates inflammation and oxidative stress in the pathogenesis of UC is not clear. Aims: The purpose of this study was to use a dextran sulfate sodium salt (DSS)-induced murine colitis model, and determine the effects of NaB and the related molecular mechanisms. Methods: Colitis model was induced in mice by administration of 2.5%(wt/vol) DSS. 0.1 M NaB in drinking water, or intraperitoneal injection of NaB (1 g/kg body weight) was given during the study period. In vivo imaging was performed to detect abdominal reactive oxygen species (ROS). Western blotting and RT-PCR were used to determine the levels of target signals. Results: The results showed that NaB decreases the severity of colitis as determined by an improved survival rate, colon length, spleen weight, disease activity index (DAI), and histopathological changes. NaB reduced oxidative stress as determined by a reduction in abdominal ROS chemiluminescence signaling, inhibition of the accumulation of myeloperoxidase and malondialdehyde, and restoration of glutathione activity. NaB activated the COX-2/Nrf2/HO-1 pathway by increasing the expressions of COX-2, Nrf2, and HO-1 proteins. NaB inhibited the phosphorylation of NF-κB and activation of NLRP3 inflammasomes, and reduced the secretion of corresponding inflammatory factors. Furthermore, NaB promoted the occurrence of mitophagy via activating the expression of Pink1/Parkin. Conclusions: In conclusion, our results indicate that NaB improves colitis by inhibiting oxidative stress and NF-κB/NLRP3 activation, which may be via COX-2/Nrf2/HO-1 activation and mitophagy. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the analgesic effect of perineural injection of BoNT/A on neuropathic pain induced by sciatic nerve chronic constriction injury (CCI) and possible mechanisms. SD rats were randomly divided into Sham group, CCI group and BoNT/A group. Paw mechanical withdrawal threshold (pMWT) and paw thermal withdrawal latency (pTWL) of each group were detected at different time points after surgery. The expression of myelin markers, autophagy markers and NLRP3 inflammasome-related molecules in injured sciatic nerves were examined at 12 days after surgery. Moreover, C-fiber evoked potential in spinal dorsal horn was recorded. The expression of SNAP-25, neuroinflammation and synaptic plasticity in spinal dorsal horn of each group were examined. Then rats treated with BoNT/A were randomly divided into DMSO group and Wnt agonist group to further explore the regulatory effect of BoNT/A on Wnt pathway. We found that pMWT and pTWL of ipsilateral paw were significantly decreased in CCI group compared with Sham group, which could be improved by perineural injection of BoNT/A at days 7, 9 and 12 after surgery. The peripheral analgesic mechanisms of perineural injection of BoNT/A might be related to the protective effect on myelin sheath by inhibiting NLRP3 inflammasome and promoting autophagy flow, while the central analgesic mechanisms might be associated with inhibition of neuroinflammation and synaptic plasticity in spinal dorsal horn due to inhibiting SNAP-25 and Wnt pathway. As a new route of administration, perineural injection of BoNT/A can relieve CCI induced neuropathic pain probably via both peripheral and central analgesic mechanisms. [ABSTRACT FROM AUTHOR]

A hollow fiber-supported liquid membrane (HFSLM) configuration with a large membrane surface area per volume is becoming more viable and feasible to use on an industrial scale. However, the hollow fiber (HF) forms a thicker skin outer layer than its flat-sheet equivalents, resulting in lower membrane fluxes and more unsatisfactory performance. Therefore, this study investigated the effect of HF spinning parameters such as bore liquid type, air gap distance (3–12 cm), and air relative humidity (64–100 wt%) on the properties and performance of HFSLM for levulinic acid (LA) extraction. The HF membranes were characterized in terms of morphology, contact angle, porosity, and membrane tensile strength. Polyethersulfone-based HF membrane prepared using 60% v/v dimethylacetamide as bore liquid at 6 cm air gap distance and 86% air relative humidity resulted in the highest LA extraction of 72.2%. The membrane had a dual symmetric finger-like structure with an open porous structure. The value of the outer fiber surface contact angle, porosity, and tensile stress was 94.1°, 77.57%, and 1,524.7 kPa, respectively. An optimal spinning condition is crucial in producing the best HF structure for improving the HFSLM performance in LA extraction. [ABSTRACT FROM AUTHOR]

Selenium (Se), as a trace element, is widely found in animals in the form of selenomethionine, which can provide nutrition to the body and has anti-inflammatory effects to prevent inflammatory damage in animals. In the past decade, there have been many studies on piglet diseases caused by selenium deficiency; however, under Se deficiency, the relationship between LncRNA-MORC3, inflammatory injury, and tight junctions in piglets has not yet been studied. We established piglet selenium deficiency models divided into three groups and obtained small intestinal tissues after 35 days of feeding. Small intestinal epithelial IPEC-J2 cells were divided into three groups, and samples were collected after 24 h of culture for qPCR and Western blot experiments. First, we found that Se deficiency led to an increase in LncRNA-MORC3 expression in piglets in vivo and in vitro. We found that the binding site of NLRP3 on LncRNA-MORC3 and the expression trends of both were the same: Se deficiency increased the secretion of NLRP3 and the expression levels of the inflammatory factors Caspase-1, ASC, IL-1β, IL-17, IL-6, IL-10, and TNF-α, which are related to the NLRP3-Caspase-1/IL-1β signaling pathway. At the same time, Se deficiency decreased the expression levels of the tight junction factors ZO-1, Z0-2, Occludin, E-cadherin, and ZEB-1. This result showed that the tight junctions were disrupted. Herein, we demonstrated that Se deficiency promotes the expression of both LncRNA-MORC3 and inflammatory factors in piglets to activate the NLRP3-Caspase-1/IL-1β signaling pathway and disrupt tight junctions. Ultimately, these factors lead to inflammatory damage in piglet small intestinal tissues. [ABSTRACT FROM AUTHOR]

There is much excitement surrounding recent research of promising, mechanistically novel psychotherapeutics – psychedelic, anesthetic, and dissociative agents – as they have demonstrated surprising efficacy in treating central nervous system (CNS) disorders, such as mood disorders and addiction. However, the mechanisms by which these drugs provide such profound psychological benefits are still to be fully elucidated. Microglia, the CNS's resident innate immune cells, are emerging as a cellular target for psychiatric disorders because of their critical role in regulating neuroplasticity and the inflammatory environment of the brain. The following paper is a review of recent literature surrounding these neuropharmacological therapies and their demonstrated or hypothesized interactions with microglia. Through investigating the mechanism of action of psychedelics, such as psilocybin and lysergic acid diethylamide, ketamine, and propofol, we demonstrate a largely under-investigated role for microglia in much of the emerging research surrounding these pharmacological agents. Among others, we detail sigma-1 receptors, serotonergic and γ-aminobutyric acid signalling, and tryptophan metabolism as pathways through which these agents modulate microglial phagocytic activity and inflammatory mediator release, inducing their therapeutic effects. The current review includes a discussion on future directions in the field of microglial pharmacology and covers bidirectional implications of microglia and these novel pharmacological agents in aging and age-related disease, glial cell heterogeneity, and state-of-the-art methodologies in microglial research. [ABSTRACT FROM AUTHOR]

Endometriosis (EMS) is a gynecological disease that leads to pathological conditions, which are connected to the initiation of pro-inflammatory cytokine production. Inflammation plays a vital role in the pathogenesis of EMS. The activation and formation of cytoplasmic inflammasome complexes is considered an important step of inflammation and a key regulator of pyroptosis, a form of cell death. NLR family pyrin domain containing 3 (NLRP3) inflammasome complex modulates innate immune activity and inflammation. The NLRP3 inflammasome activates cysteine protease caspase-1, which produces active pro-inflammatory interleukins (ILs), including IL-1β and IL-18. The aim of this review article was to discuss the involvement of NLRP3 inflammasome assembly and its activation in the pathophysiology of EMS and target related pathways in designing appropriate therapeutic approaches. Dysregulation of sex hormone signaling pathways was associated with over-activation of the NLPR3 inflammasome. In this study, we demonstrated the involvement of NLRP3 inflammasome signaling pathways in the pathophysiology of EMS. The manuscript also discusses the beneficial effects of targeted therapy through synthetic inhibitors of NLRP3 signaling pathways to control EMS lesions. [ABSTRACT FROM AUTHOR]

Leptin, an adipose tissue-derived hormone, exhibits potent tumor promoting effects through various mechanisms. Cathepsin B, a member of the lysosomal cysteine proteases, has been shown to modulate the growth of cancer cells. In this study, we have investigated the role of cathepsin B signaling in leptin-induced hepatic cancer growth. Leptin treatment caused significant increase in the levels of active cathepsin B through the axis of endoplasmic reticulum stress and autophagy induction without significant effects on pre- and pro-forms of cathepsin B. Interestingly, inhibition of cathepsin B signaling by gene silencing or treatment with a selective pharmacological inhibitor (CA-074) prevented leptin-enhanced viability of hepatic cancer cell and suppressed progression of cell cycle, indicating the critical role of cathepsin B in leptin-induced hepatic cancer growth. We have further observed that maturation of cathepsin B is required for NLRP3 inflammasomes activation, which is implicated in the growth of hepatic cancer cell. The crucial roles of cathepsin B maturation in leptin-induced hepatic cancer growth and NLRP3 inflammasomes activation were confirmed in an in vivo HepG2 tumor xenograft model. Taken together, these results demonstrate that cathepsin B signaling plays a pivotal role in leptin-induced hepatic cancer cell growth by activating NLRP3 inflammasomes. [ABSTRACT FROM AUTHOR]

The innate immune system, as the first line of cellular defense, triggers a protective response called inflammation when encountered with invading pathogens. Inflammasome is a multi-protein cytosolic signaling complex that induces inflammation and is critical for inflammation-induced pyroptotic cell death. Inflammasome activation has been found associated with neurodegenerative disorders (NDs), inflammatory diseases, and cancer. Autophagy is a crucial intracellular quality control and homeostasis process which removes the dysfunctional organelles, damaged proteins, and pathogens by sequestering the cytosolic components in a double-membrane vesicle, which eventually fuses with lysosome resulting in cargo degradation. Autophagy disruption has been observed in many NDs presented with persistent neuroinflammation and excessive inflammasome activation. An interplay between inflammation activation and the autophagy process has been realized over the last decade. In the case of NDs, autophagy regulates neuroinflammation load and cellular damage either by engulfing the misfolded protein deposits, dysfunctional mitochondria, or the inflammasome complex itself. A healthy two-way regulation between both cellular processes has been realized for cell survival and cell defense during inflammatory conditions. Therefore, clinical interest in the modulation of inflammasome activation by autophagy inducers is rapidly growing. In this review, we discuss the structural basis of inflammasome activation and the mechanistic ideas of the autophagy process in NDs. Along with comments on multiple ways of neuroinflammation regulation by microglial autophagy, we also present a perspective on pharmacological opportunities in this molecular interplay pertaining to NDs. [ABSTRACT FROM AUTHOR]

The p21-activated kinase 1 (PAK1), an effector protein of the small G protein Rac and cell division cycle protein 42 (Cdc42), is highly expressed in cardiac tissue. Although a large number of studies have explored the molecular basis and biological function of PAK1, research on PAK1 as a therapeutic target for cardiotoxicity remains in a stage of continuous innovation, and further clarification of its role in cardiotoxicity is required. In this review, we examine the important role of PAK1 in the programmed death (apoptosis, autophagy, and pyroptosis) of cardiomyocytes, and its involvement in oxidative stress and inflammatory responses, which are based on mitochondrial dysfunction and calcium homeostasis imbalance. We also summarize the related signaling pathways through which PAK1 may cause oxidative stress and inflammatory response in cardiotoxicity, and discuss the PAK1-mediated contributions of the gut microbiome and micro RNAs to cardiotoxicity. We propose that PAK1 holds great promise for novel therapeutic strategies to facilitate improvements in the treatment of complex and diverse cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains the fifth most common malignant tumor and the third leading cause of cancer death, despite the decline in incidence and mortality worldwide over the past five decades. Currently, the roles of Helicobacter pylori (H. pylori) in the development of GC have been established. The effects of H. pylori are mediated through interactions of H. pylori pathogen-associated molecular patterns (PAMPs) with pattern-recognition receptors (PRRs) located on immune and epithelial cells. It is known that this interaction leads to the generation of reactive oxygen species (ROS), activation of the mechanisms of angiogenesis, epithelial–mesenchymal transformation (EMT), and immunological tolerance. Not all this excludes the possibility that H. pylori may have an effect not only on the induction, but also on the mechanisms of GC progression. In this review, we will consider the main structural elements of the innate immune system and the mechanisms of their interaction with H. pylori; the possible role of H. pylori in GC progression; relationship of H. pylori with clinical and pathological characteristics and prognosis of GC, as well as data on the effect of eradication therapy on long-term results of GC patient treatment. [ABSTRACT FROM AUTHOR]

Background and Objective: An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze the clinical studies that assessed the pharmacokinetics of victim drugs of this drug–disease interaction in the presence of different scenarios of cytokine modulation in comparison with baseline conditions. Methods: We conducted a systematic review by searching the PubMed-MEDLINE database from inception until February 2022 to retrieve prospective and/or retrospective observational studies, population pharmacokinetic studies, phase I studies, and/or case series/reports that investigated the impact of cytokine modulation on the pharmacokinetic behavior of victim drugs. Only studies providing quantitative pharmacokinetic data of victim drugs by comparing normal status versus clinical conditions with documented cytokine modulation or by assessing the influence of anti-inflammatory biological agents on metabolism and/or transport of victim drugs were included. Results: Overall, 26 studies were included. Rheumatoid arthritis (6/26; 23.1%) and sepsis (5/26; 19.2%) were the two most frequently investigated pro-inflammatory clinical scenarios. The victim drug most frequently assessed was midazolam (14/26; 53.8%; as a probe for cytochrome P450 [CYP] 3A4). Cytokine modulation showed a moderate inhibitory effect on CYP3A4-mediated metabolism (area under the concentration–time curve increase and/or clearance decrease between 1.98-fold and 2.59-fold) and a weak-to-moderate inhibitory effect on CYP1A2, CYP2C9, and CYP2C19-mediated metabolism (in the area under the concentration–time curve increase or clearance decrease between 1.29-fold and 1.97-fold). Anti-interleukin-6 agents showed remarkable activity in counteracting downregulation of CYP3A4-mediated activity (increase in the area under the concentration–time curve between 1.75-fold and 2.56-fold). Conclusions: Cytokine modulation may cause moderate or weak-to-moderate downregulation of metabolism/transport of victim drugs, and this may theoretically have relevant clinical consequences. [ABSTRACT FROM AUTHOR]

The infectious paradigms have recently led to the recognition interplay of complex phenomenon underpinning disease diagnosis and prognosis. Evidently, parasitic infection studies are depicting converging trends of the epigenetic, environmental, and microbiome contributions, assisting pathogen-directed modulations of host biological system. The molecular details of epigenetic variations and memory, along with the multi-omics data at the interface of the host–pathogen level becomes strong indicator of immune cell plasticity, differentiation, and pathogen survival. Despite being one of the most important aspects of the disease's etiopathology, the epigenetic regulation of host–pathogen interactions and evolutionary epigenetics have received little attention thus far. Recent evidence has focused on the growing need to link epigenetic and microbiome modulations on parasite phenotypic plasticity and pathogen-induced host phenotypic plasticity for designing futuristic therapeutic regimes. Leishmaniasis is a neglected tropical illness with varying degrees of disease severity that is linked to a trans-species and epigenetic heredity process, including the pathogen-induced host and strain-specific modulations. The review configures research findings aligning to the epigenetic epidemiology niche, involving co-evolutionary epigenetic inheritance and plasticity disease models. The epigenetic exemplars focus on the host–pathogen interactome expanse at the macrophage—inflammasome axis. [ABSTRACT FROM AUTHOR]

Nutraceuticals, the active compounds found abundant in most of the natural products, have shown beneficial effects on human health. Their absorption when consumed is limited owing to their poor solubility and unsuitable chemical and physical properties. In order to empower the beneficial properties and enhance the efficacy of nutraceuticals, nanotechnological approaches have ventured in as a frontier to improve the bioavailability. An updated overview on this area is the need of the hour to explore the importance of nanocarriers in delivering the nutraceuticals more effectively. This overview initially started with the introduction of nutraceuticals their importance, limitations and challenges encountered during their absorption. Traditional route of delivering nutraceuticals and limitations have been described. Different types of nano-based systems for effectively delivering the nutraceuticals at the targeted site have also been highlighted. Finally, some of the novel nano-based carrier systems used in effectively encapsulating the nutraceuticals both at in vitro and in vivo animal models have also been critically reviewed with additional data toward their synthesis and other characteristics. From the overview, it was clear that the nutraceuticals with potential health benefits could not be absorbed in the gastro-intestinal tract owing to their bioavailability and stability. Nano-based delivery systems such as niosomes, nanogels, nanocapsules etc. showed effective loading of these labile nutraceuticals protecting them from various pH conditions thereby delivering them at the targeted site. Further, the nanocarriers were found effective in delivering the anticancer bioactives at the damaged site leaving the surrounding environment unaffected. Finally, the limitations pertaining to toxicity need to be addressed by framing effective guidelines and policies prior to human and animal use. [ABSTRACT FROM AUTHOR]

Looking at the literature focused on molecularly imprinted polymers (MIPs) for protein, it soon becomes apparent that a remarkable increase in scientific interest and exploration of new applications has been recorded in the last several years, from 42 documents in 2011 to 128 just 10 years later, in 2021 (Scopus, December 2021). Such a rapid threefold increase in the number of works in this field is evidence that the imprinting of macromolecules no longer represents a distant dream of optimistic imprinters, as it was perceived until only a few years ago, but is rapidly becoming an ever more promising and reliable technology, due to the significant achievements in the field. The present critical review aims to summarize some of them, evidencing the aspects that have contributed to the success of the most widely used strategies in the field. At the same time, limitations and drawbacks of less frequently used approaches are critically discussed. Particular focus is given to the use of a MIP for protein in the assembly of electrochemical sensors. Sensor design indeed represents one of the most active application fields of imprinting technology, with electrochemical MIP sensors providing the broadest spectrum of protein analytes among the different sensor configurations. [ABSTRACT FROM AUTHOR]

The main objective of this paper is to design and implement High throughput, area efficient AES encryption algorithm on FPGA for security purposes. The high speed and area efficiency is achieved by designing an area efficient and high throughput structural S-Box architecture for AES encryption process. A combinational logic circuit based Rijndael Low area high speed S-Box is designed. The results compared with conventional S-Box. The speed and propagation delay of the S-Box are calculated for the designed S-Box. The proposed S-Box is used in AES encryption process. To further increase the speed of the encryption process efficient structure of Mix column is also proposed. This Mix column structure is used to achieve high throughput. The proposed S-Box and Mix Column are used in AES encryption. This proposed AES structure is implemented in FPGA Virtex 5.The results are compared with the conventional implementation. [ABSTRACT FROM AUTHOR]

COVID-19-caused neurological problems are the important post-CoV-2 infection complications, which are recorded in ~ 40% of critically ill COVID-19 patients. Neurodegeneration (ND) is one of the most serious complications. It is necessary to understand its molecular mechanism(s), define research gaps to direct research to, hopefully, design new treatment modalities, for predictive diagnosis, patient stratification, targeted prevention, prognostic assessment, and personalized medical services for this type of complication. Individualized nano-bio-medicine combines nano-medicine (NM) with clinical and molecular biomarkers based on omics data to improve during- and post-illness management or post-infection prognosis, in addition to personalized dosage profiling and drug selection for maximum treatment efficacy, safety with least side-effects. This review will enumerate proteins, receptors, and enzymes involved in CoV-2 entrance into the central nervous system (CNS) via the blood–brain barrier (BBB), and list the repercussions after that entry, ranging from neuroinflammation to neurological symptoms disruption mechanism. Moreover, molecular mechanisms that mediate the host effect or viral detrimental effect on the host are discussed here, including autophagy, non-coding RNAs, inflammasome, and other molecular mechanisms of CoV-2 infection neuro-affection that are defined here as hallmarks of neuropathology related to COVID-19 infection. Thus, a couple of questions are raised; for example, "What are the hallmarks of neurodegeneration during COVID-19 infection?" and "Are epigenetics promising solution against post-COVID-19 neurodegeneration?" In addition, nano-formulas might be a better novel treatment for COVID-19 neurological complications, which raises one more question, "What are the challenges of nano-bio-based nanocarriers pre- or post-COVID-19 infection?" especially in the light of omics-based changes/challenges, research, and clinical practice in the framework of predictive preventive personalized medicine (PPPM / 3P medicine). [ABSTRACT FROM AUTHOR]

The wireless network (WN) has become an integral part of the living habits of human beings. Most of the crypto chips are broadly utilized in WN application to assure the security of information. The functional correctness of cryptographic devices should be verified to authenticate the precision of the secrecy of the information. In the IC industry correctness of the wireless sensing device can be verified by scan design-based testing. The scan chain-based testing is the most popularly used testing technique due to its increased fault coverage and improved test quality. It also acts as a hacking tool and recovers sensitive data through side-channel attacks like power, time, or hamming distance. This paper presents the state-of-art-of secure mechanism to protect the scan chain from the side-channel attack using the obfuscation technique and logic locking Scheme. The proposed methodology provides direct access to internal data to the authorized test engineer. Although, the security synthesis creates a controllable confusion between the reverse-engineered netlist and the original design. The proposed secure design protects the design from a hamming distance-based attack, brute force attack, and hill-climbing attack. Then evaluate the security and overhead of the suggested approach using ISCAS'89 and ITC'99 test circuits. [ABSTRACT FROM AUTHOR]

Rechargeable batteries have gained a lot of interests due to rising trend of electric vehicles to control greenhouse gases emissions. Among all type of rechargeable batteries, lithium air battery (LAB) provides an optimal solution, owing to its high specific energy of 11,140 Wh/kg comparable to that of gasoline 12,700 Wh/kg. However, LABs are not widely commercialized yet due to the reactivity of the lithium anode with the components of ambient air such as moisture and carbon dioxide. To address this challenge, it is important to understand the effects of moisture on the electrochemical performance of LAB. In this review, the effects of ambient air on the electrochemical performance of LAB have been discussed. The literature on the deterioration in the battery capacity and cyclability due to operation in ambient environment and degradation of lithium anode due to exothermic reaction between lithium and water is reviewed and explained. The effects of using oxygen-selective membrane (OSM) to block moisture and CO 2 contamination has also been discussed, along with suitable materials that can act as OSM. It is concluded that the utilization of OSM can not only make the safer operation of LAB in ambient air but could also enhance the electrochemical performance of LAB. Future direction of the research work required to address the associated challenges is also provided. [ABSTRACT FROM AUTHOR]

Segmentation of intracranial aneurysm images acquired using magnetic resonance angiography (MRA) is essential for medical auxiliary treatments, which can effectively prevent subarachnoid hemorrhages. This paper proposes an image segmentation model based on a dense convolutional attention U-Net, which fuses deep and rich semantic information with shallow-detail information for adaptive and accurate segmentation of MRA-acquired aneurysm images with large size differences. The U-Net model serves as a backbone, combining dense block and convolution block attention module (CBAM). The dense block is composed of a batch normalization layer, an randomly rectified linear unit activation function, and a convolutional layer, for mitigation of vanishing gradients, for multiplexing of aneurysm features, and for improving the network training efficiency. The CBAM is composed of a channel attention module and a spatial attention module, improving the segmentation performance of feature discrimination and enhancing the acquisition of key feature information. Owing to the large variation of aneurysm sizes, multi-scale fusion is performed during up-sampling, for adaptive segmentation of MRA-acquired aneurysm images. The model was tested on the MICCAI 2020 ADAM dataset, and its generalizability was validated on the clinical aneurysm dataset (aneurysm sizes: < 3 mm, 3–7 mm, and > 7 mm) supplied by the Affiliated Hospital of Qingdao University. A good clinical application segmentation performance was demonstrated. [ABSTRACT FROM AUTHOR]