Good Practices and Initiatives for the Control and Elimination of Hepatitis B in the World: A Scoping Review.

Hepatitis B virus (HBV) infection remains a significant global public health challenge, leading to considerable morbidity and mortality. Implementation of effective strategies and novel initiatives is necessary to control and eliminate HBV. To identify the key approaches and actions used worldwide for HBV control and elimination, we conducted a comprehensive scoping review. We searched various sources, including PubMed, Scopus, Web of Science, Google Scholar, the official websites of the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), and relevant articles and reports published in the past decade. Our inclusion criteria focused on studies that reported on strategies for HBV control and elimination, provided evidence of their effectiveness, and assessed their impact on public health outcomes. We included 16 articles in our review, which highlighted a range of strategies, such as universal HBV vaccination, prevention of mother-to-child transmission, mass screening programs, and treatment of chronically infected individuals. These strategies have shown promising results in reducing HBV transmission rate, improving health outcomes, and making progress toward HBV elimination. Moreover, several challenges, including limited access to care, low awareness, stigma, and funding constraints, hinder the effectiveness of elimination programs. The findings underscore the importance of sustained efforts and investment in comprehensive strategies for HBV control and elimination. It is crucial to address barriers to care and enhance public awareness to achieve the goal of eliminating HBV as a public health threat by 2030.

Development of alginate and alginate sulfate/polycaprolactone nanoparticles for growth factor delivery in wound healing therapy.

Connective tissue growth factor (CTGF) holds great promise for enhancing the wound healing process; however, its clinical application is hindered by its low stability and the challenge of maintaining its effective concentration at the wound site. Herein, we developed novel double-emulsion alginate (Alg) and heparin-mimetic alginate sulfate (AlgSulf)/polycaprolactone (PCL) nanoparticles (NPs) for controlled CTGF delivery to promote accelerated wound healing. The NPs' physicochemical properties, cytocompatibility, and wound healing activity were assessed on immortalized human keratinocytes (HaCaT), primary human dermal fibroblasts (HDF), and a murine cutaneous wound model. The synthesized NPs had a minimum hydrodynamic size of 200.25 nm. Treatment of HaCaT and HDF cells with Alg and AlgSulf2.0/PCL NPs did not show any toxicity when used at concentrations <50 µg/mL for up to 72 h. Moreover, the NPs' size was not affected by elevated temperatures, acidic pH, or the presence of a protein-rich medium. The NPs have slow lysozyme-mediated degradation implying that they have an extended tissue retention time. Furthermore, we found that treatment of HaCaT and HDF cells with CTGF-loaded Alg and AlgSulf2.0/PCL NPs, respectively, induced rapid cell migration (76.12% and 79.49%, P<0.05). Finally, in vivo studies showed that CTGF-loaded Alg and AlgSulf2.0/PCL NPs result in the fastest and highest wound closure at the early and late stages of wound healing, respectively (36.49%, P<0.001 on day 1; 90.45%, P<0.05 on day 10), outperforming free CTGF. Double-emulsion NPs based on Alg or AlgSulf represent a viable strategy for delivering heparin-binding GF and other therapeutics, potentially aiding various disease treatments.

Role of Insulin Use and Social Determinants of Health on Non-melanoma Skin Cancer: Results From the Behavioral Risk Factor Surveillance System.

BACKGROUND: Non-melanoma skin cancer (NMSC) is a frequent type of malignancy with a steadily increasing incidence rate worldwide. Although NMSC was shown to be associated with diabetes, no studies have addressed the extent to which insulin use influences the risk of NMSC in light of social determinants of health (SDOH). We conducted a quantitative study that examined the interplay between insulin use, SDOH, additional covariates, and NMSC among individuals with diabetes. METHODS: We based our analysis on the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a national survey conducted yearly in the US. We performed weighted chi-squared test, logistic regression, and survival analyses on 8685 eligible participants with diabetes enrolled in the BRFSS. RESULTS: Kaplan Meier survival curves showed higher probability of NMSC event-free survival for participants with diabetes using insulin compared to participants with diabetes not using insulin (log-rank test P < .001). Significant associations were detected between insulin use and reduced odds of NMSC (OR .56; 95% CI: .38-.82), and decreased hazard (HR .36; 95% CI: .21-.62), along with indices of SDOH. CONCLUSIONS: Our findings suggest that socioeconomic differences related to the healthcare system and behavioral patterns are linked to discrepancies in the use of insulin and the development of NMSC.

Diabetes and the social, biologic, and behavioral determinants of endometrial cancer in the United States.

BACKGROUND: Endometrial cancer is one of the most common types of cancer that affects women's reproductive system. The risk of endometrial cancer is associated with biologic, behavioral and social determinants of health (SDOH). The focus of the work is to investigate the cumulative effect of this cluster of covariates on the odds of endometrial cancer that heretofore have only been considered individually. METHODS: We conducted a quantitative study using the Behavioral Risk Factor Surveillance System (BRFSS) national data collected in 2020. Data analysis using weighted Chi-square test and weighted logistic regression were carried out on 84,118 female study participants from the United States. RESULTS: Women with diabetes mellitus were approximately twice as likely to have endometrial cancer compared to women without diabetes (OR 1.54; 95%CI: 1.01-2.34). Biologic factors that included obesity (OR 3.10; 95% CI: 1.96-4.90) and older age (with ORs ranging from 2.75 to 7.21) had a significant increase in the odds of endometrial cancer compared to women of normal weight and younger age group of 18 to 44. Among the SDOH, attending college (OR 1.83; 95% CI: 1.12-3.00) was associated with increased odds of endometrial cancer, while renting a home (OR 0.50; 95% CI: 0.28-0.88), having other arrangements (OR 0.05; 95% CI: 0.02-0.16), being divorced (OR 0.55; 95% CI: 0.30-0.99), and having higher incomes ranging from $35,000 to $50,000 (OR 0.35; 95% CI: 0.16-0.78), and above $50,000 (OR 0.29; 95% CI: 0.14-0.62), were all associated with decreased odds of endometrial cancer. As for race, Black women (OR 0.24; 95% CI: 0.07-0.84) and women of other races (OR 0.37; 95% CI: 0.15-0.88) were shown to have lower odds of endometrial cancer compared to White women. CONCLUSION: Our results revealed the importance of adopting a comprehensive approach to the study of the associated factors of endometrial cancer by including social, biologic, and behavioral determinants of health. The observed social inequity in endometrial cancer among women needs to be addressed through effective policies and changes in social structures to advocate for a standardized healthcare system that ensures equitable access to preventive measures and quality of care.

Preparation of coated MgFe layered double hydroxide nanoparticles on cement kiln dust and intercalated with sodium dodecyl sulfate as an intermediate layer for the adsorption of estrogen from water.

Estrogenic hormones, found as micropollutants in water systems, give rise to grave concerns for human health and marine ecosystems, triggering a cascade of adverse effects. This research presents an innovative manufacturing approach using nanoscale layered double hydroxides of magnesium and iron, with sodium dodecyl sulfate surfactant, to create highly efficient sorbent cement kiln dust (CKD) based beads (CKD/MgFe-SDS-LDH-beads). These beads effectively remove estrone from water. Optimization of the preparation process considered factors like molar Mg/Fe ratio, CKD dosage, pH, and SDS dosage using Response Surface Methodology (RSM). The adsorption process was well-characterized by Langmuir isotherm and pseudo-second-order kinetic models, demonstrating a remarkable 6.491 mg/g sorption capacity. Results proved that the calcite was the main component of the CKD with miners of dolomite, and quartz. Adsorption capacity, surface charges, and the availability of vacant sites may be the main mechanisms responsible of removal process. Experimental tests confirmed the beads' potential for estrone removal, aligning with the Bohart-Adams and Thomas-BDST models. This study introduces a promising, eco-friendly solution for addressing water contamination challenges.

Social and racial inequalities in diabetes and cancer in the United States.

Background: Cancer and diabetes are among the leading causes of morbidity and mortality worldwide. Several studies have reported diabetes as a risk factor for developing cancer, a relationship that may be explained by associated factors shared with both diseases such as age, sex, body weight, smoking, and alcohol consumption. Social factors referred to as social determinants of health (SDOH) were shown to be associated with the risk of developing cancer and diabetes. Despite that diabetes and social factors were identified as significant determinants of cancer, no studies examined their combined effect on the risk of developing cancer. In this study, we aim at filling this gap in the literature by triangulating the association between diabetes, indices of SDOH, and the risk of developing cancer. Methods: We have conducted a quantitative study using data from the Behavioral Risk Factor Surveillance System (BRFSS), whereby information was collected nationally from residents in the United States (US) with respect to their health-related risk behaviors, chronic health conditions, and the use of preventive services. Data analysis using weighted regressions was conducted on 389,158 study participants. Results: Our findings indicated that diabetes is a risk factor that increases the likelihood of cancer by 13% (OR 1.13; 95%CI: 1.05-1.21). People of White race had higher odds for cancer compared to African Americans (OR 0.44; 95%CI: 0.39-0.49), Asians (OR 0.27; 95%CI: 0.20-0.38), and other races (OR 0.56; 95%CI: 0.46-0.69). The indices of SDOH that were positively associated with having cancer encompassed unemployment (OR 1.78; 95%CI: 1.59-1.99), retirement (OR 1.54; 95%CI: 1.43-1.67), higher income levels with ORs ranging between 1.16-1.38, college education (OR 1.10; 95%CI: 1.02-1.18), college graduates (OR 1.31; 95%CI: 1.21-1.40), and healthcare coverage (OR 1.44; 95%CI: 1.22-1.71). On the other hand, the indices of SDOH that were protective against having cancer were comprised of renting a home (OR 0.86; 95%CI: 0.79-0.93) and never married (OR 0.73; 95%CI: 0.65-0.81). Conclusion: This study offers a novel social dimension for the association between diabetes and cancer that could guide setting strategies for addressing social inequities in disease prevention and access to healthcare.

Eco-friendly remediation of tetracycline antibiotic from polluted water using waste-derived surface re-engineered silica sand.

A new green reactive adsorbent (calcium ferric oxide silica sand (CFO-SS)) made from wastepaper sludge ash and ferric ions was synthesised and shown to remove tetracycline antibiotics (TC) from contaminated water effectively. The synthesised sand was dried at 95 °C, and a series of batch and fixed bed experiments were performed to determine the optimum operating conditions. Results showed that the adsorption capacity of the CFO-SS increases with the concentration gradient between the solid and liquid phases. 0.3 g of the new adsorbent was proven sufficient to remove more than 90% of the TC at a pollutant dose of 50 mg/L in 50 mL of simulated groundwater with an agitation speed of 200 rpm for 3 h. The adsorption isotherm followed the Langmuir isotherm model, with a loading capacity of 21.96 mg/g at pH 7, while the Pseudo second-order model best described the absorption kinetics. The adsorption mechanisms proposed included electrostatic interaction, intraparticle diffusion, hydrogen bonding, and cation-π interactions. Characterisation investigations revealed that the newly precipitated oxides on silica sand play an essential role in TC adsorption support. In fixed-bed experiments, it was discovered that reducing the flow rate and inflow concentration of TC and increasing the sorbent mass significantly extended the lifetime of the produced sorbent in the packed column. The measured breakthrough curves were best fit with the Adams-Bohart and the Clark models, as they provided the highest square root number (R2) values. Finally, considering the efficacy of CFO-SS in TC adsorption performance, it can be noted that the novel synthesised reactive material is an efficient and environmentally friendly material for TC removal, and it presents a potential solution to resolving the challenge of TC-rich groundwater.

ACCEPTANCE OF THE COVID-19 VACCINE AND ITS RELATED FACTORS AMONG IRAQI ADOLESCENTS: A CROSS-SECTIONAL STUDY.

OBJECTIVE: The aim: To evaluate the acceptance rate of COVID-19 vaccine among adolescents and exploring the association factors that affect the acceptability of the vaccine. PATIENTS AND METHODS: Materials and methods: The study is descriptive cross-sectional study based on online survey conducted on 541 adolescents in Iraqi middle Euphrates provinces. Survey data was collected from November 28, 2021 to April 20, 2022. RESULTS: Results: The study showed that about 53% (288 adolescents out of total 541) had not been vaccinated yet and approximately 55% of the not vaccinated adolescents refused to take the vaccine. The mean reasons of this hesitancy were falsified information, insufficient information, concerned about safety and effectiveness of the vaccine. The parents whether infected with COVID-19 or vaccinated considered as strong independent factors that will increase acceptance of vaccination among the adolescents while afraid from the vaccine was considerable independent factor that decrease the acceptance rate. CONCLUSION: Conclusions: High hesitancy rate toward COVID-19 vaccination among adolescents and their parents play significant role model in increasing the acceptability while concerning of the vaccine safety decreasing acceptability.

Subsurface flow constructed wetlands for treating of simulated cadmium ions-wastewater with presence of Canna indica and Typha domingensis.

The presence of toxic cadmium ions in the wastewater resulted from industrial sector forms the critical issue for public health and ecosystem. This study determines the ability of four vertical subsurface flow constructed wetlands units in the treatment of simulated wastewater laden with cadmium ions. This was achieved through using sewage sludge byproduct as alternative for the traditional sand to be substrate for aforementioned units in order to satisfy the sustainable concepts; however, Canna indica and Typha domingensis can apply to enhance the cadmium removal. The performance of constructed wetlands has been evaluated through monitoring of the pH, dissolved oxygen (DO), temperature, and concentrations of cadmium (Cd) in the effluents for retention time (0.5-120 h) and metal concentration (5-40 mg/L). The results demonstrated that the Cd removal percentage was exceeded 82% beyond 5 days and for concentration of 5 mg/L; however, this percentage was decreased with smaller retention time and higher metal concentration. The Grau second-order kinetic model accurately simulated the measurements of effluent Cd concentrations as a function of retention times. The FT-IR analysis indicated the existence of certain functional groups capable of enhancing the Cd removal. The treated wastewater's pH, DO, temperature, total dissolved solids (TDS), and electrical conductivity (EC) all meet the requirements for irrigation water.

Controlling metal ion migration in contaminated groundwater with Iraqi clay barriers for water resource protection.

This study investigates the effectiveness of using Iraqi clay as a low-permeability layer to prevent the migration of lead and nickel ions in groundwater-aquifers. Tests of batch operation have been conducted to determine the optimal conditions for removing Pb2+ ions, which were found to be 120 minutes of contact time, a pH of 5, 0.12 g of clay per 100 mL of solution, and an agitation of 250 rpm. These conditions resulted in a 90% removal efficiency for a 50 mg L-1 initial concentration of lead ions. To remove nickel ions with an efficiency of 80%, the optimal conditions were 60 minutes of contact time, a pH of 6, 12 g of clay per 100 mL of solution, and an agitation of 250 rpm. Several sorption models were evaluated, and the Langmuir formula was found to be the most effective. The highest sorption capacities were 1.75 and 137 mg g-1 for nickel and lead ions, respectively. The spread of metal ions was simulated using finite element analysis in the COMSOL multiphysics simulation software, taking into account the presence of a clay barrier. The results showed that the barrier creates low-discharge zones along the down-gradient of the barrier, reducing the rate of pollutant migration to protect the water sources.

RNA-sequencing revealed apple pomace ameliorates expression of genes in the hypothalamus associated with neurodegeneration in female rats fed a Western diet during adolescence to adulthood.

OBJECTIVES: Apple pomace, a waste byproduct of apple processing, is rich in nutrients (e.g. polyphenols and soluble fiber) with the potential to be neuroprotective. The aim of this study was to employ RNA-sequencing (RNASeq) technology to investigate diet-gene interactions in the hypothalamus of rats after feeding a Western diet calorically substituted with apple pomace. METHODS: Adolescent (age 21-29 days) female Sprague-Dawley rats were randomly assigned (n = 8 rats/group) to consume either a purified standard diet, Western (WE) diet, or Western diet calorically substituted with 10% apple pomace (WE/AP) for 8 weeks. RNA-seq was performed (n = 5 rats/group) to determine global differentially expressed genes in the hypothalamus. RESULTS: RNA-seq results comparing rats fed WE to WE/AP revealed 15 differentially expressed genes in the hypothalamus. Caloric substitution of WE diet with 10% apple pomace downregulated (q < 0.06) five genes implicated in brain aging and neurodegenerative disorders: synuclein alpha, phospholipase D family member 5, NADH dehydrogenase Fe-S protein 6, choline O-acetyltransferase, and frizzled class receptor 6. DISCUSSION: Altered gene expression of these five genes suggests that apple pomace ameliorated synthesis of the neurotransmitter, acetylcholine, in rats fed a WE diet. Apple pomace, a rich source of antioxidant polyphenols and soluble fiber, has been shown to reverse nonalcoholic fatty liver disease (NAFLD). Diet-induced NAFLD decreases hepatic de novo synthesis of choline, a precursor to acetylcholine. Based on preclinical evidence, apple pomace has the potential to be a sustainable functional food for maintaining brain function and for reducing the risk of neurodegeneration.

Polymeric nanoparticles in the diagnosis and treatment of myocardial infarction: Challenges and future prospects.

Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide. Despite extensive efforts to provide early diagnosis and adequate treatment regimens, detection of MI still faces major limitations and pathological MI complications continue to threaten the recovery of survivors. Polymeric nanoparticles (NPs) represent novel noninvasive drug delivery systems for the diagnosis and treatment of MI and subsequent prevention of fatal heart failure. In this review, we cover the recent advances in polymeric NP-based diagnostic and therapeutic approaches for MI and their application as multifunctional theranostic tools. We also discuss the in vivo behavior and toxicity profile of polymeric NPs, their application in noninvasive imaging, passive, and active drug delivery, and use in cardiac regenerative therapy. We conclude with the challenges faced with polymeric nanosystems and suggest future efforts needed for clinical translation.

Multibiomarker responses after exposure to a sublethal concentration of thiamethoxam in the African honeybee (Apis mellifera intermissa).

Thiamethoxam is an insecticide mainly used in agriculture to control insect pests. However, non-target insect species, such as honeybees, may also be impacted. In this study, adults of Apis mellifera intermissa were orally exposed under laboratory conditions to a sublethal concentration of thiamethoxam (CL25= 0.17 ng/µl) for 9 days and the effects were evaluated at the biochemical level, by monitoring specific oxidative stress and neuronal biomarkers. Results showed an increase in the antioxidant enzymes, glutatione-S-transferase (GST), catalase (CAT) and glutathione peroxidase (GPx) and in content of malondialdehyde (MDA). The activity of acetylcholinesterase (AChE) was downregulated as evidence of a neurotoxic action and no significant change was observed in glutathione (GSH). Exposure to the insecticide thiamethoxam induced oxidative stress and defense mechanisms affecting honeybee physiology.

Effect of different surface treatments on the microhardness and colour change of artificial enamel lesions.

BACKGROUND: To investigate the effect of three different surface treatments on the microhardness and colour change of artificial enamel lesions. MATERIALS AND METHODS: One hundred bovine teeth were randomly assigned into four groups. Artificial enamel lesions were created using demineralizing solution for all groups except the sound enamel group. Different surface treatments were then performed G1: resin-infiltrant; G2: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP); G3: artificial saliva; G4: Sound Enamel. Each group was subdivided into three subgroups, where each subgroup was subjected to a different testing method. Subgroup 1: surface microhardness; subgroup 2: cross-sectional microhardness; subgroup 3: colour measurement. Statistical analysis was performed by ANOVA, followed by Tukey's post hoc test. RESULTS: Sound enamel group recorded the highest surface and cross-sectional microhardness results. No significant difference was found between the resin-infiltrant group and CPP-ACP regarding surface and cross-sectional microhardness at different lesion depths. Resin-infiltrant group showed the least colour change (∆E) results compared to the other groups. CONCLUSION: Resin-infiltrant can effectively enhance surface microhardness and enamel resistance to demineralization, additionally, reduces the staining susceptibility of white spot lesions (WSLs) after treatment. CPP-ACP application for 4 weeks seems to improve surface microhardness; however, has a limited effect in resisting staining of WSLs after treatment. © 2022 Australian Dental Association.

Type III secretion by Yersinia pseudotuberculosis is reliant upon an authentic N-terminal YscX secretor domain.

YscX was discovered as an essential part of the Yersinia type III secretion system about 20 years ago. It is required for substrate secretion and is exported itself. Despite this central role, its precise function and mode of action remain unknown. In order to address this knowledge gap, this present study refocused attention on YscX to build on the recent advances in the understanding of YscX function. Our experiments identified an N-terminal secretion domain in YscX promoting its secretion, with the first five codons constituting a minimal signal capable of promoting secretion of the signal less ß-lactamase reporter. Replacing the extreme YscX N-terminus with known secretion signals of other Ysc-Yop substrates revealed that the YscX N-terminal segment contains non-redundant information needed for YscX function. Further, both in cis deletion of the YscX N-terminus in the virulence plasmid and ectopic expression of epitope-tagged YscX variants again lead to stable YscX production but not type III secretion of Yop effector proteins. Mislocalisation of the needle components, SctI and SctF, accompanied this general defect in Yops secretion. Hence, a coupling exists between YscX secretion permissiveness and the assembly of an operational secretion system.

Precipitation of (Mg/Fe-CTAB) - Layered double hydroxide nanoparticles onto sewage sludge for producing novel sorbent to remove Congo red and methylene blue dyes from aqueous environment.

Preparation of new sorbent from precipitation of nano-sized (Mg/Fe-CTAB)- layered double hydroxide (LDH) on the surfaces of sewage sludge byproduct to remove the anionic and cationic dyes was the focal point of this work. The presence of nanoparticles and enlarged of interlayers by CTAB intercalation have increased the sludge surface area from 5.34 to 10.32 m2/g. The CTAB mass 0.03 g/50 mL, sludge dosage 1 g/50 mL and (Mg/Fe) molar ratio 2 were the best preparation conditions required to obtain effective sorbent with efficiencies exceeded 93% for MB and CR dyes. These efficiencies were obtained under operational conditions for batch study of 0.5 g coated sludge per 50 mL colored dye solution, initial pH 3 (for CR) and 12 (for MB), and time 3 h for 10 mg/L dyes at 200 rpm. Models of Langmuir and pseudo second-order have a high capability in the representation of sorption records with maximum capacities of adsorption 163.6 and 132.6 mg/g for CR and MB dye, respectively. The X-ray diffraction analysis proved that the calcite occurred mainly at 2θ = 29.8° while quartz corresponded to the 21, 26.6, 36.4, 36.9, 50.1, 60.01 and 68.4°. Characterization tests showed that nano-sized particles of magnesium/iron were precipitated on the sludge due to the formation of hydrotalcite-like compounds with an increase in the percentages of Mg and Fe from 0.87 and 1.36 to 4.25 and 3.03%, respectively. The results showed that the electrostatic attraction, intra-particle diffusion and hydrogen bonding were predominant mechanisms for removal of CR and MB onto coated sludge.

Shared parameter and copula models for analysis of semicontinuous longitudinal data with nonrandom dropout and informative censoring.

Analysis of longitudinal semicontinuous data characterized by subjects' attrition triggered by nonrandom dropout is complex and requires accounting for the within-subject correlation, and modeling of the dropout process. While methods that address the within-subject correlation and missing data are available, approaches that incorporate the nonrandom dropout, also referred to informative right censoring, in the modeling step are scarce due to the computational intensity and possible intractable integration needed for its implementation. Appreciating the complexity of this problem and the need for a new methodology that is feasible for implementation, we propose to extend a framework of likelihood-based marginalized two-part models to account for informative right censoring. The censoring process is modeled using two approaches: (1) Poisson censoring for the count of visits before dropout and (2) survival time to dropout. Novel consideration was given to the proposed joint modeling approaches for the semicontinuous and censoring components of the likelihood function which included (1) shared parameter, and (2) Clayton copula. The cross-part and within-part correlations were accounted for through a complex random effect structure that models correlated random intercepts and slopes. Feasibility of implementation, and accuracy of these approaches were investigated using extensive simulation studies and clinical application.

Modulation of Neuro-Inflammatory Signals in Microglia by Plasma Prekallikrein and Neuronal Cell Debris.

Microglia, the resident phagocytes of the central nervous system and one of the key modulators of the innate immune system, have been shown to play a major role in brain insults. Upon activation in response to neuroinflammation, microglia promote the release of inflammatory mediators as well as promote phagocytosis. Plasma prekallikrein (PKall) has been recently implicated as a mediator of neuroinflammation; nevertheless, its role in mediating microglial activation has not been investigated yet. In the current study, we evaluate the mechanisms through which PKall contributes to microglial activation and release of inflammatory cytokines assessing PKall-related receptors and their dynamics. Murine N9-microglial cells were exposed to PKall (2.5 ng/ml), lipopolysaccharide (100 ng/ml), bradykinin (BK, 0.1 µM), and neuronal cell debris (16.5 µg protein/ml). Gene expression of bradykinin 2 receptor (B2KR), protease-activated receptor 2 (PAR-2), along with cytokines and fibrotic mediators were studied. Bioinformatic analysis was conducted to correlate altered protein changes with microglial activation. To assess receptor dynamics, HOE-140 (1 µM) and GB-83 (2 µM) were used to antagonize the B2KR and PAR-2 receptors, respectively. Also, the role of autophagy in modulating microglial response was evaluated. Data from our work indicate that PKall, LPS, BK, and neuronal cell debris resulted in the activation of microglia and enhanced expression/secretion of inflammatory mediators. Elevated increase in inflammatory mediators was attenuated in the presence of HOE-140 and GB-83, implicating the engagement of these receptors in the activation process coupled with an increase in the expression of B2KR and PAR-2. Finally, the inhibition of autophagy significantly enhanced the release of the cytokine IL-6 which were validated via bioinformatics analysis demonstrating the role of PKall in systematic and brain inflammatory processes. Taken together, we demonstrated that PKall can modulate microglial activation via the engagement of PAR-2 and B2KR where PKall acts as a neuromodulator of inflammatory processes.

A Comprehensive Review for Groundwater Contamination and Remediation: Occurrence, Migration and Adsorption Modelling.

The provision of safe water for people is a human right; historically, a major number of people depend on groundwater as a source of water for their needs, such as agricultural, industrial or human activities. Water resources have recently been affected by organic and/or inorganic contaminants as a result of population growth and increased anthropogenic activity, soil leaching and pollution. Water resource remediation has become a serious environmental concern, since it has a direct impact on many aspects of people's lives. For decades, the pump-and-treat method has been considered the predominant treatment process for the remediation of contaminated groundwater with organic and inorganic contaminants. On the other side, this technique missed sustainability and the new concept of using renewable energy. Permeable reactive barriers (PRBs) have been implemented as an alternative to conventional pump-and-treat systems for remediating polluted groundwater because of their effectiveness and ease of implementation. In this paper, a review of the importance of groundwater, contamination and biological, physical as well as chemical remediation techniques have been discussed. In this review, the principles of the permeable reactive barrier's use as a remediation technique have been introduced along with commonly used reactive materials and the recent applications of the permeable reactive barrier in the remediation of different contaminants, such as heavy metals, chlorinated solvents and pesticides. This paper also discusses the characteristics of reactive media and contaminants' uptake mechanisms. Finally, remediation isotherms, the breakthrough curves and kinetic sorption models are also being presented. It has been found that groundwater could be contaminated by different pollutants and must be remediated to fit human, agricultural and industrial needs. The PRB technique is an efficient treatment process that is an inexpensive alternative for the pump-and-treat procedure and represents a promising technique to treat groundwater pollution.

Discovery of a potent and dual-selective bisubstrate inhibitor for protein arginine methyltransferase 4/5.

Protein arginine methyltransferases (PRMTs) have been implicated in the progression of many diseases. Understanding substrate recognition and specificity of individual PRMT would facilitate the discovery of selective inhibitors towards future drug discovery. Herein, we reported the design and synthesis of bisubstrate analogues for PRMTs that incorporate a S-adenosylmethionine (SAM) analogue moiety and a tripeptide through an alkyl substituted guanidino group. Compound AH237 is a potent and selective inhibitor for PRMT4 and PRMT5 with a half-maximal inhibition concentration (IC50) of 2.8 and 0.42 nmol/L, respectively. Computational studies provided a plausible explanation for the high potency and selectivity of AH237 for PRMT4/5 over other 40 methyltransferases. This proof-of-principle study outlines an applicable strategy to develop potent and selective bisubstrate inhibitors for PRMTs, providing valuable probes for future structural studies.